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Introduction The 1978 Italian reform of psychiatric services initiated the closure of psychiatric hospitals encouraging the development of community mental health. However, there is wide variability across regions in the amount of resources devoted to community-based psychiatric care, and the range of services provided still is cause of concern. Objectives To evaluate the quality of mental health care delivered to patients with schizophrenia and related disorders taken-in-care by mental health services in four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily). Methods Thirty-one clinical indicators concerning accessibility, appropriateness, continuity, and safety were defined and estimated using healthcare utilization (HCU) databases, containing data on mental health treatments, hospital admissions, outpatient interventions, lab tests and drug prescriptions. Results A total of 70,586 prevalent patients with schizophrenia treated in 2015 were identified, of whom 1,752 were newly taken-in-care. For most patients community care was accessible and moderately intensive. However, care pathways were not implemented based on a structured assessment and only half of the patients received psychosocial treatments. One patient out of ten had access to psychological interventions and psychoeducation. Activities specifically addressed to families involved a third of prevalent patients and less than half of new patients. One patient out of six was admitted to a community residential facility, and one out of ten to a general hospital psychiatric ward (GHPW); higher values were identified in new cases. In general hospitals, one-fifth of the admissions were followed by readmission within 30 days of discharge. For two- thirds of patients continuity of community care was met, and six times out of ten a discharge from a GHPW was followed by an outpatient contact within two weeks. For cases newly taken-in-care the continuity of community care was uncommon, while the readiness of outpatient contacts after discharge was slightly more frequent. Most of the patients received antipsychotic medication, but their adherence to long-term treatment was low. Antipsychotic polytherapy was frequent and the control of metabolic side effects was poor. The variability between regions was high and consistent. Conclusions The Italian mental health system could be improved by increasing the accessibility to psychosocial interventions, improving the quality of care for newly taken-in-care patients, focusing on somatic health and mortality, and reducing regional variability. Clinical indicators demonstrate the strengths and weaknesses of the mental health system in these regions, and, as HCU databases, they could be useful tools in the routine assessment of mental healthcare quality at regional and national levels. Disclosure of Interest None Declared

Introduction The evaluation of healthcare pathways must be considered of fundamental importance. The quality of care provided to patients with severe mental disorders (SMD) does not correspond to the standards set by the recommendations. Therefore, measures such as the real coverage rate of psychiatric patients’ needs (contact coverage), by comparing epidemiological prevalence rates and the number of patients receiving adequate care, could be a valuable resource for implementing the transition to community mental health. However, simple assessment and reporting of rates of contact with mental healthcare potentially overestimate the full expected health benefits of services. Therefore, in addition to monitor the coverage rate achieved by the services, the evaluation of the effectiveness of the care provided (effective coverage) [De Silva et al. Int J Epidemiol 2014;43(2):341–53] is also of relevant importance. Objectives To measure the gap between contact and effective coverage of mental healthcare, i.e., the effectiveness of interventions provided by services for the treatment of SMD in preventing an exacerbation of psychiatric symptoms. Methods Data were retrieved from Healthcare Utilization databases of four Italian Regions (Lombardy, Emilia-Romagna, Lazio, Sicily). 45,761 newly taken-in-care cases of depression, schizophrenia, bipolar, and personality disorder were included. A variant of the self-controlled case series method was used to estimate the incidence rate ratio (IRR) for the relationship between exposure (use of different types of mental healthcare such as pharmacotherapy, generic contacts with the outpatient service, psychosocial interventions, and psychotherapies) and relapse episodes (mental illness emergency hospital admissions). Results 11,500 relapses occurred. Relapse risk was reduced (Figure) during periods covered by (i) psychotherapy for patients with depression (IRR 0.67; 95% CI, 0.49 to 0.91) and bipolar disorder (0.64; 0.29 to 0.99); (ii) psychosocial interventions for those with depression (0.74; 0.56 to 0.98), schizophrenia (0.83; 0.68 to 0.99) and bipolar disorder (0.55; 0.36 to 0.84), (iii) pharmacotherapy for those with schizophrenia (0.58; 0.49 to 0.69), and bipolar disorder (0.59; 0.44 to 0.78). Coverage with generic mental healthcare, in the absence of psychosocial/psychotherapeutic interventions, did not affect the risk of relapse. Image: Conclusions Psychosocial interventions, psychotherapies and specific pharmacotherapies can be considered particularly effective in treating patients with bipolar, depressive, and schizophrenic disorders. This study ascertained the gap between utilization of mental healthcare and effective coverage, showing that real-world data can represent a useful resource to monitor mental healthcare paths and to assess the effectiveness of a mental health system. Disclosure of InterestNone Declared

Objectives Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers.Design Case–control study.Setting Cases from the National Mesothelioma Registry (2000–2018), controls from three previous case–control studies.Methods We selected male PM incident cases diagnosed in 2000–2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002–2004 and 2012–2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses.Results The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower.Conclusions We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

Aims: A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out., Methods and Results: Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014-2015 entered in the cohort and followed up until 2019. Adherence to evidence-based recommendations [i.e. renin-angiotensin-aldosterone system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow-up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person-year) were compared between adherent and non-adherent patients. A non-parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost-effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta-blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non-adherent patients, those who adhered to ECCs, RAS inhibitors, beta-blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2-14%), 11% (7-14%), 8% (5-11%), and 4% (-1-8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta-blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta-blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively., Conclusions: Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The COVID-19 pandemic has modified the burden of disease in the population in various ways, depending on different social and economic conditions. Consequently, the pandemic has amplified health disparities, especially among the frail populations. During the pandemic, the incidence among immigrants showed a one- or two-week delay compared to natives, possibly due to delays in diagnosis and access to treatment. Health Authorities had to think new intervention strategies. As part of a project to contain the spread of SARS-CoV-2 among immigrants in Italy, training emerged as a strategic intervention objective. The training included project areas that assessed the impact of the pandemic and public health intervention on immigrants and incorporated best practices from local experiences. The training was addressed to healthcare and social workers and aimed at building institutional networks and skills in caring for vulnerable people. Additionally, the training course was designed to be adaptable and applicable in other emergency contexts.

Background: the spread of SARS-CoV-2 in the population has amplified the effects of health inequalities, particularly in the most vulnerable groups such as immigrants and refugees. An assessment of the intervention to contain the COVID-19 in these population groups was essential to define new strategies for more equitable, inclusive, and effective health policies to on health., Objectives: to provide a systematic synopsis of the impact of interventions to contain the spread of SARS-CoV-2 in immigrants., Methods: data sources included major bibliographic databases. Using a study protocol, already shared with the international scientific community, two independent researchers reviewed the citations, selected and evaluated the interventions studies. Due to the heterogeneity of the interventions, a narrative synthesis was carried out., Results: three eligible studies were identified. The first study modelled the incidence of the disease in a refugee camp in Greece, based on an intervention of sectorialization of people that accessed to services, the use of masks, the early identification and isolation of cases and their family members, and the limitation of movements within the camp. The second evaluated the impact of preventive pharmacological interventions such as the use of hydroxychloroquine, ivermectin, povidone-iodine, zinc, and vitamin C, in different dosages and combinations, to a group of immigrant workers in a city dormitory in Singapore. The third study evaluated an intervention to increase vaccination coverage within a Latino immigrant community in the United States, moving the location of vaccine supply throughout the most frequented contexts by the immigrant community to access the city services. The results of the first and second studies suggest impacts for some of the proposed interventions even if they have been partially overcome due to the use of mass vaccination. The third showed a reduction in vaccine hesitancy and an increase in vaccination uptake and a snowball effect., Conclusions: the systematic review identified few heterogeneous studies, preventing any generalization of the results. Probably, the low scientific production does not reflect the successful experiences implemented. In the case of a possible resumption of the epidemic or new emergencies, it will be necessary to rely on indirect evidence and the scientific community should consider more the responsibility to evaluate and make available the experiences gained in the field. A constant monitoring activity of the evidence that will be necessary to updating the results for suggest consolidated prevention measures to for controlling the incidence of COVID-19 in immigrants during a possible resumption of the epidemic and for application in other similarly emergency contexts.

Objectives: to evaluate the risk profile of hypospadias in Gela, an Italian National Priority Contaminated Site (NPCS) located in Sicily Region (Southern Italy), characterized by a significant excess of hypospadias in newborn residents compared to data from reference on regional, national, and international basis and, until 2014, by the presence of a petrochemical plant., Design: geographical analyses were conducted by comparing the prevalence of the Gela municipality to prevalence found in Sicily, in a territorial area bordering Gela (ALG), and in the NPCSs of Milazzo and Priolo. The geographical comparisons were conducted for the period 2010-2020, the trend within the Gela NPCS was evaluated by comparing two subperiods (2010-2014 and 2015-2020)., Setting and Participants: children up to 1 year of age with hypospadias resident in the municipality of Gela in the period 2010-2020., Main Outcomes Measures: crude odds ratios (OR) and respective 95% confidence intervals (95%CI) were used to compare the prevalence observed in Gela and that detected in the comparison areas., Results: excess risk for hypospadias was highlighted in 2010-2020 in Gela vs Sicily (OR 4.45; 95%CI 3.45-5.75), vs ALG (OR 4.29; 95%CI 3.02-6.10), and vs the NPCSs of Milazzo (OR 2.32; 95%CI 1.32-4.07) and Priolo (OR 2.37; 95%CI 1.55-3.62). The between-period comparisons in Gela did not show an important difference between 2010-2014 and 2015-2020 (OR 1.37; 95%CI 0.83-2.24), with a prevalence of 98.9 and 72.4 per 10,000, respectively., Conclusions: the prevalence of hypospadias in 2015-2020 remains very high, although decreasing when compared to 2010-2014 period. The Gela data, despite the refinery being closed after 2014, suggest a complex situation in which multiple risk factors may play a role.

Background: A pooled study on Italian asbestos cement plant cohorts observed mortality risk for asbestos-related diseases. This study analysed the mortality of workers cohort of an asbestos cement plant in Syracuse, Italy., Methods: Workers' vital status and causes of death, during 1970-2018, were identified in regional health databases. Standardized mortality ratios (SMRs) by sex and temporal variables were calculated., Results: Of the 900 cohort's subjects (636 men, 259 women, 5 unknown sex), for 867 the vital ascertainment was possible: 505 died during study period. All-cause mortality is similarly to the expected among men and lower among women. Pleural and lung malignant neoplasms (MN) exceeded in men (SMR=27.1, SMR=1.95), retroperitoneal and peritoneal MN in both sexes, no cases of larynx MN were observed. Mortality excess for ovarian MN (SMR=1.5) and asbestosis in both sexes (men: SMR=431.9, women: SMR=116.6) were found., Conclusions: Exceeding mortality from asbestos-related diseases, particularly in men was highlighted.

In Italy, despite strong community-based mental health services, needs assessment is unsatisfactory. Using the Mental Health Clustering Tool (MHCT) we adopted a multidimensional and non-diagnosis dependent approach to assign mental health services users with similar needs to groups corresponding to resources required for effective care. We tested the MHCT in nine Departments of Mental Health in four Italian regions. After a brief training, 318 professionals assessed 12,938 cases with a diagnosis of schizophrenia, depression, bipolar disorder and personality disorder through the MHCT. 53% of cases were 40-59 years, half were females, 51% had a diagnosis of schizophrenia, 48% of cases were clinically severe. Clusters included different levels of clinical severity and diagnostic groups. The largest cluster was 11 (ongoing recurrent psychosis), with 18.9% of the sample, followed by cluster 3 (non-psychotic disorders of moderate severity). The MHCT could capture a variety of problems of people with mental disorders beyond the traditional psychiatric assessment, therefore depicting service population from a different standpoint. Following a brief training, MHCT assessment proved to be feasible. The automatic allocation of cases made the attribution to clusters easy and acceptable by professionals. To what extent clustering provide a sound base for care planning will be the matter of further research., (© 2023. The Author(s).)

Objectives: the BIGEPI project, co-funded by INAIL, has used big data to identify the health risks associated with short and long-term exposure to air pollution, extreme temperatures and occupational exposures., Design: the project consists of 5 specific work packages (WP) aimed at assessing: 1. the acute effects of environmental exposures over the national territory; 2. the acute effects of environmental exposures in contaminated areas, such as Sites of National Interest (SIN) and industrial sites; 3. the chronic effects of environmental exposures in 6 Italian longitudinal metropolitan studies; 4. the acute and chronic effects of environmental exposures in 7 epidemiological surveys on population samples; 5. the chronic effects of occupational exposures in the longitudinal metropolitan studies of Rome and Turin., Setting and Participants: BIGEPI analyzed environmental and health data at different levels of detail: the whole Italian population (WP1); populations living in areas contaminated by pollutants of industrial origin (WP2); the entire longitudinal cohorts of the metropolitan areas of Bologna, Brindisi, Rome, Syracuse, Taranto and Turin (WP3 and WP5); population samples participating in the epidemiological surveys of Ancona, Palermo, Pavia, Pisa, Sassari, Turin and Verona (WP4)., Main Outcome Measures: environmental exposure: PM10, PM2,5, NO2 and O3 concentrations and air temperature at 1 Km2 resolution at national level. Occupational exposures: employment history of subjects working in at least one of 25 sectors with similar occupational exposures to chemicals/carcinogens; self-reported exposure to dust/fumes/gas in the workplace. Health data: cause-specific mortality/hospitalisation; symptoms/diagnosis of respiratory/allergic diseases; respiratory function and bronchial inflammation., Results: BIGEPI analyzed data at the level of the entire Italian population, data on 2.8 million adults (>=30 yrs) in longitudinal metropolitan studies and on about 14,500 individuals (>=18 yrs) in epidemiological surveys on population samples. The population investigated in the longitudinal metropolitan studies had an average age of approximately 55 years and that of the epidemiological surveys was about 48 years; in both cases, 53% of the population was female. As regards environmental exposure, in the period 2013-2015, at national level average values for PM10, PM2.5, NO2 and summer O3 were: 21.1±13.6, 15.1±10.9, 14.7±9.1 and 80.3±17.3 µg/m3, for the temperature the average value was 13.9±7.2 °C. Data were analyzed for a total of 1,769,660 deaths from non-accidental causes as well as 74,392 incident cases of acute coronary event and 45,513 of stroke. Epidemiological investigations showed a high prevalence of symptoms/diagnoses of rhinitis (range: 14.2-40.5%), COPD (range: 4.7-19.3%) and asthma (range: 3.2-13.2%). The availability of these large datasets has made it possible to implement advanced statistical models for estimating the health effects of short- and long-term exposures to pollutants. The details are reported in the BIGEPI papers already published in other international journals and in those published in this volume of E&P., Conclusions: BIGEPI has confirmed the great potential of using big data in studies of the health effects of environmental and occupational factors, stimulating new directions of scientific research and confirming the need for preventive action on air quality and climate change for the health of the general population and the workers.

Background: Italy can be viewed as a laboratory to assess the quality of mental healthcare delivered in a community-oriented system, especially for severe mental disorders, such as personality disorders. Although initiatives based on clinical indicators for assessing the quality of mental healthcare have been developed by transnational-organisations, there is still no widespread practice of measuring the quality of care pathways delivered to patients with severe mental disorders in a community-oriented system, especially using administrative healthcare databases. The aim of the study is to evaluate the quality of care delivered to patients with personality disorders taken-in-care by mental health services of four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily)., Methods: A set of thirty-three clinical indicators, concerning accessibility, appropriateness, continuity, and safety of care, was implemented using regional healthcare utilization databases, containing data on mental health treatments and diagnosis, hospital admissions, outpatient interventions and exams and drug prescriptions., Results: 31,688 prevalent patients with personality disorders treated in 2015 were identified, of whom 2,331 newly taken-in-care. One-in-10 patients received a standardized assessment, the treatment discontinuity affected half of the cases. 12.7% of prevalent patients received at least one hospitalization, 10.6% in the newly taken-in-care cohort. 6-out-of-10 patients had contact with community-services within 14 days from hospital discharge. Access to psychotherapy and psychoeducational treatments was low and delivered with a low intensity. The median of psychosocial interventions per person-year was 19.1 and 9.4, respectively, in prevalent and newly taken-in-care cases. Nearly 50% of patients received pharmacological treatments., Conclusions: Healthcare utilization databases were used to systematically evaluate and assess service delivery across regional mental health systems; suggesting that in Italy the public mental health services provide to individuals with personality disorders suboptimal treatment paths., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Mental health (MH) care often exhibits uneven quality and poor coordination of physical and MH needs, especially for patients with severe mental disorders. This study tests a Population Health Management (PHM) approach to identify patients with severe mental disorders using administrative health databases in Italy and evaluate, manage and monitor care pathways and costs. A second objective explores the feasibility of changing the payment system from fee-for-service to a value-based system (e.g., increased care integration, bundled payments) to introduce performance measures and guide improvement in outcomes., Methods: Since diagnosis alone may poorly predict condition severity and needs, we conducted a retrospective observational study on a 9,019-patient cohort assessed in 2018 (30.5% of 29,570 patients with SMDs from three Italian regions) using the Mental Health Clustering Tool (MHCT), developed in the United Kingdom, to stratify patients according to severity and needs, providing a basis for payment for episode of care. Patients were linked (blinded) with retrospective (2014-2017) physical and MH databases to map resource use, care pathways, and assess costs globally and by cluster. Two regions (3,525 patients) provided data for generalized linear model regression to explore determinants of cost variation among clusters and regions., Results: Substantial heterogeneity was observed in care organization, resource use and costs across and within 3 Italian regions and 20 clusters. Annual mean costs per patient across regions was €3,925, ranging from €3,101 to €6,501 in the three regions. Some 70% of total costs were for MH services and medications, 37% incurred in dedicated mental health facilities, 33% for MH services and medications noted in physical healthcare databases, and 30% for other conditions. Regression analysis showed comorbidities, resident psychiatric services, and consumption noted in physical health databases have considerable impact on total costs., Conclusions: The current MH care system in Italy lacks evidence of coordination of physical and mental health and matching services to patient needs, with high variation between regions. Using available assessment tools and administrative data, implementation of an episodic approach to funding MH could account for differences in disease phase and physical health for patients with SMDs and introduce performance measurement to improve outcomes and provide oversight., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Stroke is the leading global cause of permanent disability and the second leading cause of dementia within the first year of the event. Systematic quality improvement interventions such as Audit & Feedback (A&F) can monitor and improve the performance of post-stroke care in conjunction with the use of quality indicators (QIs). The scientific literature shows limited studies on quality improvement and QIs design for poststroke rehabilitation. In Italy, the National Outcomes Evaluation Programme (PNE) annually provides several QIs concerning the acute wards. On the contrary, indicators for quality assessment of post-acute stroke rehabilitation are not available nationwide. In recent years, the Italian Ministry of Health has funded a national network project, the aim of which is to provide and evaluate the effectiveness of A&F strategies in healthcare improvement. Part of this project is the development of a set of IQs for ischemic stroke rehabilitation used to conduct an A&F. In this study, we describe the design and development process of these QIs from administrative databases and report the results of the pilot test conducted on a small sample of Sicilian rehabilitation facilities, comparing them from 2019 to 2021. Feedback from the participating centers was mainly positive, and the quality indicators were found to be comprehensible and appreciated. However, the study highlighted the need for better adherence to indicators measuring processes of rehabilitation care. The set of quality indicators presented in this study, relevant to inpatient settings, could be considered a starting point on which to base quality improvement initiatives both nationally and internationally.

Background: A mesothelioma cluster in Biancavilla (Sicily, Italy), drew attention to fluoro-edenite, a fibre classified by International Agency for Research on Cancer as carcinogenic to humans. Significant excesses in mortality and morbidity were observed for respiratory diseases and a significant excess of pneumoconiosis hospitalizations was reported., Objective: Aim of this study is to assess the characters of the lung damage in Biancavilla residents hospitalized with pneumoconiosis or asbestosis diagnoses., Methodology: Medical records, available radiographs and computed tomography scans were collected. The obtained imaging was reviewed by a panel of three specialists and focused on pleural and parenchymal abnormalities. Cases with an ILO-BIT or ICOERD score equal or greater than 2 were considered positive for a pneumoconiosis-like damage, cases with a score lower than 2 or insufficient quality of imaging were considered inconclusive. If no pneumoconiotic aspects were present the cases were classified as negative., Results: Out of 38 cases, diagnostic imaging for 25 cases were found. Ten cases out of 25 showed asbestosis-like features, nine subjects were considered negative. In six patients' results were inconclusive., Conclusions: Asbestosis-like features were substantiated in Biancavilla residents without known occupational exposure to asbestos. Further studies to estimate population respiratory health are required. Experimental studies on the fibrogenic potential of fluoro-edenite are needed.

Background: The assessment of the quality of care pathways delivered to people with severe mental disorders in a community-based system remains uncommon, especially using healthcare utilization databases. The aim of the study was to evaluate the quality of care provided to people with bipolar disorders taken-in-care by mental health services of four Italian areas (Lombardy, Emilia-Romagna, Lazio, province of Palermo)., Methods: Thirty-six quality indicators were implemented to assess quality of mental health care for patients with bipolar disorders, according to three dimensions (accessibility and appropriateness, continuity, and safety). Data were retrieved from healthcare utilization (HCU) databases, which contain data on mental health treatments, hospital admissions, outpatient interventions, laboratory tests and drug prescriptions., Results: 29,242 prevalent and 752 incident cases taken-in-care by regional mental health services with a diagnosis of bipolar disorder in 2015 were identified. Age-standardized treated prevalence rate was 16.2 (per 10,000 adult residents) and treated incidence rate 1.3. In the year of evaluation, 97% of prevalent cases had ≥ 1 outpatient/day-care contacts and 88% had ≥ 1 psychiatric visits. The median of outpatient/day-care contacts was 9.3 interventions per-year. Psychoeducation was provided to 3.5% of patients and psychotherapy to 11.5%, with low intensity. 63% prevalent cases were treated with antipsychotics, 71.5% with mood stabilizers, 46.6% with antidepressants. Appropriate laboratory tests were conducted in less than one-third of prevalent patients with a prescription of antipsychotics; three quarters of those with a prescription of lithium. Lower proportions were observed for incident patients. In prevalent patients, the Standardized Mortality Ratio was 1.35 (95% CI: 1.26-1.44): 1.18 (1.07-1.29) in females, 1.60 (1.45-1.77) in males. Heterogeneity across areas was considerable in both cohorts., Conclusions: We found a meaningful treatment gap in bipolar disorders in Italian mental health services, suggesting that the fact they are entirely community-based does not assure sufficient coverage by itself. Continuity of contacts was sufficient, but intensity of care was low, suggesting the risk of suboptimal treatment and low effectiveness. Care pathways were monitored and evaluated using administrative healthcare databases, adding evidence that such data may contribute to assess the quality of clinical pathways in mental health., (© 2023. The Author(s).)

Objectives: We explored temporal variations in disease burden of ambient particulate matter 2.5 μm or less in diameter (PM 2.5 ) and ozone in Italy using estimates from the Global Burden of Disease Study 2019. Methods: We compared temporal changes and percent variations (95% Uncertainty Intervals [95% UI]) in rates of disability adjusted life years (DALYs), years of life lost, years lived with disability and mortality from 1990 to 2019, and variations in pollutant-attributable burden with those in the overall burden of each PM 2.5 - and ozone-related disease. Results: In 2019, 467,000 DALYs (95% UI: 371,000, 570,000) were attributable to PM 2.5 and 39,600 (95% UI: 18,300, 61,500) to ozone. The crude DALY rate attributable to PM 2.5 decreased by 47.9% (95% UI: 10.3, 65.4) from 1990 to 2019. For ozone, it declined by 37.0% (95% UI: 28.9, 44.5) during 1990-2010, but it increased by 44.8% (95% UI: 35.5, 56.3) during 2010-2019. Age-standardized rates declined more than crude ones. Conclusion: In Italy, the burden of ambient PM 2.5 (but not of ozone) significantly decreased, even in concurrence with population ageing. Results suggest a positive impact of air quality regulations, fostering further regulatory efforts., Competing Interests: DB reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer for the European Society for Paediatric Infectious Diseases 2022 Conference, outside the submitted work. LM reports financial support for the present manuscript from the Italian Ministry of Health for the project “Ricerca Corrente 34/2017” as payments made to institution (Institute for Maternal and Child Health IRCCS Burlo Garofolo), which is a public institute. NP reports Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Bayer AG as personal payments. GR reports consulting fees from Akebia Pharmaceuticals, AstraZeneca, Alexion Pharmaceutical, BioCryst Pharmaceuticals, Silence Therapeutics, and Janssen R&D LLC; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim and Novartis as travel reimbursements; all outside the submitted work. The remaining authors declare that they do not have any conflicts of interest., (Copyright © 2023 Conti, Fornari, Ferrara, Antonazzo, Madotto, Traini, Levi, Cernigliaro, Armocida, Bragazzi, Cadum, Carugno, Crotti, Deandrea, Cortesi, Guido, Iavicoli, Iavicoli, La Vecchia, Lauriola, Michelozzi, Scondotto, Stafoggia, Violante, Abbafati, Albano, Barone-Adesi, Biondi, Bosetti, Buonsenso, Carreras, Castelpietra, Catapano, Cattaruzza, Corso, Damiani, Esposito, Gallus, Golinelli, Hay, Isola, Ledda, Mondello, Pedersini, Pensato, Perico, Remuzzi, Sanmarchi, Santoro, Simonetti, Unim, Vacante, Veroux, Villafañe, Monasta and Mantovani.)

Background: The stratification of the general population according to health needs allows to provide better-tailored services. A simple score called Multisource Comorbidity Score (MCS) has been developed and validated for predicting several outcomes. The aim of this study was to evaluate whether the ability of MCS in predicting 1-year mortality improves by incorporating socioeconomic data (as measured by a deprivation index)., Methods: Beneficiaries of the Italian National Health Service who in the index year (2018) were aged 50-85 years and were resident in the Sicily region for at least 2 years were identified. For each individual, the MCS was calculated according to his/her clinical profile, and the deprivation index of the census unit level of the individual's residence was collected. Frailty models were fitted to assess the relationship between the indexes (MCS and deprivation index) and 1-year mortality. Akaike information criterion and Bayesian information criterion statistics were used to compare the goodness of fit of the model that included only MCS and the model that also contained the deprivation index. The models were further compared by means of the area under the receiver operating characteristic curve (AUC)., Results: The final cohort included 1,062,221 individuals, with a mortality rate of 15.6 deaths per 1,000 person-years. Both MCS and deprivation index were positively associated with mortality.The goodness of fit statistics of the two models were very similar. For MCS only and MCS plus deprivation index models, Akaike information criterion were 17,013 and 17,038, respectively, whereas Bayesian information criterion were 16,997 and 17,000, respectively. The AUC values were 0.78 for both models., Conclusion: The present study shows that socioeconomic features as measured by the deprivation index did not improve the capability of MCS in predicting 1-year risk of death. Future studies are needed to investigate other sources of data to enhance the risk stratification of populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rea, Ferrante, Scondotto and Corrao.)

Ensuring adequate quality of care to patients with severe mental disorders remains a challenge. The implementation of clinical indicators aimed at assessing the quality of health care pathways delivered is crucial for the improvement of mental health services (MHS). This study aims to evaluate the quality of care delivered to patients who are taken-into-care with depressive disorders by MHS. Thirty-four clinical indicators concerning accessibility, appropriateness, continuity, and safety were estimated using health care utilization databases from four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily). A total of 78,924 prevalent patients treated for depressive disorders in 2015 were identified, of whom 15,234 were newly engaged by MHS. During the year of follow-up, access to psychotherapeutic interventions was low, while the intensity was adequate; 5.1% of prevalent patients received at least one hospitalization in a psychiatric ward (GHPW), and 3.3% in the cohort of newly engaged in services. Five-out-of-10 patients had contact with community services within 14 days after GHPW discharge, but less than half of patients were persistent to antidepressant drug therapy. Furthermore, prevalent patients showed an excess of mortality compared to the general population (SMR = 1.35; IC 95%: 1.26-1.44). In conclusion, the quality of health care is not delivered in accordance with evidence-based mental health standards. Evaluation of health interventions are fundamental strategies for improving the quality and equity of health care.

A prognostic scoring system that can differentiate β-thalassemia patients based on mortality risk is lacking. We analysed data from 3145 β-thalassemia patients followed through a retrospective cohort design for the outcome of death. An a priori list of prognostic variables was collected. β Coefficients from a multivariate cox regression model were used from a development dataset (n = 2516) to construct a formula for a Thalassemia International Prognostic Scoring System (TIPSS) which was subsequently applied to a validation dataset (n = 629). The median duration of observation was 10.0 years. The TIPSS score formula was constructed as exp (1.4 × heart disease + 0.9 × liver disease + 0.9 × diabetes + 0.9 × sepsis + 0.6 × alanine aminotransferase ≥42 IU/L + 0.6 × hemoglobin ≤9 g/dL + 0.4 × serum ferritin ≥1850 ng/mL). TIPSS score thresholds of greatest differentiation were assigned as <2.0 (low-risk), 2.0 to <5.0 (intermediate-risk), and ≥5.0 (high-risk). The TIPSS score was a good predictor for the outcome of death in the validation dataset (AUC: 0.722, 95%CI: 0.641-0.804) and survival was significantly different between patients in the three risk categories (P < 0.001). Compared to low-risk patients, the hazard ratio for death was 2.778 (95%CI: 1.335-5.780) in patients with intermediate-risk and 6.431 (95%CI: 3.151-13.128) in patients with high-risk. This study provides a novel tool to support mortality risk categorization for patients with β-thalassemia that could help management and research decisions., Competing Interests: Declaration of competing interest Khaled M. Musallam has been or is a consultant for Novartis, Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, CRISPR Therapeutics and Vifor Pharma. Efthymia Vlachaki received hononaria from DEMO S.A. Pharmaceutical Industry and Novartis. Alessia Pepe is the principal investigator of the MIOT project that receives ‘non-profit support’ from industrial sponsorships (Chiesi Farmaceutici S.p.A. and Bayer) and she received speakers' honoraria from Chiesi Farmaceutici S.p.A. Ali T. Taher has been or is consultant for Novartis, Celgene Corp (Bristol Myers Squibb), Vifor Pharma, Silence Therapeutics and Ionis Pharmaceuticals; and received research funding from Novartis, Celgene Corp (Bristol Myers Squibb), La Jolla Pharmaceutical Company, Roche, Protagonist Therapeutics and Agios Pharmaceuticals. Vijay G Sankaran serves as an advisor to and/or has equity in Novartis, Forma, Cellarity, Ensoma, and Branch Biosciences. Aurelio Maggio has been or is a member of advisory boards for Novartis, Celgene Corp (Bristol Meyers Squibb) and Bluebird Bio. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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

Objectives: To measure the gap between contact and effective coverage of mental healthcare (MHC)., Materials and Methods: 45,761 newly referred cases of depression, schizophrenia, bipolar disorder, and personality disorder from four Italian regions were included. A variant of the self-controlled case series method was adopted to estimate the incidence rate ratio (IRR) for the relationship between exposure (i.e., use of different types of MHC such as pharmacotherapy, generic contact with the outpatient services, psychosocial intervention, and psychotherapy) and relapse (emergency hospital admissions for mental illness)., Results: 11,500 relapses occurred. Relapse risk was reduced during periods covered by (i) psychotherapy for patients with depression (IRR 0.67; 95% CI: 0.49 to 0.91) and bipolar disorder (0.64; 0.29 to 0.99); (ii) psychosocial interventions for those with depression (0.74; 0.56 to 0.98), schizophrenia (0.83; 0.68 to 0.99), and bipolar disorder (0.55; 0.36 to 0.84), (iii) pharmacotherapy for patients with schizophrenia (0.58; 0.49 to 0.69), and bipolar disorder (0.59; 0.44 to 0.78). Coverage with generic care, in absence of psychosocial/psychotherapeutic interventions, did not affect risk of relapse., Conclusion: This study ascertained the gap between contact and effective coverage of MHC and showed that administrative data can usefully contribute to assess the effectiveness of a mental health system., Competing Interests: Author GC received research support from the European Community (EC), the Italian Agency of Drug (AIFA), and the Italian Ministry for University and Research (MIUR). He took part to a variety of projects that were funded by pharmaceutical companies (i.e., Novartis, GSK, Roche, AMGEN, and BMS). He also received honoraria as member of Advisory Board from Roche. Author AL was employed by ASST Lecco. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Corrao, Monzio Compagnoni, Barbato, D’Avanzo, Di Fiandra, Ferrara, Gaddini, Saponaro, Scondotto, Tozzi, Carle, Carbone, Chisholm and Lora.)

Background: Preterm birth is a major worldwide public health concern, being the leading cause of infant mortality. Understanding of risk factors remains limited, and early identification of women at high risk of preterm birth is an open challenge. Objective: The aim of the study was to develop and validate a novel pre-pregnancy score for preterm delivery in nulliparous women using information from Italian healthcare utilization databases. Study Design: Twenty-six variables independently able to predict preterm delivery were selected, using a LASSO logistic regression, from a large number of features collected in the 4 years prior to conception, related to clinical history and socio-demographic characteristics of 126,839 nulliparous women from Lombardy region who gave birth between 2012 and 2017. A weight proportional to the coefficient estimated by the model was assigned to each of the selected variables, which contributed to the Preterm Birth Score. Discrimination and calibration of the Preterm Birth Score were assessed using an internal validation set (i.e., other 54,359 deliveries from Lombardy) and two external validation sets (i.e., 14,703 and 62,131 deliveries from Marche and Sicily, respectively). Results: The occurrence of preterm delivery increased with increasing the Preterm Birth Score value in all regions in the study. Almost ideal calibration plots were obtained for the internal validation set and Marche, while expected and observed probabilities differed slightly in Sicily for high Preterm Birth Score values. The area under the receiver operating characteristic curve was 60%, 61% and 56% for the internal validation set, Marche and Sicily, respectively. Conclusions: Despite the limited discriminatory power, the Preterm Birth Score is able to stratify women according to their risk of preterm birth, allowing the early identification of mothers who are more likely to have a preterm delivery.

Purpose: To measure indicators of timeliness and continuity of treatments on patients with schizophrenic disorder in 'real-life' practice, and to validate them through their relationship with relapse occurrences., Methods: The target population was from four Italian regions overall covering 22 million beneficiaries of the NHS (37% of the entire Italian population). The cohort included 12,054 patients newly taken into care for schizophrenic disorder between January 2015 and June 2016. The self-controlled case series (SCCS) design was used to estimate the incidence rate ratio of relapse occurrences according to mental healthcare coverage., Results: Poor timeliness (82% and 33% of cohort members had not yet started treatment with psychosocial interventions and antipsychotic drug therapy within the first year after they were taken into care) and continuity (27% and 23% of patients were persistent with psychosocial interventions, and antipsychotic drug therapy within the first 2 years after starting the specific treatment) were observed. According to SCCS design, 4794 relapses occurred during 9430 PY (with incidence rate of 50.8 every 100 PY). Compared with periods not covered by mental healthcare, those covered by psychosocial intervention alone, antipsychotic drugs alone and by psychosocial intervention and antipsychotic drugs together were, respectively, associated with relapse rate reductions of 28% (95% CI 4-46%), 24% (17-30%) and 44% (32-53%)., Conclusion: Healthcare administrative data may contribute to monitor and to assess the effectiveness of a mental health system. Persistent use of both psychosocial intervention and antipsychotic drugs reduces risk of severe relapse., (© 2021. The Author(s).)

Aims: To evaluate the quality of mental health care delivered to patients with schizophrenia and related disorders taken-in-care by mental health services in four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily)., Methods: Thirty-one clinical indicators concerning accessibility, appropriateness, continuity and safety were defined and estimated using healthcare utilisation (HCU) databases, containing data on mental health treatments, hospital admissions, outpatient interventions, lab tests and drug prescriptions., Results: A total of 70 586 prevalent patients with schizophrenia and related disorders treated in 2015 were identified, of whom 1752 were newly taken-in-care by the facilities of regional mental health services. For most patients community care was accessible and moderately intensive. However, care pathways were not implemented based on a structured assessment and only half of the patients received psychosocial treatments. One patient out of ten had access to psychological interventions and psychoeducation. Activities specifically addressed to families involved a third of prevalent patients and less than half of new patients. One patient out of six was admitted to a community residential facility, and one out of ten to a General Hospital Psychiatric Ward (GHPW); higher values were identified in new cases. In general hospitals, few patients had a length of stay (LoS) of more than 30 days, while one-fifth of the admissions were followed by readmission within 30 days of discharge. For two-thirds of patients, continuity of community care was met, and six times out of ten a discharge from a GHPW was followed by an outpatient contact within 2 weeks. For cases newly taken-in-care, the continuity of community care was uncommon, while the readiness of outpatient contacts after discharge was slightly more frequent. Most of the patients received antipsychotic medication, but their adherence to long-term treatment was low. Antipsychotic polytherapy was frequent and the control of metabolic side effects was poor. The variability between regions was high and consistent in all the quality domains., Conclusions: The Italian mental health system could be improved by increasing the accessibility to psychosocial interventions, improving the quality of care for newly taken-in-care patients, focusing on somatic health and mortality, and reducing regional variability. Clinical indicators demonstrate the strengths and weaknesses of the mental health system in these regions, and, as HCU databases, they could be useful tools in the routine assessment of mental healthcare quality at regional and national levels.

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.)

Introduction: Prevalence of Parkinson's disease (PD) increases with the advanced ages, representing a relevant health burden. Accurate prevalence estimates are of fundamental need in order to adjust the supply of health services for these patients. The availability of administrative health data from the National Health System provides a useful resource to assess the burden of diseases. Our aim was to evaluate the prevalence of PD through the use of administrative data in the Sicily region., Methods: We have identified all the subjects affected by PD in Sicily in 2017 by gathering data from three regional health administrative databases: the hospital discharge records, the medical exemption databases, and the pharmacological prescription database. Prevalence rates and 95% confidence intervals (CI) have been calculated across 5-year age classes., Results: PD patients identified through database searching were 24,674, giving a prevalence of 488/100,000 (95%CI 481.9-494.1) inhabitants. Prevalence was higher among men (514.5/100,000; 95%CI 505.6-523.6) and reached a peak in the 85-89 age class (3203.8/100,000; 95%CI 3095.2-3315.1)., Discussion: Our prevalence estimates of PD were higher when compared to previous epidemiological surveys conducted in Sicily. These findings are, however, comparable to other studies conducted in Italy that identified cases through administrative databases. Using health databases is a feasible strategy to assess the burden of PD., (© 2021. Fondazione Società Italiana di Neurologia.)

In β-thalassaemia, the severity of inherited β-globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long-term outcomes remain limited. We analysed data from 2109 β-thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as β 0 /β 0 , β 0 /β + , β + /β + , β 0 /β ++ , β + /β ++ , and β ++ /β ++ . Patients were followed from birth until death or loss to follow-up. The median follow-up time was 34·1 years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, β 0 and β + mutations showed similar risk profiles. Upon adjustment for demographics and receipt of conventional therapy, patients with β 0 /β 0 , β 0 /β + , or β + /β + had a 2·104-increased risk of death [95% confidence interval (CI): 1·176-3·763, P = 0·011] and 2·956-increased odds of multiple morbidity (95% CI: 2·310-3·784, P < 0·001) compared to patients in lower genotype severity groups. Cumulative survival estimates by age 65 years were 36·8% for this subgroup compared with 90·2% for patients in lower genotype severity groups (P < 0·001). Our study identified mortality and morbidity risk estimates across various genotype severity groups in patients with β-thalassaemia and suggests inclusion of both β + and β 0 mutations in strata of greatest severity., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: to evaluate and validate the adoption of an algorithm for the identification of cases of congenital anomalies (CAs) to improve the performance of the Congenital Malformations Registry of Sicily Region (Southern Italy)., Design: an algorithm was used to identify congenital anomalies on a sample of hospital discharge records (SDO) with ICD-9-CM code between 740-759 on any of the diagnoses within the first year of life, together with a sample of healthy births equal to 5% of total births for the same period. The identified cases were evaluated through the clinical record analysis., Setting and Participants: the analysed sample was composed of 4,271 cases identified between June 2013 and December 2014 along with 3,993 SDO without any code of MC (5% of the total volume of births in the same period)., Main Outcome Measures: positive predictive value (VPP) and negative predictive value (VPN) were computed by means of the comparison between the algorithm outcomes and the clinical record verification., Results: 4,271 potentially malformed records involving 3,381 subjects born in the Sicilian territory have been identified. Among the hospital discharge records that it was possible to verify, the application of the algorithm led to the exclusion of 924 cases: of these, 62 proved to be false negatives (VPN: 93.3). The valid cases were 1,179, while the cases to be evaluated 617: the comparison between algorithm and clinical record analysis led to a VPP of 91.7 and 72.1, respectively, for valid and to be evaluated., Conclusions: the tested algorithm proved to be a useful tool for identifying SDO potentially related to congenital anomalies. In the overall sample, the algorithm provided an outcome consistent with the clinical record assessment in 87.4% (2,379) of cases.

Introduction: Owing to their inherent vulnerabilities, the burden of COVID-19 and particularly of its control measures on migrants has been magnified. A thorough assessment of the value of the interventions for COVID-19 tailored to migrants is essential for improving their health outcomes as well as promoting an effective control of the pandemic. In this study, based on evidence from primary biomedical research, we aimed to systematically identify health interventions for COVID-19 targeting migrants and to assess and compare their effectiveness. The review will be conducted within a programme aimed at defining and implementing interventions to control the COVID-19 pandemic in Italy, funded by the Italian Ministry of Health and conducted by a consortium of Italian regional health authorities., Methods and Analyses: Data sources will include the bibliographic databases MEDLINE, Embase, LOVE Platform COVID-19 Evidence, and Cochrane Central Register of Controlled Trials. Eligible studies must evaluate health interventions for COVID-19 in migrants. Two independent reviewers will screen articles for inclusion using predefined eligibility criteria, extract data of retained articles and assess methodological quality by applying the Cochrane Risk of Bias tool. Disagreements will be resolved through consensus or arbitrated by a third reviewer if necessary. In synthesising the evidence, we will structure results by interventions, outcomes and quality. Where studies are sufficiently homogenous, trial data will be pooled and meta-analyses will be performed. Data will be reported according to methodological guidelines for systematic review provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Ethics and Dissemination: This is a review of existing literature, and ethics approval is not required. We will submit results for peer-review publication and present at relevant conferences. The review findings will be included in future efforts to develop evidence-informed recommendations, policies or programmatic actions at the national and regional levels and address future high-quality research in public health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008-2013 and 2014-2019., Methods: We compared the two eras, era1: 2008-13, era2: 2014-19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled., Results: In the population hospitalized for DFU in 2008-2013, 59.1% of males and 40.9% of females died, whilst in 2014-2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p < 0.001), just as CKD was severe (14.5% vs. 4%, p < 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07-2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37-2.95, p <0.001) and eGFR less than 92 ml/min (OR 2.84, 95% CI 1.51-5.34, p 0.001) were independently associated with risk of death., Conclusions: Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To develop a population-based risk stratification model (COVID-19 Vulnerability Score) for predicting severe/fatal clinical manifestations of SARS-CoV-2 infection, using the multiple source information provided by the healthcare utilisation databases of the Italian National Health Service., Design: Retrospective observational cohort study., Setting: Population-based study using the healthcare utilisation database from five Italian regions., Participants: Beneficiaries of the National Health Service, aged 18-79 years, who had the residentship in the five participating regions. Residents in a nursing home were not included. The model was built from the 7 655 502 residents of Lombardy region., Main Outcome Measure: The score included gender, age and 29 conditions/diseases selected from a list of 61 conditions which independently predicted the primary outcome, that is, severe (intensive care unit admission) or fatal manifestation of COVID-19 experienced during the first epidemic wave (until June 2020). The score performance was validated by applying the model to several validation sets, that is, Lombardy population (second epidemic wave), and the other four Italian regions (entire 2020) for a total of about 15.4 million individuals and 7031 outcomes. Predictive performance was assessed by discrimination (areas under the receiver operating characteristic curve) and calibration (plot of observed vs predicted outcomes)., Results: We observed a clear positive trend towards increasing outcome incidence as the score increased. The areas under the receiver operating characteristic curve of the COVID-19 Vulnerability Score ranged from 0.85 to 0.88, which compared favourably with the areas of generic scores such as the Charlson Comorbidity Score (0.60). A remarkable performance of the score on the calibration of observed and predicted outcome probability was also observed., Conclusions: A score based on data used for public health management accurately predicted the occurrence of severe/fatal manifestations of COVID-19. Use of this score may help health decision-makers to more accurately identify high-risk citizens who need early preventive or treatment interventions., Competing Interests: Competing interests: GC received research support from the European Community (EC), the Italian Agency of Drug (AIFA), the Italian Ministry of Education, University and Research (MIUR), and the Italian Health Ministry. He took part in a variety of projects that were funded by pharmaceutical companies (ie, Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria as member of Advisory Board from Roche. GM received honoraria for participation as speaker/chairman in national/international meetings from Boehringer Ingelheim, Ferrer, Medtronic, Menarini, Merck Serono, Recordati and Servier., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings., Objective: The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID., Methods: A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010-2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association., Results: From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015-2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively., Conclusion: The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010-2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings., (© 2021. The Author(s).)

Background: The incidence of stroke in high-income countries has been on the decline; however, few epidemiological surveys have been conducted in recent years to specifically estimate the incidence along with outcome of stroke, in Italy. This study aimed to examine the incidence and case fatality rates of stroke in an elderly Italian population., Methods: A cohort of 2200 people > 65 years was randomly stratified from the total elderly population of Bagheria, Italy. A 9-year prospective population-based study was performed (19,800 person/years)., Results: We identified 112 first-ever strokes, 53 females and 59 males: 82 (73.1%) ischemic, 13(11.6%) intracerebral haemorrhages, 6 (5.35%) subarachnoid haemorrhages, while 11(9.8%) were classified as undetermined strokes. The crude overall annual incidence was 5.65 per 1000 (95%CI: 4.61 to 6.70) for first-ever stroke. The overall crude incidence rates were 4.74 per 1000 (5.08 for males and 4.46 for females) for ischemic stroke, 0.65 (0.99 for males and 0.37 for females) for intracerebral haemorrhage, and 0.03 for subarachnoid haemorrhage. The incidence rate for first-ever stroke was 5.4 per 1000 (95% CI: 5.36 to 5.45) after adjustment for the 2015 World population and 5.56 (95% CI: 5.52 to 5.61), compared to the 2015 European population. Overall case fatality rates for first-ever stroke was 8.19% at 28 days and 24.1% at 1 year., Conclusion: Our study shows that in the elderly population investigated, stroke incidence and case fatality rates resulted being lower, compared to those from Italian and most European populations. Similar to previous studies, these rates increased linearly with age and were higher in males.

Background: The benefits of chronic polytherapy in reducing readmissions and death after myocardial infarction (MI) have been clearly shown. However, real-world evidence shows poor medication adherence and large geographic variation, suggesting critical issues in access to optimal care. Our objectives were to measure adherence to polytherapy, to compare the amount of variation attributable to hospitals of discharge and to community-based providers, and to identify determinants of adherence to medications., Methods: This is a population-based study. Data were obtained from the information systems of the Lazio and Tuscany Regions, Italy (9.5 million inhabitants). Patients hospitalized with incident MI in 2010-2014 were analyzed. The outcome measure was medication adherence, defined as a Medication Possession Ratio (MPR) ≥ 0.75 for at least 3 of the following drugs: antiplatelets, β-blockers, ACEI/ARBs, statins. A 2-year cohort-study was performed. Cross-classified multilevel models were applied to analyze geographic variation. The variance components attributable to hospitals of discharge and community-based providers were expressed as Median Odds Ratio (MOR)., Results: A total of 32,962 patients were enrolled. About 63% of patients in the Lazio cohort and 59% of the Tuscan cohort were adherent to chronic polytherapy. Women and patients aged 85 years and over were most at risk of non-adherence. In both regions, adherence was higher for patients discharged from cardiology wards (Lazio: OR = 1.58, p < 0.001, Tuscany: OR = 1.59, p < 0.001) and for patients with a percutaneous coronary intervention during the index admission. Relevant variation between community-based providers was observed, though when the hospital of discharge was included as a cross-classified level, in both Lazio and Tuscany regions the variation attributable to hospitals of discharge was the only significant component (Lazio: MOR = 1.30, p = 0.001; Tuscany: MOR = 1.31, p = 0.001)., Conclusion: Adherence to best practice treatments after MI is not consistent with clinical guidelines, and varies between patient groups as well as within and between regions. The variation attributable to providers is affected by the hospital of discharge, up to two years from the acute episode. This variation is likely to be attributable to hospital discharge processes, and could be reduced through appropriate policy levers.

Introduction: Randomized clinical trials showed that bortezomib, in addition to conventional chemotherapy, improves survival and disease progression in multiple myeloma (MM) patients not eligible for stem cell transplantation. The aim of this retrospective population-based cohort study is the evaluation of both clinical and economic profile of bortezomib-based versus conventional chemotherapy in daily clinical practice., Methods: Healthcare utilization databases of six Italian regions were used to identify adult patients with non-transplant MM, who started a first-line therapy with bortezomib-based or conventional chemotherapy. Patients were matched by propensity score and were followed from treatment start until death, lost to follow-up or study end-point. Overall survival (OS) and restricted mean survival time (RMST) were estimated using the Kaplan-Meier method. Association between first-line treatment and risk of death was estimated by a conditional Cox proportional regression model. Average mean cumulative costs were estimated and compared between groups., Results: In the period 2010-2016, 3509 non-transplant MM patients met the inclusion criteria, of which 1157 treated with bortezomib-based therapy were matched to 1826 treated with conventional chemotherapy. Median OS and RMST were 33.9 and 27.9 months, and 42.9 and 38.4 months, respectively, in the two treatment arms. Overall, these values corresponded to a HR of death of 0.79 (95% CI 0.71-0.89) over a time horizon of 84 months. Average cumulative cost were 83,839 € and 54,499 €, respectively, corresponding to an incremental cost-effectiveness ratio of 54,333 € per year of life gained, a cost coherent with the willingness-to-pay thresholds frequently adopted from Western countries., Conclusions: These data suggested that, in a large cohort of non-transplant MM patients treated outside the experimental setting, first-line treatment with bortezomib-based therapy was associated with a favourable effectiveness and cost-effectiveness profile., Competing Interests: Conflict of interest statement: Giovanni Corrao received research support from the European Community (EC), the Italian Agency of Drugs (AIFA), and the Italian Ministry for University and Research (MIUR). He took part in a variety of projects that were funded by pharmaceutical companies (i.e. Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria as a member of the advisory board to Roche. The other authors declare that they have no conflicts of interest to disclose., (© The Author(s), 2021.)

Background and Aims: Diabetes mellitus (DM) has been associated with higher incidence of severe cases of COVID-19 in hospitalized patients, but it is unknown whether DM is a risk factor for the overall COVID-19 incidence. The aim of present study was to investigate whether there is an association of DM with COVID-19 prevalence and case fatality, and between different DM medications and risk for COVID-19 infection and death., Methods and Results: retrospective observational study on all SARS-CoV-2 positive (SARS-CoV-2 + ) cases and deaths in Sicily up to 2020, May 14th. No difference in COVID-19 prevalence was found between people with and without DM (RR 0.92 [0.79-1.09]). Case fatality was significantly higher in SARS-CoV-2 + with DM (RR 4.5 [3.55-5.71]). No diabetes medication was associated with differences in risk for SARS-Cov2 infection., Conclusions: in Sicily, DM was not a risk factor for COVID-19 infection, whereas it was associated with a higher case fatality., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more complications. Nine independent variables were included in the investigation as predictors. Logistic regression models were used for Group A [transfusion-dependent thalassaemia (TDT)], Group B [transfused non-TDT (NTDT)] and Group C (non-transfused NTDT). Statistically significant predictors included age (years), haemoglobin levels, hepatic transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase] and left-ventricular ejection fraction (LVEF) for Group A; age (years), age at first chelation (months), ALT and LVEF for Group B; and age (years), mean serum ferritin (SF) levels and LVEF for Group C. The area under the receiver operating characteristic curve was 84·5%, 82·1% and 80·0% for Groups A, Group B and Group C respectively, suggesting the models had good discrimination. Finally, the CoRS for each group was categorised into four risk classes (low, intermediate, high, and very high) using the centiles of its distribution. In conclusion, we have developed a CoRS for TS that can assist physicians in prospectively tailoring patients' treatment., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Erythropoiesis-stimulating agents (ESAs), are used for treating chronic kidney disease (CKD)-related anemia, contributing to CKD costs. The study was aimed at investigating direct healthcare costs of CKD patients treated with ESAs and the potential savings achievable by increasing the use of biosimilars and preventing inappropriate ESA use., Methods: A multi-center, cohort study was conducted using claims databases of five large Italian geographic areas. Yearly mean direct healthcare costs per patient were estimated, stratifying by CKD stage. The total yearly cost and potential savings related to ESA use were estimated: (a) considering 25/50/75% of originator ESA substitution with biosimilars; (b) eliminating inappropriate ESA dispensing., Results: During the study period, the ESA-related yearly mean cost represented 17% of total yearly costs in stage I-III, decreasing to 13% in stage IV-V and 6% in dialysis. Among originator users, assuming a 25% of biosimilar uptake, the annual cost-savings of ESA treatment would represent 10.5% of total ESA costs in CKD stage I-V and 7.7% in dialysis. Among incident ESA users for which hemoglobin levels were available, 9% started inappropriately ESA treatment, increasing to 62.0% during the first year of maintenance therapy. Hypothesizing prevention of the first inappropriate ESA dispensing, the total yearly cost-savings would amount to €35 772, increasing to €167 641 eliminating the inappropriate dispensing during maintenance therapy., Conclusions: Higher use of lowest cost ESA, prevention of inappropriate ESA use as well as other strategies aimed at slowing down the progressive renal impairment are essential for minimizing clinical and economic burden of CKD., (© 2020 John Wiley & Sons Ltd.)