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Living in areas with higher levels of surrounding greenness and access to urban green areas have been associated with beneficial health outcomes. Some studies suggested a beneficial influence on mortality, but the evidence is still controversial. We used longitudinal data from a large cohort to estimate associations of two measures of residential greenness exposure with cause-specific mortality and stroke incidence. We studied a population-based cohort of 1,263,721 residents in Rome aged [Formula: see text], followed from 2001 to 2013. As greenness exposure, we utilized the leaf area index (LAI), which expresses the tree canopy as the leaf area per unit ground surface area, and the normalized difference vegetation index (NDVI) within 300- and [Formula: see text] buffers around home addresses. We estimated the association between the two measures of residential greenness and the outcomes using Cox models, after controlling for relevant individual covariates and contextual characteristics, and explored potential mediation by air pollution [fine particulate matter with aerodynamic diameter [Formula: see text] [Formula: see text] and [Formula: see text]] and road traffic noise. We observed 198,704 deaths from nonaccidental causes, 81,269 from cardiovascular diseases [CVDs; 29,654 from ischemic heart disease (IHD)], 18,090 from cerebrovascular diseases, and 29,033 incident cases of stroke. Residential greenness, expressed as interquartile range (IQR) increase in LAI within [Formula: see text], was inversely associated with stroke incidence {hazard ratio (HR) 0.977 [95% confidence interval (CI): 0.961, 0.994]} and mortality for nonaccidental [HR 0.988 (95% CI: 0.981, 0.994)], cardiovascular [HR 0.984 (95% CI: 0.974, 0.994)] and cerebrovascular diseases [HR 0.964 (95% CI: 0.943, 0.985)]. Similar results were obtained using NDVI with 300- or [Formula: see text] buffers. Living in greener areas was associated with better health outcomes in our study, which could be partly due to reduced exposure to environmental hazards. Further research is required to understand the underlying mechanisms. https://doi.org/10.1289/EHP2854.

Background Standardized mortality surveillance data, capable of detecting variations in total mortality at population level and not only among the infected, provide an unbiased insight into the impact of epidemics, like COVID-19 (Coronavirus disease). We analysed the temporal trend in total excess mortality and deaths among positive cases of SARS-CoV-2 by geographical area (north and centre-south), age and sex, taking into account the deficit in mortality in previous months. Methods Data from the Italian rapid mortality surveillance system was used to quantify excess deaths during the epidemic, to estimate the mortality deficit during the previous months and to compare total excess mortality with deaths among positive cases of SARS-CoV-2. Data were stratified by geographical area (north vs centre and south), age and sex. Results COVID-19 had a greater impact in northern Italian cities among subjects aged 75–84 and 85+ years. COVID-19 deaths accounted for half of total excess mortality in both areas, with differences by age: almost all excess deaths were from COVID-19 among adults, while among the elderly only one third of the excess was coded as COVID-19. When taking into account the mortality deficit in the pre-pandemic period, different trends were observed by area: all excess mortality during COVID-19 was explained by deficit mortality in the centre and south, while only a 16% overlap was estimated in northern cities, with quotas decreasing by age, from 67% in the 15–64 years old to 1% only among subjects 85+ years old. Conclusions An underestimation of COVID-19 deaths is particularly evident among the elderly. When quantifying the burden in mortality related to COVID-19, it is important to consider seasonal dynamics in mortality. Surveillance data provide an impartial indicator for monitoring the following phases of the epidemic, and may help in the evaluation of mitigation measures adopted.

We studied the potential synergy between air pollution and meteorology and their impact on mortality in nine European cities with data from 2004 to 2010. We used daily series of Apparent Temperature (AT), measurements of particulate matter (PM10), ozone (O3), and nitrogen dioxide (NO2) and total non-accidental, cardiovascular, and respiratory deaths. We applied Poisson regression for city-specific analysis and random effects meta-analysis to combine city-specific results, separately for the warm and cold seasons. In the warm season, the percentage increase in all deaths from natural causes per °C increase in AT tended to be greater during high ozone days, although this was only significant for all ages when all causes were considered. On low ozone days, the increase in the total daily number of deaths was 1.84% (95% CI 0.87, 2.82), whilst it was 2.20% (95% CI 1.28, 3.13) in the high ozone days per 1 °C increase in AT. Interaction with PM10 was significant for cardiovascular (CVD) causes of death for all ages (2.24% on low PM10 days (95% CI 1.01, 3.47) whilst it is 2.63% (95% CI 1.57, 3.71) on high PM10 days) and for ages 75+. In days with heat waves, no consistent pattern of interaction was observed. For the cold period, no evidence for synergy was found. In conclusion, some evidence of interactive effects between hot temperature and the levels of ozone and PM10 was found, but no consistent synergy could be identified during the cold season.

In several volcanic areas of Italy, arsenic levels exceed European regulatory limits (10 μg/L in drinking water). There is still uncertainty about health risks from arsenic at low-medium doses (<100 μg/L). A large population-based study using an administrative cohort of residents in the Viterbo province (Central Italy), chronically exposed to low-medium arsenic levels via drinking water, was investigated to evaluate the effects of a lifetime exposure to arsenic on mortality from cancers and chronic diseases. The study population consisted of 165,609 residents of 17 municipalities, followed from 1990 until 2010. Average individual arsenic exposure at the first residence (AsI) was estimated through a space-time modeling approach using residential history and arsenic concentrations from water supply. A time-dependent Cumulative Arsenic dose Indicator (CAI) was calculated, accounting for daily water intake and exposure duration. Mortality Hazard Ratios (HR) were estimated by gender for different diseases using Cox proportional models, adjusting for individual and area-level confounders. A flexible non-parametric approach was used to investigate dose-response relationships. Mean AsI exposure was 19.3 μg/L, and average exposure duration was 39.5 years. Associations of AsI and CAI indicators with several diseases were found, with greatest risks found for lung cancer in both sexes (HR = 2.61 males; HR = 2.09 females), myocardial infarction, peripheral arterial disease and COPD in males (HR = 2.94; HR = 2.44; HR = 2.54 respectively) and diabetes in females (HR = 2.56). For lung cancer and cardiovascular diseases dose-response relationship is modelled by piecewise linear functions revealing effects even for doses lower than 10 μg/L, and no threshold dose value was identified as safe for health. Results provide new evidence for risk assessment of low-medium concentrations of arsenic and contribute to the ongoing debate about the threshold-dose of effect, suggesting that even concentrations below 10 μg/L carry a mortality risk. Policy actions are urgently needed in areas exposed to arsenic like in the Viterbo province, to comply with current EU regulations.

Introduction: Heart valve diseases constitute a significant public health challenge with substantial clinical and economic implications. The ageing population, coupled with advancements in surgical techniques, has led to increased hospitalizations for cardiac valve interventions over the past decade. Despite progress, the economic burden of heart valve diseases remains underexplored, particularly in the context of the Italian healthcare system. This study aims to comprehensively assess the economic burden of heart valve diseases in Italy through a real-world analysis. Methods: Using data from the national Italian Hospital Discharge Records (SDO), we identified the number of adult patients undergoing interventions on the aortic, mitral, and tricuspid valves, along with the associated costs borne by the National Health System. Additionally, we estimated indirect costs by analyzing social security benefit applications related to valve diseases from 2016 to 2019. Results: A notable rise in hospitalizations for cardiac valve interventions, particularly for the aortic (+53.3%) and mitral valves (+29.5%) was revealed through the study period. In-hospital mortality rates declined, reflecting advancements in perioperative care. The economic burden of heart valve diseases in Italy was substantial, with hospitalization costs reaching €808 million in 2018. Social security benefit applications also increased, adding an annual cost of €29 million. Conclusions: Heart valve diseases represent a growing clinical and socio-economic challenge in Italy. This study underscores the imperative for a multidisciplinary approach to effectively manage these conditions. Emphasizing prevention, early diagnosis, and timely interventions is crucial to mitigate the economic impact and enhance the quality of life for patients.

Evidence on the health effects of extreme temperatures and air pollution is copious. However few studies focused on their interaction. The aim of this study is to evaluate daily PM10 and ozone as potential effect modifiers of the relationship between temperature and natural mortality in 25 Italian cities. Time-series analysis was run for each city. To evaluate interaction, a tensor product between mean air temperature (lag 0–3) and either PM10 or ozone (both lag 0–5) was defined and temperature estimates were extrapolated at low, medium, and high levels of pollutants. Heat effects were estimated as percent change in mortality for increases in temperature between 75th and 99th percentiles. Results were pooled by geographical area. Differential temperature-mortality risks by air pollutants were found. For PM10, estimates ranged from 3.9% (low PM10) to 14.1% (high PM10) in the North, from 3.6% to 24.4% in the Center, and from 7.5% to 21.6% in the South. Temperature-related mortality was similarly modified by ozone in northern and central Italy, while no effect modification was observed in the South. This study underlines the synergistic effects of heat and air pollution on mortality. Considering the predicted increase in heat waves and stagnation events in the Mediterranean countries such as Italy, it is time to enclose air pollution within public health heat prevention plans.

Background Alzheimer Disease (AD) represents a growing global health concern with profound socioeconomic implications, with predictions indicating a potential 50% increase in AD cases in Italy over the next 30 years. Timely diagnosis remains challenging due to the slow progression of symptoms and limited accessibility to advanced diagnostic tools, yet it remains one of the few tools available to prevent and alter the clinical course of the disease. The aim of this study is to build a cost-of-illness model to estimate the number of AD patients managed by the National Health Service, analyzing their use of hospital care, and estimating the social costs through real-world data. Methods The analysis encompassed a multifaceted approach, combining real-world data analysis from different sources for the period 2014–2019. Health direct costs related to AD in Italy were estimated thanks to the Italian database of all hospital discharges and a Local Health Unit database (400,000 residents) collecting all information on resource consumption related to AD. The National Social Security System database was used to estimate social security costs (disability compensations) related to Attendance Allowance (AA) recognitions. Results In Italy a prevalence of 413,715 AD patients was estimated, with annual health direct costs per patient equal to €3,779. Annual social security costs related to AA recognitions amounted to 240 million euros. Overall, the analysis estimated an annual total cost exceeding 1.8 billion euros. Conclusions This study provides a comprehensive exploration of the multifaceted burden of AD in Italy, shedding light on its economic dimensions. The results underscore the urgency of prioritizing AD on political agendas, especially in the face of the projected global surge in AD cases. The study advocates for proactive policy interventions and informed healthcare decision-making to address the complex challenges posed by AD.

In many places, daily mortality has been shown to increase after days with particularly high or low temperatures, but such daily time-series studies cannot identify whether such increases reflect substantial life shortening or short-term displacement of deaths (harvesting). To clarify this issue, we estimated the association between annual mortality and annual summaries of heat and cold in 278 locations from 12 countries. Indices of annual heat and cold were used as predictors in regressions of annual mortality in each location, allowing for trends over time and clustering of annual count anomalies by country and pooling estimates using meta-regression. We used two indices of annual heat and cold based on preliminary standard daily analyses: ) mean annual degrees above/below minimum mortality temperature (MMT), and ) estimated fractions of deaths attributed to heat and cold. The first index was simpler and matched previous related research; the second was added because it allowed the interpretation that coefficients equal to 0 and 1 are consistent with none (0) or all (1) of the deaths attributable in daily analyses being displaced by at least 1 y. On average, regression coefficients of annual mortality on heat and cold mean degrees were 1.7% [95% confidence interval (CI): 0.3, 3.1] and 1.1% (95% CI: 0.6, 1.6) per degree, respectively, and daily attributable fractions were 0.8 (95% CI: 0.2, 1.3) and 1.1 (95% CI: 0.9, 1.4). The proximity of the latter coefficients to 1.0 provides evidence that most deaths found attributable to heat and cold in daily analyses were brought forward by at least 1 y. Estimates were broadly robust to alternative model assumptions. These results provide strong evidence that most deaths associated in daily analyses with heat and cold are displaced by at least 1 y. https://doi.org/10.1289/EHP1756.

Background Recent real-world studies revealed high proportions of patients with metastatic urothelial cancer (mUC) do not receive any systemic therapy. This study describes the demographics, clinical characteristics, treatment rate and related predictive factors, healthcare resource utilization, and direct medical costs of patients with mUC receiving systemic therapy (or not) in the inpatient setting in Italy. Methods This retrospective observational study used the national hospital discharge database (Scheda di Dimissione Ospedaliera) to describe incident adult (≥ 18 years) patients with a first hospitalization for mUC (index) from 2017-2018, identified by a combination of ICD-9-CM ( International Classification of Diseases, Ninth Revision, Clinical Modification ), medical procedure, and diagnosis-related group codes. A model was fitted to identify factors associated with receiving inpatient chemotherapy and/or radiotherapy. Results Of 3674 patients with mUC identified, 1014 (27.6%) were treated with inpatient chemotherapy and/or radiotherapy and 2660 (72.4%) were not treated. The median age at index was 71 and 78 years for treated and untreated patients, and the mean (SD) Charlson Comorbidity Index (CCI) score was 0.3 (0.8) and 0.6 (1.1), respectively. Primary tumor location was the bladder in 87.2% of patients. Cardiovascular disease and renal function impairment were more prevalent in untreated (22.6% and 13.2%) vs treated (16.7% and 7.8%) patients. Older age (odds ratio [ p -value]) (0.94 [< 0.001]), female sex (0.82 [0.035]), and higher CCI score (0.82 [< 0.001]) were all associated with a lower likelihood of receiving inpatient systemic treatment. The first year was the costliest: estimated national projected costs during the 36-month follow-up from first hospitalization for mUC were €34.3 million (95% CI, €30.3-€60.0 million) and €31.8 million (95% CI, €28.1-€56.0 million) when estimated after 1 year. Conclusions Our findings indicate a low rate of inpatient systemic therapy for patients with mUC in Italy (driven by older age, female sex, and high comorbidity burden), with a large economic burden despite a high nontreatment rate. Although this study provides a partial capture of the treatment pathway in Italy, the results are consistent with other European studies with similar designs and highlight the need to better identify the reasons for not administering inpatient systemic chemotherapy and/or radiotherapy.

Background Models evaluating both costs and economic benefits of assisted reproductive technology (ART) implementation are lacking. This constitutes a major limitation in the decision-making process of resource allocation. Herein, we aimed to estimate the economic and social impact of female infertility in Italy and examine the benefits generated by investment in ART from a national perspective. Methods A retrospective cohort study was conducted using the Italian Hospital Discharge Records database to identify women aged 18–50 undergoing ART between 2014 and 2016 in Italy. Patients were followed for up to 36 months after the first ART complete cycle. Hospitalization costs were analyzed nationally, while outpatient care and drug consumption costs were assessed in a sub-analysis using administrative databases from LHU Umbria 2. A fiscal impact model was developed from a governmental perspective, projecting lifetime tax revenues and public expenditures associated with the ART birth cohort, including costs for healthcare, education, pensions, and social transfers. All future values were discounted at 3% in line with Italian economic evaluation guidelines. Results A total of 33,713 women met the inclusion criteria. During the follow-up, 48.4% achieved pregnancy resulting in childbirth. The average hospital care cost per patient was €5,853, with a projected national expenditure of €337 million for ART management. Younger women (18–33 years) had the highest success rates (61.8%). Assuming 16,300 live births, the model estimated net fiscal benefits of €3.3 billion over the lifetime of these individuals, equivalent to €203,856 per live birth. Conclusion This study highlights the economic and fiscal benefits of ART, emphasizing the need for policies promoting early access to treatment. ART investment represents a strategic approach to mitigate demographic decline, with each live birth substantially contributing to national fiscal stability. Key points • Investing in Assisted Reproductive Technology (ART) within national health systems can generate significant economic returns, substantially exceeding initial healthcare expenditures. • Public funding of ART contributes positively to national economies by increasing future tax revenues and addressing demographic challenges related to declining fertility.