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Abstract Waste is part of the agenda of the European Environment and Health Process and included among the topics of the Sixth Ministerial Conference on Environment and Health. Disposal and management of hazardous waste are worldwide challenges. We performed a systematic review to evaluate the evidence of the health impact of hazardous waste exposure, applying transparent and a priori defined methods. The following five steps, based on pre-defined systematic criteria, were applied. 1. Specify the research question, in terms of “Population-Exposure-Comparators-Outcomes” (PECO). Population: people living near hazardous waste sites; Exposure: exposure to hazardous waste; Comparators: all comparators; Outcomes: all diseases/health disorders. 2. Carry out the literature search, in Medline and EMBASE. 3. Select studies for inclusion: original epidemiological studies, published between 1999 and 2015, on populations residentially exposed to hazardous waste. 4. Assess the quality of selected studies, taking into account study design, exposure and outcome assessment, confounding control. 5. Rate the confidence in the body of evidence for each outcome taking into account the reliability of each study, the strength of the association and concordance of results. Fifty-seven papers of epidemiological investigations on the health status of populations living near hazardous waste sites were selected for the evidence evaluation. The association between 95 health outcomes (diseases and disorders) and residential exposure to hazardous waste sites was evaluated. Health effects of residential hazardous waste exposure, previously partially unrecognized, were highlighted. Sufficient evidence was found of association between exposure to oil industry waste that releases high concentrations of hydrogen sulphide and acute symptoms. The evidence of causal relationship with hazardous waste was defined as limited for: liver, bladder, breast and testis cancers, non-Hodgkin lymphoma, asthma, congenital anomalies overall and anomalies of the neural tube, urogenital, connective and musculoskeletal systems, low birth weight and pre-term birth; evidence was defined as inadequate for the other health outcomes. The results, although not conclusive, provide indications that more effective public health policies on hazardous waste management are urgently needed. International, national and local authorities should oppose and eliminate poor, outdated and illegal practices of waste disposal, including illegal transboundary trade, and increase support regulation and its enforcement.

High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). LDL-apheresis, used in these patients to reduce LDL-C levels, has been shown to also affect HDL levels and composition. We studied LDL-apheresis effects on six FH and nine FCH subjects’ serum capacity to modulate cellular cholesterol efflux, an index of HDL functionality, and to load macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and macrophage cholesterol loading capacity (CLC) were measured before, immediately after, and two days after LDL-apheresis. The procedure reduced total cholesterol (TC), LDL-C, and apoB plasma levels (−69%, −80% and −74%, respectively), parameters only partially restored two days later. HDL-C and apoA-I plasma levels, reduced after LDL-apheresis (−27% and −16%, respectively), were restored to almost normal levels two days later. LDL-apheresis reduced serum aqueous diffusion (AD) CEC, SR-BI-CEC, and ABCA1-CEC. AD and SR-BI were fully restored whereas ABCA1-CEC remained low two days later. Sera immediately and two days after LDL-apheresis had a lower CLC than pre-LDL-apheresis sera. In conclusion, LDL-apheresis transiently reduces HDL-C levels and serum CEC, but it also reduces also serum capacity to deliver cholesterol to macrophages. Despite a potentially negative effect on HDL levels and composition, LDL-apheresis may counteract foam cells formation.

Background : Maxillar atrophy is a prevalent condition associated with diminished bone volume, which precludes the conventional placement of dental implants. Sinus floor lift is a surgical procedure that aims to address this atrophy through the insertion of a graft within the sinus cavity. A multitude of techniques have been documented in the international literature for the management of the sinus bone window, though each approach has its own set of advantages and disadvantages. Methods : The present study is a retrospective analysis of traditional sinus floor lift surgery, comparing the outcomes of two surgical approaches: placement of a collagen membrane over the maxillary lateral bone window with or without bone tacks. The study enrolled a total of 48 consecutive patients. Twenty-four patients underwent sinus floor lift surgery, with the placement of a collagen membrane over the maxillary lateral bone window without bone tacks (control group). The remaining 24 patients underwent the same procedure, but with bone tacks (study group). All patients received an amoxicillin 875 mg + clavulanic acid 125 mg administration for six days and underwent Cone Beam Computed Tomography (CBCT) before the sinus floor lift surgery and six months later before the implant surgery. The parameters measured on the preoperative Cone Beam Computed Tomography (CBCT) scan included residual bone, the preoperative thickness of the lateral bone in the center, and the distance between the lateral wall and the medial wall of the sinus. Only the bone height increment was measured on the postoperative CBCT scan. Postoperative complications and the visual analogue scale (VAS) score were also recorded. A statistical analysis was performed, and the correlation between the parameters was evaluated using Pearson's correlation coefficient. A comparison of the mean of the parameters between the treatment group and the control group was conducted using the t -test. Results and Conclusions : The study group was found to have superior outcomes in terms of bone height increment ( p = 0.001) and VAS after 7 days ( p = 0.11) compared to the control group. The novel application of bone tacks on the collagen membrane over the bone window following sinus elevation surgery was associated with superior outcomes in terms of bone height and reduced pain at seven days, as measured by the VAS, with no postoperative complications.

Objective: The aim of this study was to compare the efficacy of voice therapy combined with standard anti-reflux therapy in reducing symptoms and signs of laryngopharyngeal reflux (LPR)., Methods: A randomised clinical trial was conducted. Fifty-two patients with LPR diagnosed by 24 h multichannel intraluminal impedance-pH monitoring were randomly allocated in two groups: medical treatment (MT) and medical plus voice therapy (VT). Clinical symptoms and laryngeal signs were assessed at baseline and after 3 months of treatment with the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Voice Handicap Index (VHI) and GRBAS scales., Results: Groups had similar scores at baseline. At 3-month follow-up, a significant decrease in RSI and RFS total scores were found in both groups although it appeared to be more robust in the VT group. G and R scores of the GRBAS scale significantly improved after treatment in both groups, with better results in the VT group. The VHI total score at 3 months improved more in the VT group (VHI delta 9.54) than in the MT group (VHI delta 5.38) (p < 0.001)., Conclusions: The addition of voice therapy to medications and diet appears to be more effective in improving treatment outcomes in subjects with LPR. Voice therapy warrants consideration in addition to medication and diet when treating patients with LPR., (Copyright © 2024 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Atmospheric pollution has been recognized as the greatest environmental threat to human health. The population of the Venafro Valley, southern Italy, is exposed to emissions from a Waste-To-Energy (WTE) and a cement plant and potentially also to another WTE located in the neighboring region of Lazio; also, the vehicular atmospheric pollution situation is critical. In order to assess the environmental health risk of residents in eight municipalities of the Venafro Valley, a retrospective residential cohort study during 2006-2019 was carried out., Methods: Four exposure classes were defined by natural-break method, using a dispersion map of nitrogen dioxides (chosen as proxy of industrial pollution). The association between the industrial pollution and cause-specific mortality/morbidity of the cohort was calculated using the Hazard Ratio (HR) through a multiple time-dependent and sex-specific Cox regression adjusting for age, proximity to main roads and socio-economic deprivation index., Results: Results showed, for both sexes, mortality and morbidity excesses in the most exposed class for diseases of the circulatory system and some signals for respiratory diseases. Particularly, mortality excesses in both sexes in class 3 for diseases of the circulatory system [men: HR = 1.37 (1.04-1.79); women: HR = 1.27 (1.01-1.60)] and for cerebrovascular diseases [men: HR = 2.50 (1.44-4.35); women: HR = 1.41 (0.92-2.17)] were observed and confirmed by morbidity analyses. Mortality excesses for heart diseases for both sexes [men-class 3: HR = 1.32 (0.93-1.87); men-class 4: HR = 1.95 (0.99-3.85); women-class 3: HR = 1.49 (1.10-2.04)] and for acute respiratory diseases among women [HR = 2.31 (0.67-8.00)] were observed. Morbidity excesses in both sexes for ischemic heart diseases [men-class 3: HR = 1.24 (0.96-1.61); women-class 4: HR = 2.04 (1.04-4.02)] and in class 4 only among men for respiratory diseases [HR = 1.43 (0.88-2.31)] were also found., Conclusions: The present study provides several not-negligible signals indicating mitigation actions and deserve further investigations. For future studies, the authors recommend enriching the exposure and lifestyle profile using tools such as questionnaires and human biomonitoring., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Several models and scores have been released to predict early mortality in patients undergoing surgery for a ruptured abdominal aortic aneurysm (rAAA). These scores included above all preoperative factors and they could be useful to deny surgical repair. The aim of the study was to evaluate intraoperative predictors of in-hospital mortality in patients undergoing open surgical repair (OSR) for a rAAA., Methods: Between January 2007 and December 2020, 265 patients were admitted at our tertiary referral hospital for a rAAA. Two-hundred-twenty-two patients underwent OSR. Intra-operative factors were analyzed by means of univariate analysis (step 1). Associations of procedure variables with in-hospital mortality rates were sought based on a multivariate Cox regression analysis (step 2)., Results: Overall, in-hospital mortality rate was 28.8% (64 cases). Multivariate Cox regression analysis reported that operation time >240 minutes (P=0.032, OR 2.155, CI 95% 1.068-4.349), and hemoperitoneum (P<0.001, OR 3.582, CI 95% 1.749-7.335) were negative predictive factors for in-hospital mortality. Patency of at least one hypogastric artery (P=0.010; OR 0.128, CI 95% 0.271-0.609), and infrarenal clamping (P=0.001; OR 0.157, CI 95% 0.052-0.483) had a protective role in reducing in-hospital mortality rate., Conclusions: Operation time >240 minutes, and hemoperitoneum affected in-hospital mortality in patients undergoing OSR for rAAA. Patency of at least one hypogastric artery, and infrarenal clamping had a protective role. Further studies are needed to validate these outcomes. A validated predictive model could be useful to help the physicians in communication with patients' relatives.

Objective: The aim of this study was to adapt and validate the Italian version of the singing Voice Handicap Index-10 (SVHI-10-IT)., Methods: 99 Italian singers were enrolled in the study. All subjects underwent videolaryngostroboscopic examination and were asked to fill out the self-reported 10-item SVHI-10-IT. Laryngostroboscopic examination was pathological in 56 subjects (study group) (56.6%), while it was normal in the remaining 43 singers (control group) (43.4%). Dimensionality, test retest and internal validity for SVHI-10-IT were performed. Videolaryngostroboscopy was used as gold-standard for external validity., Results: The items of SVHI-10-IT were uni-dimensional and Cronbach's α was 0.853 (95% CI = 0.805-0.892). High and comparable area under curve (AUC:0.93 95% CI = 0.88-0.98) values indicate a good ability of the scale to distinguish between the study and control groups. Based on balanced sensitivity (Se = 83.9%) and specificity (Sp = 86.0%), the optimal cut-off score for a singer's perceived voice handicap was 12., Conclusions: The SVHI-10-IT is a reliable and valid instrument to evaluate the self-reported singing voice handicap among singers. It can also be used as a quick screening tool since a score higher than 12 is indicative of a problematic voice as perceived by singers., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Objectives: The differential diagnosis between idiopathic inflammatory myopathies (IIM) and muscular dystrophies (MD) may be challenging. We analysed the potential role of muscular magnetic resonance imaging (MRI) in the differential diagnosis between IIM and MD., Methods: MRI of patients (91 IIM and 43 MD), studied with a standardised protocol, have been collected. The presence of oedema, muscular atrophy and intramuscular adipose changes were evaluated. Moreover, we computed a composite score for each MRI item to better discriminate between the two diseases., Results: Oedema was significantly more prevalent in IIM compared with MD in pelvis muscles (p<0.001), anterior lodge and medial lodges (p=0.044) of the thighs. Adipose infiltration/substitution and muscular atrophy were more prevalent in MD, in particular adipose tissue was prevalent in all the compartments of the thighs (p<0.05), atrophy was prevalent at the thighs and pelvis muscles (p<0.001). The probability of IIM increased with higher oedema score and decreased with higher atrophy and intramuscular adipose infiltration/substitution scores., Conclusions: A different distribution of muscular involvement between IIM and MD has been identified. Muscular MRI may be useful in the differential diagnosis, potentially reducing the number of muscular biopsies that may be reserved only for doubtful cases.

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

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

Nonalcoholic fatty liver disease (NAFLD)-associated liver fibrosis is likely related to coronary artery disease (CAD) by the mediation of systemic inflammation. This study aimed at evaluating the predictive value of neutrophil-to-lymphocyte-ratio (NLR) and fibrosis-4 index (FIB-4), indices of inflammation and fibrosis, respectively, on CAD mortality. Data from 1460 CAD patients (1151 males, age: 68 ± 10 years, mean ± SD) were retrospectively analyzed. Over a median follow-up of 26 months (interquartile range (IQR) 12−45), 94 deaths were recorded. Kaplan−Meier survival analysis revealed worse outcomes in patients with elevation of one or both biomarkers (FIB-4 > 3.25 or/and NLR > 2.04, log-rank p-value < 0.001). In multivariate Cox regression analysis, the elevation of one biomarker (NLR or FIB-4) still confers a significant independent risk for mortality (hazard ratio (HR) = 1.7, 95% confidence interval (95% CI): 1.1−2.7, p = 0.023), whereas an increase in both biomarkers confers a risk corresponding to HR = 3.5 (95% CI: 1.6−7.8, p = 0.002). Categorization of patients with elevated FIB-4/NLR could provide valuable information for risk stratification and reduction of residual risk in CAD patients.

Oxidative stress and inflammation are key factors in cardiometabolic diseases. We set out to evaluate the relationship between serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) with cardiometabolic risk factors in coronary artery disease (CAD) patients, and their additive and multiplicative interactive effects on outcomes (cardiac death/CD and hard events (HE)-death plus reinfarction). A total of 2712 patients (67 ± 11 years, 1960 males) who underwent coronary angiography was retrospectively analyzed and categorized into no-CAD patients ( n =806), stable-CAD patients ( n =1545), and patients with acute myocardial infarction (AMI) ( n =361). UA and NLR were reciprocally correlated and associated with cardiometabolic risk factors. During a mean follow-up period of 27 ± 20 months, 99-3.6% deaths, and 213-7.8% HE were registered. The Kaplan-Meier survival estimates showed significantly worse outcomes in patients with elevated UA or NLR levels. Multivariate Cox regression analysis demonstrated that NLR independently predicted CD and HE. There was no multiplicative interaction between UA and NLR; however, the use of measures of additive interaction evidenced a positive additive interaction between UA and NLR for CD and HE. Although it is clear that correlation does not imply causation, the coexistence of NRL and UA appears to have a synergistic effect, providing further information for the risk stratification of CAD patients., Competing Interests: The authors declare no conflicts of interest.

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.

Environmental noise can induce detrimental health effects such as cardiovascular disease (CVD). The relationship between vehicular traffic noise pollution and CVD was investigated through a retrospective residential cohort study in the city of Pisa. Four exposure classes were defined for noise pollution, using noise propagation maps. The association between noise exposures and cause-specific mortality or hospitalization of the subjects of the cohort was calculated using the hazard ratio (HR) for night and day through a multiple time-dependent and sex-specific Cox regression adjusting for age, the socio-economic deprivation index, and traffic air pollution. Mortality excess for CVD and risk trends for a 1 decibel noise increment were observed among the most exposed women (mortality: HRnight class4 1.15 (1.03-1.28); Trend night 1.007 (1.002-1.012); HRday class4 1.14 (1.02-1.27); Trend day 1.008 (1.003-1.013)), particularly for ischaemic disease (mortality: Trend night 1.008 (0.999-1.017); Trend day 1.009 (0.999-1.018)) and cerebrovascular disease (mortality: HRnight class3 1.23 (1.02-1.48), HRday class3 1.24 (1.03-1.49)). Hospitalization analyses confirm mortality results. A decreased risk for hospitalization was also observed among the most exposed men (HRday class4 0.94 (0.88-1.01), particularly for ischaemic disease (HRnight class4 0.90 (0.80-1.02); HRday class4 0.86 (0.77-0.97)) and cerebrovascular disease (HRnight class4 0.89 (0.78-1.01)). Authors recommend the adoption of prevention measures aimed at mitigating noise and the activation of a monitoring of the risk profile in the Pisa population updating both the residential cohort and health data.

In the province of Lecce (southern Italy), a higher incidence of lung cancer (LC) among men compared to regional and national data was reported. In a sub-area in the center of the province (cluster area), the incidence and mortality for LC was even higher. PROTOS is a case-control study aimed at investigating possible risk factors for LC in the province area. A total of 442 patients with LC and 1326 controls matched by sex and age living in the province of Lecce for at least 10 years were enrolled and georeferenced; they filled in a questionnaire with their personal information and exposures. For each risk factor, an Odds Ratio adjusted for all the other variables was calculated. The risk of LC increased with excessive use of alcohol in women, for those subjects with a family cancer history, for each increase in pack/year of cigarettes, for men more exposed considering the industrial district in the cluster area, and for those using pesticides in agriculture without wearing personal protective equipment. The higher incidence of adenocarcinoma in both sexes suggests that, in addition to cigarette smoking, concurrent exposures to other environmental, occupational, and life-style factors may play a role in increased cancer risk and should be more deeply explored.

Risk perception (RP) evaluation during pregnancy and its relationship with lifestyles are considered useful tools for understanding communities living in high-risk areas and preventing dangerous exposure. It is well known that exposure to pollutants and less-healthy lifestyles may result in increased disease occurrence during life. Our work investigated environmental RP through ad hoc questionnaires administered to 611 mothers within the NEHO birth cohort, recruited in three heavily contaminated areas of Southern Italy. Four different RP indices, an exploratory factorial analysis (EFA), and a latent class analysis were evaluated from questionnaires. The highest values of risk perception index were observed in the Milazzo site (0.64 ± 0.16) and the lowest in the Crotone site (0.5 ± 0.18). EFA revealed four latent factors, including different items describing environmental pollution, and subjects were classified into four latent classes with different RP indices. Significant RP profiles were different among the sites ( p < 0.001). Our results did not demonstrate any association between RP and lifestyles during pregnancy. Improving healthy lifestyle behaviours, particularly in polluted areas, would generate co-benefits by preventing further risk factors. As remediation interventions can take a long time, it needs to improve healthy lifestyles in residents until remediation is completed.

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

Purpose: Robotic assistance could increase the rate of ileo-colic intra-corporeal anastomosis (ICA) during robotic right colectomy (RRC). However, although robotic ICA can be accomplished with several different technical variants, it is not clear whether some of these technical details should be preferred. An evaluation of the possible advantage of one respect to another would be useful., Methods: We conducted a systematic review of literature on technical details of robotic ileo-colic ICA, from which we performed a meta-analysis of clinical outcomes. The extracted data allowed a comparative analysis regarding the outcome of overall complication (OC), bleeding rate (BR) and leakage rate (LR), between (1) mechanical anastomosis with robotic stapler, versus laparoscopic stapler, versus totally hand-sewn anastomosis and (2) closure of enterocolotomy with manual double layer, versus single layer, versus stapled., Results: A total of 30 studies including 2066 patients were selected. Globally, the side-to-side, isoperistaltic anastomosis, realized with laparoscopic staplers, and double-layer closure for enterocolotomy, is the most common technique used. According to the meta-analysis, the use of robotic stapler was significantly associated with a reduction of the BR with respect to mechanical anastomosis with laparoscopic stapler or totally hand-sewn anastomosis. None of the other technical aspects significantly influenced the outcomes., Conclusions: ICA fashioning during RRC can be accomplished with several technical variants without evidence of a clear superiority of anyone of these techniques. Although the use of robotic staplers could be associated with some benefits, further studies are necessary to draw conclusions.

Background: the exposure to a coal-fired power plant has been shown to increase mortality both for cardiovascular and respiratory causes among an exposed cohort in comparison with a cohort of unexposed. Hazard ratios between 1.30 and 1.90 were found for cardiovascular and respiratory mortality., Objectives: to estimate the individual life shortening among the exposed due to power plant emissions., Design: survival for cardiovascular and respiratory disease in the exposed vs unexposed groups was estimated by the Kaplan-Meier method. For each gender and exposure, a fictitious cohort with a cumulative 30-year follow up was built combining three subcohorts of age at entry of 55-64, 65-74, and 75-84 years, with 10 years of follow up each. Survivals at 10 years in the 55-64-year subcohort were used as initial risks for 65-74-year subcohort; then, survivals at 10 years of the 65-74-year subcohort were used as initial risk in the 75-84-year subcohort. Eventually, 30-years cumulative follow up cohorts were obtained by gender and exposure. Individual life-shortening in people exposed was estimated as time from death of an exposed subject to the subsequent time when the unexposed cohort reached the same risk of the exposed subject at that time of the death. Here, it is proposed a method to take into account causes other than those considered., Setting and Participants: 144,018 subjects aged 55-74 years at entry of both genders belonging to the open cohort of residents of 12 municipalities (including Savona) from 2001 to 2013 in the area where the coal-fired power plant of Vado-Quiliano (Liguria Region, Northern Italy) is located., Main Outcome Measures: individual life shortening., Results: after 5 years of follow up, the individual life shortening due to cardiorespiratory causes varied between 972 and 1,822 days for males and from 612 and 1,578 days among females. Taking into account other causes of death, reduces slightly (3% for males of 75 years at death) the estimate of life shortening found in this study. The comparison between the cohorts requires that the exposed and unexposed groups are comparable, except for the exposure, and that causes other than those considered are taken into account. Socioeconomic status had been found to have little effect on cause-specific death risk indicating that, at least in terms of socioeconomic status, the exposed and unexposed groups were similar. Taking into account causes other than those considered slightly reduced the found estimates (3% at age 75 in males). According to the proposal, the life-shortening for the considered causes is easy to calculate and provides an individual indicator of damage. Inferring from group statistics individual estimates could be the most controversial point of this approach. The proposed estimates are the most credible estimate of individual damage for each occurred death among the exposed people., Conclusions: an increased hazard ratio for a wide series of causes is equivalent to a life shortening among the exposed. A method to produce reasonable estimates of life-shortening is proposed as the effect of exposure at individual level. This approach is simple and do not require sophisticated statistical tools. It appears a promising approach for other settings.

Background and Aims: Whether there is a gender difference in the impact of elevated plasma Lp(a) levels on recurrent coronary events remains unclear. We, therefore, evaluated the association between Lp(a) levels and the occurrence of major adverse coronary events in a large series of coronary patients (32% women)., Methods: This single-center prospective cohort study investigated 3034 consecutive patients admitted to the Coronary Care Unit with a diagnosis of coronary ischemia. According to the inclusion criteria, 2374 patients completed the follow-up (mean of 2 years). The end-points were non-fatal myocardial infarction (MI), revascularization and coronary deaths., Results: Elevated Lp(a) levels were significantly associated with rate of revascularization, but not with non-fatal MI and cardiac death. According to Lp(a) stratification (≤30 mg/dl, >30-50 mg/dl and ≥50 mg/dl), there was a significant rise of revascularization events in the whole sample of participants, with a trend in hazard ratio (HR) of 1.23 (95% CI 1.04-1.46) and a 6% rise for every 10 mg/dl increment in Lp(a) levels. This effect was mainly driven by women (HR 2.04, 95%CI 1.33-3.12) who showed a 14% incremental risk for every 10 mg/dl rise in Lp(a) levels., Conclusions: In patients with coronary artery disease, elevated plasma Lp(a) levels were found to be a potentially useful predictor of the need for coronary revascularizations, especially in women., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chronic arsenic (As) exposure is a critical public health issue. The As metabolism can be influenced by many factors. The objective of this study is to verify if these factors influence As metabolism in four Italian areas affected by As pollution. Descriptive analyses were conducted on 271 subjects aged 20-49 in order to assess the effect of each factor considered on As methylation. Percentages of metabolites of As in urine, primary and secondary methylation indexes were calculated as indicators for metabolic capacity. The results indicate that women have a better methylation capacity (MC) than men, and drinking As-contaminated water from public aqueducts is associated with poorer MC, especially in areas with natural As pollution. In areas with anthropogenic As pollution occupational exposure is associated with a higher MC while smoking with a poorer MC. Dietary habits and genetic characteristics are probably implicated in As metabolism. BMI, alcohol consumption and polymorphism of the AS3MT gene seem not to influence As MC. Arsenic metabolism may be affected by various factors and in order to achieve a comprehensive risk assessment of As-associated disease, it is crucial to understand how these factors contribute to differences in As metabolism.

Introduction: Environmental pollution has been progressively becoming one of the main risk factors to human diseases. In particular, populations living in high-contaminated sites are particularly exposed to environmental toxicants, with consequent increased risks to human health. In Italy, there are currently ongoing three epidemiological etiological studies aimed at evaluating the association between exposure to inorganic and organic chemicals and presence of biological markers of early effects in population living in three National Priority Contaminated Sites (NPCSs). Specifically, the correlations concern preclinical indicators of liver disease in Priolo NPCS, thyroid diseases in Milazzo-Valle del Mela NPCS and cardiovascular risk and kidney damage in Crotone NPCS., Methods and Analysis: Overall, approximately 1300 subjects of both sexes will be enrolled in the three NPCSs according to specific inclusion criteria. For each subject, serum and urine specimens are collected, on which the determination of biological markers of exposure and early effects for the selected outcomes are performed. Individual information on environmental and occupational exposure, medical history, diet and life habits is obtained through questionnaires provided by web platform. In Milazzo-Valle del Mela and Crotone NPCSs, not invasive instrumental and imaging examinations are performed in order to evaluate further risk factors of thyroid carcinoma and cardiovascular disease, respectively., Ethics and Dissemination: The protocol studies have been approved by the Ethics Committees responsible for the three involved NPCSs: the Ethics Committee 'Catania 2' for the NPCS of Priolo (21 July 2017, n. 500/2017/CECT2), the Ethics Committee of the University Hospitals of Messina for the NPCS of Milazzo-Valle del Mela (19 February 2018, n.2/2018); the Ethics Committee of the Region of Calabria for the NPCS of Crotone (20 July 2017, n. 174). Results will be disseminated among policy-makers, citizens, stakeholders and scientific community through the organisation of conferences and events, and the publication on international peer/reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Since the 1990s, in areas with natural geothermal manifestations studies on the association between exposure to pollutants and health effect have become increasingly relevant. These emissions consist of water vapor mixed with carbon dioxide, hydrogen sulfide (H 2 S), methane and, to a lesser extent, rare gases and trace elements in volatile forms. Considering the indications of the World Health Organization and the growth in the use of geothermal energy for energy production, this review aims to report studies exploring the health status of the populations living in areas where geothermal energy is used to produce heat and electricity. Studies on the health effects of the general population exposed to emissions from both natural geothermal events and plants using geothermal energy at domestic or commercial level have been considered between 1999 and 2019. Studies were classified into those based on health indicators and those based on proxy-individual level exposure metrics. Both statistically significant results (p<0.05) and interesting signals were commented. The 19 studies selected (New Zealand, Iceland and Italy) provide heterogeneous results, with an increased risk for several tumor sites. Exposure to H 2 S low concentrations is positively associated with an increment of respiratory symptoms, anti-asthma drugs use, mortality for respiratory diseases and lung cancer. Exposure to H 2 S high levels is inversely related to cancer mortality but associated with an increase in hospitalization for respiratory diseases, central nervous system disorders and cardiovascular diseases. The results indicate that the health of populations residing in areas rich in geothermal emissions presents some critical elements to be explored. The two major limitations of the studies are the ecological design and the inadequate exposure assessment. The authors suggested the prosecution and the systematization of health surveillance and human biomonitoring activities associated with permanent control of atmospheric emissions from both industrial and natural plants., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Coal-fired thermal power plants represent a significant source of air pollutants, especially sulfur dioxide (SO 2 ) that has been associated with an increased risk of mortality and morbidity for respiratory and cardiovascular disease. A coal power plant in Vado Ligure (Italy) (CPP VL ) started in 1970 was stopped in 2014 by the Prosecutor's Office on the grounds of environmental and health culpable disaster., Objective: To investigate the association between the exposure of residents to atmospheric pollutants emitted by CPP VL and the risk of mortality and hospitalization, considering both cancer and non-cancer causes in a population-based cohort study., Methods: SO 2 and nitrogen oxides (NO x ), estimated using the ABLE-MOLOCH-ADMS-Urban dispersion model, were selected as representative surrogates of exposure to CPP VL emissions (SO 2 -CPP VL ) and cumulative emissions from other sources of pollution (NO x -MS), respectively. The relationship between each health outcome and categories of exposure to SO 2 -CPP VL was estimated by the Hazard Ratio (HR) using multiple sex-specific Cox regression models, adjusted for age, exposure to NO x -MS, and socio-economic deprivation index using SO 2 -CPP VL first quartile as a reference., Results: 144,019 individuals were recruited (follow-up 2001-2013). An excess of mortality was found for all natural causes (men: 1.49; 95% CI 1.38-1.60; women: 1.49; 95% CI 1.39-1.59), diseases of the circulatory system (men: 1.41; 95% CI 1.24-1.56; women: 1.59; 95% CI 1.44-1.77), of the respiratory system (men: 1.90; 95% CI 1.47-2.45; women: 1.62; 95% CI 1.25-2.09), and of the nervous system and sense organs (men: 1.34; 95% CI 0.97-1.86; women: 1.38; 95% CI 1.03-1.83), and in men for trachea, bronchus, and lung cancers (1.59; 95% CI 1.26-2.00). Results of hospitalization analysis were consistent with those of mortality., Conclusion: Results obtained, also when considering multiple sources of exposure, indicate that exposure to CPP emissions represents a risk factor for selected health outcomes as well as the urgently adoption of primary prevention measures and of a specific surveillance programme., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the present research, we evaluated the health effects of exposure to the municipal waste incinerator (MWI) in Pisa, Italy, through a population-based cohort design. The individual exposure pattern in the area was estimated through CALPUFF dispersion models of NO χ (developed by Atmospheric Studies Group Earth Tech, Lowell, Massachusetts), used as pollution proxies of the MWI and the relevant industrial plant, and through land-use regression for NO χ due to traffic pollution. Using Cox regression analysis, hazard ratios (HR) were estimated adjusting for exposure to other sources of pollution, age, and socioeconomic deprivation. An adjusted linear trend of HR (HRt) over the categories of exposure, with the relative 95% CI and p-value, was also calculated. Mortality and hospital discharge were studied as impact outcomes. Mortality analysis on males showed increased trends of mortality due to natural causes (HRt p < 0.05), the tumor of the lymphohematopoietic system (HRt p = 0.01), cardiovascular diseases (HRt p < 0.01); in females, increased trends for acute respiratory diseases (HRt p = 0.04). Morbidity analysis showed a HRt for lymphohematopoietic system tumor in males (HRt p = 0.04). Some of the excesses are in agreement with previous evidence on the health effects of MWIs, although the observation in males but not in females, suggests a cautious interpretation. Confounding due to other sources of exposure cannot be ruled out. The evidence was considered important in the decision-making process of the waste cycle.

Background: Swallowing impairment is frequently present in patients with idiopathic inflammatory myopathies (IIMs), and it represents an important cause of morbidity, dramatically reducing the quality of life of patients. Moreover, dysphagia is associated to a worst prognosis. Unfortunately, no standardized instrumental techniques for the assessment of the upper gastrointestinal tract in IIM patients are available. In this study, we explored the characteristics of the alterations in the upper gastrointestinal tract using oro-pharyngeal-esophageal scintigraphy (OPES) in a cohort of IIM patients and we correlated the alterations with clinical parameters., Methods: A total of 51 IIM patients were examined with OPES, both with liquids and semisolids, and the data acquired were examined to compute the transit time and the percentage of retention at oral, pharyngeal, and esophageal level. Patient-reported outcome data (PRO) on dysphagia, disease activity, and clinical parameters were collected., Key Results: Oro-pharyngeal-esophageal scintigraphy identified at least one alteration in all patients, particularly with the semisolid test and oral and pharyngeal levels presented a higher frequency of involvement compared to the esophageal tract (P < 0.05). A very good correlation between dysphagia severity assessed by PRO and many OPES results was identified. In patients with a shorter disease duration, there was a higher prevalence of alterations at the oral and pharyngeal level and they were correlated to higher swallowing difficulties and higher disease activity parameters., Conclusions & Inferences: Our results showed that OPES may represent a novel reproducible tool to assess dysphagia in IIM patients, thus opening new possibilities to evaluate dysphagia in these patients., (© 2019 John Wiley & Sons Ltd.)

In 2008, some general practitioners (GPs) in the area of Empoli (Tuscany Region, Central Italy), reported to the Local Health Authority (LHA), an unusually high frequency of leukemia deaths among their patients residing in a one of the municipalities of the area. The LHA decided to carry out an epidemiological investigation. An interdepartmental working group was set up, led by the Department of Prevention of the LHA, and made up of representatives of the Institute for Study, Prevention and Cancer Network (ISPRO, Florence), the G. Monasterio Foundation/ Institute of Clinical Physiology of the National Council for Research (CNR) of Pisa, the University of Pisa, the Regional Environmental Protection Agency and community members. Several epidemiological analyses were carried out (namely incidence and mortality analysis, assessment of the residential history of all cases and micro-geographical incidence evaluation, assessment and quantification of local environmental pressures, evaluation of congenital abnormalities). The investigation took over two years to be completed. The work agenda was shared with community members, who contributed to decision-making, study design and the communication plan. Thanks to the interaction with community members, researchers had the chance to become aware of their information needs and of local knowledge concerning the research issues. The final report was published online and presented to citizens in several public meetings. Direct involvement of the local community during project development was found to be useful to reduce the perceived distance between public authorities and the local population, as highlighted in the guidelines on cancer cluster investigations.

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.

Exposure to air pollution has been shown to increase the risk of developing chronic respiratory diseases. The largest crude oil first treatment plant in Italy emits harmful polluting substances. This cross-sectional study assesses the occurrence of respiratory symptoms in a sample of the adult population living near the plant. A proximal and a reference area were defined in order to recruit 200 subjects. Each subject performed a spirometry test and completed a questionnaire. Associations between the distance from the plant and selected respiratory outcomes were assessed (distance-based approach). The prevalence of outcomes between a proximal and a reference area (area-based approach) were also compared. Odds ratios were adjusted for potential confounders. Living near the plant was associated with a higher prevalence of respiratory symptoms, with significant associations for severe dyspnoea equivalent to the halving of risk as the distance of residence from the plant increased by 1 km (adjusted odds ratio (OR) 0.48, confidence interval at the 95% probability level (95% CI): 0.25⁻0.92). Several signals emerged for respiratory allergic symptoms. The area-based approach generally confirmed the results obtained with the distance-based approach. This is the first study to be carried out on a crude oil first treatment plant aimed at assessing the association with the occurrence of respiratory symptoms. These findings contribute to the evidence supporting the need for a space⁻time surveillance system in the investigated area.

Objectives: understanding how selected media conveyed the news about the presentation of the results of the Health Impact Assessment study (HIA) in Val D'Agri (Southern Italy): what conceptual frames are used and their variation over time, the association of topics covered (issues), frames and actors., Design: content analysis of the CNR press review in the period between the presentation of HIA results (06.09.2017-02.01.2018). Descriptive statistics analysis and multiple regression models, with stepwise selection of the most significant variables., Setting and Participants: 138 articles read by two authors independently, with analysis of the goodness of concordance. The articles are coded with 6 characteristics; 7 actors, 4 issues, 2 general frames, 4 specific frames., Main Outcome Measures: associations among issues, frames, actors., Results: the «alarmist tone» is associated with interviews to politicians while the citation of the study is associated with the «assertive tone». The statement «there are no problems» is related to interviews to «non-independent researchers» and «companies». The «trivialization of research» is associated with citations or interviews of «non-independent researchers» and interviews with «companies». The characterization of «propaganda» frame is done by the presence of interviews to «politicians» and the citation of «public administration», which plays a protective role. The «conflict» is associated with interviews to «public administration» and «politicians», as well as with the appearance in opening articles. The presence in the articles of «evidence-based measures», «governance measures» and «legal measures» has increased following the presentation of HIA results., Conclusion: the main frames (mutually exclusive) were useful for the analysis. The specific frames help to articulate the analysis, while the issues illustrate the contents. The observations of media in this limited period may be repeated and applied in other cases, and used to monitor the impact of existing risk prevention actions, and to better analyze risk perception at the local level.

Introduction: Congenital anomalies (CAs) represent one of the main cause of foetal death, infant mortality and morbidity, and long-term disability. CAs have been object of systematic registration activity for a long-time in many geographical areas in Europe and worldwide. CAs are often associated with disabilities of different types and severity, including the developed Countries worldwide. According to the World Health Organization (WHO), each year approximately 3,2 million of children worldwide are born with a CA and approximately 300,000 newborns with a diagnosis of birth defect die within the first 28 days of life. In Europe, CAs are the leading cause of perinatal mortality: the European Surveillance of Congenital Anomalies (EUROC AT) network estimated a perinatal mortality associated with CAs of 9.2 per 10,000 births in 2008-2012. In Italy, the Ministry of Health estimates that, on the average of 500,000 births each year, about 25,000 present at least one CA. Moreover, approximately 25% of infant mortality is due to CAs and about 50% of infant mortality is attributable to perinatal morbidity, almost always of prenatal origin. Regarding long-term survival, a recent population study conducted between 1985 and 2003 in the UK estimated a 20.5-year survival of 85.5% of children born with at least one CA. According to the Centre for Disease Control and Prevention, approximately 3.3% of live births in the United States have a severe birth defect. Since CAs represent a significant public health issue, an effective primary prevention strategy should be a priority for public policies and healthcare system. Regarding aetiology, although in many cases the cause is still unknown, it has been hypothesized that CAs may be developed during the first trimester of pregnancy as a result of hereditary polygenic defects or of a gene-environment interaction. The aetiology is predominantly multifactorial, caused by complex interactions between genes and environment, which modify the normal embryo-foetal development, especially during the organogenesis phase. In particular, environmental factors (e.g., chemical toxicants, infection agents, maternal disease, and exogenous factors) can have preconceptional mutagenic action, postconceptional teratogenic effects, periconceptional endocrine disruption or epigenetic action. Regarding genetic causes, there are genetic chromosomal aberrations or dysgeneses. Furthermore, socioeconomic factors affect reproductive health by differentiating the exposure to the other risk factors as well as the access to prevention measures. In recent years, the importance of the environment as a major factor of reproductive risk has been highlighted. An individual may be exposed to pollutants present in the workplace and the population may be exposed to multiple sources of environmental contamination of water, soil, and air matrices. Pregnant women and the developing foetus are particularly sensitive to the effects of environmental exposure., Objective: The aim of the present working paper is to produce an updated review of the epidemiological evidence on the risk of CAs associated with environmental exposures, socioeconomic, and main individual risk factors, such as cigarette smoking and alcohol consumption, according to the approach proposed by Pirastu et al. 2010 in the framework of the SENTIERI Project (the Italian Epidemiological Study of Residents in National Priority Contaminated Sites)., Design and Methods: Literature search was carried out in PubMed, following the SENTIERI project criteria to evaluate evidence, by selecting articles in English or Italian language published from 2011 to 2016 regarding human studies. For this review, descriptive and analytical epidemiological studies (cohort, case-control, cross-sectional, and ecological), systematic reviews, and metanalyses reporting association estimates between the outcome and at least one of the risk factors were selected. As in Pirastu et al., the sources of environmental exposure have been classified into four macrocategories: industries, mines, landfills, and incinerators. The sources of individual exposure considered were: active and passive cigarette smoking, alcohol consumption, socioeconomic status (SES), occupational and environmental exposures related to air pollutants from vehicular traffic only. The obtained results were assessed according to the evaluation criteria on the epidemiological evidence related to the association between the outcome and exposures predefined and published by the SENTIERI working group (WG). For the evidence assessment, the SENTIERI WG criteria favoured firstly primary sources and quantitative metanalyses, secondly, consistency among sources. The evaluation of the epidemiological evidence for the association between outcome and the exposure has been classified into three categories: sufficient (S), limited (L), inadequate (I)., Results: Industries: during the period under review, six single studies evaluating the association between industrial sites exposure and the risk of CAs were found. The epidemiological evidence of association between outcome and exposure has been considered limited. Mines: from the bibliographic research, three single studies investigating possible cause-effect relationship between maternal residential proximity to mines and the risk of CAs have been collected providing inadequate epidemiological evidence. Landfills: during the period under review, one systematic review and one literature review evaluating the causal associations between maternal residential proximity to landfills and CAs were identified. The epidemiological evidence is limited and concerns almost exclusively sites containing industrial or hazardous waste. Incinerators: a systematic review has been selected; it concludes that the evidence for the association between maternal residential proximity to incinerators and CAs are inadequate. Cigarette smoking: the literature search identified eight systematic reviews with metanalysis, five multicentre studies, and ten single studies assessing the causal association between maternal and/or paternal exposure to smoking and the risk of CAs in the offspring providing sufficient evidence for a causal association between maternal exposure to cigarette smoke and the risk of congenital heart defects, oro-facial clefts, neural tube defects, and gastrointestinal malformations. Alcohol: three systematic reviews with metanalysis, two metanalyses, one multicentre study, and four single studies were collected for the period under review. The acquired literature has provided limited epidemiological evidence for associations between alcohol consumption and CAs in the nervous system, particularly for anencephaly and spina bifida. Socioeconomic status: the evidence of an association with socioeconomic factors was inadequate due to an insufficient number of studies selected during the period under consideration. Occupational exposure: the literature search collected one metanalysis, eight multicentre studies, and five single studies. The epidemiological evidence for associations between paternal occupational exposure to solvents and neural tube defects and between maternal pesticide exposure and gold-facial clefts were judged limited. Air pollution: two systematic reviews with metanalyses, two multicentre studies, and nine single studies were selected by literature search; the epidemiological evidence for a causal association between air pollutants exposure and the risk of CAs is still to be considered limited., Conclusions: For future epidemiological studies, a better exposure assessment, using in particular more accurate spatial measurements or models, a standardized case definition, a larger sample and more accurate control of the recognized or presumed confounding variables are needed.

Arsenic is ubiquitous and has a potentially adverse impact on human health. We compared the distribution of concentrations of urinary inorganic arsenic plus methylated forms (uc(iAs+MMA+DMA)) in four Italian areas with other international studies, and we assessed the relationship between uc(iAs+MMA+DMA) and various exposure factors. We conducted a human biomonitoring study on 271 subjects (132 men) aged 20-44, randomly sampled and stratified by area, gender, and age. Data on environmental and occupational exposure and dietary habits were collected through a questionnaire. Arsenic was speciated using chromatographic separation and inductively coupled mass spectrometry. Associations between uc(iAs+MMA+DMA) and exposure factors were evaluated using the geometric mean ratio (GMR) with a 90% confidence interval by stepwise multiple regression analysis. The 95th percentile value of uc(iAs+MMA+DMA) for the whole sample (86.28 µg/L) was higher than other national studies worldwide. A statistical significant correlation was found between uc(iAs+MMA+DMA) and occupational exposure (GMR: 2.68 [1.79-4.00]), GSTT gene (GMR: 0.68 [0.52-0.80]), consumption of tap water (GMR: 1.35 [1.02-1.77]), seafood (GMR: 1.44 [1.11-1.88]), whole milk (GMR: 1.34 [1.04-1.73]), and fruit/vegetables (GMR: 1.37 [1.03-1.82]). This study demonstrated the utility of uc(iAs+MMA+DMA) as a biomarker to assess environmental exposure. In a public health context, this information could be used to support remedial action, to prevent individuals from being further exposed to environmental arsenic sources., Competing Interests: The authors declare no conflict of interest.

The effects of noise on students' health, well-being, and learning are of growing concern among both the general public and policy-makers in Europe. Several studies have highlighted the consequences of noise on children's learning and performance at school. This study investigates the relationship between noise judgment in school goers aged 11-18 and noise measurements aimed at evaluating their exposure at school. For this purpose, a questionnaire was administered to 521 individuals in 28 classrooms in eight schools of four cities in Italy, with different environmental characteristics. Using a Likert-type scale, a selected set of responses related to noise generated an Annoyance Index (AI) score for each student and a classroom median score (MAI). From the noise data acquired, a global noise score (GNS) was assigned to each classroom. A higher AI was found in industrialized areas and among younger students. No significant differences in noise judgment were found by gender. A significant inverse correlation was described between MAI and GNS, thus the better the acoustic quality of the classrooms, the less the perceived noise and annoyance. The results show that noise perception and consequent disturbance are highly correlated with classroom acoustics, and confirm that annoyance represents the most widespread subjective response to noise., Competing Interests: The authors declare no conflict of interest.

Objectives: to evaluate the associations among the emissions produced by "Centro olio Val d'Agri" (COVA), with mortality and hospitalization of residents in the Viggiano and Grumento Nova Municipalities, located in Val d'Agri (Basilicata Region, Southern Italy)., Design: residential cohort study., Settings and Participants: Lagrangians dispersion models to estimate the level of exposure at the address of residence to NOX concentrations as tracers of COVA emissions. Based on the tertile of NOX distribution, individual exposure was classified and a Cox model analysis was performed (hazard ratio, HR, trend with relative 95%CI). The association among exposure to NOX and the cohort mortality/hospitalization was evaluated considering age, socioeconomic status, and distance from the high traffic density road. The cohort included 6,795 residents (73,270 person-years) in the period 2000-2014., Main Outcome Measures: causes of mortality and hospitalization due to cardio-respiratory diseases, recognised as associated to air pollution, with medium-short latency induction period, consistent with the period of operation at the COVA., Results: increasing trends were observed on three exposure classes for mortality due to circulatory system diseases (HR trend: 1.19; 95%CI 1.02-1.39), stronger considering women (HR trend: 1.19; 95%CI 1.02-1.39). From hospitalizations results, an increased risk emerges for respiratory diseases (HR trend: 1.12; 95%CI 1.01-1.25) and, for women, for diseases of the circulatory system (HR trend: 1.19; 95%CI 1.03-1.38), for ischemic diseases (HR trend: 1.33; 95%CI 1.02-1.74) and respiratory diseases (HR trend: 1.22; 95%CI 1.03-1.46)., Conclusions: the excesses of mortality and hospitalization emerged in areas most exposed to pollutants of industrial origin are relevant for preventive actions. It is recommended to define and implement a surveillance system for the entire resident population based on indicators of environmental pollution and related health outcomes on the basis of the scientific literature and the results achieved by the present study.

Waste is part of the agenda of the European Environment and Health Process and included among the topics of the Sixth Ministerial Conference on Environment and Health. Disposal and management of hazardous waste are worldwide challenges. We performed a systematic review to evaluate the evidence of the health impact of hazardous waste exposure, applying transparent and a priori defined methods. The following five steps, based on pre-defined systematic criteria, were applied. 1. Specify the research question, in terms of "Population-Exposure-Comparators-Outcomes" (PECO)., Population: people living near hazardous waste sites; Exposure: exposure to hazardous waste; Comparators: all comparators; Outcomes: all diseases/health disorders. 2. Carry out the literature search, in Medline and EMBASE. 3. Select studies for inclusion: original epidemiological studies, published between 1999 and 2015, on populations residentially exposed to hazardous waste. 4. Assess the quality of selected studies, taking into account study design, exposure and outcome assessment, confounding control. 5. Rate the confidence in the body of evidence for each outcome taking into account the reliability of each study, the strength of the association and concordance of results.Fifty-seven papers of epidemiological investigations on the health status of populations living near hazardous waste sites were selected for the evidence evaluation. The association between 95 health outcomes (diseases and disorders) and residential exposure to hazardous waste sites was evaluated. Health effects of residential hazardous waste exposure, previously partially unrecognized, were highlighted. Sufficient evidence was found of association between exposure to oil industry waste that releases high concentrations of hydrogen sulphide and acute symptoms. The evidence of causal relationship with hazardous waste was defined as limited for: liver, bladder, breast and testis cancers, non-Hodgkin lymphoma, asthma, congenital anomalies overall and anomalies of the neural tube, urogenital, connective and musculoskeletal systems, low birth weight and pre-term birth; evidence was defined as inadequate for the other health outcomes. The results, although not conclusive, provide indications that more effective public health policies on hazardous waste management are urgently needed. International, national and local authorities should oppose and eliminate poor, outdated and illegal practices of waste disposal, including illegal transboundary trade, and increase support regulation and its enforcement.

Background: in SENTIERI surveillance system, the health risk assessment in the contaminated sites (CSs) was carried out considering the socioeconomic deprivation index (ID-SENTIERI) at the municipal level as a confounder. Pasetto et al. discussed the use of IDs in ecological studies and proposed to examine the role of ID-SENTIERI as a confounder., Objectives: to evaluate the initial conditions necessary for the role of confounding, i.e., the verification of an association of the ID-SENTIERI with the risk of some of the diseases for which evidence of a relationship with the socioeconomic state (SES) is documented in the literature., Design: the methodological approach is to exploit ecological correlations in order to assess the relationship between ID and the occurrence of mortality or congenital malformations (CMs)., Setting and Participants: mortality and CM data from municipalities in the regions of Emilia-Romagna (Northern Italy), Tuscany (Central Italy), and Campania (Southern Italy) were used. Mortality for all causes, all tumours, and lung cancers were analysed for the period 1995-2008. For the CMs, data from the regional registries of Emilia-Romagna, Tuscany, and Campania in the periods 1995-2011, 1992-2011, 2004-2010, respectively, were used. Analyses of the relationship between mortality/CMs and ID-SENTIERI were carried out according to cause, region, gender, and demographic amplitude classes using a GAM-Poisson regression model., Results: the mortality analyses show that, for the male population of the three regions under study, the relationship between ID and mortality is increasing for each outcome for municipalities with less than 50,000 inhabitants; while results for female population differ from region to region. The results of the CMs show growing associations, considering only municipalities under 10,000 inhabitants., Conclusions: the results of the study suggest that scientific evidence of an association between SES and health should be evaluated taking into account the gender, the study area, and the demographic size of the municipalities. For ID to be used as a confounding variable, it must be associated with the outcomes for which the influence of socioeconomic factors in the reference areas has been ascertained. If there is no such association, the ID cannot be used as a confounder, as it could lead to distortions of estimates and such distortions are difficult to predict. In these cases, ad hoc IDs should be produced.

Introduction: The limited scientific knowledge on the relationship between exposure and health effects in relation to geothermal activity motivated an epidemiologic investigation of Tuscan geothermal area., Aim: This study aims at describing mortality of populations living in Tuscan municipalities in the period 2003-2012., Method: Sixteen municipalities were included in the study area: eight in the northern and eight in the southern area. Mortality data come from the Regional Mortality Registry of Tuscany. Fifty-four causes of death, considered of interest for population health status or consistent with "Project SENTIERI" criteria, are analyzed., Results: Results show a worse mortality profile in the southern area, especially in males, for whom excesses of all cancers and some causes of cancer emerge, while in the northern area an excess of cerebrovascular diseases among females merits attention. Further and more appropriate studies are needed to clarify the etiology of some diseases and to better assess a potential cause-effect relationship.

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.