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.

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.

Unmasking the Hidden Danger: A Decade-Long Systematic Review of Case-Control Studies on Single Occupational Risks and Prostate Cancer.

The present systematic review addresses the influence of occupational exposures on prostate cancer risk. Eleven studies were analyzed for a range of occupational exposures, including but not limited to firefighting, physical activity, night shift work, chemical exposure, and solar ultraviolet radiation. The results of the review reveal that firefighters exposed to harmful substances, individuals engaged in physically strenuous work, and workers with chronic night shift routines showed an increased likelihood of developing prostate cancer. Moreover, the review identified an increased risk associated with exposure to certain chemicals, including alkylphenolic compounds and benzene-related substances. The evidence underscores the importance of considering the cumulative effect of multiple risk factors in a comprehensive risk assessment. However, the conclusions indicate the necessity for further research to deepen these relationships and develop more effective strategies for the prevention of prostate cancer.

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.

[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.

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.

Changes in physical activity levels, eating habits and psychological well-being during the Italian COVID-19 pandemic lockdown: Impact of socio-demographic factors on the Florentine academic population.

The confinement and lockdown imposed by the COVID-19 pandemic have produced restrictions in the lifestyle of Italian citizens with variations in their psychological well-being. The aim of the study was to identify changes and relationship with socio-demographic parameters. An online survey was administered to 1383 subjects (1007 females and 307 males) working in the University of Florence, Italy. Three validated questionnaires were used for the survey: the Global Physical Activity Questionnaire, the Med Diet Score and the Psychological General Well-Being Index-A. All the subjects were asked to complete the questionnaires twice, in order to attain a picture of the habits before and a later time point during confinement. Our results show that work-related physical activity was decreased, along with an increase in sedentary behaviour (from 07:22±03:20 to 08:49±03:41 h:min; p<0.001, ES = 0.38), whereas recreational physical activity was increased (vigorous exercise varied from 568.5 ± 838.6 to 833.7 ± 1263.0 METs; p<0.002, ES = 0.25). Eating habits changed according to the place where meals were eaten, with an increased habit for breakfast and snacks and a slight increase in alcohol consumption. Psychological well-being decreased (Index from 21.4±3.9 to 18.0±5.3; p<0.001, ES = 0.723), especially in terms of vitality and positive thinking. The socio-demographic variables affecting these variations were mostly represented by age, gender and working conditions: young age and self-employment conditions can be considered factors for the changes in daily habits induced by confinement that may affect psychological well-being.

Estimate of environmental and occupational components in the spatial distribution of malignant mesothelioma incidence in Lombardy (Italy).

INTRODUCTION: Measuring and mapping the occurrence of malignant mesothelioma (MM) is a useful means to monitor the impact of past asbestos exposure and possibly identify previously unknown sources of asbestos exposure. OBJECTIVE: Our goal is to decompose the observed spatial pattern of incidence of MM in the Lombardy region (Italy) in gender-specific components linked to occupational exposure and a shared component linked to environmental exposure. MATERIALS AND METHODS: We selected from the Lombardy Region Mesothelioma Registry (RML) all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in the period 2000-2016. We mapped at municipality level crude incidence rates and smoothed rates using the Besag York and Mollié model separately for men and women. We then decomposed the spatial pattern of MM in gender-specific occupational components and a shared environmental component using a multivariate hierarchical Bayesian model. RESULTS: We globally analyzed 6226 MM cases, 4048 (2897 classified as occupational asbestos exposure at interview) in men and 2178 (780 classified as occupational asbestos exposure at interview) in women. The geographical analysis showed a strong spatial pattern in the distribution of incidence rates in both genders. The multivariate hierarchical Bayesian model decomposed the spatial pattern in occupational and environmental components and consistently identified some known occupational and environmental hot spots. Other areas at high risk for MM occurrence were highlighted, contributing to better characterize environmental exposures from industrial sources and suggesting a role of natural sources in the Alpine region. CONCLUSION: The spatial pattern highlights areas at higher risk which are characterized by the presence of industrial sources - asbestos-cement, metallurgic, engineering, textile industries - and of natural sources in the Alpine region. The multivariate hierarchical Bayesian model was able to disentangle the geographical distribution of MM cases in two components interpreted as occupational and environmental.

A Panel Study on Lung Function and Bronchial Inflammation among Children Exposed to Ambient SO2 from an Oil Refinery.

To determine the acute effects on respiratory function of children exposed to sulphur dioxide (SO2), we conducted two population-based longitudinal investigations near a major oil refinery. We enrolled 233 children, age 8⁻14, in Sarroch (Italy). The first study entailed five monthly spirometric visits (Panel 5). In a subgroup, children positive for history of respiratory symptoms were tested weekly (20 times) with spirometry and fractional exhaled nitric oxide (FeNO) measurement (Panel 20). Baseline questionnaires and daily diaries were recorded. SO2, NO2, PM10 and O3 were measured by monitoring stations. Multiple regression models were fitted. Using a multipollutant model, we found that a 10 µg/m³ SO2 increase at lag0⁻2 days determined a percent variation (PV) of -3.37 (90% confidence interval, CI: -5.39; -1.30) for forced expiratory volume after one second (FEV1) in Panel 5 and a PV = -3.51 (90% CI: -4.77; -2.23) in Panel 20. We found a strong dose-response relation: 1-h SO2 peaks >200 µg/m³ at lag2 days = FEV1 PV -2.49. For FeNO, we found a PV = 38.12 (90% CI: 12.88; 69.01) for each 10 µg/m³ SO2 increase at 8-h time lag and a strong dose-response relation. Exposure to SO2 is strongly associated with reduction of lung function and an increase in airway inflammation. This new evidence of harmful effects of SO2 peaks should induce regulatory intervention.

Mesothelioma incidence and asbestos exposure in Italian national priority contaminated sites.

Objectives This study aimed to (i) describe mesothelioma incidence in the Italian national priority contaminated sites (NPCS) on the basis of data available from the Italian National Mesothelioma Registry (ReNaM) and (ii) profile NPCS using Bayesian rank analysis. Methods Incident cases of mesothelioma and standardized incidence ratios (SIR) were estimated for both genders in each of the 39 selected NPCS in the period 2000-2011. Age-standardized rates of Italian geographical macro areas were used to estimate expected cases. Rankings of areas were produced by a hierarchical Bayesian model. Asbestos exposure modalities were discussed for each site. Results In the study period, 2683 incident cases of mesothelioma (1998 men, 685 women) were recorded. An excess of mesothelioma incidence was confirmed in sites with a known past history of direct use of asbestos (among men) such as Balangero (SIR 197.1, 95% CI 82.0-473.6), Casale Monferrato (SIR 910.7, 95% CI 816.5-1012.8), and Broni (SIR 1288.5, 95% CI 981.9-1691.0), in sites with shipyards and harbors (eg, Trieste, La Spezia, Venice, and Leghorn), and in settings without documented direct use of asbestos. The analysis ranked the sites of Broni and Casale Monferrato (both genders) and Biancavilla (only for women) the highest. Conclusions The present study confirms that asbestos pollution is a risk for people living in polluted areas, due to not only occupational exposure in industrial settings with direct use of asbestos but also the presence of asbestos in the environment. Epidemiological surveillance of asbestos-related diseases is a fundamental tool for monitoring the health profile in NPCS.

Geographical patterns of mesothelioma incidence and asbestos exposure in Lombardy, Italy.

BACKGROUND: Measuring malignant mesothelioma (MM) occurrence is a useful means to monitor the impact of past asbestos exposure and possibly identify new sources of asbestos exposure. OBJECTIVES: Aim of this study is to describe the results of the MM registry of the Lombardy Region, North-West Italy, the most populated (currently, 10 million inhabitants) and industrialised Italian region. METHODS: We extracted from the Lombardy Region Mesothelioma Registry (Registro Mesoteliomi Lombardia, RML) database all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in 2000 through 2012. For each Province, we calculated crude and standardised incidence rates using Italy 2001, European, and world (Segi's) standard populations. To examine spatial patterns of MM occurrence across municipalities we drew maps of crude rates smoothed according to the Besag, York and Mollié (BYM) method. RESULTS: We recorded 4442 MM cases (2850 in men and 1592 in women), representing about one fourth of MM cases occurring in Italy. Occupational exposure was more frequent in men (73.6%) than in women (38.2%). The crude regional rates were 4.7 per 100,000 person-years in men and 2.5 per 100,000 person-years in women. The highest rates were observed in the Pavia Province (crude rates: 8.7 per 100,000 in men and 5.3 and per 100,000 person-years in women). CONCLUSIONS: This study documented high MM occurrence in both genders, attributable to extensive asbestos exposure in the past.

Spatial analysis of incidence of cutaneous melanoma in the Friuli Venezia Giulia region in the period 1995-2005.

Incidence distribution of cutaneous melanoma depends on phenotypic characteristics of population and geographic location. In Italy, in the period 1999-2003 Friuli Venezia Giulia (FVG) region had the second highest incidence rates for males and the third for females. We analysed melanoma and lip cancer incidence data of the FVG cancer registry for the period 1995-2005. We used Bayesian hierarchical spatial models to describe the spatial pattern by gender. We decomposed the geographical distribution of the risk in two parts: a component linked to chronic exposure and a component related to intermittent exposure. In order to model the chronic component we considered the geographical distribution of incidence cases of lip cancer, for which chronic occupational solar radiation exposure is a documented risk factor. We also analysed the distribution by site and we calculated standardised rates for body surface area. This study documents a significant gradient in the incidence of cutaneous melanoma in FVG. High-standardized incidence rates are present in the area of Trieste and in the coastal area. The descriptive analysis by age group and by site, showed risks associated with intermittent exposures in both genders. For the coastal area the risk is especially high for sites traditionally linked to high cumulative exposures (face and neck), especially among men. The results suggest diagnostic preventive interventions in the populations living in the area of Trieste, given the high rates observed in the young age groups.

[Risk profiling in cancer surveillance in contaminated sites: an example from the ISS-AIRTUM collaborative study]. / Sintesi del profilo di incidenza di tumore nei SIN: un esempio dallo studio collaborativo ISS-AIRTUM.

Epidemiological surveillance on high risk environmental areas or areas covered by cancer registration yields long inventories of relative risks. Summaries of the results' tables must be produced to identify priorities and tailor public health actions. The aim is, therefore, to draw conclusions from each area's disease profile, or from the area signature of each disease.With this inmind, we used data on cancer incidence from 17 Cancer Registries that participated in the ISS-AIRTUM (National Institute of Health-Italian Network of Cancer Registries) study, and we produced conditional and marginal rankings of areas/diseases using a multivariate hierarchical Bayesian model. In this context, it is important to obtain an uncertainty evaluation by calculating the credibility intervals of ranks. The areas marginal ranking shows a large overlapping of credibility intervals, such that it is not possible to speak of a limited number of ISS-AIRTUM areas as being particularly affected. Every ISS-AIRTUMarea, therefore,must be considered individually and ordering themby ranking of cancer incidence wouldn't be appropriate. Instead,marginal ranking of diseases highlights the impact of asbestos exposure in all the analyzed areas.

Fetal striatal grafting slows motor and cognitive decline of Huntington's disease.

OBJECTIVE: To assess the clinical effect of caudate-putaminal transplantation of fetal striatal tissue in Huntington's disease (HD). METHODS: We carried out a follow-up study on 10 HD transplanted patients and 16 HD not-transplanted patients. All patients were evaluated with the Unified HD Rating Scale (UHDRS) whose change in motor, cognitive, behavioural and functional capacity total scores were considered as outcome measures. Grafted patients also received morphological and molecular neuroimaging. RESULTS: Patients were followed-up from disease onset for a total of 309.3 person-years (minimum 5.3, median 11.2 years, maximum 21.6 years). UHDRS scores have been available since 2004 (median time of 5.7 years since onset, minimum zero, maximum 17.2 years). Median post-transplantation follow-up was 4.3 years, minimum 2.8, maximum 5.1 years. Adjusted post-transplantation motor score deterioration rate was reduced compared to the pretransplantation period, and to that of not-transplanted patients by 0.9 unit/years (95% CI 0.2 to 1.6). Cognitive score deterioration was reduced of 2.7 unit/years (95% CI 0.1 to 5.3). For grafted patients the 2-year post-transplantation [(18)F]fluorodeoxyglucose positron emission tomography (PET) showed striatal/cortical metabolic increase compared to the presurgical evaluation; 4-year post-transplantation PET values were slightly decreased, but remained higher than preoperatively. [(123)I]iodobenzamide single photon emission CT demonstrated an increase in striatal D2-receptor density during postgrafting follow-up. CONCLUSIONS: Grafted patients experienced a milder clinical course with less pronounced motor/cognitive decline and associated brain metabolism improvement. Life-time follow-up may ultimately clarify whether transplantation permanently modifies the natural course of the disease, allowing longer sojourn time at less severe clinical stage, and improvement of overall survival.

Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related dysfunctions in motor coordination and contextual memory in mice: role of oxidative stress.

The aim of this study was to evaluate the effects of olive oil phenols on brain aging in mice and to verify whether the antioxidant and antiinflammatory activities of these polyphenols were involved. C57Bl/6J mice were fed from middle age to senescence with extra-virgin olive oil (10% wt/wt dry diet) rich in phenols (total polyphenol dose/day, 6 mg/kg). Behavioral tests were employed to assess cognitive, motor, and emotional behavior after 6 or 12 months of treatment. Parameters of oxidative status and inflammation were measured in different brain areas at the same times and evaluated for correlation with behavioral changes. The treatment with olive oil phenols improved contextual memory in the step-down test to levels similar to young animals and prevented the age-related impairment in motor coordination in the rotarod test. This motor effect was correlated with reduced lipid peroxidation in the cerebellum (p<0.05), whereas the memory effect did not correlate with oxidation or inflammation parameters. In conclusion, this work points out that natural polyphenols contained in extra-virgin olive oil can improve some age-related dysfunctions by differentially affecting different brain areas. Such a modulation can be obtained with an olive oil intake that is normal in the Mediterranean area, provided that the oil has a sufficiently high content of polyphenols.

Nasal cell DNA methylation, inflammation, lung function and wheezing in children with asthma.

AIMS: DNA methylation is increasingly proposed as a mechanism for underlying asthma-related inflammation. However, epigenetic studies are constrained by uncertainties on whether samples that can be easily collected in human individuals can provide informative results. METHODS: Two nasal cell DNA samples were collected on different days by nasal brushings from 35 asthmatic children aged between 8 and 11 years old. We correlated DNA methylation of IL-6, iNOS, Alu and LINE-1 with fractional exhaled nitric oxide, forced expiratory volume in 1 s and wheezing. RESULTS: Fractional exhaled nitric oxide increased in association with lower promoter methylation of both IL-6 (+29.0%; p = 0.004) and iNOS (+41.0%; p = 0.002). Lower IL-6 methylation was nonsignificantly associated with wheezing during the week of the study (odds ratio = 2.3; p = 0.063). CONCLUSION: Our findings support the use of nasal cell DNA for human epigenetic studies of asthma.

Asthma symptoms, lung function, and markers of oxidative stress and inflammation in children exposed to oil refinery pollution.

OBJECTIVES: Little is known about the effects of exposure to petroleum refinery emissions on respiratory health in children. We evaluated lung function and markers of inflammation and oxidative stress in children and adolescents with and without asthma or wheezing symptoms living in a petrochemical polluted area (Sarroch, Sardinia) versus a reference area (Burcei). METHODS: Parents of 275/300 6- to 14-year-old children living in Sarroch and parents of 214/323 children living in Burcei answered a questionnaire on respiratory symptoms and risk factors. Measurements of forced expiratory volume after 1 second (FEV(1)) and of forced expiratory flow rates at 25-75% of vital capacity (FEF(25-75)) were available in 27 and 23 asthma/wheezing-positive subjects and in 7 and 54 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively; for fractional exhaled nitric oxide (FE(NO)) corresponding figures were 27 and 24 and 8 and 55 in Sarroch and in Burcei, respectively. Malondialdehyde-deoxyguanosine (MDA-dG) adduct levels in nasal mucosa were measured in 12- to 14-year-old adolescents (8 and 14 asthma/wheezing-positive and 20 and 28 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively). Air pollutants were assessed during 3 weeks, starting 1 week before lung function, FE(NO), and MDA-dG measurements. Generalized linear models were used to estimate the effect of the area of residence adjusting for confounders. RESULTS: Weekly average concentrations of sulfur dioxide were 6.9-61.6 µg/m(3) in Sarroch versus 0.3-7.6 µg/m(3) in the rural area of Burcei; of nitrogen dioxide, 5.2-28.7 µg/m(3) versus 1.7-5.3 µg/m(3); and of benzene, 1.8-9.0 µg/m(3) versus 1.3-1.5 µg/m(3), respectively. Children living in Sarroch versus children living in the reference area showed an increase in wheezing symptoms {adjusted prevalence ratio=1.70 [90% confidence interval (CI)=1.01; 2.86]}; a decrease in lung function [variation in FEV(1)=-10.3% (90% CI=-15.0; -6.0%) and in FEF(25-75)=-12.9% (90% CI=-20.7; -4.3%)]; an increase in bronchial inflammation [variation in FE(NO)=+35% (90% CI=11.7; 80.1%)]; and an increase in MDA-dG adducts of +83% (90% CI=22.9; 174.1%). CONCLUSIONS: Data from this small study are consistent with the role of environmental pollutants on lung function and inflammation.

A hierarchical Bayesian approach to multiple testing in disease mapping.

We propose a Bayesian approach to multiple testing in disease mapping. This study was motivated by a real example regarding the mortality rate for lung cancer, males, in the Tuscan region (Italy). The data are relative to the period 1995-1999 for 287 municipalities. We develop a tri-level hierarchical Bayesian model to estimate for each area the posterior classification probability that is the posterior probability that the municipality belongs to the set of non-divergent areas. We show also the connections of our model with the false discovery rate approach. Posterior classification probabilities are used to explore areas at divergent risk from the reference while controlling for multiple testing. We consider both the Poisson-Gamma and the Besag, York and Mollié model to account for extra Poisson variability in our Bayesian formulation. Posterior inference on classification probabilities is highly dependent on the choice of the prior. We perform a sensitivity analysis and suggest how to rely on subject-specific information to derive informative a priori distributions. Hierarchical Bayesian models provide a sensible way to model classification probabilities in the context of disease mapping.

The methodological and conceptual aspects of mortality studies in psychiatry.

An extensive literature documented a mortality differential for natural causes between psychiatric patients and the general population. Less clear is the pattern for cancer diseases. Methodological problems arise when trying to explain such mortality gap: selection bias and reverse causation; time-dependent confounders that are also intermediate variables; complex relationships within a life course have to be considered. We try to explain such problems in terms of causal graphs. Excess risk for causes of death which are not attributable to higher prevalence of risk factors or treatment side-effects and higher mortality rates for avoidable causes have been also documented. These findings underline the need for research on health promotion and preventive programs targeted to psychiatric patients.