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Objectives The aim of the study was to investigate the incidence of AIDS-defining cancers ( ADCs) and virus-related and non-virus-related non- AIDS-defining cancers ( NADCs) in HIV-infected patients compared with the general population, and to assess the risk factors associated with these malignancies. Methods We performed a retrospective cohort study for the period from 1999 to 2009 of HIV-infected patients residing in the Local Health Authority of Brescia (northern Italy). Observed cancers in patients with HIV infection were compared with expected cancers in the population living in the same area using standardized incidence ratios ( SIRs). Risk factors were assessed using Poisson regression analysis. Results A total of 5090 HIV-infected patients were included in the study, with 32 390 person-years of follow-up. We recorded 416 tumours in 390 HIV-infected patients. Two hundred of these (48.1%) were ADCs, 138 (33.2%) were non-virus-related NADCs and 78 (18.7%) were virus-related NADCs. An increased risk ( SIR = 4.2) of cancers overall was found in HIV-infected patients. A large excess of ADCs ( SIR = 31.0) and virus-related NADCs ( SIR = 12.3) was observed in HIV-infected patients, while the excess risk for non-virus-related NADCs was small ( SIR = 1.6). The highest SIRs were observed for Kaposi sarcoma among ADCs and for Hodgkin lymphoma among virus-related NADCs. Conversely, among non-virus-related NADCs, SIRs for a broad range of malignancies were close to unity. In multivariate analysis, increasing age and CD4 cell count < 50 cells/μL were the only factors independently associated with all cancers. Conclusions Among HIV-infected people there was an excess of ADCs and also of NADCs, particularly those related to viral infections. Ageing and severe immunodeficiency were the strongest predictors. [ABSTRACT FROM AUTHOR]

Background Cross-sectional studies report an increasing prevalence of allergic diseases, such as rhinitis and asthma. Not thoroughly known, instead, is the natural history of allergic sensitization and the progress of the allergic disease-related symptoms. Aim The purpose of this study was to evaluate longitudinally the skin reactivity for the most common aeroallergens and the allergic symptoms in an urban population living in Perugia, a town of central Italy with a low-level of air pollution exposure. Methods In the 1998–1999 period 788 subjects were tested for skin reactivity to a panel of aeroallergens and underwent the administration of a questionnaire. These same subjects were part of a cohort of 1200 subjects who participated in a previous epidemiological study performed in 1984–1985 using the same tools. Subjects were aged between 14 and 64 years at the time of the first survey. Results In the present survey 196 subjects (24.9%) had skin reactivity to at least one aeroallergen, while in the previous survey 143 subjects (18.1%) had skin prick-test reactivity. The increase of the skin reactivity between the two observations was highly significant ( P<0.001) and was mainly observed in subjects <40-years old. The greatest increment in skin reactivity was seen to Dermatophagoides pteronyssinus (house dust mite) allergen. Data obtained from questionnaires showed that subjects who declared allergic symptoms increased from 341 (43.3%) to 380 (48.2%). However, the increase was significant ( P<0.01) only in subjects who had a positive association between allergic symptoms and prick-test reactivity and was greater for rhino-conjunctivitis than for asthma-related symptoms. Conclusions In a cohort of urban population of the centre of Italy, exposed to a low and stable level of air pollution, the sensitization to common aeroallergens increased with time, mostly in people <40-years of age. The greatest increment was found for indoor allergens such as Dermatophagoides pteronysimus. A significant increase in allergic symptoms, mainly related to rhino-conjunctivitis, was observed only in the presence of positive prick test. [ABSTRACT FROM AUTHOR]

In conjunction with the LITE mission an intensive LIDAR measurement campaign was carried out in Napoli (40°50’ N-14°10’E, at sea level) and Potenza (40°36’N-15°44’ E,820 ma.s.l.). The LITE experiment, flying on board the Space Shuttle in the period September 10–19, 1994, represents the first attempt to perform global coverage LIDAR measurements from space. The LITE experiment was planned to provide measurements of clouds, tropospheric and stratospheric aerosols, stratospheric temperature and density, characteristics of the planetary boundary level as well as surface albedo. Because of the relative distance between LITE ground tracks and the two southern Italy validation stations for all passes, measurements carried out in Napoli and Potenza were primarily aimed at validation of LITE stratospheric measurements. In the present preliminary analysis Potenza LIDAR measurements in coincidence with the orbit 128 LITE overpass, are reported and discussed. Potenza LIDAR data show a good agreement with LITE data in terms of aerosol scattering ratio both at 355 nm and 532 nm (R[sub A,355] and R[sub A,532] ); the two data sets appearing to be highly correlated. LITE vs. Potenza LIDAR measurements of R[sub A,355] and R[sub A,532] display a correlation coefficient of 0.72 and 0.86, respectively. Stratospheric aerosol dimensional characteristics are determined starting from the measured values of the Ångstrom coefficient. [ABSTRACT FROM AUTHOR]

Reports the impact of heat waves on mortality in Rome, Italy during June-August 2003. Method used by the Rome Local Health Authority to assess the three heat waves; Data on the estimated number of excess deaths resulting from high temperatures; The increase in the average annual number of deaths during 1995-2002; How daily excess mortality was defined; The mean daily temperature during June-August 2003; Statistics on the dead; Editorial note discussing failure of the heat health-watch warning system (HHWWS) in Rome, the excess mortality during three heat waves, and socioeconomic factors having an impact on the health of elderly people.

The prediction of neurologic outcome in comatose patients after cardiac arrest (CA) has been investigated and the findings were summarized in a practice parameter of the American Academy of Neurology (1). These guidelines did not include the EEG as a reliable outcome indicator but recent studies on continuous EEG recorded during TH have re-evaluated the role of EEG (2–4). These studies underline the utility of a simplified classification system of EEG patterns and point to which pattern attains reliable predictive value both for good and bad outcomes. These reports are of high clinical relevance because, until today, the possibility of identifying early prognostic indicators of good outcome in patients surviving to CA has not been investigated. At the best of our knowledge, only few multicentre prospective studies (4–6) analyzed the prognostic value of EEG and SEP recorded in the same patient after CA as single predictor but none analyzed the diagnostic accuracy of the association of these two tests. We present the study protocol of Italian Multicentre Study about prognostic value of EEG and SEP in comatose patients after CA (ProNeCA) proposed by study group of “Intraoperative and Intensive Care Clinical Neurophysiology” of the Italian Society of Clinical Neurophysiology. [ABSTRACT FROM AUTHOR]

In urban areas, environmental exposures to air pollution, extreme temperatures and noise as well as socio-economic inequalities are amplified. Urban green spaces offer dual benefits: they help mitigate climate change and improve public health by fostering connection to nature, reducing noise and air pollution, mitigating the urban heat island effect, and promoting physical activity. Within the 2023 "Cobenefici di Salute ed equità a supporto dei piani di risposta ai cambiamenti climatici in Italia" project funded by the Ministry of Health, we identified health indicators to assess climate action co-benefits, including those on cardiovascular disease mortality and morbidity, birth outcomes and mental health. An increase of 0.1 in the Normalized Difference Vegetation Index (NDVI) was found to be associated with a 3% reduction in cardiovascular mortality rates (95% CI: -4% to -1%). Such estimates will be applied in health impact assessment studies to help guide effective climate adaptation and public health strategies.

Background/objectives: The study aim was to evaluate the association between UPF consumption and semen quality in a sample of healthy young men in Italy., Methods: A cross-sectional analysis was carried out using data from 126 participants (mean age ± SD 20.0 ± 1.2 years) enrolled in the FASt randomized controlled trial. Food intake was assessed through the European Prospective Investigation into Cancer and Nutrition (EPIC) FFQ. Food items were categorized according to the Nova classification based on their purpose and extent of processing as follows: (1) unprocessed/minimally processed foods; (2) processed culinary ingredients; (3) processed foods; and (4) UPFs. The weight ratio (%) between each Nova group (g/d) and total food (g/d) was then calculated. For semen analyses, sperm volume, concentration, motility and morphology were measured. The associations between UPF consumption (quarters of) and semen quality parameters were estimated using multivariable-adjusted linear regression models., Results: Participants consuming high UPFs (Q4), compared to those in the bottom category of intake (Q1), had a lower sperm concentration (β = -54.16 × 10 6 cell/mL; 95%CI: -92.91 to -15.40; p for trend = 0.0020 across fourths) and progressive motility (β = -14.17%; 95%CI: -28.25 to -0.09; p for trend = 0.036). The percentage of normal morphology cells had a tendency to decrease amongst subjects consuming more UPFs compared to those with the lowest intake., Conclusions: A large dietary intake of UPFs was inversely associated with sperm concentration and progressive motility in reproductive-age men. These findings suggest that dietary recommendations for improving male fertility and sperm health should also recommend limiting UPFs.

Background: There are about 7,000 rare diseases that affect 10% of the world population. Primary biliary cholangitis, an autoimmune chronic liver disease of the interlobular bile ducts, is one of the most common causes of chronic cholestasis. However, it is a rare, often underdiagnosed and undertreated, disease which can lead to cirrhosis and liver failure. We aimed to assess the proportion of undetected primary biliary cholangitis patients in primary care through a clinical management process., Methods: We made two extractions of the clinical data concerning liver diseases, risk factors and laboratory tests from the databases of a sample of general practitioners, with a check and correction of mistakes. The clinical data of the patients without liver disease and major risk factors, and with serum Alkaline Phosphatase above the laboratory reference values, were re-evaluated by each general practitioner with an expert gastroenterologist. The patients with elevated Alkaline Phosphatase values and without evidence of intrahepatic or extrahepatic causes of cholestasis were considered suspected for primary biliary cholangitis and assessed for antimitochondrial antibodies test and specialist' s evaluation, according to present guidelines., Results: A total of 20,480 adults attending 14 general practitioners in the province of Brescia, Northern Italy, were included in the study. Nine patients had a prior primary biliary cholangitis diagnosis, with a prevalence of 43.9/100000. After excluding 2094 (10.2%) patient with liver diseases or other causes of cholestasis, 121 subjects with Alkaline Phosphatase above the reference values were re-evaluated by the general practitioners and gastroenterologist, and 27 patients without symptoms or signs of cholestasis were considered suspected for primary biliary cholangitis: 9 of them were tested for antimitochondrial antibodies, and three new primary biliary cholangitis cases were detected (+33%)., Discussion and Conclusions: This study shows that there is a not negligible burden of undetected cases of adult rare diseases that can be diagnosed in primary care, through a disease management procedure, without modifying the routine clinical practice.

Background: Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated., Aim: We performed a national survey to investigate the listing criteria, comorbidities, and outcomes., Methods: In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years., Results: From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence)., Conclusions: Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death., Competing Interests: Conflict of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Ruminants play an important role in economic sustenance in many developing countries. Abortion is one of the most important causes of economic losses in sheep livestock and, for this reason, it is very important to know, at an early stage, which pathogens caused abortion., Aim: The aim of the study is to obtain data about the distribution of abortifacient pathogens in the Italian regions of Latium and Tuscany, the awareness of the distribution of infectious agents causing abortion could allow the development of an appropriate vaccination and prophylaxis plan, to avoid major economic losses., Methods: 388 abortions were collected during the 2015-2018 period. Organs, tissues, and swabs were subjected to DNA extraction and then analyzed with commercial q-PCR kits for the detection of the most common abortion pathogens circulating in these geographical areas., Results: The positivity in 148 abortions was 56% for Chlamydia abortus , 14% for Coxiella burnetii , 16% for Salmonella spp, 12% for Toxoplasma gondii, and 2% for Neospora caninum . Interesting results were obtained for cases of abortions with co-infection of abortion pathogens., Conclusion: Diagnosing the cause of abortion remains a multifaceted process that may also include non-infectious factors such as deficiencies and toxicities. Further research is needed also to assess the role of low pathogen concentrations and co-infections in the abortions of sheep., Competing Interests: The authors declare no conflict of interest.

Objective: To estimate prevalence and incidence of thrombotic Primary Antiphospholipid Syndrome (PAPS) in the general population aged 18-49 years., Methods: The study was carried out in Valtrompia, a valley in northern Italy, in 2011-2015. The identification of PAPS cases leveraged three integrated sources: 1) Rheumatology Unit at the University Hospital; 2) General Practitioners; 3) hospital discharge codes of patients admitted for thrombotic events., Results: Prevalence and incidence were estimated as 22.9 (95% C.I. 11.4-41.0) and 5.0 (2.6-8.7) cases per 100,000 individuals, respectively. The estimates were 28.3 and 4.8, and 17.2 and 5.1 in males and females, respectively. The type of disease onset was mainly of arterial type in men and venous in women., Conclusions: Thrombotic PAPS was found to be a rare disease in this population-based study. Prevalence and incidence were not significantly different between males and females aged 18-49 years, but a different type of onset was observed., (Copyright © 2023. Published by Elsevier Inc.)

Results: One hundred and fifty five subjects aged 20-59 years underwent (i) liver ultrasound (US), (ii) clinical and anthropometric evaluations, (iii) blood tests, and (iv) assessment of dietary habits. According to US evaluation, 73 of them had severe, moderate, or mild liver steatosis (NAFLD patients) and 82 had no liver steatosis (healthy controls). Fifty-eight NAFLD patients and 73 controls completed the study. Among NAFLD patients, 26 (45%) downgraded steatosis severity, 12 of which achieved complete steatosis regression (21%). Three of the healthy controls developed NAFLD. The NAFLD patients improved their dietary habits and reduced BMI and waist circumference, during the study period, more than healthy controls. Liver steatosis remission/regression was independent of changes in BMI or liver enzymes and was more frequent among patients with mild steatosis at baseline., Conclusions: Mediterranean dietary advices, without a personalised meal planning, were efficient in reducing/remitting NAFLD, especially among patients with mild disease, which argues in favour of early identification and lifestyle intervention. This trial is registered with NCT03300661., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Barbara Zanini et al.)

Objectives: to estimate the impact of daily exposure to extreme air temperatures (heat and cold) on cause-specific mortality in Italy and to evaluate the differences in the association between urban, suburban and rural municipalities., Design: time series analyses with two-stage approach were applied: in the first stage, multiple Poisson regression models and distributed lag non-linear models (DLNM) were used to define the association between temperature and mortality; in the second one, meta-analytic results were obtained by adopting BLUP (Best Linear Unbiased Prediction) coefficients at provincial level, which were then used to estimate the Attributable Fractions of cause-specific deaths., Setting and Participants: cause-specific deaths from 2006to 2015 in Italy have been analysed by region and overall., Main Outcome Measures: 5,648,299 total deaths included. Fractions (and relative 95% empirical confidence interval) of deaths attributable to increases from 75th to 99th percentiles of temperature, for heat, and decreases from 25th to 1st percentile, for cold., Results: the overall impact of air temperature on causespecificmortality is higher for heat than for cold. When considering heat, the attributable fraction is higher for diseases of the central nervous system (3.6% 95% CI 1.9-4.9) and mental health disease (3.1% 95% CI 1.7-4.4), while considering cold, ischemic disease (1.3% 95% CI 1.1-1.6) and diabetes (1.3% 95% CI 0.7-1.8) showed the greater impact. By urbanization level, similar impacts were found for cold temperature, while for heat there was an indication of higher vulnerability in rural areas emerged., Conclusions: results are relevant for the implementation and promotion of preventive measures according to climate change related increase in temperature. The available evidence can provide the basis to identify vulnerable areas and population subgroups to which address current and future heat and cold adaptation plans in Italy.

Background: Analyses of coronavirus disease 19 suggest specific risk factors make communities more or less vulnerable to pandemic-related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics., Methods: We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality., Results: We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100 000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden., Conclusion: These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Introduction: Air pollution and extreme temperatures have been associated with multiple adverse health effects, especially on the cardiovascular and respiratory systems. The evidence of a relationship between daily exposures and mortality from metabolic, nervous and mental causes needs to be strengthened. The aim of this study is to investigate the association between daily exposure to fine particulate matter (PM2.5) and extreme temperatures (heat and cold) with cause-specific mortality in the entire Italian population., Methods: The daily counts of deaths from natural, cardiovascular, respiratory, metabolic, diabetes, nervous and mental causes were provided by Istat at the municipal level for the period 2006-2015. Through the application of machine-learning models based on satellite data and spatiotemporal variables, population-weighted exposures to daily mean PM2.5 (2013-2015) and air temperature (2006-2015) were estimated at municipality level. Time-series models adjusted for seasonal and long-term trends were applied, and associations between the above exposures and different causes of death at the national level were estimated., Results: The study found a marked effect of PM2.5 on deaths from nervous causes, with a % increase of risk (IR%) of 6.55% (95% confidence interval: 3.38%-9.81%) per PM2.5 increases of 10 µg/m3. The study also highlighted significant effects of low and high temperatures on all study outcomes. The effects were greater for high temperatures. In particular, the effects of heat, expressed as a % increase in risk per temperature increase from the 75th to the 99th percentile, show the highest associations with mortality from nervous causes (58.3%; 95%CI: 49.7%-67.5%), mental causes (48.4%; 95%CI: 40.4%-56.9%), respiratory causes 45.8%; 95%CI: 39.7%-52.1%) and metabolic causes (36.9%; 95%CI: 30.6%-43.5%)., Discussion: The study showed a strong association between daily exposure to PM2.5 and extreme temperatures, especially heat, with mortality outcomes, especially those under-investigated, such as diabetes, metabolic, nervous and mental causes.

Objectives: to provide evidence of the health impacts of climate change in Italy., Design: descriptive study., Setting and Participants: the indicators published in the 2022 Lancet Countdown report were adapted and refined to provide the most recent data relevant to Italy., Main Outcome Measures: twelve indicators were measured, organized within five sections mirroring those of the 2022 Lancet Countdown report: climate change impacts, exposures, and vulnerabilities; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement., Results: the overall picture depicted by the analysis of the 12 indicators reveals two key findings. First, climate change is already affecting the health of Italian populations, with effects not being uniform across the Country and with the most vulnerable groups being disproportionately at risk. Second, results showed that Italy's mitigation response has been partial, with major costs to human health. Accelerated climate change mitigation through energy system decarbonisation and shifts to more sustainable modes of transport could offer major benefits to health from cleaner air locally and from more active lifestyles, and to climate change from reduction of global warming. The decarbonisation of agricultural systems would similarly offer health co-benefits to Italian population. Conclusions: through accelerated action on climate change mitigation, Italy has the opportunity of delivering major and immediate health benefits to its population. Developing a key set of local indicators to monitor the impacts of climate change and evaluate response actions, in terms of adaptation and mitigation, can help support and enhance policy and action to fight climate changes.

Objectives: to estimate the impact (number of deaths and attributable fraction) of air pollution (chronic exposure to PM2.5 and NO2) and high summer temperatures (acute exposure) on mortality in Italy., Design: observational study. Time series analysis (for estimating acute effects of air temperature), and computation of deaths attributable to heat/pollution using standard health impact assessment functions., Setting and Participants: for the assessment of the impact due to chronic exposure to air pollutants, the study period considered was 2016-2019. For the assessment of the acute effects of air temperature and related impacts, the municipal daily series of deaths from all causes relating to the period 2003-2015 were used., Main Outcome Measures: mortality for all causes (effects and impacts of acute exposure to air temperature), cause-specific mortality (impact of chronic exposure to pollution)., Results: concerning chronic exposure to PM2.5, each year during 2016-2019, 72,083 deaths (11.7%) were estimated to be attributable to annual mean levels of PM2.5 above 5 µg/m3 (WHO-2021 Air Quality Guideline value). Of these, 39,628 were estimated in the regions of the Po Valley and 10,232 in the 6 Italian cities with >500,000 inhabitants. With reference to acute effects of air temperature, over 14,500 deaths (2.3%) were estimated to be attributable to daily temperature increases from the 75th to the 99th percentile of the municipality-specific distribution for the year 2015. Conclusions: high air pollution concentrations and summer temperatures are two environmental risk factors extremely relevant for public health. Although the prevention and mitigation interventions carried out in recent years have contributed to reducing the exposure of the population, there are still alarming numbers of deaths attributable to high levels of particulate matter, nitrogen oxides, and air temperature in the Italian population.

Background/aim: Extreme temperatures have impact on the health and occupational injuries. The construction sector is particularly exposed. This study aims to investigate the association between extreme temperatures and occupation injuries in this sector, getting an insight in the main accidents-related parameters., Methods: Occupational injuries in the construction sector, with characteristic of accidents, were retrieved from Italian compensation data during years 2014-2019. Air temperatures were derived from ERA5-land Copernicus dataset. A region based time-series analysis, in which an over-dispersed Poisson generalized linear regression model, accounting for potential non-linearity of the exposure- response curve and delayed effect, was applied, and followed by a meta-analysis of region-specific estimates to obtain a national estimate. The relative risk (RR) and attributable cases of work-related injuries for an increase in mean temperature above the 75th percentile (hot) and for a decrease below the 25th percentile (cold) were estimated, with effect modifications by different accidents-related parameters., Results: The study identified 184,936 construction occupational injuries. There was an overall significant effect for high temperatures (relative risk (RR) 1.216 (95% CI: (1.095-1.350))) and a protective one for low temperatures (RR 0.901 (95% CI: 0.843-0.963)). For high temperatures we estimated 3,142 (95% CI: 1,772-4,482) attributable cases during the studied period. RRs from 1.11 to 1.30 were found during heat waves days. Unqualified workers, as well as masons and plumbers, were found to be at risk at high temperatures. Construction, quarry and industrial sites were the risky working environments, as well as specific physical activities like working with hand-held tools, operating with machine and handling of objects. Contact with sharp, pointed, rough, coarse 'Material Agent' were the more risky mode of injury in hot conditions., Conclusions: Prevention policies are needed to reduce the exposure to high temperatures of construction workers. Such policies will become a critical issue considering climate change., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: We aimed at investigating the relationship between particulate matter (PM) and daily admissions for cardiovascular diseases (CVDs) at national level in Italy., Methods and Results: Daily numbers of cardiovascular hospitalizations were collected for all 8084 municipalities of Italy, in the period 2013-2015. A satellite-based spatiotemporal model was used to estimate daily PM10 (inhalable particles) and PM2.5 (fine particles) concentrations at 1-km2 resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and cardiovascular admissions. Flexible functions were estimated to explore the shape of the associations at low PM concentrations, also in non-urban areas. We analysed 2 154 810 acute hospitalizations for CVDs (25% stroke, 24% ischaemic heart diseases, 22% heart failure, and 5% atrial fibrillation). Relative increases of total cardiovascular admissions, per 10 µg/m3 variation in PM10 and PM2.5 at lag 0-5 (average of last 6 days since admission), were 0.55% (95% confidence intervals: 0.32%, 0.77%) and 0.97% (0.67%, 1.27%), respectively. The corresponding estimates for heart failure were 1.70% (1.28%, 2.13%) and 2.66% (2.09%, 3.23%). We estimated significant effects of PM10 and PM2.5 also on ischaemic heart diseases, myocardial infarction, atrial fibrillation, and ischaemic stroke. Associations were similar between less and more urbanized areas, and persisted even at low concentrations, e.g. below WHO guidelines., Conclusion: PM was robustly associated with peaks in daily cardiovascular admissions, especially for heart failure, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: assessment of the health effects on the resident population around the incinerator for municipal solid waste in Valmadrera (Lombardy Region, Northern Italy) in relation to the exposure level to the pollutants produced by the plant., Design: historical cohort study, based on the resident population from 2003 to 2016 in the study area. With a dispersion model, based on PM10 emitted by the plant, three areas of exposure (high, medium, low) were defined and, on the basis of the residence of the cohort, different exposure levels were attributed to the subjects. The association between level of exposure and health effects were estimated by comparing the high and medium exposure levels with the low exposure level, using a Cox model, adjusted for age and socioeconomic deprivation index., Main Outcome Measures: mortality rates, hospitalization rates, cancer incidence rates, and perinatal outcomes were analysed for the main causes potentially associated with exposure to incineration plants., Results: the subjects enrolled in the cohort were 106,056 (1,000,242 person-years). There were no statistically significant excesses of risk for almost all the outcomes investigated. Excessive mortality and hospitalization were found for liver/biliary cancers (HR women: 2.57; 95%CI 1.15-2.79; HR men: 2.22; 95%CI 1.10-4, 84). In the municipality where the plant is located, an excess prevalence (OR 1.78; 95%CI 1.43-2.21) of hepatitis C was found., Conclusions: the results suggest the absence of a relationship between residence in areas with different levels of pollutants emitted by the plant and the onset of almost all diseases. The associated causes do not have aetiological plausibility with exposure to pollutants from waste incineration. In particular, for liver/liver and biliary cancer, the association with infectious causes rather than exposure to environmental pollutants is more plausible.

Back in December 2019, the novel coronavirus disease 2019 (Covid-19) started rapidly spreading worldwide, especially in Italy that was among the most affected countries. The geographical distribution of air pollution and Covid-19 mortality in Italy suggested atmospheric pollution as a worsening factor of severe Covid-19 health outcomes. The present nationwide ecological study focused on all 107 Italian territorial areas, aiming to assess the potential association between Particulate Matter concentration, less than 2.5 μm in diameter (exposure), and Covid-19 mortality rate (outcome) throughout 2020, by looking at 28 potential confounders. A potential positive association between exposure and outcome was observed when performing a multivariate regression analysis with a Negative Binomial model, suggesting that an increase of 1 μg/m 3 in the exposure is associated with an increase of 9.0% (95% CI: 6.5%-11.6%) in the average Covid-19 mortality rate, conditional on all 28 potential confounders. A sensitivity analysis, based on the E-value, shows that a hypothetical unmeasured confounder would have to be associated with both PM 2.5 concentration and Covid-19 mortality rate by a rate ratio of at least 1.40-fold each to explain away the exposure-outcome association, conditional on all 28 covariates included in the main analysis model. Moreover, the Observed Covariate E-value (OCE) was reported to provide a contextualization of the E-value on the observed covariates included in the study. The OCE sensitivity analysis shows that a set of unknown confounders similar in size and magnitude to the set of the considered climatic factors could potentially explain away the estimated exposure-outcome association. Consequently, the role of climatic factors in the Covid-19 pandemic is worth of further investigation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/aim: The relationship between air pollution and respiratory morbidity has been widely addressed in urban and metropolitan areas but little is known about the effects in non-urban settings. Our aim was to assess the short-term effects of PM10 and PM2.5 on respiratory admissions in the whole country of Italy during 2006-2015., Methods: We estimated daily PM concentrations at the municipality level using satellite data and spatiotemporal predictors. We collected daily counts of respiratory hospital admissions for each Italian municipality. We considered five different outcomes: all respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), lower and upper respiratory tract infections (LRTI and URTI). Meta-analysis of province-specific estimates obtained by time-series models, adjusting for temperature, humidity and other confounders, was applied to extrapolate national estimates for each outcome. At last, we tested for effect modification by sex, age, period, and urbanization score. Analyses for PM 2.5 were restricted to 2013-2015 cause the goodness of fit of exposure estimation., Results: A total of 4,154,887 respiratory admission were registered during 2006-2015, of which 29% for LRTI, 12% for COPD, 6% for URTI, and 3% for asthma. Daily mean PM 10 and PM 2.5 concentrations over the study period were 23.3 and 17 μg/m 3 , respectively. For each 10 μg/m 3 increases in PM 10 and PM 2.5 at lag 0-5 days, we found excess risks of total respiratory diseases equal to 1.20% (95% confidence intervals, 0.92, 1.49) and 1.22% (0.76, 1.68), respectively. The effects for the specific diseases were similar, with the strongest ones for asthma and COPD. Higher effects were found in the elderly and in less urbanized areas., Conclusions: Short-term exposure to PM is harmful for the respiratory system throughout an entire country, especially in elderly patients. Strong effects can be found also in less urbanized areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Previous studies reported a link between short-term exposure to environmental stressors (air pollution and air temperature) and atherothrombotic cardiovascular diseases. However, only few of them reported consistent associations with venous thromboembolism (VTE). Our aim was to estimate the association between daily air temperature and particulate matter (PM) air pollution with hospital admissions for pulmonary embolism (PE) and venous thrombosis (VT) at national level in Italy., Methods: We collected daily hospital PE and VT admissions from the Italian Ministry of Health during 2006-2015 in all the 8,084 municipalities of Italy, and we merged them with air temperature and daily PM10 concentrations estimated by satellite-based spatiotemporal models. First, we applied multivariate Poisson regression models at province level. Then, we obtained national overall effects by random-effects meta-analysis., Results: This analysis was conducted on 219,952 PE and 275,506 VT hospitalizations. Meta-analytical results showed weak associations between the two exposures and the study outcomes in the full year analysis. During autumn and winter, PE hospital admissions increased by 1.07% (95% confidence intervals [CI]: 0.21%; 1.92%) and 0.96% (95% CI: 0.07%; 1.83%) respectively, per 1 °C decrement of air temperature in the previous 10 days (lag 0-10). In summer we observed adverse effects at high temperatures, with a 1% (95% CI: 0.10%; 1.91%) increasing risk per 1 °C increment. We found no association between VT and cold temperatures., Conclusion: Results show a significant effect of air temperature on PE hospitalizations in the cold seasons and summer. No effect of particulate matter was detected., (Copyright © 2021. Published by Elsevier B.V.)

Background: Short-term exposure to particulate matter (PM) has been related to mortality worldwide. Most evidence comes from studies conducted in major cities, while little is known on the effects of low concentrations of PM and in less urbanized areas. We aim to investigate the relationship between PM and all-cause mortality at national level in Italy., Methods: Daily numbers of all-cause mortality were collected for all 8092 municipalities of Italy, from 2006 to 2015. A satellite-based spatiotemporal model was developed to estimate daily PM 10 (inhalable particles) and PM 2.5 (fine particles) concentrations at 1-km resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and mortality at province level, and then, results were pooled with a random-effects meta-analysis. Associations were estimated by combination of age and sex and degree of urbanization of the municipalities. Flexible functions were estimated to explore the shape of the associations at low PM concentrations., Results: We analyzed 5,884,900 deaths (40% among subjects older than 85 years, 60% occurring outside the main urban areas). National daily mean (interquartile range) PM 10 and PM 2.5 concentrations were 23 (14) μg/m 3 and 15 (11) μg/m 3 , respectively. Relative increases of mortality per 10 μg/m 3 variation in lag 0-5 (average of last six days since death) PM 10 and PM 2.5 were 1.47% (95% Confidence Intervals (CI): 1.15%, 1.79%) and 1.96% (1.33%, 2.59%), respectively. Associations were highest among elderly and women for PM 10 only, similar between rural and urbanized areas, and were present even at low concentrations, e.g., below WHO guidelines., Conclusions: Air pollution was robustly associated with peaks in daily all-cause mortality in Italy, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines (2021) for PM 10 and PM 2.5 are not sufficient to protect public health.

Background: Identifying individual and contextual factors that influence adolescent well-being is a research priority. This study aimed to assess the prevalence of symptoms of mental health problems and some related factors in Italian adolescents in 2017-2018., Methods: The present study was a cross-sectional survey among 3002 students aged 15-16 years who resided in two Italian provinces, in North and South Italy. Symptoms of mental health problems were assessed using the SDQ and CES-DC, and students' risk-taking behaviors and school climate perception were assessed. All information was collected anonymously. Logistic regression models were used to assess the associations of tobacco and alcohol use, screen time, bullying, and school climate with symptoms of mental health problems., Results: One student out of five reported symptoms of mental health problems, with a more than double proportion among girls than boys (28.7% vs 10.4% with depressive symptoms, respectively). Thirty percent and 40% of students smoked tobacco or drank alcoholic beverages at least once in the past month, and more than 40% reported being victims or authors of bullying in the past 6 months. Smoking behavior, alcohol consumption, screen time, bullying, and negative school climate had 1.2- to 3.3-fold increased odds of symptoms of mental health problems without substantial differences between sexes and geographical areas., Conclusions: Tobacco and alcohol use, screen time, bullying, and school climate were independently associated with symptoms of mental health problems in a large sample of 15-16-year-old Italian adolescents without substantial gender and geographical differences.

Lombardy, the most populated and industrialized Italian region, was the epicentre of the first wave (March and April 2020) of COVID-19 in Italy and it is among the most air polluted areas of Europe. We carried out an ecological study to assess the association between long-term exposure to particulate matter (PM) and nitrogen dioxide (NO 2 ) on COVID-19 incidence and all-cause mortality after accounting for demographic, socioeconomic and meteorological variables. The study was based on publicly available data. Multivariable negative binomial mixed regression models were fitted, and results were reported in terms of incidence rate ratios (IRRs) and standardized mortality ratios (SMR). The effect of winter temperature and humidity was modelled through restricted cubic spline. Data from 1439 municipalities out of 1507 (95%) were included in the analyses, leading to a total of 61,377 COVID-19 cases and 40,401 deaths from all-causes collected from February 20th to April 16th and from March 1st to April 30th, 2020, respectively. Several demographic and socioeconomic variables resulted significantly associated with COVID-19 incidence and all-cause mortality in a multivariable fashion. An increase in average winter temperature was associated with a nonlinear decrease in COVID-19 incidence and all-cause mortality, while an opposite trend emerged for the absolute humidity. An increase of 10 μg/m 3 in the mean annual concentrations of PM 2.5 and PM 10 over the previous years was associated with a 58% and 34% increase in COVID-19 incidence rate, respectively. Similarly, a 10 μg/m 3 increase of annual mean PM 2.5 concentration was associated with a 23% increase in all-cause mortality. An inverse association was found between NO 2 levels and COVID-19 incidence and all-cause mortality. Our ecological study showed that exposure to PM was significantly associated with the COVID-19 incidence and excess mortality during the first wave of the outbreak in Lombardy, Italy., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Preschool children with clinically-diagnosed asthma have a higher rate of emergency department visits and consume more resources for management than older children. However, no clinical trials have yet been performed measuring the impact of a combined diagnostic, therapeutic and educational pathway regimen for evaluation of wheezing control in children aged less than 6 years. The purpose of the present study was to assess the impact of a pediatric program developed in Italy, the Diagnostic Therapeutic Educational Pathway (DTEP), for asthma management in children less than 6 years old attending an asthma referral center., Methods: This is a retrospective population-based cohort study performed in children with asthma aged 0-5 years, attending at "Io e l'Asma center", Brescia, Italy between September 2007 and December 2014. The incidence rates (IRs) of hospitalization, emergency room visits, use of outpatient services and drug usage for dyspnea, wheezing, or respiratory symptoms were evaluated for time periods prior to and after DTEP intervention., Results: A total of 741 patients, aged 0-5 years completed the DTEP, including 391 and 350 children aged 0-2 and 3-5 years, respectively. The percentage of children aged 0-2 and 3-5 years showing improved control of wheezing symptoms during the 1st to 3rd visit interval as a result of the DTEP intervention increased from 39.5 to 60.9% and from 25.5 to 75.5%, respectively. During these periods, the IRs showed a significant decrease for all outcomes, from-8.6% to - 80.4%. Although specific IRs for drug prescriptions declined, particularly for LABA plus corticosteroids, antibiotics, and systemic corticosteroids, they increased for SABA, inhaled corticosteroid and leukotriene receptor antagonist usage., Conclusions: The results suggest that a real-world assessment of the integrated DTEP program for preschool children provides evidence for improved wheezing control and reduction of adverse therapeutic related outcomes.

Backgrounds: Patients at greatest risk of severe clinical conditions from coronavirus disease 2019 (COVID-19) and death are elderly and comorbid patients. Increased levels of cardiac troponins identify patients with poor outcome. The present study aimed to describe the clinical characteristics and outcomes of a cohort of Italian inpatients, admitted to a medical COVID-19 Unit, and to investigate the relative role of cardiac injury on in-hospital mortality., Methods and Results: We analyzed all consecutive patients with laboratory-confirmed COVID-19 referred to our dedicated medical Unit between February 26th and March 31st 2020. Patients' clinical data including comorbidities, laboratory values, and outcomes were collected. Predictors of in-hospital mortality were investigated. A mediation analysis was performed to identify the potential mediators in the relationship between cardiac injury and mortality. A total of 109 COVID-19 inpatients (female 36%, median age 71 years) were included. During in-hospital stay, 20 patients (18%) died and, compared with survivors, these patients were older, had more comorbidities defined by Charlson comorbidity index ≥ 3(65% vs 24%, p = 0.001), and higher levels of high-sensitivity cardiac troponin I (Hs-cTnI), both at first evaluation and peak levels. A dose-response curve between Hs-cTnI and in-hospital mortality risk up to 200 ng/L was detected. Hs-cTnI, chronic kidney disease, and chronic coronary artery disease mediated most of the risk of in-hospital death, with Hs-cTnI mediating 25% of such effect. Smaller effects were observed for age, lactic dehydrogenase, and D-dimer., Conclusions: In this cohort of elderly and comorbid COVID-19 patients, elevated Hs-cTnI levels were the most important and independent mediators of in-hospital mortality.

Polychlorinated biphenyls (PCBs) are human carcinogens, based on sufficient evidence for melanoma and limited evidence for non-Hodgkin lymphoma and breast cancer. Few data are available for liver cancer, although PCBs cause it in rats and determined liver damage in poisoned people. We investigated the association between PCB serum levels and hepatocellular carcinoma (HCC) with a case-control study in a PCB-polluted area in North Italy. We enrolled prospectively 102 HCC incident cases and 102 age and gender-matched hospital controls. Serum concentrations of 33 PCB congeners were determined by a gas chromatograph coupled to mass spectrometry. Of 102 HCC cases, 62 who had lost < 3 kg of body weight in past 3 years were included in the analysis (67.7% males, mean age 68 years). The odds ratio (OR) for HCC for 3rd compared to 1st tertile of PCB distribution was 1.76 (95% confidence interval 0.62-5.03) for total PCB, adjusting for socio-demographic variables and risk factors for HCC by logistic regression. For most PCB congeners, ORs > 1.5 or 2 were found, although the 95% CIs included the null value for almost all of them. This preliminary study suggests that PCBs might play a role in HCC development.

Background: Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions., Objectives: To investigate the prevalence of skin disorders in a highly PCB polluted area in northern Italy, with locally produced food as the main source of human contamination, and evaluate the association between skin lesions and PCB serum levels, taking account of possible confounders., Materials & Methods: Thirty-three PCB congeners were quantitatively assessed and a total of 189 subjects were equally divided into three groups using the tertiles of total PCB serum concentrations. All subjects underwent a clinical examination and were interviewed on their risk factors and history of skin diseases., Results: No statistically significant difference was found in the prevalence of skin cancer, nevi, pigmentary disorders as well as inflammatory and infectious skin diseases among the three PCB exposure groups. It should be noted that the use of questionnaires to assess subjects' past sun exposure and photoprotection is intrinsically flawed due to random error., Conclusion: Our study does not support the hypothesis that chronic PCB exposure, through the ingestion of contaminated food, determines an increased risk of developing skin diseases.

Background: Italy was the first country outside China to experience the impact of the COVID-19 pandemic, which resulted in a significant health burden. This study presents an analysis of the excess mortality across the 107 Italian provinces, stratified by sex, age group and period of the outbreak., Methods: The analysis was performed using a two-stage interrupted time-series design using daily mortality data for the period January 2015-May 2020. In the first stage, we performed province-level quasi-Poisson regression models, with smooth functions to define a baseline risk while accounting for trends and weather conditions and to flexibly estimate the variation in excess risk during the outbreak. Estimates were pooled in the second stage using a mixed-effects multivariate meta-analysis., Results: In the period 15 February-15 May 2020, we estimated an excess of 47 490 [95% empirical confidence intervals (eCIs): 43 984 to 50 362] deaths in Italy, corresponding to an increase of 29.5% (95% eCI: 26.8 to 31.9%) from the expected mortality. The analysis indicates a strong geographical pattern, with the majority of excess deaths occurring in northern regions, where few provinces experienced increases up to 800% during the peak in late March. There were differences by sex, age and area both in the overall impact and in its temporal distribution., Conclusion: This study offers a detailed picture of excess mortality during the first months of the COVID-19 pandemic in Italy. The strong geographical and temporal patterns can be related to the implementation of lockdown policies and multiple direct and indirect pathways in mortality risk., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Crohn's disease (CD) and ulcerative colitis, two forms of inflammatory bowel disease (IBD), are chronic and relapsing conditions of the gastrointestinal tract both characterized by long lasting chronic inflammation and increased risk of dysplasia and colorectal cancer (CRC). The aim of our study was to evaluate the interobserver agreement about IBD-associated dysplasia among pathologists belonging to the Italian Group for Inflammatory Bowel Diseases (IG-IBD P)., Methods: The present multicenter survey was performed using telepathology, supported by an open source E-learning platform. Biopsy specimens from 30 colonoscopies and from 20 patients were included. The glass slides of any case, including clinical and endoscopic data, were digitalized and uploaded on the E-learning platform. All the digital slides were grouped in 54 diagnostic "blocks". Blinded histopathological evaluation on all the digital slides was performed by 20 gastrointestinal pathologists. Closed-ended questions about (1) the occurrence of IBD; (2) the classification of IBD (as UC or CD); (3) the presence of active versus quiescent disease; (4) the presence of dysplasia; (5) the possible association of dysplasia with the sites of disease (dysplasia-associated lesion or mass-DALM vs adenoma-like mass-ALM); (6) the grading of dysplasia according to the ECCO guidelines (negative, indefinite, low grade, high grade categories) and (7) the presence of associated serrated features, were proposed in each case. Inter-observer agreement was evaluated by mean agreement percentage and kappa statistic, when suitable., Results: The diagnosis of IBD was confirmed in 19 of 20 patients, 17 of 19 being classified as UC, 2 as CD. The mean interobserver agreement percentages about (1) the evidence of IBD, (2) the presence of either UC or CD and (3) the activity grading resulted to be 80%, 69% and 86%, respectively. Dysplasia was detected in 8/20 patients, with moderate agreement between pathologists (mean 72%, k 0.48). Particularly, low grade dysplasia was found in 13 biopsies (combined k 0.38), whereas high grade dysplasia in 8 (combined k 0.47). When the endoscopic and histopathological data were combined, features consistent with DALM were found in 6 of 20 patients with low grade dysplasia and those consistent with ALM in 2 patients with low grade dysplasia in a single biopsy (mean agreement: 86%). An associated serrated pattern was discovered in 4 patients (7 biopsies)., Conclusions: Our study showed moderate interobserver agreement about the histopathological detection and classification of IBD-associated dysplasia. Further efforts should be undertaken to integrate the histopathological data with both the ancillary tests and molecular investigations.

Objectives: to assess the impact of a cement plant emissions on mortality, hospitalizations, and cancer incidence in the residents of the municipality of Pederobba (Veneto Region, Northern Italy)., Design: retrospective residential cohort study., Setting and Participants: the study was conducted in Pederobba and in 7 neighbouring municipalities (Cavaso Del Tomba, Cornuda, Crocetta del Montello, Monfumo, Segusino, Valdobbiadene, Vidor). The cohort included 12,116 residents in Pederobba (151,784 person-years) and 49,004 residents in the neighbouring municipalities (660,268 person-years) in the period 1996-2017. On the basis of the model estimate of the annual average concentration of nitrogen dioxide (NO2), the municipality of Pederobba was divided into an area with higher exposure of NO2 and another one at lower exposure of NO2. Two comparisons were made: the first between the residents in Pederobba and residents in the neighbouring municipalities; the second between people residing in Pederobba in the higher and in the lower exposure areas., Main Outcome Measures: analysis of cause-specific mortality and hospitalization and cancer incidence, with particular attention to the diseases for which there is evidence of association with exposure to air-pollutants. For cancer incidence, available data were limited to the municipalities of Pederobba, Cavaso Del Tomba, Cornuda, Crocetta del Montello, and Monfumo for the period 1996-2015., Results: the comparison among Pederobba and the 7 neighbouring municipalities showed that within Pederobba residents there was: • a slight increase in the risk of death from all causes in women, due to circulatory diseases (HR 1.29; 95%CI 1.15-1.45), in particular ischaemic heart disease (HR 1.55; 1.27-1.89) and cerebrovascular diseases (HR 1.35; 1.06-1.72); • a moderate increase in hospitalizations for circulatory diseases, such as heart failure (HR 1.17; 1.00-1.37) and cerebrovascular diseases (HR 1.41; 1.17 -1.70), especially in elderly women; • a slight increase in hospitalizations for respiratory diseases, especially in older women (HR 1.19; 1.04-1.37); • no difference were observed in cancer incidence, neither for all nor for single cancer sites, in both genders.The comparison between residents in the higher exposure area and those in the lower exposure area showed no difference in mortality, hospitalizations, and cancer incidence., Conclusions: higher mortality and hospitalization rates from circulatory and respiratory causes detected in Pederobba compared to the neighbouring municipalities were not confirmed by the comparison between residents in the higher and in the lower exposure area. Overall, data did not show a clear, well-characterized relationship between the exposure to pollutants emitted by the cement plant and the onset of chronic diseases. The excess of mortality and hospitalization for cardiovascular and cerebrovascular diseases, reported especially in older women, deserves further investigation, because of the complex cause-effect relations of these diseases., Competing Interests: None declared

Background: Serum polychlorinated biphenyls (PCBs) have been associated with some chronic diseases, but little evidence exists on their possible relationship with neurodegenerative diseases. We aimed to assess the relationship between PCB exposure and the occurrence of dementia and Parkinson disease in a prospective cohort study in a highly polluted area (Brescia-Caffaro)., Methods: PCB exposure was assessed by measuring serum levels of 24 congeners. Data on the onset of dementia and Parkinson disease were retrieved by the Brescia Health Protection Agency Database. We used Poisson regression models adjusted for possible confounders to calculate rate ratios (RRs). A mediation analysis was performed to evaluate the mediatory role of cardiovascular diseases., Results: 699 subjects without neurologic diseases at baseline were enrolled (48.1% males, 63.2 years of mean age) in 2001-2013 and followed up to 2018. During a mean follow-up of 8.8 years, 36 and 20 subjects developed dementia and Parkinson disease. Subjects in the 2nd and 3rd tertiles of the total PCBs distribution, compared with those in the 1st tertile, had a higher risk of dementia (RR = 2.30 and RR = 4.35). The estimates for Parkinson disease included the null value with wide confidence intervals. In the mediation analysis, the association between PCB exposure and dementia was dominated by the direct pathway and not by the hypertension-mediated pathway., Conclusions: We observed a positive association between total PCBs serum levels and the onset of dementia not mediated by hypertension. For Parkinson, the unstable risk estimates did not allow to draw a conclusion on a possible association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: to assess the temporal variation in excess total mortality and the portion of excess explained by COVID-19 deaths by geographical area, gender, and age during the COVID-19 epidemic., Design: descriptive analysis of temporal variations of total excess deaths and COVID-19 deaths in the phase 1 and phase 2 of the epidemic in Italy., Setting and Participants: 12 Northern cities and 20 Central-Southern cities from December 2019 to June 2020: daily mortality from the National Surveillance System of Daily Mortality (SiSMG) and COVID-19 deaths from the integrated COVID-19 surveillance system., Main Outcome Measures: total mortality excess and COVID-19 deaths, defined as deaths in microbiologically confirmed cases of SARS-CoV-2, by gender and age groups., Results: the largest excess mortality was observed in the North and during the first phase of the epidemic. The portion of excess mortality explained by COVID-19 decreases with age, decreasing to 51% among the very old (>=85 years). In phase 2 (until June 2020), the impact was more contained and totally attributable to COVID-19 deaths and this suggests an effectiveness of social distancing measures., Conclusions: mortality surveillance is a sensible information basis for the monitoring of health impact of the different phases of the epidemic and supporting decision making at the local and national level on containment measures to put in place in coming months.

Food Frequency Questionnaires (FFQs) are valuable research tools in nutritional epidemiology. This study aimed to develop and validate a new semi-quantitative FFQ, specifically designed for the Italian population and best fitted for self-administration. During the development process, we adapted to Italian needs the validated FFQ proposed by the Fred Hutchinson Cancer Research Center, revising food items, food frequency scale, portion sizes, and time frame. To assess the validity of the proposed FFQ, we compared the estimated daily intake using FFQ with the mean of 3-day food diaries and one 24-hour recall (considered as reference method). The validation process was conducted among a cohort of 51 healthy subjects enrolled in a clinical trial. Four statistical tests were applied on 23 estimated nutrient intakes. Spearman's coefficients ranged from 0.223 (sodium) to 0.748 (alcohol) and were good (≥0.50) and acceptable (0.20-0.49) for 7 and 16 nutrients, respectively. Cross classification showed a good agreement (≥50% in the same tertile or ≤10% in the opposite tertile) for 7 nutrients. The weighted Cohen's kappa values indicated an acceptable outcome (0.20-0.60) for 13 nutrients. Bland Altman plots did not show heteroscedasticity in the error terms, despite the presence of a bias. Our study provided a new Italian semi-quantitative FFQ for self-administration with an acceptable validation level. Its definitive release requires additional refinements and efforts., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Air pollution is a well-known problem for human health, especially for children living in highly polluted urban areas. This study aimed to assess the relationship between airborne pollutants concentration and biomarkers of DNA damage in the buccal mucosa cells of pre-school children. DNA damage was investigated with comet test in saliva leukocytes taken from sputum of 3- to 6-year-old children living in Brescia, Northern Italy, collected during two consecutive winter seasons (2012-2013). The daily levels of PM10, PM2.5, NO 2 , CO, SO 2 , benzene and O 3 in urban air were collected for the whole period. A questionnaire filled in by the children's parents was used to evaluate indoor and outdoor exposure. DNA damage in saliva leukocytes was evaluated in 152 children and the means of tail intensity and visual score as DNA damage were 6.2 ± 4.3 and 182.1 ± 30.9, respectively. No demographic and indoor or outdoor exposure variable was associated with the two measures of DNA damage. No significant association between air pollution and DNA damage in children's buccal leukocytes was found. In this study, the comet assay does not appear to be a valuable biomarker to detect DNA damage in children exposed to high levels of air pollutants, such as PM10, PM2.5 and NO 2 .

This study aimed to assess the longitudinal association between PCB exposure and the subsequent occurrence of hypertension in a highly polluted area. The study subjects had at least one PCB serum measurement between 2003 and 2014 and were followed up to the end of 2017. Hypertension cases were obtained from the Brescia Health Protection Agency database. Risk ratios of hypertension for total PCBs, high-, middle- and low-chlorinated groups and some common congeners were estimated using Poisson regression models. 1031 subjects were included (43.4% males, mean age 45.3 years). 229 subjects developed hypertension during the follow-up. Total PCBs, middle- and high-chlorinated PCBs, and particularly PCB congeners 138, 153 and 180 were associated with an about 2-fold increased risk of hypertension comparing the third with first tertile of distribution. After lipid-standardization of PCB serum values, the excess risk showed only a slight attenuation. A dose-response linear relationship of the risk of hypertension by PCB serum concentrations as continuous variables was also observed. The PCBs-hypertension association was stronger in overweight/obese subjects than those with normal body mass index. In this prospective cohort study the serum levels of total and middle to high chlorinated (≥6 Cl) PCBs were associated with an increased risk of hypertension, particularly among overweight/obese subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Quality of working life has been shown to play a key role in reducing strain inside and outside the workplace, supporting the fulfillment of workers' wellbeing and increasing workforce productivity. Van Laar et al. in 2007 developed the Work-Related Quality of Life (WRQoL) scale that was applied to several different work environments and translated into nine languages., Objectives: We aimed to test and validate an Italian version of the WRQoL scale., Methods: A cross-sectional design was conducted to collect a sample of healthcare professionals (N=430) in 8 hospitals in the Northwest of Italy. Internal consistency of each scale was tested through Cronbach's alpha. A Confirmatory factor analysis was performed. Independent samples t-tests and ANOVA were performed to determine whether the scores on the subscales differed according to various socio-demographic variables., Results: A seven factors structure was confirmed (Control at work; General well-being; Home-work interface; Stress at Work; Job and career satisfaction; Working conditions; Employee Engagement; χ2=682.453, p<.001; χ2 and df(251) ratio=2.71; CFI=.90; RMSEA=.06; SRMR=.06). All subdimensions showed Cronbach's alphas ≥ 0.70 but for Stress at Work (alpha 0.65). The subscales differentiated between groups of people according to several socio-demographic characteristics (i.e., profession, age, length of employment)., Discussion: The Italian version of WRQoL is a brief and sufficiently reliable tool that can contribute to a more complex and complete evaluation of the psychological well-being at work due to its multidimensionality. Overall, the use of this tool in occupational health practice, in addition to that of other instruments already available, should prove useful in monitoring workers' well-being before and after interventions.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma and limited evidence for non-Hodgkin lymphoma (NHL). However present findings on the association of PCB exposure and NHL are still controversial. This study examined the relationship between PCB serum levels and risk of NHL in a Northern Italy area (Brescia province), where a chemical factory produced PCBs from 1938 to 1984, causing human contamination. A case-control study of 215 NHL patients and 215 control subjects was conducted. Cases and controls were assayed for serum levels of 33 PCB congeners. No associations were found between risk of NHL and serum levels of total PCBs (OR = 0.51; 95% CI: 0.25-1.04 for highest vs lowest quartile) or specific PCB congeners. The study confirmed a strong association of NHL with HCV infection (OR = 3.60; 95% CI: 1.30-10.02). This case-control study does not support the hypothesis of an association between current serum levels of PCBs and NHL development in the general population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Soft tissue sarcoma (STS) is a heterogeneous group of rare neoplasms whose aetiology is largely unknown. Dioxin and dioxin-like compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and polychlorinated biphenyls (PCBs), are potential risk factors for STS., Objectives: To investigate the relation of 17 PCBs congeners, assessed in human plasma, with STS risk., Methods: We conducted a case-control study in Italy, including 52 STS cases and 99 hospital-based controls. Selected PCB were extracted by high-performance liquid chromatography (HPLC) and measured with gas chromatography-mass spectrometry (GC-MS). Odds ratios (OR), and the corresponding 95% confidence intervals (CI), were estimated through multivariate logistic regression models., Results: The most frequently detected PCB congeners were 138, 170, 180 and 149 (detected in 40-77% of controls). The OR for the sum of all 17 PCB congeners was 1.20 (95% CI 0.50-2.92). In categorical analysis no consistent association was found for individual congeners and for groups based on Wolff's classification or the degree of chlorination. For continuous estimates, borderline positive associations emerged for Wolff's groups 2A (OR 1.23, 95% CI 0.97-1.55), 2B (OR 1.34, 95% CI 1.00-1.77, and 3 (OR 1.19, 95% CI 0.96-1.49), for moderately (OR 1.20, 95% CI 0.96-1.51) and highly (OR 1.18, 95% CI 0.99-1.41) chlorinated PCBs, and for congeners 170 (OR 1.26, 95% CI 0.98-1.63), 180 (OR 1.26, 95% CI 0.97-1.64) and 138 (OR 1.45, 95% CI 1.02-2.04)., Discussion: Most associations between PCBs and STS risk were not significant, but, given the limited sample size, we cannot exclude moderate associations.

This study aimed to evaluate the association between personal and job characteristics and the risk of upper limb work-related musculoskeletal disorders (WMSDs) among operating room nurses (ORNs). To this end, we collected data from 148 ORNs working at 8 Italian hospitals and measured any upper limb disabilities experienced in the previous year using the Italian version of the disabilities of the arm, shoulder and hand (DASH) questionnaire. The associations between personal and job characteristics and risk of upper limb WMSDs were estimated by unconditional logistic regression models. The prevalence of upper limb WMSDs was 45.9%. Multivariate analysis showed the "female gender" and "monthly hours spent working as a scrub nurse" to be directly associated with a higher DASH score (adjusted OR for gender = 5.37, 95% CI: 1.65-17.51, p < 0.01; adjusted OR for monthly hours as scrub nurse = 3.09, 95% CI: 1.33-7.19, p < 0.01). Overall, our findings indicate that a full-time job (>120 h/month) as a scrub nurse significantly increases the risk of developing upper limb WMSDs among female ORNs. Thus, to reduce such risk in this particularly sensitive population, we recommend urgent implementation of ergonomic interventions on surgical equipment alongside job rotation and medical surveillance programs.

Air pollution has well-known harmful effects on human beings, causing both acute and chronic diseases. Some data suggest that genetic damage occurring early in life may influence the risk of having cancer and other chronic diseases in adulthood. Therefore, there is a growing interest in studying the genotoxic activity of air pollution, and especially particulate matter. The aim of this study was to analyze airborne particulate matter (PM 10 ) collected in an industrialized town of Northern Italy. PM 10 was sampled in six areas of the town, divided in three distinct dimensional classes (<0.5 μm; 0.5-3 μm and 3-10 μm), and analyzed for the quantification of polynuclear aromatic hydrocarbons and metals contents. A model-based approach using diagnostic ratios and toxic equivalency factor was also followed. Concurrently, biological assays were performed for the assessment of mutagenicity and genotoxicity in bacteria, human and plant cells. Mutagenicity was observed in bacteria and human cells, with a clear dose-response relationship, induced above all by the finest PM samples (PM 0.5 and PM 0.5-3 ), which contained the largest number of polycyclic aromatic hydrocarbons. DNA damage, such as chromosomal aberrations and micronuclei, was also found in Allium cepa root cells, but without a clear relationship with the tested doses. The in-vitro models utilized showed to be good indicators of air quality for mutagenicity. Chemical analyses evidenced high content of polycyclic aromatic hydrocarbons, metals and semi-metals in PM extracts. Polycyclic aromatic hydrocarbons, metals and mutagenicity can be ascribed mainly to vehicular traffic (in terms of both exhausted gases emission and mechanical losses), which represents a constant and ubiquitous source of human exposure, and to steel working, carried out within the urban area., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Particulate matter (PM) air pollution is one of the major causes of death worldwide, with demonstrated adverse effects from both short-term and long-term exposure. Most of the epidemiological studies have been conducted in cities because of the lack of reliable spatiotemporal estimates of particles exposure in nonurban settings. The objective of this study is to estimate daily PM 10 (PM < 10 μm), fine (PM < 2.5 μm, PM 2.5 ) and coarse particles (PM between 2.5 and 10 μm, PM 2.5-10 ) at 1-km 2 grid for 2013-2015 using a machine learning approach, the Random Forest (RF). Separate RF models were defined to: predict PM 2.5 and PM 2.5-10 concentrations in monitors where only PM 10 data were available (stage 1); impute missing satellite Aerosol Optical Depth (AOD) data using estimates from atmospheric ensemble models (stage 2); establish a relationship between measured PM and satellite, land use and meteorological parameters (stage 3); predict stage 3 model over each 1-km 2 grid cell of Italy (stage 4); and improve stage 3 predictions by using small-scale predictors computed at the monitor locations or within a small buffer (stage 5). Our models were able to capture most of PM variability, with mean cross-validation (CV) R 2 of 0.75 and 0.80 (stage 3) and 0.84 and 0.86 (stage 5) for PM 10 and PM 2.5 , respectively. Model fitting was less optimal for PM 2.5-10 , in summer months and in southern Italy. Finally, predictions were equally good in capturing annual and daily PM variability, therefore they can be used as reliable exposure estimates for investigating long-term and short-term health effects., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite the progress in HIV care, adherence to follow up remains critical. Disengagement impairs the benefit of HIV care and the increasing number of data that associates failed retention with worse outcomes has led public health institutions to consider retention in care as a new tool to fight against HIV pandemic. Objective: The aim of this retrospective, observational study was to estimate the burden of disengagement and reengagement in care in our HIV cohort and to identify the characteristics of our LTFU and reengaged patients. Moreover, we build our cascade of care to explore how closely our center aligned with the "90-90-90" targets. Methods: From the local electronic database we extracted all HIV-infected patients with at least one contact with HIV Clinic between 2012 and 2018 excluding deceased and transferred patients. Our definition of LTFU was based on the lack of any visit during at least 1 year after the last visit. Patients re-engaged were defined as those firstly considered as LTFU patients who subsequently were newly linked to HIV care. Results: About 8% of patients were lost to follow up during the period of study, with a rate of less than 2% per year and 14.1% of them were re-engaged in care. The cascade of care shows, among HIV cases diagnosed between 2011 and 2018, 86.7% patients retained in care, 94.1% of whom were on cART and 95.6% of whom were virologically suppressed. A higher attrition was found among infections diagnosed since 2011 than before 2011, such as women, patients coming from foreign countries and those with poor virological control. Conclusions: The retention rate found in our cohort is high and is in accordance with the 90-90-90 strategy. Nevertheless, understanding disengagement and re-engagement determinants is important to strengthen retention in care in the most fragile population.

Background: The World Health Organization conditionally recommends systematic screening of tuberculosis (TB) and Latent Tuberculosis Infection (LTBI) among asylum seekers (AS) from high-burden countries, but the effectiveness of different screening approaches is controversial., Methods: We report the results of a retrospective cohort analysis of TB and LTBI screening among consecutive AS in Brescia, Italy during 2015-2016. TB screening was based on symptoms, LTBI screening on the tuberculin skin test (TST). Logistic regression analysis was performed to identify factors associated with screening uptake., Results: Of 2904 registered AS 2567 (88.4%) were evaluated for TB, 62 (2.4%) had symptoms and active TB yield was 155/100,000. Prevalence and incidence TB rates were 545/100,000 persons and 220/100,000 person-years. Questionnaire screening identified 28.6% (4/14) prevalent cases. Of 2303 (89.7%) AS with TST result, the positivity rate was 36.6% (843/2303). Of the 843 candidates for LTBI treatment 413 (49.0%) completed the screening. LTBI treatment was prescribed to 190 (47.9%) of 397 eligible individuals, 10.8% (91) completed treatment., Conclusions: TB prevalence and incidence rates were high in this AS population, but symptom-based screening performed poorly. LTBI cascade losses were significant and mainly attributable to the defragmentation of the health care system., (Copyright © 2018. Published by Elsevier Ltd.)