Background and Objectives: Clinical risk management is essential to patient safety. Nurses are strategically positioned to identify unsafe conditions, near misses, and adverse events. This study assessed nurses’ knowledge of selected clinical risk management definitions, perceptions of patient safety, and self-reported experience of patient-safety event reporting in a cardiovascular hospital in Southern Italy. Methods: A cross-sectional anonymous survey was conducted among registered nurses using a structured questionnaire. Knowledge was measured through a 0–4 index based on correct answers regarding safety culture, near miss, sentinel event, and incident reporting. Perceived overall patient safety was analyzed as an ordinal outcome, and ever reporting of patient-safety events as a binary outcome. Multivariable regression models explored associated factors. Results: The study included 88 nurses; 75.0% were female, and the median age was 47 years (IQR 37–54). Overall, 77.3% reported previous updating on risk management. The median knowledge index was 3 (IQR 2–4), and 62.5% answered at least three of four items correctly. Patient-safety culture domains received high importance scores, with medians ranging from 9 to 10. Overall patient safety was rated as good, very good, or excellent by 63.6% of respondents, and 61.4% had reported at least one patient-safety event. Knowledge was associated with gender and years of professional experience. Higher perceived safety was associated with perceived technological adequacy and patient confidence in care. Conclusions: Beyond the setting-specific findings, the study illustrates how combining factual knowledge, perceived safety, reporting experience, and locally relevant process indicators may support organizational diagnosis and help identify areas requiring more focused quality-improvement assessment.

Background and aims Human Epidermal Growth Factor Receptor 2-positive (HER2+) breast cancer poses significant therapeutic challenges, particularly concerning treatment administration pathways and their associated costs. This study evaluates the managerial and economic impacts of different therapeutic administration scenarios for HER2-positive breast cancer patients, focusing on optimizing hospital workflows, resource utilization, and patient outcomes in Italian oncological centers. Methods A decision tree model was developed to simulate and compare five treatment administration pathways: Standard, Drug-Change, Drug Day, Dedicated Ambulatory, and Optimal Pathway scenarios. The model integrates patient and healthcare professional (HCP) activity and waiting times, infusion chair occupation, and direct and indirect costs. Sensitivity analyses assessed variability in model outcomes. Results Switching from endovenous (EV) to subcutaneous (SC) administration substantially reduced patient throughput times and HCP workloads. The Optimal Pathway scenario yielded the highest resource optimisation, reducing HCP activity time by up to 48 hours, infusional chair occupational time by up to 150 hours, and patients’ total time by up to 753 hours per 100 patients monthly. Cost analyses indicated significant savings in both direct and indirect cost for all the proposed scenarios in comparison to the Standard one. Conclusion The adoption of SC formulations and innovative pathway optimizations enhances treatment organizational efficiency and reduces both direct and indirect costs. These findings underscore the value of tailored approaches to administration based on the structural and organizational characteristics of individual oncology centers, aligning with current Italian healthcare reforms.

Bariatric surgery (BS) has short- and medium-term benefits in improving metabolic syndrome (MetS) components, but its long-term impact remains incompletely characterized. This systematic review and meta-analysis aimed to quantify the long-term effects of BS (≥ 5 years) on fasting blood glucose (FBG), HDL cholesterol, triglycerides (TG), waist circumference (WC), and systolic and diastolic blood pressure (SBP and DBP). A comprehensive literature search was conducted across relevant databases. Eligible studies included randomized controlled trials and observational cohorts reporting pre- and postsurgical metabolic outcomes after at least 5 years of follow-up. Random-effects meta-analyses and meta-regressions were performed. Fifty-four articles (49 cohorts and five RCTs), including 37,840 baseline participants, were analyzed. BS was associated with significant improvements across all outcomes, with effect sizes varying by study design. Pooled estimates ranged from -22.97 to -44.68 mg/dL for FBG, +10.25 to +11.94 mg/dL for HDL, -54.11 to -59.59 mg/dL for TG, -20.55 cm for WC, -7.82 to -9.76 mmHg for SBP, and -4.80 to -6.48 mmHg for DBP. Meta-regression showed stronger effects in patients with higher baseline values. BS provides sustained, long-term improvements in all major MetS components. However, these findings are primarily driven by studies on Roux-en-Y gastric bypass, whereas long-term data on sleeve gastrectomy remain limited. High-quality longitudinal evidence on sleeve gastrectomy is needed to improve the generalizability of these results to contemporary surgical practice.

AIM: This analysis aimed to assess the annual International Unit (IU) consumption and costs of prophylaxis therapies with extended half-life recombinant FVIII (EHL-rFVIII), targeting a traditional trough level of 1% and the higher levels of 3% and 5% recommended by recent guidelines and expert consensus, using a theoretical pharmacokinetic model. METHODS: A pharmacokinetic model was developed to calculate annual treatment IU consumption and costs of EHL-rFVIII products to sustain different trough levels (1%, 3% and 5%) in adult patients with hemophiliaA in Italy. The model assumed a one-year perspective and assessed two scenarios: one with lower frequency of administration and one with higher frequency. RESULTS: The related annual treatment per-patient cost increased as the trough level increased. The per-patient annual cost was & euro;117,811 to achieve a trough level of 1%, & euro;351,543 to achieve a 3% trough level and & euro;585,905 to achieve a 5% trough level. The increase in dose frequency (alternative scenario), that is the reduction of time between infusions, reduced the estimated doses to achieve the pre-defined FVIII levels. CONCLUSIONS: These results suggest the need for further discussion about the trough levels to target with the actual EHL-rFVIII and the prophylaxis dose and regimen selection for each patient, also considering all treatment options available and the economic implications.

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease in which systemic corticosteroids remain first-line therapy despite limited evidence, especially in fibrotic forms. This study aimed to identify clinical, radiological, and biological features associated with functional response to steroids. We retrospectively analyzed 43 consecutive patients with HP treated with systemic corticosteroids and followed for at least 6 months. Patients were classified according to changes in forced vital capacity (FVC) as responders (≥5% increase), non-responders (≥5% decrease), or indifferent (±5%). Eighteen patients (42%) were responders, 15 (35%) indifferent, and 10 (23%) non-responders. Non-responders showed a consistently worse functional trajectory. A fibrosing high-resolution computed tomography pattern and baseline consolidations were more frequent in this group, as were precipitating antibodies against P. notatum and A. fumigatus. Conversely, bronchoalveolar lavage lymphocytosis >20% was more common among responders. Baseline FVC% and relative diffusing capacity of the lung for carbon monoxide were higher in non-responders, whereas demographic characteristics, smoking history, antigen exposure, comorbidities and autoantibody positivity did not differ significantly across groups. Fewer than half of patients experienced functional improvement after steroid therapy. Radiological fibrosis, consolidations, and specific precipitating antibodies were associated with lack of response, whereas bronchoalveolar lavage lymphocytosis predicted improvement. These findings highlight the heterogeneity of HP and may help identify patients unlikely to benefit from corticosteroids, supporting earlier consideration of alternative therapeutic strategies.

Background/Objectives: Psoriasis is a chronic inflammatory skin disease leading to substantial psycho-physical and social burden and reduced quality of life. Biologic agents have transformed its therapeutic landscape. This real-world Italian study described the pattern of treatment with biologic drugs in patients with psoriasis. Methods: A retrospective observational study was conducted using administrative databases from Italian Local Health Units, covering nearly 12 million individuals. The study included adults with psoriasis identified from January 2015 to March 2025 by hospitalization, co-payment exemption code, or topical anti-psoriatic prescriptions. Patients initiating a biologic drug (anti-TNFα, anti-IL12/23, anti-IL17, and anti-IL23) were selected and further analyzed in terms of treatment switching, drug survival, and healthcare resource utilization and related costs within the first year after biologic initiation, and compared. Results: A total of 10,270 biologic-naïve adult patients was included in the analysis (anti-TNFα N = 5078; anti-IL12/23 N = 767; anti-IL17 N = 2574; anti-IL23 N = 1851). Most patients (95.0%) starting an anti-IL23 agent did not switch. Compared with anti-TNFα, initiating an anti-IL23 inhibitor was associated with a significant reduced risk of switching (HR = 0.186; 95%CI: 0.144-0.240; p < 0.001). According to the cost analysis stratified by switching status, remaining on the index biologic was associated with a lower economic burden. Although differences between switchers vs. non-switchers among anti-IL23 users did not reach statistical significance (€12,052 vs. €11,406, respectively, p = 0.132), data support the economic advantage associated with greater treatment stability. Conclusions: Anti-IL23 agents showed effective, durable first-line use with potential long-term clinical and economic benefits in moderate-to-severe psoriasis.

NTM pulmonary disease (NTM-PD) is frequently associated with low body mass index and weight loss, yet comprehensive nutritional evaluation at diagnosis remains limited. We conducted a multicenter observational study across eight Italian referral centers to assess nutritional status and physical performance in newly diagnosed NTM-PD patients. Assessments included anthropometry, nutritional and physical activity questionnaires, bioelectrical impedance analysis, handgrip strength, gait speed, and pulmonary function tests in order to identify nutritional phenotypes and sarcopenia according to EWGSOP2 definition. 69 patients (77

Metabolic dysfunction-associated steatohepatitis (MASH) in the past known as non-alcoholic steatohepatitis (NASH) is a chronic liver disease that poses significant epidemiological, clinical and socio-economic challenges. Given the limited availability of data on disease burden, this systematic literature review aimed to describe epidemiology, mortality, quality of Life (QoL) and socio-economic burden associated with NASH/MASH. A systematic literature review was carried out in PubMed (Medline) and Embase using the terms “NASH/MASH” and terms related to epidemiology, mortality, QoL and resource utilization and costs. The search covered publications from January 1, 2014, to January 16, 2024, and was restricted to articles published in English, Italian and Spanish. A two steps screening phase was performed, and relevant data were extracted from the included articles following a full-text assessment. Among the retrieved studies, 25 included epidemiological data, 14 addressed mortality, 11 focused on QoL, and 9 focused on resource utilization and economic burden. Within the different populations assessed, the prevalence of NASH/MASH ranged from 18

The management of cancer risk for BRCA pathogenic variants (PV) carriers varies depending on countries, with different strategies. However, some strategies lack of cost-effectiveness evidence. This study fills this gap assessing the cost-effectiveness of a combined ovarian cancer (OC) surveillance and prevention strategy in BRCA1/2 PV carriers. The developed Markov decision model simulated the progression of breast cancer and OC in BRCA1/2 PV carriers separately. The model estimated benefits and costs associated with three OC surveillance strategies: Surveillance-Surgery (SS), annual surveillance until salpingo-oophorectomy (SO) and radical mastectomy (RM) at appropriate age; Only-Surgery (OS), without surveillance, and No preventive Intervention (NI). Extensive literature review informed the model. The analysis adopted the Italian NHS perspective and a lifetime horizon, with direct healthcare costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio as outcome measures. Base-case, deterministic and probabilistic sensitivity analyses were performed. In BRCA1 PV carriers, SS yielded lifetime cost savings of €8 382 and €2 008 compared to NI and OS, respectively, while also gaining 2.65 and 0.45 QALYs per patient. Similar trends were observed for BRCA2 PV carriers. Sensitivity analyses confirmed SS as the dominant strategy across all scenarios, with a > 80

Major Depressive Disorder (MDD) is a leading cause of disability worldwide, with significant economic and social burden. However, studies assessing the overall socio-economic burden (direct, indirect and intangible costs) are scarce. This study aims to evaluate the socioeconomic burden imposed by MDD on patients referred to specialist medical centers in Italy. An observational, multicenter, longitudinal cost of illness study was conducted on patients aged 18–65 years with a diagnosis of MDD starting antidepressant therapy. Healthcare resources consumption and productivity loss were collected over 1-year follow-up to estimate per-patients MDD costs. Depressive symptoms were assessed with various clinical scales. Health Related Quality of Life (HRQoL) was assessed with the EQ-5D-5 L. MDD severity decreased during the observational period, as reported by all clinical scales, with a notable improvement in HRQoL scores. The main costs associated with MDD patients were indirect costs, €386.3 per patient-month at baseline, declining to €179.9 in the last 6 months. Direct medical costs peaked in the first 3 months (€155.9 per patient-month), compared to baseline (€55,09 per patient-month), then decreased. Costs were significantly associated with and increased with the number of depressive episodes (129.71;7.59-251.83) and the augmentation of Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) score (7.92;2.02–13.82). Our results suggest that MDD is a mental health issue with socio-economic burden that varies with symptoms severity. Indirect costs represent the main expense for MDD patients. These findings highlight the complexity and burden of MDD, emphasizing the importance of prioritizing depressive disorders in public health. • Major Depressive Disorder (MDD) is a leading cause of disabilities worldwide, with significant economic and social impacts. • During the study period, MDD severity decreased as reported by clinical scales and an improvement of HRQoL was observed. • Economic burden was driven by indirect costs. As regard, the direct medical costs, these increased during the first 3 months and then decreased overtime. • The number of depressive episodes and the increase in QIDS-SR16 score were factors that significantly influenced the disease costs. • MDD is associated with high socio-economic burden, emphasizing the importance of including MDD as a public-health priority.

Wind turbines generate considerable seismic noise and interfere with sensitive instruments, such as permanent and temporary seismic sensors installed nearby, hampering their detection capabilities. This study investigates the seismic noise emission from one of Italy's largest wind farms, consisting of 69 turbines (2 MW each), located in northeastern Sardinia. Characterizing the noise emission from this wind farm is of particular importance due to its proximity to the Italian candidate site for hosting the Einstein Telescope (ET), the third-generation observatory for gravitational waves. We run a passive seismic experiment, “Wind turbIne Noise assEsSment in the Italian site candidate for Einstein Telescope” (WINES), using a linear array of nine broadband stations, installed at increasing distances from the wind farm. Spectral analysis, based on the retrieval of spectrograms and power spectral densities at all stations, shows a significant increase in noise amplitude when the wind farm is in operation. The reconstruction of noise polarization points out that the noise wavefield originates from a direction consistent with the wind farm's location. We recognize four dominant fixed spectral peaks at 3.4, 5.0, 6.8, and 9.5 Hz, corresponding to the modes of vibration of the wind turbine towers. While decreasing in amplitude with distance, the 3.4 Hz peak remains detectable up to 13 km from the nearest turbine. Assuming an amplitude decay model of the form r−α, where r is the distance, we estimate a damping factor of α∼2, which remains rather constant for each of the four main peaks, an observation that we relate to the good geomechanical characteristics of the local terrain, consisting of granitoid rocks. To better evaluate the possible impact of the wind farm noise emission on the ET, we also analyze the seismic data from two permanent stations bordering the ET candidate site area, each equipped with both a surface sensor and a borehole sensor at approximately 250 m depth. Power spectral density analysis for the surface and borehole sensors exhibits similar results and very low noise levels. When the wind farm operates at full capacity, the borehole sensors show an effective noise suppression at depth in the frequency range of interest (1–10 Hz). However, small residual spectral peaks at 3.4 Hz and between 4–6 Hz remain detectable.

IMPORTANCE Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. OBJECTIVE To estimate the worldwide burden of SAH. DESIGN, SETTING, AND PARTICIPANTS Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. EXPOSURES SAH and 14 modifiable risk factors. MAIN OUTCOMES AND MEASURES Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs). RESULTS In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF]=51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF=14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. CONCLUSIONS AND RELEVANCE Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

OBJECTIVE:To develop and validate a patient-reported definition of acute calcium pyrophosphate (CPP) crystal arthritis in people with crystal-proven CPP deposition (CPPD) disease. METHODS:Consecutive patients with crystal-proven CPPD disease from seven centres across four countries were enrolled in a cross-sectional study. In each centre, patient-reported outcomes on the features of acute CPP crystal arthritis were collected. The expert opinion of an independent rheumatologist was the reference standard. We developed definitions based on multivariable logistic regression model with backward selection of predictors and classification and regression tree (CART) approaches. RESULTS:Two hundred and forty-six patients [mean age 73.2 years (s.d. 10.7), 65.9% female] were enrolled. At the time of the assessment, acute CPP crystal arthritis was diagnosed in 96/246 (39.0%) participants.Patient-reported joint warmth, patient-reported joint swelling, time from pain onset to peak, and self-reported acute CPP crystal inflammatory arthritis were included in the multivariable logistic model. This model had good discrimination (optimism-adjusted c-index: 0.92; 95% CI: 0.89, 0.95) and calibration (optimism-adjusted calibration slope: 0.95; 95% CI: 0.71, 1.19; optimism-adjusted calibration-in-the-large: 0.005; 95% CI: -0.37, 0.37) in the internal validation. Probability threshold ≥0.53 had sensitivity of 0.83 (95% CI: 0.74, 0.90) and specificity of 0.86 (95% CI: 0.79, 0.91). Performances were similar in the internal-external cross-validation. The CART identified patient-reported acute CPP crystal inflammatory arthritis, followed by joint swelling and joint warmth as the most informative variables for ascertaining acute CPP crystal arthritis [sensitivity 0.83 (95% CI: 0.72, 0.91) and specificity 0.83 (95% CI: 0.74, 0.90)]. CONCLUSION:We developed and initially validated easy-to-use patient-reported definitions for acute CPP crystal arthritis for use in clinical trials and observational research in CPPD.

Lebrikizumab is a novel monoclonal antibody that targets interleukin-13, a pivotal factor in atopic dermatitis (AD). Previous studies revealed a positive benefit–risk profile of lebrikizumab as treatment for patients with moderate-to-severe AD. In Italy, lebrikizumab has been approved and reimbursed as treatment for patients with severe AD (aged 12 years or older and with an Eczema Area and Severity Index (EASI) ≥ 24). However, data on economic impact of lebrikizumab in these subjects are still scarce. This study aimed to assess the budget impact of lebrikizumab in Italian patients with severe AD, according to Italian Medicine Agency (AIFA) reimbursement criteria, from the Italian National Healthcare System (NHS) perspective. The budget impact analysis model was used to estimate the economic impact of lebrikizumab as treatment of patients with severe AD by comparing the total budget expenditure under two scenarios: scenario A, which includes the current standard of care with biologic agents (dupilumab and tralokinumab), and scenario B, which includes dupilumab and tralokinumab along with the introduction of lebrikizumab. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The clinical data input was based on published evidence, pivotal clinical trial, and expert opinion. Cost data was retrieved from the Italian tariff and literature. One-way sensitivity analysis was conducted to assess the robustness of the model. The base case analysis, conducted over a 3-year period, estimated that the number of patients treated with lebrikizumab increased from 1198 in the first year to 5849 in the final year of the simulation. The adoption of lebrikizumab for patient treatment resulted in a cumulative cost-saving of €3.3 million in 3 years (€786 thousand in the first year, − €1.7 million in the second year, and − €2.4 in the last year). The number of patients potentially eligible to the treatment, the injection site reaction cost, and the injection site reaction rate were the main drivers of the findings. The availability of lebrikizumab as treatment for patients with severe AD would result in cost savings for Italy. Given the paucity of economic data on lebrikizumab, new economic studies should be conducted to confirm these findings.

BACKGROUND: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant health problem with especially increased prevalence, morbidity and mortality in patients with cancer. This study aimed at assessing the economic impact of tinzaparin in patients with cancer associated thrombosis (CAT).METHODS: A budget impact model (BIM) was developed to assess the economic impact of tinzaparin as treatment for patients with CAT. The analysis was conducted over a 3-year time horizon and by adopting the Italian Healthcare system perspective. The model estimated and compared direct medical costs associated with tinzaparin (scenario with tinzaparin) to the ones associated without tinzaparin (scenario where only enoxaparin is available). Epidemiological data as well as VTE events’ rates were retrieved from literature, while costs data were retrieved from the Italian rate tables. The model estimated the economic impact as well as the economic variation associated with drug wastage and VTE management.RESULTS: The model estimated 2,090, 4,202 and 5,429 patients potentially eligible to the treatment during the first, second and third year, respectively. The use of tinzaparin resulted in a cost saving of about €3 millions over 3 years (−€446,378 during the first, −€1,025,848 during the second, and −€1,657,508 during the third year). In the same timeframe, the use of tinzaparin also resulted in decreased costs associated with drug wastage (−€738,604) and recurrent VTE management (−€404,470).CONCLUSIONS: Tinzaparin for the management of CAT patients has the potential for substantial savings, compared to treatments currently available. Stakeholders may consider these data to improve healthcare resource allocation in the Italian setting

OBJECTIVE:To date, there is no shared national guideline in Italy for the management of reproductive health in rheumatic diseases (RHRD). The Italian Society for Rheumatology (SIR) has committed to developing clinical practice recommendations to provide guidance on both management and treatment regarding RHRD in Italy. METHODS:Using the GRADE-ADOLOPMENT methodology, a systematic literature review was conducted to update the scientific evidence that emerged after the publication of the reference recommendations from the American College of Rheumatology. A multidisciplinary group of 18 clinicians with specialist experience in rheumatology, allergy and clinical immunology, internal medicine, nephrology, gynecology and obstetrics, and neonatology, a professional nurse, a clinical psychologist, and a representative from the National Association of Rheumatic Patients discussed the recommendations in collaboration with the evidence review working group. Subsequently, a group of stakeholders was consulted to examine and externally evaluate the developed recommendations. RESULTS:Recommendations were formulated for each area of interest: contraception, assisted reproductive technology, preconception counseling, and use of drugs before, during, and after pregnancy and during breastfeeding, considering both paternal and maternal exposure. CONCLUSIONS:The new SIR recommendations provide the rheumatology community with a practical guide based on updated scientific evidence for the management of RHRD.

Stage 3 chronic kidney disease (CKD) often remains undiagnosed until more severe symptoms appear. This study assessed awareness and management of CKD among Italian general practitioners (GPs), focusing on early detection and current practices. A nation-wide, retrospective observational study was conducted using data from The Health Improvement Network (THIN®) database. Each participant was required to have had at least one interaction with a GP for either medical or administrative purposes (considering the index date), and to have a minimum of three years of retrospective data available from January 2021 to June 2022. The study evaluated the proportion of individuals aged ≥ 40 years who underwent a second serum creatinine test after ≥ 90 days, referrals to nephrologists, and CKD diagnosis confirmation and categorization. Multivariable Poisson regression models analyzed data to identify associations between patient characteristics and outcomes, in both the overall cohort and in the sub-group with available urine albumin-to-creatinine ratio (uACR) measurement. Among 347,548 adults aged ≥ 40 years, 18,002 (5.2

The area in the municipalities of Lula, Bitti, and Onanì in Sardinia (Italy) is a candidate for hosting the “Einstein Telescope” (ET, the third-generation gravitational wave detector), given the extremely low level of natural and anthropogenic seismic noise at this site. For the same unique characteristics of this area, the multi-disciplinary geophysical far-field observatory “Faber” (PNRR-Meet project) will be set up. However, the strength and persistence of wind make this area exceptionally favorable for the exploitation of wind energy, as testified by the nearby Buddusò wind park that, consisting of 69 turbines and about 130 MW of total installed power, is the largest in Italy. It is well known that wind turbines are an important source of seismic noise between 1 and 10 Hz, posing a relevant concern for noise contamination of ET as it will operate in the same frequency range. In the context of the seismic characterization of such a candidate site, the WINES experiment (Wind turbIne Noise assEsSment in the Italian site candidate for the Einstein Telescope) provided a two-month-long passive seismic recording of nine broad-band stations placed at increasing distances from the Buddusò wind park. The aim of the experiment was the evaluation of the noise generated by the wind park in terms of amplitude, spectral content, and decay with distance, in relation to the wind park operation. Analyzing the frequency spectra at all stations, the spectral imprint of the wind park manifests through sharp, well-defined spectral peaks at 3.4, 5.0, 6.8, and 9.4 Hz, even in conditions of absent or moderate wind speed (0-3 m/s). With stronger winds (>20 m/s), all spectra increase their amplitude by an order of magnitude, and the sharpest and most persistent peaks are found at 3.5, 5.2, and 6.8 Hz. In both wind conditions, the amplitude of such peaks decreases with distance, being clearly distinguishable up to 5-6 km from the wind park. We use these spectral peaks to derive an empirical relationship for their amplitude vs. distance, highlighting a well-behaved exponential decay that translates into a two-orders-of-magnitude decrease within 10 km distance. Lastly, considering the assumption that the generated seismic noise propagates as Rayleigh waves, the continuous recordings along the array have been used for the estimation of the direction of noise arrival at each station. Signal coherence allows the recovery of this information for stations within 5 km from the wind park, showing a dominant back-azimuth of the incoming signal that is fully compatible with the position of the wind park with respect to each station.

INTRODUCTION Longer life expectancies and increasing prevalence of chronic diseases drive up demand for healthcare services and related costs. In Italy, 32% of people aged 65 and over, and 48% of those over 85, have major chronic conditions and multimorbidity [1]. In 2019, individuals aged 65 and over accounted for 46% of hospital admissions and 60% of pharmaceutical expenditures, highlighting the significant burden of aging on the healthcare system [2]. In terms of costs, population’s segments with high prevalence of chronic conditions account for a large portion of healthcare spending [3,4,5]. Accurate predictions of future costs for the whole population and for key segments is crucial for healthcare planning. AIMS To predict yearly direct healthcare costs based on data of past National Health Service (NHS) resources utilization for the whole population and for high impacting segments. As a motivating example, we applied our approach to the dialysis patients’ segment. METHODS Using administrative healthcare databases, we traced NHS resource utilization (i.e., access to inpatient and outpatient services, drug dispensations) and associated costs for each individual aged ≥18 assisted by the Health Protection Agency of Bergamo (Northern Italy) between 2011 and 2023. We analyzed total cost (TC) as the sum of all services and dispensations costs, total scheduled cost (TSC) as the sum of scheduled inpatient visits, all outpatient visits and dispensations costs, and scheduled services cost (SSC) as the sum of scheduled inpatient visits and all outpatient visits costs. In the present abstract we focused on TC prediction. We used a supervised machine learning approach, namely random forest (RF) algorithm with 500 trees, to address the prediction problem [6,7]. We trained the algorithm on the 70% of individuals’ data from 2011 to 2015 (n=815,553) with their TC in 2016 as outcome. The 373 input variables included demographic features (such as age and sex) and NHS utilization data over the 4-years period 2011-2014 and in 2015 alone, in order to assess if 2016 cost was more associated with subjects’ behavior over the preceding year or with their historic behavior. As test sets, we used the remaining 30% of the dataset (hereafter 2011-16 set) and the subsequent years’ datasets (2012-17, 2013-18, 2014-19, 2015-20, 2016-21, 2017-22, and 2018-23 sets). We considered variable importance, measured as the percent increase in mean squared error (MSE) when a given variable is permuted, as a measure of each predictor’s impact on the outcome. For each test set, actual and predicted TCs for the whole population were calculated as the sum of all individuals’ actual and predicted TCs, respectively. The ratio of the difference between predicted and actual population TCs to actual population TCs was used as measure of the prediction error (PE). PE=0% indicates a perfect prediction, PE >0% or <0% suggests overestimation or underestimation of the actual TC. Finally, we defined dialysis patients as those who had at least one access to outpatient dialysis services. For this segment, we calculated the mean and sum of predicted and actual TCs, and PE. Also, we derived a variability interval for the mean predicted TC based on the 2.5 and 97.5 quantiles of the distribution of the mean TCs predicted by each tree for subjects included in the segment. RESULTS The mean actual annual population TC in the period from 2011 to 2023 was €1,023,636,867 (range: 944,632,707 – 1,111,657,382). High-cost subjects (>€15,000 yearly), accounting for less than 1% of the annual population, absorbed more than 27% of annual TC. Top 3 most important variables in the RF were the number of outpatient accesses to dialysis over the preceding year, and the frequency of laboratory tests and outpatient services over the 4 preceding years. Figure 1 shows the PEs calculated across all test sets, overall and in the dialysis patients’ segment. Overall, PEs ranged from -3.1 to -1.9 across 2011-16 to 2014-19 sets (for 2014-19 set, actual annual population TC: €1,031,200,509; predicted annual population TC: €1,011,869,922), and widely increased from 2015-20 (range from -6.9 to 8.7; for 2015-20 set, actual annual population TC: €944,632,707; predicted annual population TC: €1,026,878,752) For the dialysis patients’ segment, the lowest PE (-0.7%) was observed in the 2011-16 set (actual mean TC: €38,536; predicted mean TC [variability interval]: €38,259 [35,542 – 41,112]), while the highest was -5.4% in the 2016-21 set (actual mean TC: €38,883; predicted mean TC [variability interval]: €36,785 [33,967 – 39,342]). CONCLUSIONS Using a machine learning approach, we predicted healthcare TCs based on individual data of past utilization of NHS for the whole population and a high impacting segment. Predictions based on the algorithm trained on data from 2011 to 2015 were consistent until 2019, understandable given the COVID-19 pandemic in 2020. Results highlight the pandemic’s impact on the model performance, leading to overestimation of the actual TC in 2020 and underestimations thereafter. Future steps include the identification of key segments and the update of the training algorithm on the subsequent years’ datasets. This is a useful tool to assist HPA in resource allocation, e.g. as an integration to the monitoring of chronic diseases in the population.