Early mortality from malignant mesothelioma in Italy as a proxy of environmental exposure to asbestos in children.

Malignant mesothelioma (MM) is a rare neoplasm caused by asbestos. Mortality from MM in ≤50 years old people, considering the long latency, is likely related to asbestos exposure in childhood. Mortality from MM (C45, ICD10 code) is described among ≤50 years (ys) old people in Italy, in 2003-2016. National and regional Standardized Rates (SRs) were computed by age-class. The North-South trend of regional SRs, increasing in >50ys age-class, showed a flat cline in ≤50ys old people. Municipal Standardized Mortality Ratios (SMRs) were computed, with respect to regional figures, for ≤50 ys old population. In Italy, 487 people ≤50 ys old died from MM, in 2003-2016 (2.5% of all MM deaths), corresponding to 35/year. The highest SMRs were observed in Northern Regions, the most industrialized areas. Exceeding SMRs were found in 10 municipalities where former asbestos-cement plants, shipyards, and a quarry contaminated by fluoro-edenite fibres were present. Early mortality from MM, proxy of childhood environmental asbestos exposure, deserves particular concern.

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.

Epidemiological surveillance of mesothelioma mortality in Italy.

BACKGROUND: Malignant mesothelioma (MM) is causally linked to asbestos exposure with an estimated etiological fraction of 80% or more. METHODS: Standardized rates of all mesothelioma (C45, ICD-10) and malignant pleural mesothelioma (C45.0, ICD-10) mortality in Italy were computed at national and regional levels, for the period 2003-2014. Standardized Mortality Ratios (SMRs, with 95% Confidence Intervals) were calculated for each of the 8047 Italian municipalities, for both diseases, with respect to Regional figures. A geographical clustering analysis at municipal level was performed, applying SatScan methods. RESULTS: In Italy, 16,086 persons (about 1,340/year) died for MM, in analysed period. National Standardized rates of MM mortality are 3.65/100,000 in men and 1.09/100,000 in women, with an increasing annual trend, among male population. The highest rates were found in men from Northern Regions. Significant clusters (p < 0.10) were found corresponding to areas that hosted major asbestos-cement plants, naval shipyards, petrochemical plants and refineries. Furthermore, excesses were found corresponding to chemical and textile industries; the latter involving, particularly, female population. Excesses were found also in areas near the chrysotile mine of Balangero, and in Biancavilla, a town with a stone quarry contaminated by fluoro-edenitic fibres; an excess of MM mortality was observed among male population living in a minor island where a Navy shipyard is located. CONCLUSIONS: Mortality for mesothelioma in Italy is still increasing, twenty-six years after the asbestos ban. Epidemiological surveillance of mesothelioma mortality allows to detect the temporal trend of the disease and highlights previously unknown or underestimated sources of asbestos exposure.

[Health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy)]. / Impatto sulla salute delle fibre di amianto presenti in affioramenti naturali nell'area del Pollino (Basilicata).

OBJECTIVES: to estimate the health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy). DESIGN: geographic mortality, hospitalization, and incidence study. Setting and participant s: population resident in 12 Municipalities of Mount Pollino area with naturally occurring asbestos fibres. MAIN OUTCOME MEASURES: standardized mortality ratio (SMR) and standardized hospitalization rate (SHR) for asbestos-related diseases; standardized incidence ratio (SIR) for mesotheliomas. Result s: in the area of Mount Pollino, where asbestos fibres naturally occur, especially in the sub-area in which fibres are close to dwellings and settlements, it was observed: • a significant excess of mesothelioma incidence (SIR: 208; CI95% 111-355; 13 observed); • a non-significant excess of hospitalization for malignant pleural neoplasms (SHR: 176; CI95% 93-335; 9 observed); • a significant excess for mortality and hospitalization for pneumoconiosis (SMR: 534; CI95% 345-824; 20 observed - SHR: 245; CI95% 149-405; 15 observed); • a significant excess for hospitalization (SHR: 852; CI95% 290-2,506; 3 observed) for asbestosis. CONCLUSION: it is necessary to continue environmental monitoring and environmental remediation in the area with higher asbestos exposure. It is suggested to implement a permanent process of epidemiological surveillance in this same area. A communication plan with local administrators, general practitioners, school teachers, media, and the resident population at large should be realized.

Spatial distribution of kidney disease in the contaminated site of Taranto (Italy).

BACKGROUND: Exposure to heavy metals has been associated with kidney disease. We investigated the spatial distribution of kidney disease in the industrially contaminated site of Taranto. METHODS: Cases were subjects with a first hospital discharge diagnosis of kidney disease. Cases affected by specific comorbidities were excluded. Standardized Hospitalization Ratios (SHRs) were computed for low/high exposure area and for modeled spatial distribution of cadmium and fine particulate matter. RESULT: Using the high/low exposure approach, in subjects aged 20-59 years residing in the high exposure area a significant excess of hospitalization was observed in males and a non-significant excess in females. No excesses were observed in subjects aged 60 years and over. The analysis by the modeling approach did not show a significant association with the greatest pollution impact area. CONCLUSION: Due to the excesses of hospitalization observed in the high/low exposure approach, a continuing epidemiological surveillance of residents and occupational groups is warranted.

Congenital Anomalies in Contaminated Sites: A Multisite Study in Italy.

The health impact on populations residing in industrially contaminated sites (CSs) is recognized as a public health concern especially in relation to more vulnerable population subgroups. The aim of this study was to estimate the risk of congenital anomalies (CAs) in Italian CSs. Thirteen CSs covered by regional CA registries were investigated in an ecological study. The observed/expected ratios (O/E) with 90% confidence intervals (CI) for the total and specific subgroups of CAs were calculated using the regional areas as references. For the CSs with waste landfills, petrochemicals, and refineries, pooled estimates were calculated. The total number of observed cases of CAs was 7085 out of 288,184 births (prevalence 245.8 per 10,000). For some CSs, excesses for several CA subgroups were observed, in particular for genital and heart defects. The excess of genital CAs observed in Gela (O/E 2.36; 90% CI 1.73-3.15) is consistent with findings from other studies. For CSs including petrochemical and landfills, the pooled risk estimates were 1.10 (90% CI 1.01-1.19) and 1.07 (90% CI 1.02-1.13), respectively. The results are useful in identifying priority areas for analytical investigations and in supporting the promotion of policies for the primary prevention of CAs. The use of short-latency effect indicators is recommended for the health surveillance of the populations residing in CSs.

Reference rates for cohort studies in Italy: an essential tool in occupational and residential cohort studies. / Aggiornamento dei tassi di mortalità in Italia, strumento fondamentale per la conduzione di studi di coorte occupazionali e residenziali.

The cohort study aims to test the hypothesis of an association between specific exposure/s and adverse health outcomes. The cohorts include the subjects who experience the exposure/s and are followed up over time to ascertain the health outcomes. This contribution presents the database for the analysis of mortality studies which is made available for public institutions carrying out cohort studies in Italy. The rates were computed from official mortality data from ISTAT. The database contains 141 causes or groups of causes for the years 1970-2012 ensuring correspondence with subsequent editions of ICD (International Classification of Diseases) VIII, IX and X.

[SENTIERI-ReNaM: Integration of incidence, mortality, and hospitalization: general remarks and a focus on mesothelioma]. / SENTIERI-ReNaM: Integrazione di incidenza, mortalità e ospedalizzazione: considerazioni generali e applicazione al mesotelioma.

The integration of current data sources is now a practice widely used in epidemiology, especially in the environmental field. To better describe the health profile of populations residing in proximity to areas characterized by a "strong environmental pressure", the combined use of multiple indicators (i.e., mortality, hospitalization, cancer incidence) is recommended. To choose an indicator is complex, as indicators should be contextualized and they need to be related to the several issues involved in the studied pathology. This chapter explores the general considerations that are to be addressed both at the time of the study design, during the selection of outcomes and of the proper data sources, and at the time of the discussion of the results, when different and complementary data are compared. A special focus is devoted to the case of mesothelioma.

[SENTIERI-ReNaM: Discussion and concluding remarks]. / SENTIERI-ReNaM: Discussione e considerazioni conclusive.

SENTIERI-ReNaM Project analysed the incidence of malignant mesothelioma (MM) for the period 2000-2011 in 39 National Priority Contaminated Sites (NPCSs), and assessed the overall impact of mesothelioma in different types of NPCSs. In the study period, 2,683 incident cases of malignant mesothelioma were recorded: 1,998 males (74.5%), 685 females (25.5%). Excluding cases with non attributable exposure and those non interviewed, exposure was identified in 1,926 cases (70% of all cases): 1,541 males (occupational exposure: 1,414; environmental exposure: 82), 385 females (occupational exposure: 103; environmental exposure: 141). Women experienced mainly environmental and domestic exposures to asbestos. Standard Incidence Ratio (SIR) excesses were observed in men in 27 out of 39 NPCSs and defects in the remaining 12; in women, 20 NPCSs showed SIR excesses, defects in 15; in 4 NPCSs no MM cases occurred among female population. The highest rates were found in NPCSs with asbestos-cement plants (Broni and Casale Monferrato), respectively, 98 per 100,000 per year and 68.6 in men, 72.1 and 45.8 in women. Excluding these two sites, the highest incidence rates were found in the group with harbours and shipyards, where the rates were, respectively, 13.2 among men and 2.5 among women. The results of this report will be communicated to national and local institutions, as well as to NPCSs resident populations.

Peritoneal mesothelioma in Italy: Trends and geography of mortality and incidence.

INTRODUCTION: Peritoneal mesothelioma, a very rare and lethal malignancy, has not been investigated as extensively as pleural mesothelioma, although the role of asbestos exposure in its occurrence is well-known. Data from Italy are relevant, as it was the largest European asbestos producer, and asbestos was widely used in many economic activities. METHODS: A population-based mortality and incidence analysis was performed in Italy. Data sources were the National Multiple-causes-of-death Database (1995-2010) and the Italian Mesothelioma Register (1993-2008). RESULTS: We found an increasing trend of age standardized mortality rates in men, but no clear trend in women; moreover, we showed significant risks of death in several northern regions, formerly heavy asbestos users; finally, mortality/incidence ratios similar for both genders (about 0.8) were estimated. CONCLUSIONS: The study, based on national data, showed a higher risk of mortality from and incidence of peritoneal mesothelioma in areas with formerly heavy exposure to asbestos.

[SENTIERI Project: rationale and objectives]. / Razionale e obiettivi del Progetto SENTIERI.

The Istituto Superiore di Sanità (National Institute of Health-ISS), in partnership with a network of Italian national and regional scientific institutions, initiated the SENTIERI Project (Epidemiological Study of Residents in Italian Contaminated Sites-NPCSs), the objectives, methods and initial results of which were published by Epidemiologia & Prevenzione in 2010 and 2011. In the course of 2013, some of the SENTIERI Project findings were published in international scientific journals, and the "SENTIERI approach" was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. The present Report, set up jointly by ISS and the Italian Network of Cancer Registries (AIRTUM), as anticipated in the 2011 Report, aims to provide, for each of the 18 National Priority Contaminated Sites included in the SENTIERI Project where the Italian Association of Cancer Registries is active, a mortality update to 2010, analyses of cancer incidence (1996-2005 in 17 NPCSs) and of hospital discharges (2005-2010), as is explained in detail in Chapter 2, pertaining to the project's materials and methods. The results of the analyses for each NPCS are presented in Chapter 3, while Chapter 4 includes a critical appraisal, a discussion of the methodological approach and a series of concluding remarks. The second section of the Report takes an in-depth look at important issues of public health and scientific research in contaminated sites. This Report represents an important step towards implementing a permanent epidemiological surveillance system in Italy's contaminated sites, the ultimate goal of the SENTIERI Project.

[SENTIERI Project: materials and methods]. / Materiali e metodi del Progetto SENTIERI.

The Report considers three health outcomes - mortality, cancer incidence and hospital discharges - studied using homogenous methods and using data from official sources, namely the National Institute of Statistics (Istat), Italian Network of Cancer Registries (AIRTUM) and the Health Ministry. The timeframes of observation are: 2003-2010 for mortality, 1996-2005 for cancer incidence and 2005-2010 for hospital discharges. The causes of death are those examined by the SENTIERI Project. Hospital discharges are analysed with reference to the main diagnosis. The study of cancer incidence applies to the sites selected by AIRTUM. Statistical parameters (SMR, Standardized Mortality Ratio; SIR, Standardized Incidence Ratio; SHR, Standardized Hospitalization Ratio) were computed with a 90% confidence interval; the estimators were adjusted for age and socioeconomic status.

[SENTIERI Project: results]. / Risultati del Progetto SENTIERI.

Of the 18 National Priority Contaminated Sites (NPCSs) analysed in this Report, some have a single source of environmental contamination (such as fluoro-edenite in Biancavilla). In most cases, however, we are looking at multiple heterogeneous sources of contamination. In this respect, the a priori causal evaluation of the association between diseases and environmental exposures in NPCSs, based on epidemiological evidence, can help trace the health impact back to specific types of environmental exposure. There are several cases in which the project's findings have been consistent with a priori evidence: stomach cancer (both genders, excess cancer incidence) in the Fidenza NPCS; stomach cancer (women, excess mortality, cancer incidence and hospital discharges) in the Laguna di Grado e Marano NPCS; excess hospitalisation from respiratory diseases in Brescia-Caffaro, Milazzo and Terni Papigno NPCSs; excesses for non-Hodgkin lymphomas and melanoma (incidence and hospitalisation in men and women) and breast cancer (incidence and hospital discharges, women) in Brescia-Caffaro NPCS. In preorder to properly evaluate the population's health profile, we must also observe whether results remain consistent for all three health outcomes or in both genders. The first is the case of excess mortality, cancer incidence and hospital discharges for bladder cancer (men) in Porto Torres and diseases of the urinary tract in the Basso bacino del fiume Chienti NPCS). Gender consistency is observed, for instance, for all cancer in Bolzano, Porto Torres, Venice, Litorale Domizio Flegreo, Priolo, and Taranto, for all causes in Taranto, Litorale Domizio Flegreo and Trieste. The health impact in the various NPCSs needs to be considered carefully and used as a springboard for further analytical research that could confirm and explain causal links to specific environmental exposures. The observations can, however, already be considered as a basis for mandatory primary prevention measures.

[SENTIERI Project: discussion and conclusions]. / Discussione e conclusioni del Progetto SENTIERI.

The SENTIERI Project represents the first comprehensive analysis of the health impact of residence in National Priority Contaminated Sites (NPCSs). For the first time, it considers three distinct health outcomes: mortality (2003-2010), cancer incidence (1996- 2005) and hospital discharges (2005-2010). The Report includes a commentary explaining methodology and approach, as well as remarks on the causal association between environmental exposures and investigated health outcomes based on the a priori assessments of the epidemiological evidence; the main implications for public health and scientific research priorities are also presented. The approach put forward by SENTIERI was among those sanctioned by the World Health Organization to conduct an initial description of the health status of residents of contaminated sites. Results relating to individual diseases that can be traced back to a single agent, such as asbestiform fibres, can be easily analysed. The Biancavilla NPCS (where the fluoro-edenite asbestiform fibre was found) displays excesses of pleural mesothelioma and its proxy, malignant pleural tumours, as does Priolo, where asbestos coexists with other pollutants. Increased risk was also recorded in NPCSs adjacent to the coast hosting harbour areas (such as Trieste, Taranto and Venice) or comprising industrial areas specialising in the production of chemicals (Laguna di Grado e Marano, Priolo and Venezia) and steel (Taranto, Terni, Trieste). Increases of pathologies, such as cancer and respiratory diseases, connected to more than one agent, in industrial sites with multiple and diverse sources of exposures, prove harder to interpret. There are also more complex cases in which results do not appear consistent in the three databases or by gender (such as lung cancer in Venice, where mortality and hospital discharges have only increased among women). In order to adequately examine these we must consider factors such as the appropriateness of the health outcome showing the increase, considering latency and the length of the observation period. Of further interest are results relating to diseases of the urinary tract such as kidney failure in the NPCSs of Basso bacino del fiume Chienti, Taranto, Milazzo and Priolo. Overall, the results discussed above are consistent with the previous findings pertaining to mortality for 1995-2002. The present analysis also introduces a new element - the study of cancer incidence and hospital discharges - which can tell us a great deal about diseases with high survival rates or non lethal ones. The first is the case of thyroid cancer, which presents increases in both databases and for both genders in a number of NPCSs (Brescia-Caffaro, Laghi di Mantova, Milazzo, Sassuolo- Scandiano and Taranto). The study of cancer incidence and hospital discharges also revealed cancer excesses for melanoma, breast cancer and non Hodgkin lymphoma in Brescia-Caffaro NPCS where PCBs (Polychlorinated biphenyl) are the site's main pollutant. PCBs, according to the 2013 evaluation of the International Agency for Research on Cancer, are ascertained human carcinogens for melanoma and probable carcinogens for breast cancer and non-Hodgkin lymphoma. The results pertaining to cancer incidence in the 17 NPCSs can also be presented using rankings by area or disease analyzed by a multivariate hierarchical Bayesian model. These rankings reveal an overlapping of credibility intervals, such that it is not possible to speak of a limited number of cancer sites or of certain NPCSs as being particularly affected. Every NPCS, therefore, must be considered individually and ordering them by ranking of cancer incidence wouldn't be appropriate. Data collected concerning some of the NPCSs in the context of the SENTIERI Project is so conclusive that remediation measures can immediately be put in place. This is the case in the Biancavilla and Brescia-Caffaro NPCSs. A similar conclusion can be drawn for complex locations such as Taranto, where, based on the results of SENTIERI Projects and the whole available information, we can safely conclude that exposure to environmental agents played an important role, allowing us to set in place 'Integrated evaluation of environmental and health impact procedures'. SENTIERI approach does not allow definitive causal assessments. However, as stated above, these results do provide a topic for further study without getting in the way of initiatives promoting urgent environmental remediation.

[SENTIERI KIDS: monitoring children's health in Italian polluted sites]. / SENTIERI KIDS: monitorare lo stato di salute infantile nei siti inquinati in Italia.

Protecting children's health from the effects of environmental contamination is a public health priority. In recent years, particular care has been devoted in Italy to the study of the relationship between environmental pollutants and health during infancy. The SENTIERI Project has called attention to increases in infant mortality in National Priority Contaminated Sites (NPCSs). SENTIERI KIDS provides a blueprint for the establishment of a task force charged with establishing multi and inter-disciplinary cooperation between central and regional institutions on the subject of children's health in contaminated sites. SENTIERI KIDS introduces a multiple outcome analytical model based on updated health outcomes (mortality, cancer incidence, hospital discharges) in order to establish a permanent observation system to monitor the state of health of infants residing in contaminated areas. This will pave the way for more in-depth epidemiological enquiries on an individual basis, and support the establishment and continued monitoring of primary prevention projects. Particular attention is devoted to issues of information and communication.

Health impact of the exposure to fibres with fluoro-edenitic composition on the residents in Biancavilla (Sicily, Italy): mortality and hospitalization from current data.

INTRODUCTION: The objective of this chapter is to study the health impact of the exposure to fibres with fluoro-edenitic composition on the residents in Biancavilla (Sicily, Italy), in terms of mortality and hospitalization. The diseases which international scientific literature indicates as associated with asbestos exposure were taken into consideration: mesothelioma of pleura, peritoneum, pericardium and tunica vaginalis testis, malignant neoplasm of larynx, malignant neoplasm of trachea, bronchus and lung, malignant neoplasm of ovary, pneumoconiosis; moreover, in order to describe the health profile of the study population, large groups of diseases were taken into consideration. MATERIAL AND METHODS: Current data (available in the Data Bases of the Unit of Statistics of ISS) regarding mortality and hospitalization were analyzed. Standardized Mortality Ratios, Standardized Hospitalization Ratios and Age-standardized Death Rates were calculated. The demographic background of the population residing in Biancavilla was also outlined. CONCLUSIONS: Our findings support the etiologic role of fibres with fluoro-edenitic composition in the occurrence of the above mentioned diseases, already observed in other studies.

The geographical pattern of thyroid cancer mortality between 1980 and 2009 in Italy.

BACKGROUND: Mortality for thyroid cancer (TC) is low and has been decreasing worldwide; yet few population studies based on mortality have been conducted. Several nonradiation risk factors have been associated with TC, including residence in goiter-endemic areas (as an indicator of iodine deficiency). We used mortality data to perform a spatial-temporal analysis regarding TC in Italy and investigated the association between mortality and socioeconomic status and geographical features (residing in a mountainous area is a proxy for iodine deficiency). METHODS: We analyzed data from Italy's National Mortality Database (1980-2009). To evaluate temporal trends in mortality the age-standardized death rate (ASR) was used; to identify geographic areas with excess deaths due to TC standardized mortality rates (SMR) were calculated. We also calculated the rate ratios (RR) of the ASR and the 95% CI by sex. We performed a cluster analysis to identify municipalities with major departures from expected mortality, both in the entire study period and in two separate periods to evaluate the spatial-temporal variability. Finally, we evaluated the association between mortality and index of deprivation and altitude. RESULTS: There were 16,473 deaths due to TC (10,690 females, 5783 males). The mean ASR was unsurprisingly low (0.58/100.000). There was a trend of decrease in mortality throughout Italy (-42% for 2007-2009 vs. 1980-1984), more pronounced among women. The decrease was greater in the north. Four geographic clusters were identified when considering the entire study period, two in the north and two in the south; however, the clusters in northern Italy refer to the earlier period (1980-1994) and those in southern Italy to the later period (1995-2009). Mortality was associated with residing in a mountainous area. A slight association with high socioeconomic status was found. CONCLUSIONS: This study reveals space-time differences in TC mortality in Italy. It shows an association between mortality and residing in mountainous areas, which is a proxy of iodine deficiency. The observed temporal north-south shift cannot be explained by socioeconomic differences, whereas the efficient prophylaxis program implemented in the 1980s in some areas of northern Italy can help to explain the disappearance of the clusters in those areas in the period 1995-2009.