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CAR-T therapies are a form of innovative and personalised immunotherapy in the field of onco-haematology. Diffuse large B-cell lymphoma (DLBCL) is a very aggressive form of non-Hodgkin's lymphoma (NHL) for which CAR-T therapies are approved as 3rd-line and more recently (from 11/11/2023), as 2nd-line for patients who relapse within 12 months after 1st-line chemo-immunotherapy. This study was conducted to estimate the eligible DLBCL population for CAR-T therapies in 2024 in Lazio region. Starting with a cohort of DLBCL patients from a previous work, a series of proportions were first obtained applying the eligibility criteria for CAR-T, and then applied to the annual incident cases of NHL in Lazio region. From 1,353 NHL cases, 392 (29%) were considered DLBCL of which 82% (322) received first line chemo-immunotherapy. They were then divided into two groups: with relapse ≤12 months (Group 1) and with relapse >12 months (Group 2). Fifty percent of Group 1 (46 cases) and part of those not eligible to ASCT (35%=16 cases) constitute the eligible population for CAR-T therapy as 2nd-line. From the 29 cases of Group 2, were calculated the proportions of CAR-T eligible patients among those not eligible for ASCT (35%=5 cases) and those who did not respond to salvage chemotherapy (65%=4 cases) and with post-transplant relapse (39%=3 cases). A total of 74 DLBCL patients were found to be eligible for CAR-T therapies. This study demonstrates that the use of Real World Data is a valuable tool in defining the target population for new therapeutic indications.

Objectives: To investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk-benefit profiles in clinical practice., Design: Retrospective multicentrer cohort study., Setting: Four Italian regions (Lombardy, Veneto, Lazio, Sardinia)., Methods: Data were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI)., Main Outcome Measures: Mortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use., Results: The study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk-benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65)., Conclusions: The study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This work is the third in a series of articles dedicated to the EASY-NET network programme. The first article described the rationale, structure, and methodologies; while the second evaluated the adherence of individual audit&feedback A&F interventions tested in EASY-NET to literature recommendations. This contribution provides a concise summary of the effectiveness results of A&ented by clinical and organizational areas: chronic disease management, emergency territorial and hospital care for acute conditions, post-acute rehabilitation, hospital oncology care, childbirth, and caesarean sections. In alignment with existing literature, the results on the effectiveness of A&F, in terms of measurable improvement, were observed across all settings, although to varying degrees and more significantly in processes than in outcomes. Key elements that proved to be fundamental to the implementation of A&F interventions include the importance of institutions in making A&F systematic, continuous, and a priority for healthcare professionals; the central role of the required and available data for preparing feedback; the involvement of A&F recipients in the whole path, from the design of the interventions to the discussion of results and improvement actions. A final consideration, in light of the activities conducted and the results achieved, suggests that integrating research into practice and practice into research is essential to ensure, on one hand, the transferability of evidence into operations and, on the other hand, the design of studies that are feasible and integrable into daily activities - a necessary aspect to optimize resources.

Background: Mental healthcare provision is undergoing substantial reconfiguration in many regions of the world. Such changes require a broad, evidence-based approach incorporating epidemiological data and information on local needs. The objective of this study was to estimate the prevalence of schizophrenia spectrum disorders (SSD) in the Lazio region and its geographical distribution using regional administrative healthcare databases., Methods: Cases of SSD (15-64 years old) were identified using an algorithm based on data from the hospital discharge registry (ICD IX CM: 295, 297, 298 [excl. 298.0], 299) and the ticket exemption database [code 044], between 2006 and 2019. We calculated crude, age- and gender-specific prevalence estimates on December 31, 2019. We also calculated age- and gender-adjusted prevalence to compare prevalence in different regional areas., Results: We identified 18,371 cases. The overall prevalence was 5.03 per 1000 population (95% CI 4.96-5.10). Age-adjusted prevalence estimates were 4.18 (95% CI 4.09-4.27) per 1000 for women and 5.92 (95% CI 5.81-6.04) per 1000 for men. The prevalence was higher among older age groups, in both genders. There were differences in prevalence within the region, ranging from 4.25/1000 in the province of Viterbo to 5.42/1000 in Rome and 6.02/1000 in the province of Frosinone. When we analysed the subcategories of SSD, the three most frequent conditions were schizophrenia, schizoaffective disorder, and psychosis NOS. In general, the prevalence was higher in men for all the conditions but delusional disorders and brief psychosis., Conclusions: Our results show that the overall prevalence of SSD among adults in the Lazio region is similar to those published in previous reviews, but an uneven regional distribution was observed. While possible underestimation must be considered, administrative databases represent a valuable source of information for epidemiological surveillance and healthcare planning., (© 2024. The Author(s).)

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.)

Italy is a destination country for a growing international migration, accounting for 8.4% of the total population. The COVID-19 pandemic has increased the difficulties in accessing healthcare services among immigrants, and barriers due to linguistic and cultural differences had a significant impact during the pandemic. This paper presents the methodology used in the project 'Epidemiological surveillance and control of COVID-19 in metropolitan urban areas for the containment of SARS-CoV-2 circulation in the immigrant population in Italy', carried out with the technical and financial support of the Italian Ministry of Health. This methodology is aimed to identify and select statements available in the literature, transferable to the Italian context, on the topic of interventions deemed useful in reducing the impact of the COVID-19 pandemic on the foreign population in urban/metropolitan settings.In February 2022, a systematic search was conducted in databases such as Medline, Embase, and Web of Science, as well as on national and international websites (WHO, Italian Institute of Health, and CDC), and on 'RecMap' (included in the 'COVID19 Recommendations' website) to identify guidelines containing recommendations on the management and prevention of COVID-19 among immigrants. The selected recommendations were divided into intervention areas (infection control, vaccination, screening, planning and monitoring, healthcare systems). In the first phase, a group of researchers independently assessed the inclusion of recommendations through three rounds of consensus. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was used to assess the quality of the included guidelines. In the second phase, an external group of experts independently evaluated the relevance of the included recommendations using a Likert scale. The document is the result of a collaborative work based on evidence from the literature available until that time. The adaptation and adoption of recommendations already formulated by other international organizations on the topic of preparedness and response to the COVID-19 pandemic, evaluated through a consensus process with experts, can be a valid method aimed at producing documents to inform and guide those involved in the care of immigrants in Italy, as well as promoting inclusive forms of prevention in emergency contexts.

The post-organ transplant immunosuppressive therapy includes the administration of tacrolimus (Tac) or cyclosporine (CsA), along with antimetabolites (Antim) or mTOR inhibitors, with or without prednisone. A survey was conducted to investigate clinical experience regarding the use, efficacy, safety profile, and determinants of choice of maintenance immunosuppressive therapies. The questionnaire was sent to healthcare workers of 45 transplant centers specializing in kidney (K), liver (L), heart (H), and lung (P) transplants. Seventy-one responses were received from 15 Italian regions. The indicated first-choice therapy was Tac + Antim, except in the hepatic field where Tac monotherapy was favored. According to 44.1% of respondents, the first-choice therapy has changed over the last 15 years due to the replacement of CsA with Tac and increased use of mTOR inhibitors. Regarding the determinants of the index therapy, the choice of schemes to be applied depends mainly on international guidelines, previous experience, and internal protocols within the facility (80.3%; 54.9%; 50.7%, respectively). Compared to standard therapy, the criteria guiding the prescription of different therapies mainly involve the presence of comorbidities (K: 81.3%; L: 88.2%; H: 73.3%; P: 85.7%) and the evaluation of specific clinical parameters of the recipient. Additionally, the majority of respondents are in favor of using generic versions where available. The survey reveals dimensions not detectable by current healthcare administrative flows; such integrations provide a broader picture of the factors influencing the choice of post-transplant immunosuppressive therapeutic schemes.

Background: Lung cancer is one of the most lethal cancers worldwide and patient clinical outcomes seem influenced by their socioeconomic position (SEP). Since little has been investigated on this topic in the Italian context, our aim was to investigate the role of SEP in the care pathway of lung cancer patients in terms of diagnosis, treatment and mortality., Methods: This observational retrospective cohort study included patients discharged in the Lazio Region with a lung cancer diagnosis between 2014 and 2017. In the main analysis, educational level was used as SEP measure. Multivariate models, adjusted for demographic and clinical variables, were applied to evaluate the association between SEP and study outcomes, stratified for metastatic (M) and non-metastatic (NM) cancer. We defined a diagnosis as 'delayed' when patients received their initial cancer diagnosis after an emergency department admission. Access to advanced lung cancer treatments (high-cost, novel and innovative treatments) and mortality were investigated within the 24-month period post-diagnosis. Moreover, two additional indicators of SEP were examined in the sensitivity analysis: one focusing on area deprivation and the other on income-based exemption., Results: A total of 13,251 patients were identified (37.3% with metastasis). The majority were males (> 60%) and over half were older than 70 years. The distribution of SEP levels among patients was as follow: 31% low, 29% medium-low, 32% medium-high and 7% high. As SEP increased, the risks of receiving a delayed diagnosis ((high vs low: M: OR = 0.29 (0.23-0.38), NM: OR = 0.20 (0.16-0.25)) and of mortality ((high vs low M: OR = 0.77 (0.68-0.88) and NM: 0.61 (0.54-0.69)) decreased. Access to advanced lung cancer treatments increased in accordance with SEP only in the M cohort (high vs low: M: OR = 1.57 (1.18-2.09)). The primary findings were corroborated by sensitivity analysis., Conclusions: Our study highlighted the need of public health preventive and educational programs in Italy, a country where the care pathway of lung cancer patients, especially in terms of diagnosis and mortality, appears to be negatively affected by SEP level., (© 2024. The Author(s).)

Background: Entering dialysis is a critical moment in patients' healthcare journey, and little is known about drug therapy around it. A study funded by the Italian Medicines Agency offered the opportunity to leverage data from the Lazio Regional Dialysis and Transplant Registry (RRDTL) and perform an observational study on drug use patterns before and after initiating chronic dialysis., Methods: Individuals initiating dialysis in 2016-2020 were identified from RRDTL, excluding patients with prior renal transplantation, stopping dialysis early, or dying within 12 months. Use of study drugs, predefined by clinicians, in the two years around the index date was retrieved from the drug claims register and described by semester. For each drug group, proportions of users (min 2 claims in 6 months) by semester, and intensity of treatment in terms of Defined Daily Doses (DDDs) for cardiovascular and antidiabetic agents were compared across semesters, stratifying by sex and age., Results: In our cohort of 3,882 patients we observed a general increase in drug use after initiating dialysis, with the mean number rising from 5.5 to 6.2. Cardiovascular agents accounted for the highest proportions, along with proton pump inhibitors and antithrombotics over all semesters. Dialysis-specific therapies showed the most evident increase, in particular anti-anaemics (iron 4-fold, erythropoietins almost 2-fold), anti-parathyroids (6-fold), and chelating agents (4-fold). Use of cardiovascular and antidiabetic drugs was characterised by significant variations in terms of patterns and intensity, with some differences between sexes and age groups., Conclusions: Entering dialysis is associated with increased use of specific drugs and goes along with adaptations of chronic therapies., (© 2024. The Author(s).)

Migrants may be susceptible to vaccine barriers and hesitancy. We evaluated the association between migrant status, as measured by the citizenship from a High Migratory Pressure Country (HMPC), and COVID-19 vaccination uptake in the resident population in Rome, Italy. We also investigated sex differences. We followed participants for vaccination against COVID-19 in 2021. We calculated crude- and adjusted-vaccination rates and Cox hazard ratios of vaccination for migrants compared to Italians. Among migrants from HMPCs, we estimated HRs for females compared to males, stratifying by geographical area of origin. Models were adjusted for age and deprivation index and stratified by infection history. In 2021, among 1,731,832 18-64-year-olds, migrants were 55% less likely to uptake at least one COVID-19 vaccine dose than their Italian counterpart. Past SARS-CoV-2 infection reduced the difference between migrants and Italians to 27%. Among migrants from HMPCs, we observed a slight excess of vaccination uptake among females compared to males. Focusing on geographical areas, we observed that only females from central-western Asia were 9% less likely to uptake vaccination than males. Health communication strategies oriented to migrants and considering their different languages, cultures, and health literacy should be adopted for prevention before emergencies., (© 2023. The Author(s).)

This is the second of a series of papers dedicated to the EASY-NET research programme (NET-2016-02364191). The rationale, structure and methodologies are described in the previous contribution. Scientific literature demonstrated that Audit & Feedback (A&F) is an effective strategy for continuous quality improvement and its effectiveness varies considerably according to factors that are currently little known. Some recent publication pointed out, with the contribution of an international group of experts, 15 suggestions to optimize A&F and developed a tool to evaluate their application. This tool, called REFLECT-52, includes 52 items related to the 15 suggestions and organized into four categories relating to the "Nature of the desired action", to the "Nature of the data available for feedback", to the "Feedback Display" and to the "Intervention delivery". Then, the aim of this work was to evaluate the level of adherence of A&F interventions tested in EASY-NET to suggestions from the literature by using a slightly adapted version of the REFLECT-52 tool, in its original language. In EASY-NET, 14 A&F interventions with different characteristics and in different clinical and organizational contexts were tested in seven Italian regions, each of these was evaluated by the respective research groups. Overall, the level of adherence was high in three of the four categories analysed, with some difficulties reported regarding the nature of the data available for feedback. In fact, contrary to what the literature suggests, it was not possible to send repeated feedback for some interventions and, in some cases, the data available for feedback presented a delay longer than one year. In summary, this analysis has confirmed a high level of compliance of the interventions tested with the suggestions from the literature, but it has also allowed researchers to identify critical aspects that need to be addressed for the future development of these strategies.

Background: The use of medications during pregnancy is a common event worldwide. Monitoring medicine prescriptions in clinical practice is a necessary step in assessing the impact of therapeutic choices in pregnant women as well as the adherence to clinical guidelines. The aim of this study was to provide prevalence data on medication use before, during and after pregnancy in the Italian population., Methods: A retrospective prevalence study using administrative healthcare databases was conducted. A cohort of 449,012 pregnant women (15-49 years) residing in eight Italian regions (59% of national population), who delivered in 2016-2018, were enrolled. The prevalence of medication use was estimated as the proportion (%) of pregnant women with any prescription., Results: About 73.1% of enrolled women received at least one drug prescription during pregnancy, 57.1% in pre-pregnancy and 59.3% in postpartum period. The prevalence of drug prescriptions increased with maternal age, especially during the 1st trimester of pregnancy. The most prescribed medicine was folic acid (34.6%), followed by progesterone (19%), both concentrated in 1st trimester of pregnancy (29.2% and 14.8%, respectively). Eight of the top 30 most prescribed medications were antibiotics, whose prevalence was higher during 2nd trimester of pregnancy in women ≥ 40 years (21.6%). An increase in prescriptions of anti-hypertensives, antidiabetics, thyroid hormone and heparin preparations was observed during pregnancy; on the contrary, a decrease was found for chronic therapies, such as anti-epileptics or lipid-modifying agents., Conclusions: This study represents the largest and most representative population-based study illustrating the medication prescription patterns before, during and after pregnancy in Italy. The observed prescriptive trends were comparable to those reported in other European countries. Given the limited information on medication use in Italian pregnant women, the performed analyses provide an updated overview of drug prescribing in this population, which can help to identify critical aspects in clinical practice and to improve the medical care of pregnant and childbearing women in Italy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fortinguerra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To face the second wave of COVID-19, Italy implemented a tiered restriction system with different limitation levels (yellow = medium; orange = medium-high, red = high) at the beginning of November 2020. The restrictions systematically reduced the transmission of SARS-CoV-2 with increasing strength for increasing tier. However, it is unknown whether the effect of limitations was equal between provinces with different socioeconomic levels. Therefore, we investigated the association between the province's socioeconomic level and SARS-CoV-2 infection daily reproduction number in each restriction level., Methods: We measured the province's socioeconomic level as the percentage of individuals whose 2019 total yearly income was lower than 10,000€, using the measure as a proxy of economic disadvantage. We estimated the daily reproduction number (Rt) at the province level using the SARS-CoV-2 daily incidence data from November 2020 to May 2021. We then used multilevel linear regression models with random intercepts stratified by restriction level to estimate the association between economic disadvantage and Rt. We also adjusted the analyses for potential confounders of the association between the province's economic disadvantage and the Rt: the percentage of people with 0-5 years, the quartiles of population density, and the geographical repartition., Results: Overall, we found increasing Rt in yellow (+ 0.004 p < 0.01, from Rt = 0.99 to 1.08 in three weeks) and containing effects for the orange (-0.005 p < 0.01, from Rt = 1.03 to 0.93) and the red tier (-0.014 p < 0.01, from Rt = 1.05 to 0.76). More economically disadvantaged provinces had higher Rt levels in every tier, although non-significantly in the yellow level (yellow = 0.001 p = 0.19; orange = 0.002 p = 0.02; red = 0.004 p < 0.01). The results showed that the association between economic disadvantage and Rt differed by level of restriction. The number of days into the restriction and the economic disadvantage had statistically significant interactions in every adjusted model. Compared to better off, more economically disadvantaged provinces had slower increasing trends in yellow and steeper Rt reductions in orange, but they showed slower Rt reductions in the highest tier., Conclusion: Lower tiers were more effective in more economically disadvantaged provinces, while the highest restriction level had milder effects. These results underline the importance of accounting for socioeconomic level when implementing public health measures., (© 2023. The Author(s).)

Background: A crucial step for planning effective public health policies for migrants with dementia is the collection of data on the local dimensions of the phenomenon and patients' characteristics., Objective: This study aimed to identify and characterize migrants with dementia in the Lazio region using health administrative databases., Methods: Residents with dementia aged 50 years or older, living in the Lazio region as of December 31, 2018, were identified using a validated algorithm based on hospital discharge(s), claims for antidementia drugs, and co-payment exemption for dementia. Migrants were defined as people born abroad and grouped in migrants from High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs). Overall and age-specific prevalence rates were estimated in native- and foreign-born patients., Results: Dementia was ascertained in 38,460 residents. Among them, 37,280 (96.9%) were born in Italy, 337 (0.9%) were migrants from HDCs, and 843 (2.2%) from HMPCs. Dementia prevalence was higher among natives (1.15%, 95% CI 1.14-1.16) relative to migrants from HDCs (0.60%, 95% CI 0.54-0.67) and HMPCs (0.29%, 95% CI 0.27-0.31). The prevalence of comorbidities did not differ between groups. Migrants with dementia had a lower likelihood of receiving antidementia treatments compared with natives (51.6% in migrants from HDCs, 49.3% in migrants from HMPCs, and 53.5% among Italians)., Conclusion: Routinely collected data in healthcare administrative databases can support the identification of migrants with dementia. Migrants exhibited a lower age-standardized prevalence of registered dementia and lower access to dedicated treatments than Italians. These findings are suggestive of underdiagnosis and undertreatment of dementia in migrants.

In Italy the National Outcomes Evaluation Programme, (P.N.E.) is the most comprehensive comparative evaluation of healthcare outcomes at the national level. The aim of this report is to describe the P.N.E. and some of the most relevant results achieved. The P.N.E. analysed 184 indicators on quality of care in 2015-2020 period. The data sources are the Italian Health Information Systems. The indicators reported were: proportion of surgery within 2 days after hip fracture in the elderly (HF), 30-day mortality after hospital admission for acute myocardial infarction (AMI), proportion of reoperations within 90 days of breast-conserving surgery and proportion of primary caesarean deliveries. Risk adjustment methods were used to take into account patients' characteristics. From 2010 to 2020 the proportion of interventions within 2 days after HF increased from 31.3% to 64.6%, the AMI 30-day mortality decreased from 10.4% to 8.3%, the proportion of reinterventions within 90 days of breast-conserving surgery decreased from 12.0% to 5.9% and the proportion of primary caesarean deliveries decreased from 28.4% to 22.7%. Results by area of residence showed heterogeneity of healthcare quality. We observed a general improvement in different clinical areas not always associated with a reduction of heterogeneity among areas of residence.

Objectives: to evaluate the impact of school closures, as a measure to contain the transmission of SARS-CoV-2 infection, on the psychological well-being of students of all levels starting from the 2020-2021 school year., Design: a systematic literature review was conducted according to the PRISMA 2020 Guidelines. The literature search was conducted on 4 different databases: MedLine, Embase, PsycINFO, and L.OVE Platform. Quantitative observational studies published until 10.01.2022 were included. Studies conducted during the first pandemic wave, i.e., during the 2019-2020 school year and/or during the mandatory lockdown or confinement period, were excluded. The methodological quality of the studies was assessed with validated scales. Study selection, data extraction, and quality assessment were carried out independently by two authors., Setting and Participants: children, adolescents, and young people attending all levels of education (including universities) and, for reasons related to COVID-19, having a suspension of "in presence" school or attending classes remotely., Main Outcome Measures: a. outcomes directly related to mental health: suicides, emergency department visits, and hospitalizations for psychiatric problems; anxiety and depression, emotional difficulties, feelings of loneliness and isolation; b. well-being outcomes: sleep quality, perceived well-being (by child/adolescent/youth or referred by parents); c. health-related behaviours: tobacco smoking, alcohol, drug use. Outcomes related to school/academic performance, physical health, and those related to parents were not considered., Results: after having removed duplicate articles, 2,830 records were retrieved with the bibliographic search. Twelve studies (2 uncontrolled before-after studies and 10 cross sectional surveys) were included, involving a total of 27,787 participants. Three studies involved university students, 2 involved high school students, and the remaining involved a mixed population of students attending primary and middle schools. The studies were conducted between September 2020 and April 2021. The methodological quality was rated as high in five studies and intermediate in the remaining studies. Due to the high heterogeneity of outcome measures and statistical analyses performed among the included studies, it was not possible to conduct a meta-analysis of the results of the considered publications. Nevertheless, the present review showed a clear signal of increase in mental health problems in relation to school closure or virtual instruction. In particular, results suggest evidence of association between school closure and risk of suicidal attempts or thoughts, mental health symptoms such as anxiety, depression, emotional disorders, psychological stress. Sleeping problems, drug and alcohol addiction were poorly studied., Conclusions: despite the limitations of the included studies and possible residual confounding and contamination due to restrictive measures and social isolation implemented during the pandemic, the available evidence confirms the negative impact on students' mental health associated with school closures and distance learning. Given the availability of vaccination also for young children, a long period of school closure should be avoided also in the case of the emergence of new pandemic waves.

Objectives: to describe trends of overall and intensive care hospitalization for COVID-19 since the beginning of the pandemic in Italy until June 2021, and to compare the results between foreign and Italian population., Design: retrospective observational study., Setting and Participants: hospital discharges of 28 million people living in Lombardy, Piedmont, Emilia-Romagna (Northern Italy), Toscana and Lazio (Central Italy) occurred between 22.02.2020 and 02.07.2021 in the hospitals located in each considered Region., Main Outcome Measures: two weekly outcomes were examined: 1. the overall number of COVID-19 hospitalizations; 2. the number of COVID-19 hospitalizations in intensive care units., Results: a higher COVID-19 overall and intensive care unit hospitalization was found among the foreign population compared to Italians. The association emerged only after the adjustment for age, and it was consistent among all Regions, though less marked in Lombardy. The association varied across epidemic phases., Conclusions: the issue of vulnerability of migrants to the risk of severe COVID-19 calls for a diversity-sensitive approach in prevention. The specific country of origin and the prevalence of preventable co-morbidities that are often underestimated in the migrant populations, and related to COVID-19 complications, should be taken into consideration in future analyses.

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

Objectives: to geocode all residence addresses from Lazio Health Information System in order to obtain a geographical regional database., Design: a semiautomatic and multistep geocoding procedure using several tools and software., Setting and Participants: all residence addresses of resident population of Lazio Region (Central Italy) in 2020., Main Outcome Measures: geographic coordinates at residence addresses and accuracy level of geocoding procedure for more than 1 million of addresses., Results: the 99% of residence addresses in the Lazio Region have been geocoded thanks to the purposed procedure; almost 94% of the addresses have been geocoded with a good level of accuracy (more than 56% at civic number level). In the province of Rome, the percentage of addresses geocoded with a good level of accuracy is higher (97.1%), while in the province of Rieti and Frosinone is lower (82.7% and 84.2%, respectively)., Conclusions: this method is useful to obtain accurate geographic coordinates of residences of the entire regional population. This database will be useful for several epidemiological studies in the Region.

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

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

Objectives: to investigate, for the first time, the incidence of cancer (years 2009-2015) and geographical distribution among children and adolescents with cancer diagnosis in Lazio Region (Central Italy)., Design: to compute incidence rates of childhood cancers from Lazio Region Childhood Cancer Registry (LRCCR) database, established in 2015, and to compare results with national figures for 2012 provided by the Italian cancer registries network (AIRTUM)., Setting and Participants: all new cases of malignant tumours (behaviour: /3 of ICD-O-3 classification) and all central nervous system tumours were selected, regardless of behaviour (/0, /1, /3) in children and adolescents (0-19 years) registered in the LRCCR data base., Main Outcome Measures: it was computed: • the raw and the direct standardised rates for the 0-14-year and the 15-19-year age groups for total malignant tumours of the ICCC-3 classification by area (province level and municipality of Rome); • Relative Risks (RR) for area-specific rate compared with that of the Lazio Region and 95% Confidence Intervals (95%CI)., Results: a total of 1,782 incident cases were recorded in 2009-2015; of these, 91.4% were confirmed by a pathology report. Standardized Incidence Rate for all malignant tumours is 207.2×1,000,000 (95%CI 195.5-219.5) in children and 335.1×1,000,000 (95%CI 308.9-361.2) in adolescents. Compared to the Lazio Region, a higher incidence of tumours is observed in Rome municipality (RR 1.09; 95%CI 0.98-1.20) and in the Frosinone province (RR 1.07; 95%CI 0.91-1.25) for the whole 0-19-year age group., Conclusions: compared to the pooled AIRTUM figures for 2003-2008, Lazio Region showed a higher incidence for all cancers, both in children and adolescents, and for specific tumours, such as leukaemia in children and thyroid carcinoma in adolescents. Apart from the diverse observation period, these differences may be due to a higher registry sensitivity of the childhood specialized registry compared to general population registries. The observed incidence excesses for specific geographical areas and tumours deserve further investigations. Overall, in its first seven years of activity, the Lazio childhood cancer registry was able to provide reliable epidemiological figures of cancer incidence in children and adolescents in the Italian context.

Objectives: to estimate the impact of the COVID-19 epidemic on total and cause-specific mortality in people residing and dead in the Municipality of Rome (Italy) in 2020, and to describe the causes of death of subjects with SARS-CoV-2 infection confirmed by molecular test., Design: descriptive analysis of total and cause-specific mortality in 2020 in Rome and comparison with a reference period (2015-2018 for total mortality and 2018 for cause-specific mortality); descriptive analysis of cause-specific mortality in the cohort of SARS-CoV-2 infected subjects., Setting and Participants: 27,471 deaths registered in the Lazio mortality-cause Registry, relating to people residing and died in the municipality of Rome in 2020, 2,374 of which died from COVID-19.MAIN OUCOME MEASURES: all-cause mortality by month, gender, age group and place of death, cause-specific mortality (ICD-10 codes)., Results: in the municipality of Rome in 2020, an excess of mortality from all causes equal to +10% was observed, with a greater increase in the months of October-December (+27%, +56%, and +26%, respectively) in people aged 50+, with the greatest contribution from the oldest age groups (80+) who died in the nursing homes or at home. Lower mortality was observed in the age groups 0-29 years (-30%) and 40-49 years (-13%). In 2020, COVID-19 represents the fourth cause of death in Rome after malignant tumours, diseases of the circulatory system, and respiratory diseases. Excess mortality was observed from stroke and pneumonia (both in men and women), from respiratory diseases (in men), from diabetes, mental disorders, dementia and Parkinson's disease (in women). On the contrary, mortality is lower for all cancers, for diseases of the blood and haematopoietic organs and for the causes of the circulatory system. The follow-up analysis of SARS-CoV-2 positive subjects residing in Rome shows that a share of deaths (about 20%) reports other causes of death such as cardiovascular diseases, malignant tumours, and diseases of the respiratory system on the certificate collected by the Italian National Statistics Institute., Conclusions: the 2020 mortality study highlighted excesses for acute and chronic pathologies, indicative of possible delays in the diagnosis or treatment of conditions indirectly caused by the pandemic, but also a share of misclassification of the cause of death that is recognized as COVID-19 death.

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

Background: In Europe, one of the most consistent findings is that of migrant mortality advantage in high-income countries. Furthermore, the literature shows that economic shocks, which bring worse health outcomes, can severely affect the most disadvantaged individuals. We analyse differences and changes in all-cause mortality between Italians and migrants residing in Rome before, during, and in the aftermath of the Great Recession (2001-2015) by birth-cohort., Methods: The analysis is a longitudinal open cohort study. Mortality data come from the Register of the Causes of Death (58,637 deaths) and the population denominator (n = 2,454,410) comes from the Municipal Register of Rome. By comparing three time-periods (2001-2005, 2006-2010, and 2011-2015), we analyse all-cause mortality of Rome residents born, respectively, in the intervals 1937-1976, 1942-1981, 1947-1986 (aged 25-64 years at entry into observation). Computing birth-cohort-specific death rates and applying parametric survival models with age as the time-scale, we compare mortality differences between migrants and Italians by gender, area of origin, and time-period., Results: Overall, we find a lower risk of dying for migrants than Italians regardless of gender (Women: HR = 0.61, 95% CI 0.56-0.66; Men: HR = 0.49, 95% CI 0.45-0.53), and a lower death risk over time for the total population. Nevertheless, such a pattern changes according to gender and migrants' area of origin., Conclusion: Given the relevance of international migrations in Europe, studying migrants' health has proved increasingly important. The deterioration in migrant health and the gradual weakening of migrants' mortality advantage is likely to become a public health issue with important consequences for the healthcare system of all European countries., (© 2021. The Author(s).)

Background and Purpose: Multiple sclerosis (MS) is a complex chronic, autoimmune inflammatory disease involving multidisciplinary assessments and interventions. Access to outpatient specialist and home healthcare services was explored during the pandemic outbreak and the lockdown amongst MS patients in the Lazio region. Adherence to disease-modifying therapies (DMTs) is also described., Methods: A population-based study was conducted using regional healthcare administrative databases. A validated algorithm was used to identify MS cases over the period 2011-2018. The numbers of specialist and home-based services were compared between 2019 and 2020. The medication possession ratio was used to measure adherence to DMTs., Results: A total of 9380 MS patients were identified (68% women). A decline in the number of outpatient care services between March and June 2020 compared to the previous year was observed, in particular for rehabilitation (-82%), magnetic resonance imaging (-56%) and neurological specialist services (-91%). Important year-to-year variations were observed in May and June 2020 in home-based nursing and medical care (-91%) and motor re-education services (-74%). Adherence to DMTs was higher in the first 4 months of 2019 compared to the same period of 2020 (67.1% vs. 57.0%)., Conclusions: A notable disruption of rehabilitative therapy and home-based services as well as in DMT adherence was observed. Since the pandemic is still ongoing and interruption of healthcare services could have a major impact on MS patients, it is necessary to monitor access of MS patients to healthcare resources in order to ensure adequate treatments, including rehabilitative therapies., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Medication adherence is a recognized key factor of secondary cardiovascular disease prevention. Cardiac rehabilitation increases medication adherence and adherence to lifestyle changes. This study aimed to evaluate the impact of in-hospital cardiac rehabilitation (IH-CR) on medication adherence as well as other cardiovascular outcomes, following an acute myocardial infarction (AMI)., Methods: This is a population-based study. Data were obtained from the Health Information Systems of the Lazio Region, Italy (5 million inhabitants). Hospitalized patients aged ≥ 18 years with an incident AMI in 2013-2015 were investigated. We divided the whole cohort into 4 groups of patients: ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI) who underwent or not percutaneous coronary intervention (PCI) during the hospitalization. Primary outcome was medication adherence. Adherence to chronic poly-therapy, based on prescription claims for both 6- and 12-month follow-up, was defined as Medication Possession Ratio (MPR) ≥ 75% to at least 3 of the following medications: antiplatelets, β-blockers, ACEI/ARBs, statins. Secondary outcomes were all-cause mortality, hospital readmission for cardiovascular and cerebrovascular event (MACCE), and admission to the emergency department (ED) occurring within a 3-year follow-up period., Results: A total of 13.540 patients were enrolled. The median age was 67 years, 4.552 (34%) patients were female. Among the entire cohort, 1.101 (8%) patients attended IH-CR at 33 regional sites. Relevant differences were observed among the 4 groups previously identified (from 3 to 17%). A strong association between the IH-CR participation and medication adherence was observed among AMI patients who did not undergo PCI, for both 6- and 12-month follow-up. Moreover, NSTEMI-NO-PCI participants had lower risk of all-cause mortality (adjusted IRR 0.76; 95% CI 0.60-0.95), hospital readmission due to MACCE (IRR 0.78; 95% CI 0.65-0.94) and admission to the ED (IRR 0.80; 95% CI 0.70-0.91)., Conclusions: Our findings highlight the benefits of IH-CR and support clinical guidelines that consider CR an integral part in the treatment of coronary artery disease. However, IH-CR participation was extremely low, suggesting the need to identify and correct the barriers to CR participation for this higher-risk group of patients., (© 2021. The Author(s).)

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.

Objectives: This study aimed to measure adherence to chronic polytherapy following an acute myocardial infarction (AMI) and to find out associations between adherence and the setting of AMI onset (in vs out of hospital) as well as other determinants., Design: Retrospective follow-up study., Setting: Population living in the Lazio Region, Italy., Participants: This study included 25 779 hospitalised patients with a first diagnosis of AMI in 2012-2016, after the exclusion of those with hospital admission for AMI or related causes in the previous 5 years., Primary and Secondary Outcome Measures: Patients were classified as in-hospital AMI (IH-AMI) or out of hospital AMI (OH-AMI) according to present-on-admission codes. Adherence was measured based on prescription claims during a 6-month follow-up after hospital discharge, using medication possession ratio (MPR). Adherence to chronic polytherapy was defined as MPR ≥75% to at least 3 of the following medications: antithrombotics, betablockers, ACE inhibitors/angiotensin receptor blockers and statins., Results: Among the entire cohort, 1 044 (4%) patients suffered IH-AMI. Overall, 15 440 (60%) patients were deemed adherent to chronic polytherapy. Female gender, older age, mental disorders, renal disease, asthma and ongoing concomitant treatments were factors associated with poor adherence. By contrast, patients with more severe AMI and those already taking evidence-based (E-B) drugs were more likely to be adherent. A strong association between the setting of AMI onset and adherence was observed: IH-AMI patients were 46% less likely to be adherent to E-B medications during their 6-month follow-up as compared with OH-AMI patients (OR 0.54; 95% CI 0.47 to 0.62; p<0.001)., Conclusion: Pharmacotherapy is not consistent with clinical guidelines, especially for IH-AMI patients. Our findings provide evidence on a previously unidentified groups of patients at risk for poor adherence, who might benefit from greater medical attention and dedicated healthcare interventions., 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.)

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

Background: Global migration toward Europe is increasing. Providing health assistance to migrants is challenging because numerous barriers limit their accessibility to health services. Migrants may be at a greater risk of developing asthma and receiving lower quality healthcare assistance than non-migrants. We aim to investigate whether immigrants as children and adolescents have higher rates of potentially avoidable hospitalization (PAH) for asthma compared to Italians., Methods: We performed a retrospective longitudinal study using six cohorts of 2-17-year-old residents in North and Central Italy from 01/01/2001 to 31/12/2014 (N = 1,256,826). We linked asthma hospital discharges to individuals using anonymized keys. We estimated cohort-specific age and calendar-year-adjusted asthma PAH rate ratios (HRRs) and 95% confidence intervals (95%CIs) among immigrants compared to Italians. We applied a two-stage random effect model to estimate asthma PAH meta-analytic rate ratios (MHRRs). We analyzed data by gender and geographical area of origin countries., Results: Three thousand three hundred four and 471 discharges for asthma PAH occurred among Italians and immigrants, respectively. Compared to Italians, the asthma PAH cohort-specific rate was higher for immigrant males in Bologna (HRR:2.42; 95%CI:1.53-3.81) and Roma (1.22; 1.02-1.45), and for females in Torino (1.56; 1.10-2.20) and Roma (1.82; 1.50-2.20). Asthma PAH MHRRs were higher only among immigrant females (MHRRs:1.48; 95%CI:1.18-1.87). MHRRs by area of origin were 63 to 113% higher among immigrants, except for Central-Eastern Europeans (0.80; 0.65-0.98)., Conclusion: The asthma PAH meta-analytic rate was higher among female children and adolescent immigrants compared to Italians, with heterogeneity among cohorts showing higher cohort-specific PAH also among males, with some differences by origin country. Access to primary care for children and adolescent immigrants should be improved and immigrants should be considered at risk of severe asthma outcomes and consequently targeted by clinicians.

Background: The Emergency Department (ED) can be considered an indicator of accessibility and quality and can be influenced in period of economic downturns. In the last fifteen years, the number of migrants in Italy has doubled (from 2.4 million in 2005 to 5.2 in 2019, 4.1 and 8.7% of the total population, respectively). However, evidence about migrants' healthcare use is poor, and no studies focused on the ED utilisation rate during the Great Recession are available. This study aims to analyse trends in all-cause and cause-specific ED utilisation among migrants and Italians residing in Rome, Italy, before and after 2008., Methods: Longitudinal study based on data from the Municipal Register of Rome linked to the Emergency Department Register from 2005 to 2015. We analysed 2,184,467 individuals, aged 25-64 in each year. We applied a Hurdle model to estimate the propensity to use the ED and to model how often individuals accessed the ED., Results: Migrants were less likely to be ED users than Italians, except for Africans (RR = 1.46, 95%CI 1.40-1.52) and Latin Americans (RR = 1.04, 95%CI 1.00-1.08) who had higher all-cause utilisation rates than non-migrants. Compared to the pre-2008 period, in the post-2008 we found an increase in the likelihood of being an ED user (OR = 1.34, 95%CI 1.34-1.35), and a decrease in ED utilisation rates (RR = 0.96, 95%CI 0.96-0.97) for the whole population, with differences among migrant subgroups, regardless of cause., Conclusions: This study shows differences in the ED utilisation between migrants and Italians, and within the migrant population, during the Great Recession. The findings may reflect differentials in the health status, and barriers to access primary and secondary care among migrants. In this regard, health policies and cuts in health spending measures may have played a key role, and interventions to tackle health and access disparities should include policy measures addressing the underlying factors, adopting a Health in All Policies perspective. Further researches focusing on specific groups of migrants, and on the causes and diagnoses related to the ED utilisation, may help to explain the differences observed.

Background: A set of indicators to assess the quality of care for women operated for breast cancer was developed by an expert working group of the Italian Health Ministry in order to compare the Italian regions. A study to validate these indicators through their relationship with survival was carried out., Methods: The 16,753 women who were residents in three Italian regions (Lombardy, Emilia-Romagna and Lazio) and hospitalized for breast cancer surgery during 2011 entered the cohort and were followed until 2016. Adherence to selected recommendations (i.e., surgery timeliness, medical therapy timeliness, appropriateness of complementary radiotherapy and mammographic follow-up) was assessed. Multivariable proportional hazards models were fitted to estimate hazard ratios for the association between adherence with recommendations and the risk of all-cause mortality., Results: Adherence to recommendations was 53% for medical therapy timeliness, 73% for appropriateness of mammographic follow-up, 74% for surgery timeliness and 82% for appropriateness of complementary radiotherapy. Risk reductions of 26%, 62% and 56% were observed for adherence to recommendations on medical therapy timeliness, appropriateness of complementary radiotherapy and mammographic follow-up, respectively. There was no evidence that mortality was affected by surgery timeliness., Conclusions: Clinical benefits are expected from improvements in adherence to the considered recommendations. Close control of women operated for breast cancer through medical care timeliness and appropriateness of radiotherapy and mammographic monitoring must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes., Competing Interests: Declaration of competing interest Giovanni Corrao received research support from the European Community (EC), the Italian Drugs Agency (AIFA), and the Italian Ministry of Education, University and Research (MIUR). He took part in a number of projects funded by pharmaceutical companies (i.e., Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria from Roche as a member of the Advisory Board. For the remaining authors, nothing was declared., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: A summary indicator for evaluating the breast cancer network has never been measured at the regional level. The aim is to design treemaps providing a summary description of hospitals (including breast units) and Local Health Units (LHUs) in terms of their levels of performance within the breast cancer network of the Lazio region (central Italy). The treemap structure has an intuitive design and displays information from both general and specific analyses., Methods: Patients admitted to the regional hospitals for malignant breast cancer (MBC) surgery in 2010-2017 were selected in a population-based cohort study. These quality indicators were calculated based on the international guidelines (EUSOMA, ESMO) to assess the performance in terms of volume of activity, surgery procedure, post-surgery assistance and timeliness of medical therapy or radiotherapy beginning. The quality indicators were calculated using administrative health data systematically collected at the regional level and were included in the treemap to represent the surgery or the post-surgery areas of the breast cancer clinical pathway. In order to allow aggregation of scores for different indicators belonging to the same clinical area, up to five evaluation classes were defined using the "Jenks Natural Breaks" algorithm. A score and a colour were assigned to each clinical area based on the ranking of the indicators involved. The analyses were performed on an annual basis, by the LHU of residence and by the hospital which performed the surgical intervention., Results: In 2017, 6218 surgical interventions for MBC were performed in the hospitals of Lazio. The results showed a continuous increase of the level of performance over the years. Hospitals showed higher variability in the levels of performance than the LHUs. 36% of the evaluated hospitals reached a high level of performance. An audit of the S. Filippo Neri breast unit revealed incorrect coding of the input data. For this reason, the score for the indicator for the volume of wards was re-calculated and re-evaluated, with a subsequent improvement of the level of performance. Most LHUs achieved at least an average overall level of performance, with 20% of the LHUs reaching a high level of performance., Conclusions: This is the first attempt to apply the treemap logic to a single clinical network, in order to obtain a summary indicator for the evaluation of the breast cancer care network. Our results supply decision makers with a transparent instrument of governance for heterogeneous users, directing efforts improving and promoting equity of care. The treemaps could be reproduced and adapted for other local contexts, in order to limit inappropriateness and ensure uniform levels of breast cancer care within local areas. The next step is the evaluation of audit and feedback interventions to improve the quality of care and to guarantee homogeneous levels of care throughout the region., Competing Interests: The authors have declared that no competing interests exist.

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

Background: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts or case-control studies)., Objectives: in response to the fragmented and uncoordinated research production on Covid-19, the   italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology., Methods: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges., Results: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis, interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography., Conclusions: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.

Background: one of the most affected European countries by the COVID-19 epidemic is Italy; data show the strong geographical heterogeneity of the epidemic., Objectives: to propose an analysis strategy to ascertain the non-random nature of the spatial spread of COVID-19 cases infection and identify any territorial aggregations, in order to enhance contact tracing activities in specific areas of the Lazio Region (Central Italy) and a large urban area as Rome., Methods: all cases of COVID-19 of the Lazio Region notified to the Regional Service for Epidemiology, Surveillance, and Control of Infectious Diseases (Seresmi) with daily updates from the beginning of the epidemic to April 27, 2020 were considered. The analyses were carried out considering two periods (the first from the beginning of the epidemic to April 6 and the second from the beginning of the epidemic to April 27) and two different levels of spatial aggregation: the entire Lazio region excluding the Municipality of Rome, where the 377 municipalities represent the area units, and the Municipality of Rome, where the area units under study are the 155 urban areas (ZUR). The Scan statistic of Kulldorff was used to ascertain the non-random nature of the spatial spread of infected cases and to identify any territorial aggregations of cases of COVID-19 infection, using a retrospective spatial analysis in two overlapping periods., Results: analysis was conducted at regional level in the two survey periods and revealed the presence of 7 localized clusters. In the Municipality of Rome, a single cluster (Historic Centre) was identified in the first period which includes 7 urban areas, while in the second period two distinct clusters (Omo and Farnesina) were observed., Conclusions: Scan statistics are an important surveillance tool for monitoring disease outbreaks during the active phase of the epidemic and a useful contribution to epidemiological surveillance during the COVID-19 epidemic in a specific territory.

Objectives: to describe hospitalisation, access to emergency care, and mortality of people living in marginalized urban areas which include public housing buildings in the North-West suburb of Rome, and to compare the results with those observed among people living in the neighbouring area., Design: cross sectional study., Setting and Participants: resident population in the XIII and XIV Municipality of Rome, subdivided into five urban areas, in 2011-2018., Main Outcome Measures: hospitalisation, access to emergency care, and mortality rates and rates ratios based on hospital discharges and emergency department visits derived from the Health Information Systems and from the Mortality Registry of Lazio Region (Central Italy), stratified by urban areas., Results: the results show a higher use of hospital assistance and emergency care services as well a higher mortality among residents of urban areas characterized by marginalization and social disadvantage in the North-West suburb in Rome, compared to the surrounding area. The association is stronger for the residents of ex-Bastogi, a compound particularly marginalised and socially disadvantaged, where excesses in hospitalisation, emergency care admission, and mortality of +60%, +150%, and +140%, respectively, occurred., Conclusions: the excesses of hospital use, emergency care visits, and mortality observed among the residents of marginalized urban areas suggest the need to reorganize the preventive and primary care services considering the socioeconomic disadvantage in such housing contexts. The use of both qualitative and quantitative approaches allows to understand the complexity of such contexts.

Objectives: to evaluate the impact of the SARS-CoV-2 epidemic on the access to the emergency services of the Lazio Region (Central Italy) for time-dependent pathologies, for suspected SARS-CoV-2 symptoms, and for potentially inappropriate conditions., Design: observational study., Setting and Participants: accesses to the emergency departments (EDs) of Lazio Region hospitals in the first three months of 2017, 2018, 2019, and 2020., Main Outcome Measures: total number of accesses to the emergency room and number of specific accesses for cardio and cerebrovascular diseases, for severe trauma, for symptoms, signs, and ill-defined conditions, and for symptoms related to pneumonia., Results: in the first 3 months of 2019, there were 429,972 accesses to the EDs of Lazio Region; in the same period of 2020, accesses arise to 353,806, (reduction of 21.5%), with a 73% reduction in the last three weeks of march 2020 as compared with the corresponding period of 2019. Comparing the first 3 months of the 2017-2019 with 2020, the accesses for acute coronary syndrome and acute cerebrovascular disease decreased since the 10th week up to more than 57% and 50%, respectively. The accesses due to symptoms, signs, and ill-defined conditions, proxy of potentially inappropriate conditions, decreased since the 8th week, with a maximum reduction of 70%. Access to severe trauma decreased by up to 70% in the 11th week. The accesses for pneumonia increased up to a 70% increment in the 12th week., Conclusions: the evaluation of accesses to emergency services during the SARS-CoV-2 epidemic can provide useful elements for the promotion and improvement of the planning, for the management of critical situations, and for the reprogramming of the healthcare offer based on clinical and organizational appropriateness.

Objectives: to evaluate the gap in life expectancy on the municipality of Rome, through the spatio-temporal changes in life expectancy at the birth and at 65 years old of residents in between 2006 and 2017, by gender, socioeconomic position, and health district., Design: epidemiological study based on the construction of mortality tables describing age-specific mortality rates and life expectancy at birth and at 65 years old., Setting and Participants: from the Register of the Causes of Death (ReNCaM), between 2006 to 2017, 329,426 deaths of residents in Rome were selected., Main Outcome Measures: the variation in life expectancy at birth was estimated by gender, by socioeconomic position, and by health district for four triennial observation periods from 2006 to 2017. Temporal and socioeconomic position changes, through an indicator of deprivation of a small area specific for the city of Rome, and possible geographical patterns, by observing the variation in the 15 health districts, between 2006 and 2017 were observed., Results: in Rome, between the first three-year period (2006-2008) and the last one (2015-2017), the life expectancy at birth increases, whit a gain of about 1.5 years among males (from 78.7 to 80.4 years) and just under 1 year among females (from 83.6 to 84.4 years). The increase in life expectancy, however, is not uniform in the population and the results show differences in socioeconomic position that increase in the most recent three years to 4 years for males and 2.2 years for females. The geographical analysis shows important differences in the life expectancy among health districts with differences up to about 3 years for males and 2.2 years for females at the beginning of the study period among districts in the historical centre and districts on the outskirts of the City of Rome, which are reduced to 2.7 years for males and 2.1 years for females in the most recent period., Conclusions: the analysis of geographical and socioeconomic differences of the life expectancy provides important information to identify the areas of the Municipality of Rome on which to strengthen prevention interventions and the actions to be taken for Objective 10 ("Reducing inequalities") of Agenda 2030 for sustainable development.

We are presenting here the findings of the reaction to the COVID-19 epidemic during the period March to June 2020 of those centres participating in the research EASY-NET which is on-going in Italy, funded by the Ministry of Health and co-founded by the Regional Health Authorities. The objective of EASY-NET is to evaluate the effectiveness of the audit and feedback (A&F) strategies in different clinical and organizational settings in seven regions. As a negative consequence of the COVID-19 epidemic, the activities of the project have suddenly slowed down; nevertheless, the COVID-19 epidemic represented an opportunity to apply the A&F methodology and support the healthcare within the regional authorities in order to manage and monitor the impact of this new disease. The reaction to the crisis on behalf of EASY-NET was inconsistent across the participating regions for various reasons. Factors which influenced the reaction levels in relation to the rapidity and efficiency of the implementation of the A&F strategies were as follows: the varying epidemiological impact of the COVID-19 epidemic in the various territories, the different clinical and organizational context and availability of expert research teams together with A&F procedures which had already been tested before the start of the epidemic.

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

Purpose: To analyse the drug use pattern in women with psoriasis before, during and after pregnancy., Methods: All children born (2009-2016) in a central Italian region (Lazio) to mothers with a diagnosis of psoriasis were identified. Drug use patterns (biologicals, systemic, and topical), and discontinuation and switching of drug therapies before, during, and after pregnancy were studied. Findings were compared with data from a population exposed to similar drug therapies (eg, antirheumatic drugs)., Results: Among 3499 deliveries by women affected by psoriasis, 1876 (53.6%) were diagnosed with this condition before the Last Menstrual Period (LMP). Of these, 525 (27.9%) had at least one drug prescription for psoriasis therapy during 6 months before LMP. For each class of drugs considered, there was a general decrease in its use during pregnancy. Considering the two trimesters preceding LMP and the three trimesters of pregnancy, the following percentages of prescriptions were observed: from 10.5% to 0% for biologicals, 7.2% to 2.5% for the conventional systemic drugs, and 51.1% to 9.4% for the topical treatments. After delivery, previous treatments were resumed. Similar results were observed for rheumatoid arthritis, a chronic condition., Conclusions: Majority of drugs come with warnings regarding potential embryo-fetotoxicity, which might play a role in the decision to continue treatments during pregnancy. According to our study pregnancy appears to have a significant influence on drug prescriptions of different pharmacological treatments for psoriasis., (© 2020 John Wiley & Sons Ltd.)

Objectives: 1. to describe temporal trend (2008-2017) in kidney transplant (KT) provision in the Lazio Region; 2. to measure KT outcomes by comparing three different time periods; 3. to estimate the prevalence of individuals with functioning kidney transplant., Design: cross sectional (objective 1); cohort study (objectives 2 and 3)., Setting and Participants: the study population included people residing in Lazio Region who received a kidney transplant between 2008 and 2017. Participants were selected through the integration of data from different sources: the Hospital Information System, the Regional Register of Dialysis and Transplantation, and the Regional Waiting List for Kidney Transplantation., Main Outcome Measures: standardised KT incidence rates x100,000 by year and age-specific rates were calculated separately for men and women. Mortality and failure of KT were considered as outcomes at one year; for both outcomes, the cumulative incidence x100 and raw and adjusted (by gender and age) incidence rates x100,000 person-day were calculated using a Poisson model. Raw and standardised prevalence rates x100,000 of people residing in Lazio Region with functioning KT at 31.12.2016 were calculated., Results: in the study period, 1,646 KTs were performed. The KT rate increased significantly overtime, ranging between 2.9 in 2008 and 3.6 in 2017. Rates were higher for men compared to women. For men aged 65+ incidence KT rate increased significantly: 3.5 in 2008 and 7.1 in 2017. Among women, there was an increasing trend in the age groups 0-18 and 35-49 years. The one-year mortality rate decreased from 11.9 in 2008-2010 to 4.2 in 2014-2016. The failure rate was stable: 21.4 in 2008-2010 and 19.2 in 2014-2016. The number of individuals with functioning kidney transplant was 1,148. The standardised prevalence rate was 25.8 in men and 14.6 in women., Conclusions: increased offer of renal transplantation and better outcomes were observed in Lazio region. The proposed methodology is useful for the construction of indicators to monitor over time both KT provision and outcomes.

Background: Short-term exposure to air pollution increases the risk of cardiovascular mortality and morbidity but little evidence is available on pollution effects on venous thromboembolism (VTE), a common vascular disease., Methods: We conducted a case-crossover analysis of all urgent hospitalizations for deep vein thrombosis (DVT) or pulmonary embolism (PE) among patients >35 years during the period 2006 to 2017 in Rome (Italy). We examined whether 1) short-term exposure to particulate matter with aerodynamic diameter <2.5 μg (PM 2.5 ) increases the risk of hospitalization for DVT or PE, and 2) if the associations are modified by the period of the year (warm and cold seasons), sex, age and comorbidity., Results: We found that short-term exposure to PM 2.5 was associated with an increase of PE hospitalization risk of during the warm season (April to September) of 19.6% (95% confidence intervals: 8.3, 31%) per 10 μg/m 3 , while no statistically significant effects were displayed during the cold season or the whole year or for DVT hospitalizations. The effect of PM 2.5 remained significant (%change: 21.3; 95%CI: 5.4, 39.5) after adjustment for nitrogen dioxide (NO 2 ) co-exposure (a marker of traffic sources) and when limiting to primary diagnosis of PE (%change: 19.1; 95%CI: 4.2, 36.1). Age, sex and comorbid conditions did not modify the association., Conclusions: Our results suggested a positive association between short-term exposure to PM 2.5 and pulmonary embolism during the warm period of the year while no evidence emerged for deep vein thrombosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In Italy, few multicentre population-based studies on pregnancy outcomes are available. Therefore, we established a network of population-based birth cohorts in the cities of Turin, Reggio Emilia, Modena, Bologna, and Rome (northern and central Italy), to study the role of socioeconomic factors and air pollution exposure on term low birthweight, preterm births and the prevalence of small for gestational age. In this article, we will report the full methodology of the study and the first descriptive results. We linked 2007-2013 delivery certificates with municipal registry data and hospital records, and selected singleton livebirths from women who lived in the cities for the entire pregnancy, resulting in 211,853 births (63% from Rome, 21% from Turin and the remaining 16% from the three cities in Emilia-Romagna Region). We have observed that the association between socioeconomic characteristics and air pollution exposure varies by city and pollutant, suggesting a possible effect modification of both the city and the socioeconomic position on the impact of air pollution on pregnancy outcomes. This is the largest Italian population-based birth cohort, not distorted by selection mechanisms, which has also the advantage of being sustainable over time and easily transferable to other areas. Results from the ongoing multivariable analyses will provide more insight on the relative impact of different strands of risk factors and on their interaction, as well as on the modifying effect of the contextual characteristics. Useful recommendations for strategies to prevent adverse pregnancy outcomes may eventually derive from this study.

Data from the rapid mortality surveillance system in 19 major Italian cities were used to carry out a timely assessment of the health impact of the COVID-19 epidemic. By 18 April, a + 45% excess in mortality was observed, with a higher impact in the north of the country (+ 76%). The excess was greatest among men, with an increasing trend by age. Surveillance data can be used to evaluate the lockdown and re-opening phases.

Background and Objectives: Switching between different erythropoiesis-stimulating agents (ESAs) during the first year of therapy is frequent (15-20%), much more so toward reference products than biosimilars. The objectives of this study were to investigate the frequency and identify the potential predictors of switching between biosimilar and originator ESAs during the first year of treatment in patients with chronic kidney disease (CKD), or chemotherapy-related anemia from six large Italian geographic areas in the years 2009-2015., Methods: A retrospective cohort study was conducted using six Italian regional claims databases (≥ 13 million inhabitants) during 2009-2015. Among incident epoetin users, the frequency of single, multiple, and backward switch during the first year of treatment was evaluated. Using frailty Cox models, potential predictors of first switch were identified. All analyses were stratified by the main indications for use., Results: Among 102,240 incident epoetin users, 15,853 (15.5%) switched to another epoetin during the first year of therapy; only 18% of these switched to biosimilars. Single switch was more common (62.2% of the switchers) than multiple (23.5%) or backward switch (14.3%). In cancer, the cumulative number of transfusions and iron preparations dispensed, as well as hyperparathyroidism, were predictors of switching. In CKD, the cumulative number of transfusions, number of vitamin A/D preparations dispensed, and CKD severity increased the probability of switching., Conclusions: Switching between ESAs was frequent in both CKD and cancer patients. The number of cumulative transfusions and severity of disease seemed to affect the switch.