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Introduction 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 of local needs. Objectives To estimate the prevalence of schizophrenia spectrum disorders (SSDs) in the Lazio region and its geographical distribution using the regional health information systems (HIS). Methods Cases of SSDs (15-64-year-old) were identified using an algorithm based on data from the hospital discharge registry [ICD IX CM: 295, 297, 298 (excl. 298.0)] and the ticket exemption database [code 044], between 2006 and 2019. Crude, and age- and gender-specific prevalence estimates on December 31, 2019, were calculated. To compare prevalence between different areas within the region, we calculated age- and gender-adjusted prevalence rates Results A total of 18,371 cases were identified. Crude prevalence rate was 4.29/1,000 (95% CI 4.29-4.30) and 5.93/1,000 (95% CI 5.92-5.949 for women and men, respectively. An increase in the prevalence rate by age was observed in both genders. The age- and gender-adjusted prevalence rate was 5.03/1,000 (95 % CI 4.96-5.10), with significant differences within the region, ranging from 4.25/1,000 in the province of Viterbo to 5.42/1,000 in the city of Rome and 6.02/1000 in the province of Frosinone. Conclusions Our results showed that the overall prevalence of SSDs among adults in the Lazio region is similar to estimates published in prior reviews, but an uneven regional geographical distribution was observed. While possible underestimation must be considered, HIS represents a valuable source of information useful for epidemiological surveillance and healthcare planning. Disclosure No significant relationships.

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

Introduction: The association between air pollution and cardiovascular diseases is well established. However, fewer studies focused on the relationship between air pollution and peripheral artery disease (PAD), notwithstanding that not only it is a predictor of CVD mortality but also that incidence is globally rising, particularly in low-middle income countries., Objectives: The aim of this study is to estimate the association between long-term exposure to air pollutants and the incidence of PAD in the Rome Longitudinal Study (RLS) during 2011-2019., Methods: Using the Health Information Systems, we identified the first episodes of hospitalizations with discharge diagnosis for PAD (ICD-9 codes: 440.20-24; 444.0; 444.21; 444.22; 444.81; 447.1), lower limb vascular surgery (ICD-9 codes: 38.18; 39.29; 39.50; 39.90; 84.11; 84.12; 84.15; 84.17) or drug prescription (ATC code: B01AC23) in the period 2011-2019. In order to focus on incidence, we excluded from the population at risk prevalent cases based on hospital discharges in the 10 years before enrolment (October 9th, 2011). We assigned to the participants one-year average exposure to PM 2.5 , NO 2 and black carbon (BC) from the ELAPSE Europe-wide hybrid land-use regression (LUR) models at 100 m 2 spatial resolution on the basis of their baseline geocoded addresses. We also applied Cox regression models adjusted for individual and area-level covariates. The estimates were expressed as hazard ratios (HR) and 95 % confidence intervals (95 % CI) per pollutant-specific interquartile range (IQR) increase. We also analyzed any effect modification by socio-demographic and comorbidity variables and explored concentration-response curves using natural splines with 3 degrees of freedom., Results: Starting from a population at risk of 1,719,475 subjects aged 30 years or above, a total of 14,629 incident cases were identified. An IQR (1.13 μg/m 3 ) increase in PM 2.5 was positively associated with a HR of 1.011 (95 % CI: 0.988, 1.034). Positive associations were also obtained for NO 2 ([IQR 7.86 μg/m 3 ] HR: 1.022 (95 % CI: 0.998, 1.048)) and black carbon ([IQR 0.39 x10 -5 /m] HR: 1.020 (95 % CI: 0.994, 1.047)). Effect modification analysis showed stronger associations when considering males and individuals in the 55-69 age class. Concentration-response curve for NO 2 showed a linear shape, with increases of risk already at low concentrations., Conclusions: Long-term exposure to PM 2.5 , NO 2 and BC is associated with an increased incidence of PAD, and male subjects and individuals aged between 55-69 years were at greater risk., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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.)

Although the multidisciplinary area of liver tissue engineering is in continuous progress, research in this field is still focused on developing an ideal liver tissue template. Innovative strategies are required to improve membrane stability and bioactivity. In our study, sustainable biomimetic membranes were developed by blending methacrylated chitosan (CSMA) with jellyfish collagen (jCol) for liver tissue engineering applications. The in vitro biological behaviour demonstrated the capability of the developed membranes to create a suitable milieu to enable hepatocyte growth and differentiation. The functionalization of chitosan together with the biocompatibility of marine collagen and the intrinsic membrane properties offered the ideal biochemical, topographical, and mechanical cues to the cells. Thanks to the enhanced CSMA/jCol membranes' characteristics, hepatocytes on such biomaterials exhibited improved growth, viability, and active liver-specific functions when compared to the cell fate achieved on CSMA membranes. Our study provides new insights about the influence of membrane properties on liver cells behaviour for the design of novel instructive biomaterials. The enrichment of functionalized chitosan with marine collagen represents a promising and innovative approach for the development of an appropriate platform for hepatic tissue engineering., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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).)

Restoring wild communities of large herbivores is critical for the conservation of biodiverse ecosystems, but environmental changes in the twenty-first century could drastically affect the availability of habitats. We projected future habitat dynamics for 18 wild large herbivores in Europe and the relative future potential patterns of species richness and assemblage mean body weight considering four alternative scenarios of socioeconomic development in human society and greenhouse gas emissions (SSP1-RCP2.6, SSP2-RCP4.5, SSP3-RCP7.0, SSP5-RCP8.5). Under SSP1-RCP2.6, corresponding to a transition towards sustainable development, we found stable habitat suitability for most species and overall stable assemblage mean body weight compared to the present, with an average increase in species richness (in 2100: 3.03 ± 1.55 compared to today's 2.25 ± 1.31 species/area). The other scenarios are generally unfavourable for the conservation of wild large herbivores, although under the SSP5-RCP8.5 scenario there would be increase in species richness and assemblage mean body weight in some southern regions (e.g. + 62.86 kg mean body weight in Balkans/Greece). Our results suggest that a shift towards a sustainable socioeconomic development would overall provide the best prospect of our maintaining or even increasing the diversity of wild herbivore assemblages in Europe, thereby promoting trophic complexity and the potential to restore functioning and self-regulating ecosystems. This article is part of the theme issue 'Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere'.

The EASY-NET network program (NET-2016-02364191)-effectiveness of audit and feedback (A&F) strategies to improve health practice and equity in various clinical and organizational settings), piloted a novel and more structured A&F strategy. This study compared the effectiveness of the novel strategy against the sole periodic dissemination of indicators in enhancing the appropriateness and timeliness of emergency health interventions for patients diagnosed with acute myocardial infarction (AMI) and ischemic stroke in the Lazio Region. The efficacy of the intervention was assessed through a prospective quasi-experimental design employing a pre- and post-intervention (2021-2022) comparison with a control group. Participating hospitals in the Lazio Region, where professional teams voluntarily engaged in the intervention, constituted the exposed group, while the control group exclusively engaged in routine reporting activities. Effectiveness analysis was conducted at the patient level, utilizing regional health information systems to compute process and outcome indicators. The effectiveness of the intervention was evaluated using difference-in-difference models, comparing pre- and post-intervention periods between exposed and control groups. Estimates were calculated in terms of the difference in percentage points (PP) between absolute risks. Sixteen facilities for the AMI pathway and thirteen for the stroke pathway participated in the intervention. The intervention yielded a reduction in the proportion of 30-day readmissions following hospitalization for ischemic stroke by 0.54 pp in the exposed patients demonstrating a significant difference of -3.80 pp (95% CI: -6.57; -1.03; 5453 patients, 63.7% cases) in the exposed group compared to controls. However, no statistically significant differences attributable to the implemented A&F intervention were observed in other indicators considered. These results represent the first evidence in Italy of the impact of A&F interventions in an emergency setting, utilizing aggregated data from hospitals involved in the Lazio Region's emergency network.

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).)

Aims: Septal myectomy is the treatment of choice for hypertrophic obstructive cardiomyopathy (HOCM). Around 30-60% of patients with HOCM have a secondary mitral valve regurgitation due to systolic anterior motion (SAM). We report our experience with extended septal myectomy and its impact on the incidence of concomitant mitral valve procedures., Methods: This is a retrospective study on 84 patients who underwent SM from January 2008 to February 2022. Surgical procedure was performed according to the concept of 'extended myectomy' described by Messmer in 1994. Follow-up outcomes in terms of survival, hospital admissions for heart failure or MV disease, cardiac reoperations, and pacemaker (PMK) implantation were recorded., Results: Mean age was 61 ± 15 years. Mitral valve surgery was performed in seven cases (8%); particularly only one patient without degenerative mitral valve disease underwent mitral valve surgery, with a plicature of the posterior leaflet. In-hospital mortality was 5%. Mitral valve regurgitation greater than mild was present in four patients (5%) at discharge. Twelve-year survival was 78 ± 22%. Cumulative incidence of rehospitalization for heart failure and rehospitalization for mitral valve disease was 10 ± 4 and 2.5 ± 2.5%, respectively. PMK implantation was 5% at discharge, with a cumulative incidence of 15 ± 7%. Freedom from cardiac reoperations was 100%., Conclusion: Septal myectomy for HOCM is associated with good outcomes. Although concomitant surgery on the mitral valve to address SAM and associated regurgitation has been advocated, these procedures were needed in our practice only in patients with intrinsic mitral valve disease. Adequate myectomy addresses the underlying pathophysiology in most patients., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Purpose: This study evaluates the use, benefit-risk profile, and economic impact of generic immunosuppressants (tacrolimus-TAC, cyclosporine-CsA, and mycophenolate-MYC) in kidney and liver transplant recipients compared to brand-name drugs., Patients and Methods: A retrospective multicentre observational study, involving four Italian regions, was conducted based on the national transplant Information system and regional healthcare claims data. The analysis focused on incident patients who received kidney and liver transplants between 2013 and 2019 and evaluated the use of generic of CsA, TAC, and MYC during the 30-day period following discharge. For each type of transplant and immunosuppressive agent, the benefit-risk profile of generic vs branded drugs in a two-year window was estimated by multivariate Cox models (HR; 95% CI). Furthermore, the potential cost savings per person associated with one year of treatment using generics were calculated., Results: The utilization of generic drugs showed a significant increase; over the study years, the proportion of users among kidney recipients ranged from 14.2% to 40.5% for TAC, from 36.9% to 56.7% for MYC, and from 18.2% to 94.7% for CsA. A great variability in generic uptake for region was found. A comparable risk-benefit profile between generic and branded formulations was shown for all immunosuppressors considered. Choosing generic immunosuppressants during maintenance could result in yearly savings of around 2000 euros per person for each therapy ingredient., Conclusion: The study shows an increasing proportion of patients using generic immunosuppressive drugs over time suggesting a growing acceptance of generics within the transplant community and reveals comparable risk-benefit profiles between the generic and branded formulations of TAC, CsA, and MYC. A significant variability in the use of generics immunosuppressive agents was found both at the regional level and among transplant centers and future research should delve into regional prescribing variations., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Finocchietti et al.)

Maintenance immunosuppressive therapy used in kidney transplantation typically involves calcineurin inhibitors, such as tacrolimus or cyclosporine, in combination with mycophenolate or mechanistic target of rapamycin (mTORi) with or without corticosteroids. An Italian retrospective multicentre observational study was conducted to investigate the risk-benefit profile of different immunosuppressive regimens. We identified all subjects who underwent kidney transplant between 2009 and 2019, using healthcare claims data. Patients on cyclosporine and tacrolimus-based therapies were matched 1:1 based on propensity score, and effectiveness and safety outcomes were compared using Cox models (HR; 95%CI). Analyses were also conducted comparing mTORi versus mycophenolate among tacrolimus-treated patients. Patients treated with cyclosporine had a higher risk of rejection or graft loss (HR:1.69; 95%CI:1.16-2.46) and a higher incidence of severe infections (1.25;1.00-1.55), but a lower risk of diabetes (0.66;0.47-0.91) compared to those treated with tacrolimus. Among tacrolimus users, mTORi showed non-inferiority to MMF in terms of mortality (1.01;0.68-1.62), reject/graft loss (0.61;0.36-1.04) and severe infections (0.76;0.56-1.03). In a real-life setting, tacrolimus-based immunosuppressive therapy appeared to be superior to cyclosporine in reducing rejection and severe infections, albeit with an associated increased risk of diabetes. The combination of tacrolimus and mTORi may represent a valid alternative to the combination with mycophenolate, although further studies are needed to confirm this finding., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bellini 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: Procedural volume has been documented as an important contributor to operative outcomes for most complex surgical procedures. Mitral valve repair (MVRep) has been associated with excellent results, and it is increasingly adopted in many cardiac surgical centers. We sought to investigate if procedural volume is associated with better clinical long-term outcomes after MVRep., Methods: We analyzed the 10-year outcomes after MVRep by procedural volume for each cardiac surgery center in an Italian Region, Lazio, during the last 15 years, using a regional administrative dataset., Results: Between 2006 and 2020, 4961 patients were treated in seven cardiac surgery centers for an isolated mitral valve surgery (2677 underwent MVRep). At multivariate analysis, mitral valve replacement (MVR) (vs. MVRep) resulted one of the independent predictors of 30-day mortality [adjusted odds ratio (OR) 3.40; 95% confidence interval (CI) 1.96-5.90; P  < 0.0001]. Notably, a clear association between hospital volume of mitral valve surgery (>40 per year) and high rate of MVRep (>50%) was found. At 10 years, the incidence of mortality and the rate of death and rehospitalization for heart failure after MVRep were significantly lower in high-volume vs. low-volume hospitals., Conclusion: Our data suggest that hospital volume is associated with a high rate of MVRep and long-term benefits in terms of mortality and recurrence of heart failure., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

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: Very scanty evidence is available on factors influencing the choice of immunosuppressive drug therapy after kidney transplantation., Methods: An Italian multiregional real-world study was conducted integrating national transplant information system and claims data. All patients undergoing kidney transplantation for the first time during 2009-2019 (incident patients) were considered. Multilevel logistic models were used to estimate Odds Ratio (OR) and corresponding 95% Confidence intervals. Factors with statistically significance were identified as characteristics associated with treatment regimens: cyclosporin-CsA vs tacrolimus-Tac and, within the latter group, mTOR inhibitors vs mycophenolate-MMF., Results: We identified 3,622 kidney patients undergoing transplantation in 17 hospitals located in 4 Italian regions, 78.3% was treated with TAC-based therapy, of which 78% and 22% in combination with MMF and mTOR, respectively. For both comparison groups, the choice of immunosuppressive regimens was mostly guided by standard hospital practices. Only few recipient and donor characteristics were found associated with specific regimen (donor/receipt age, immunological risk and diabetes)., Conclusions: The choice of post-renal transplant immunosuppressive therapy seems to be mostly driven by standard Centre practices, while only partially based on patient's characteristics and recognized international guidelines., (© 2023. The Author(s).)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of the dynamic events within blood vessels, histology does not report platelet and neutrophil behavior. Because of the rapid nontranscriptional response of these cells, neither single-cell RNA sequencing nor proteomics report robustly on their critical behaviors. We used intravital microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within 3 organs in mice expressing human angiotensin converting enzyme 2 (ACE-2) ubiquitously (CAG-AC-70) or on epithelium (K18-promoter). Using a neon-green SARS-CoV-2, we observed both the epithelium and endothelium infected in AC70 mice but only the epithelium in K18 mice. There were increased neutrophils in the microcirculation but not in the alveoli of the lungs of AC70 mice. Platelets formed large aggregates in the pulmonary capillaries. Despite only neurons being infected within the brain, profound neutrophil adhesion forming the nidus of large platelet aggregates were observed in the cerebral microcirculation, with many nonperfused microvessels. Neutrophils breached the brain endothelial layer associated with a significant disruption of the blood-brain-barrier. Despite ubiquitous ACE-2 expression, CAG-AC-70 mice had very small increases in blood cytokine, no increase in thrombin, no infected circulating cells, and no liver involvement suggesting limited systemic effects. In summary, our imaging of SARS-CoV-2-infected mice gave direct evidence that there is a significant perturbation locally in the lung and brain microcirculation induced by local viral infection leading to increased local inflammation and thrombosis in these organs., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: End-of-life in patients with brain cancer presents special challenges, and palliative care approach is underutilized. Patients with brain cancer, in the last months of life, receive frequent hospital readmissions, highlighting bad end-of-life care quality. Early integration of palliative care improves quality of care in advanced stage of disease and patient's quality of death., Purpose: We retrospectively analyzed a consecutive series of patients with brain cancer discharged after diagnosis to evaluate pattern of treatment and rate of hospital readmission in the last months of life., Design: Data were collected from the Lazio Region Healthcare database., Setting: Adult patients discharged with diagnosis ICD-9 191.* between January 1, 2010, and December 31, 2019 were included., Results: A total of 6672 patients were identified, and 3045 deaths were included. In the last 30 days 33% were readmitted to the hospital and 24.2% to the emergency room. 11.7% were treated with chemotherapy and 6% with radiotherapy. Most indicators of end-of-life care showed wide variability by hospital of discharge., Conclusions: Strategies to improve quality of care at the end of life and to decrease re-hospitalization and futile treatments are becoming increasingly important to improve quality of death and reduce healthcare costs. Variability observed by hospital of discharge indicates the lack of a standard approach to end-of-life care., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: The receptor for advanced glycation-end products (RAGE) and its ligands have been implicated in obesity and associated inflammatory processes as well as in metabolic alterations like diabetes. In addition, RAGE-mediated signaling has been reported to contribute to the metastatic progression of breast cancer (BC), although mechanistic insights are still required. Here, we provide novel findings regarding the transcriptomic landscape and the molecular events through which RAGE may prompt aggressive features in estrogen receptor (ER)-positive BC., Methods: MCF7 and T47D BC cells stably overexpressing human RAGE were used as a model system to evaluate important changes like cell protrusions, migration, invasion and colony formation both in vitro through scanning electron microscopy, clonogenic, migration and invasion assays and in vivo through zebrafish xenografts experiments. The whole transcriptome of RAGE-overexpressing BC cells was screened by high-throughput RNA sequencing. Thereafter, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses allowed the prediction of potential functions of differentially expressed genes (DEGs). Flow cytometry, real time-PCR, chromatin immunoprecipitation, immunofluorescence and western blot assays were performed to investigate the molecular network involved in the regulation of a novel RAGE target gene namely EphA3. The clinical significance of EphA3 was explored in the TCGA cohort of patients through the survivALL package, whereas the pro-migratory role of EphA3 signaling was ascertained in both BC cells and cancer-associated fibroblasts (CAFs). Statistical analysis was performed by t-tests., Results: RNA-seq findings and GSEA analysis revealed that RAGE overexpression leads to a motility-related gene signature in ER-positive BC cells. Accordingly, we found that RAGE-overexpressing BC cells exhibit long filopodia-like membrane protrusions as well as an enhanced dissemination potential, as determined by the diverse experimental assays. Mechanistically, we established for the first time that EphA3 signaling may act as a physical mediator of BC cells and CAFs motility through both homotypic and heterotypic interactions., Conclusions: Our data demonstrate that RAGE up-regulation leads to migratory ability in ER-positive BC cells. Noteworthy, our findings suggest that EphA3 may be considered as a novel RAGE target gene facilitating BC invasion and scattering from the primary tumor mass. Overall, the current results may provide useful insights for more comprehensive therapeutic approaches in BC, particularly in obese and diabetic patients that are characterized by high RAGE levels., (© 2023. The Author(s).)

Competing Interests: Declaration of Competing Interest All authors are member of the GRADE Guidance Group. HJS and GG are cochairs of GRADE.

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.)

Within the EASY-NET network program (NET-2016-02364191), Work Package 1 Lazio evaluates the effectiveness of a structured audit and feedback (A&F) intervention compared with the web-based regional periodic publication of indicators in improving the appropriateness and timeliness of emergency healthcare for acute myocardial infarction (AMI). This work describes the A&F methodology and presents the results of the first feedback delivered. The intervention involves sending periodic reports via e-mail to participating hospitals. The feedback reports include a set of volume and quality (process and outcome) indicators, calculated by facility through the health information system of the Lazio Region and compared with regional mean, target values and values calculated for hospitals with similar volumes of activity. Health managers and clinicians of each participating hospital represent the "feedback recipients". They are invited to organize clinical and organizational audit meetings to identify possible critical issues in the care pathway and define, where necessary, improvement actions. A total of 16 facilities are involved. Twelve facilities present high volumes in all volume indicators, while three facilities present low volumes for each indicator. Concerning the quality indicators, four facilities do not present critical indicators or had average results, three facilities do not present critical indicators but show average results in at least one of the indicators and six facilities present a critical value for at least one of the indicators. The first report highlighted some critical issues in some facilities on several indicators. During the audit meetings, each facility analyzes these issues, defining appropriate improvement actions. The outcome of these actions will be monitored through subsequent reporting to support the continuous care quality improvement process.

Background: Urban areas are disproportionately affected by multiple pressures from overbuilding, traffic, air pollution, and heat waves that often interact and are interconnected in producing health effects. A new synthetic tool to summarize environmental and climatic vulnerability has been introduced for the city of Rome, Italy, to provide the basis for environmental and health policies., Methods: From a literature overview and based on the availability of data, several macro-dimensions were identified on 1,461 grid cells with a width of 1 km 2 in Rome: land use, roads and traffic-related exposure, green space data, soil sealing, air pollution (PM 2.5 , PM 10 , NO 2 , C 6 H 6 , SO 2 ), urban heat island intensity. The Geographically Weighted Principal Component Analysis (GWPCA) method was performed to produce a composite spatial indicator to describe and interpret each spatial feature by integrating all environmental dimensions. The method of natural breaks was used to define the risk classes. A bivariate map of environmental and social vulnerability was described., Results: The first three components explained most of the variation in the data structure with an average of 78.2% of the total percentage of variance (PTV) explained by the GWPCA, with air pollution and soil sealing contributing most in the first component; green space in the second component; road and traffic density and SO 2 in the third component. 56% of the population lives in areas with high or very high levels of environmental and climatic vulnerability, showing a periphery-centre trend, inverse to the deprivation index., Conclusions: A new environmental and climatic vulnerability indicator for the city of Rome was able to identify the areas and population at risk in the city, and can be integrated with other vulnerability dimensions, such as social deprivation, providing the basis for risk stratification of the population and for the design of policies to address environmental, climatic and social injustice., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Because of poor knowledge of risks and benefits, prophylactic explantation of high BIA-ALCL risk breast implant (BI) is not indicated. Several surgical risks have been associated with BI surgery, with mortality being the most frightening. Primary aim of this study is to assess mortality rate in patients undergoing breast implant surgery for aesthetic or reconstructive indication., Materials and Methods: In this retrospective observational cohort study, Breast Implant Surgery Mortality rate (BISM) was calculated as the perioperative mortality rate among 99,690 patients who underwent BI surgery for oncologic and non-oncologic indications. Mean age at first implant placement (A1P), implant lifespan (IL), and women's life expectancy (WLE) were obtained from a literature review and population database., Results: BISM rate was 0, and mean A1P was 34 years for breast augmentation, and 50 years for breast reconstruction. Regardless of indication, overall mean A1P can be presumed to be 39 years, while mean BIL was estimated as 9 years and WLE as 85 years., Conclusion: This study first showed that the BISM risk is 0. This information, and the knowledge that BI patients will undergo one or more revisional procedures if not explantation during their lifetime, may help surgeons in the decision-making process of a pre-emptive substitution or explant in patients at high risk of BIA-ALCL. Our recommendation is that patients with existing macrotextured implants do have a relative indication for explantation and total capsulectomy. The final decision should be shared between patient and surgeon following an evaluation of benefits, surgical risks and comorbidities., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. The Author(s).)

Resident macrophages are distributed across all tissues and are highly heterogeneous due to adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophages in the sensory ganglia, which have been implicated in different conditions, including neuropathic pain development. However, it is still under debate whether macrophage accumulation in the sensory ganglia after peripheral nerve injury is due to the local proliferation of resident macrophages or a result of blood monocyte infiltration. Here, we confirmed that the number of macrophages increased in the sensory ganglia after the spared nerve injury (SNI) model in mice. Using different approaches, we found that the increase in the number of macrophages in the sensory ganglia after SNI is a consequence of the proliferation of resident CX3CR1 + macrophages, which participate in the development of neuropathic pain, but not due to infiltration of peripheral blood monocytes. These proliferating macrophages are the source of pro-inflammatory cytokines such as TNF and IL-1b. In addition, we found that CX3CR1 signaling is involved in the sNAMs proliferation and neuropathic pain development after peripheral nerve injury. In summary, these results indicated that peripheral nerve injury leads to sNAMs proliferation in the sensory ganglia in a CX3CR1-dependent manner accounting for neuropathic pain development. In conclusion, sNAMs proliferation could be modulated to change pathophysiological conditions such as chronic neuropathic pain., Competing Interests: RG, CA, MD, FG, AM, MC, MF, SD, LA, MC, CR, FC, JA, TC No competing interests declared, (© 2023, Guimarães, Aníbal-Silva et al.)

Administrative data can be precious in connecting information from different sectors. For the first time, we used data from the National Social Insurance Agency (INPS) to investigate the association between the occupational sectors and both non-accidental and accidental mortality. We retrieved information on occupational sectors from 1974 to 2011 for private sector workers included in the 2011 census cohort of Rome. We classified the occupational sectors into 25 categories and analyzed occupational exposure as ever/never have been employed in a sector or as the lifetime prevalent sector. We followed the subjects from the census reference day (9 October 2011) to 31 December 2019. We calculated age-standardized mortality rates for each occupational sector, separately in men and women. We used Cox regression to investigate the association between the occupational sectors and mortality, producing hazard ratios (HRs) and 95% confidence intervals (95%CI). We analyzed 910,559 30+-year-olds (53% males) followed for 7 million person-years. During the follow-up, 59,200 and 2560 died for non-accidental and accidental causes, respectively. Several occupational sectors showed high mortality risks in men in age-adjusted models: food and tobacco production with HR = 1.16 (95%CI: 1.09-8.22), metal processing (HR = 1.66, 95%CI: 1.21-11.8), footwear and wood (HR = 1.19, 95%CI: 1.11-1.28), construction (HR = 1.15, 95%CI: 1.12-1.18), hotels, camping, bars, and restaurants (HR = 1.16, 95%CI: 1.11-1.21) and cleaning (HR = 1.42, 95%CI: 1.33-1.52). In women, the sectors that showed higher mortality than the others were hotels, camping, bars, and restaurants (HR = 1.17, 95%CI: 1.10-1.25) and cleaning services (HR = 1.23, 95%CI: 1.17-1.30). Metal processing and construction sectors showed elevated accidental mortality risks in men. Social Insurance Agency data have the potential to characterize high-risk sectors and identify susceptible groups in the population.

Background: . In the last decades some studies observed a moderate progressive decrease in short-term mortality in incident hemodialysis patients. The aim of the study is to analyse the mortality trends in patients starting hemodialysis using the Lazio Regional Dialysis and Transplant Registry., Methods: . Patients who started chronic hemodialysis between 2008 and 2016 were included. Annual 1-year and 3-year Crude Mortality Rate*100 Person Years (CMR*100PY) overall, by gender and age classes were calculated. Cumulative survival estimates at 1 year and 3 years since the date of starting hemodialysis were presented as Kaplan-Meier curves for the three periods and compared using the log-rank test. The association between periods of incidence in hemodialysis and 1-year and 3-year mortality were investigated by means of unadjusted and adjusted Cox regression models. Potential determinants of both mortality outcomes were also investigated., Results: . Among 6,997 hemodialysis patients (64.5% males, 66.1% over 65 years old) 923 died within 1 year and 2,253 within 3 years form incidence; CMR*100PY were 14.1 (95%CI: 13.2-15.0) and 13.7 (95%CI: 13.2-14.3), respectively; both remained unchanged over the years. Even after stratification by gender and age classes no significant changes emerged. Kaplan-Meier mortality curves did not show any statistically significant differences in survival at 1 year and 3 years from hemodialysis incidence across periods. No statistically significant associations were found between periods and 1-year and 3-year mortality. Factors associated with a greater increase in mortality are: being over 65 years, born in Italy, not being self-sufficient, having systemic versus undetermined nephropathy, having heart disease, peripheral vascular disease, cancer, liver disease, dementia and psychiatric illness, and receiving dialysis by catheter rather than fistula., Conclusions: . The study shows that the mortality rate in patients with end-stage renal disease starting hemodialysis in the Lazio region was stable over 9 years., (© 2023. The Author(s).)

Background: Audit and Feedback (A&F) is one of the most common strategies used to improve quality in healthcare. However, there is still lack of awareness regarding the enabling factors and barriers that could influence its effectiveness. The aim of this study was to develop a questionnaire to measure the knowledge, attitudes and behaviors of general practitioners (GPs) regarding A&F. The study was performed in the context of the EASY-NET program (project code NET-2016-02364191)., Methods: The survey was developed according to two steps. Firstly, a scoping review was performed in order to map the literature on the existing similar instruments with the aim of identifying the sub-domains and possible items to include in a preliminary version of the questionnaire. In the second phase, the questionnaire was reviewed by a multidisciplinary group of experts and administrated to a convenience sample in a pilot survey., Results: Ten papers were included in the scoping review. The survey target and development methodology were heterogenous among the studies. The knowledge, attitudes and behaviors domains were assessed in six, nine and seven studies, respectively. In the first step, 126 pertinent items were extracted and categorized as follows: 8 investigated knowledge, 93 investigated attitudes, and 25 investigated behaviors. Then, 2 sub-domains were identified for knowledge, 14 for attitudes and 7 for behavior. Based on these results, a first version of the survey was developed via consensus among two authors and then revised by the multidisciplinary group of experts in the field of A&F. The final version of the survey included 36 items: 8 in the knowledge domain, 19 in the attitudes domain and 9 in the behaviors domain. The results of the pilot study among 15 GPs suggested a good acceptability and item relevance and accuracy, with positive answers totaling 100% and 93.3% in the proposed questions., Conclusions: The methodology used has shown to be a good strategy for the development of the survey. The survey will be administrated before and after the implementation of an A&F intervention to assess both baseline characteristics and changes after the intervention.

Introduction: A concise representation of different primary and ambulatory care quality indicators can be very useful for quickly understanding the data and defining appropriate intervention strategies. The objectives of this study are to implement a graphical representation based on the TreeMap, a tool capable of summarizing results from heterogeneous indicators, with different measurement scales and thresholds, and take advantage of TreeMap's potential to measure the indirect impact of the Sars-CoV-2 epidemic on primary and ambulatory care processes., Methods: Seven healthcare areas were considered each defined by a set of different indicators representative of the area. A discrete score ranging from 1 (very high quality) to 5 (very low quality) was assigned to the value of each indicator, based on the level of adherence to evidence-based recommendations. Finally, the score of each healthcare area is obtained as the weighted average of the scores of the representative indicators. The TreeMap is calculated for each Local health authority (Lha) of the Lazio Region. In order to assess the impact of the epidemic, a comparison was made between the results observed in 2019 and those observed in 2020., Results: As an example, the results of one of the 10 Lhas of the Lazio Region have been reported. Compared to 2019, in 2020 there was an improvement in primary and ambulatory healthcare regarding all of the evaluated areas, with the exception of the metabolic area which remained stable. "Avoidable" hospitalizations have decreased, such as those for heart failure, Copd and diabetes. The incidence of cardio-cerebrovascular events following myocardial infarction or ischemic stroke has decreased, and inappropriate visits to emergency room have reduced. Furthermore, after decades of overprescribing, the use of drugs with a high risk of inappropriateness, such as antibiotics and aerosolized corticosteroids, has significantly decreased., Discussion: The TreeMap has proven to be a valid tool for evaluating the quality of primary care, summarizing evidence from different and heterogeneous indicators. The improvements in quality levels observed in 2020, compared to 2019, should be interpreted with extreme caution because they could represent a paradox generated by the indirect effects of the Sars-CoV-2 epidemic. If, in the case of the epidemic, the distorting factors can be easily identified, in different and more ordinary evaluative analyses the "research for the causes" could be much more complex.

Background: In Italy, inhaled corticosteroids (ICSs) are inappropriately prescribed to provide relief in URTI symptoms. Extreme variation in ICS prescribing has been described at regional and sub-regional level. During 2020, extraordinary containment measures were implemented in attempt to halt Coronavirus, such as social distancing, lockdown, and the use of mask. Our objectives were to evaluate the indirect impact of the SARS-CoV-2 pandemic on prescribing patterns of ICSs in preschool children and to estimate the prescribing variability among pediatricians before and during the pandemic., Methods: In this real-world study, we enrolled all children residing in the Lazio region (Italy), aged 5 years or less during the period 2017-2020. The main outcome measures were the annual ICS prescription prevalence, and the variability in ICS prescribing, for each study year. Variability was expressed as Median Odds Ratios (MORs). If the MOR is 1.00, there is no variation between clusters (e.g., pediatricians). If there is considerable between-cluster variation, the MOR will be large., Results: The study population consisted of 210,996 children, cared by 738 pediatricians located in the 46 local health districts (LHDs). Before the pandemic, the percentage of children exposed to ICS was almost stable, ranging from 27.3 to 29.1%. During the SARS-CoV-2 pandemic, the ICS prescription prevalence dropped to 17.0% (p < 0.001). In each study year, a relevant (p < 0.001) variability was detected among both LHDs and pediatricians working in the same LHD. However, the variability among individual pediatricians was always higher. In 2020, the MOR among pediatricians was 1.77 (95% CI: 1.71-1.83) whereas the MOR among LHDs was 1.29 (1.21-1.40). Furthermore, MORs remained stable over time, and no differences were detected in ICS prescription variability before and after pandemic outbreak., Conclusions: If on one hand the SARS-CoV-2 pandemic indirectly caused the reduction in ICS prescriptions, on the other the variability in ICS prescribing habits among both LHDs and pediatricians remained stable over the whole study time span (2017-2020), showing no differences between pre- pandemic and pandemic periods. The intra-regional drug prescribing variability underlines the lack of shared guidelines for appropriate ICS therapy in preschool children, and raises equity issues in access to optimal care., (© 2023. The Author(s).)

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).)

The microbiota performs multiple functions vital to host fitness, including defense against pathogens and adaptation to dietary changes. Yet, how environmental challenges shape microbiota resilience to nutrient fluctuation remains largely unexplored. Here, we show that transient gut infection can optimize host metabolism toward the usage of carbohydrates. Following acute infection and clearance of the pathogen, mice gained more weight as a result of white adipose tissue expansion. Concomitantly, previously infected mice exhibited enhanced carbohydrate (glucose) disposal and insulin sensitivity. This metabolic remodeling depended on alterations to the gut microbiota, with infection-elicited Betaproteobacteria being sufficient to enhance host carbohydrate metabolism. Further, infection-induced metabolic alteration protected mice against stunting in the context of limited nutrient availability. Together, these results propose that alterations to the microbiota imposed by acute infection may enhance host fitness and survival in the face of nutrient restriction, a phenomenon that may be adaptive in settings where both infection burden and food precarity are prevalent.

Background: In immunosuppression after transplantation, several multi-drug approaches are used, involving calcineurin inhibitors ( CNI: tacrolimus-TAC or cyclosporine-CsA ), antimetabolites ( antiMs ), mammalian target of rapamycin inhibitors ( mTORis ), and corticosteroids. However, data on immunosuppressive therapy by organ and its space-time variability are lacking., Methods: An Italian multicentre observational cohort study was conducted using health information systems. Patients with incident transplant during 2009-2019 and resident in four regions (Veneto, Lombardy, Lazio, and Sardinia) were enrolled. The post-transplant immunosuppressive regimen was evaluated by organ, region, and year., Results: The most dispensed regimen was triple-drug therapy for the kidneys [tacrolimus (TAC) + antiM + corticosteroids = 41.5%] and heart [cyclosporin  + antiM + corticosteroids = 36.6%] and double-drug therapy for liver recipients (TAC + corticosteroids = 35.4%). Several differences between regions and years emerged with regard to agents and the number of drugs used., Conclusion: A high heterogeneity in immunosuppressive therapy post-transplant was found. Further studies are needed in order to investigate the reasons for this variability and to evaluate the risk-benefit profile of treatment schemes adopted in clinical practice., Competing Interests: MZ was employed by ARIA, S.p.a. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Marino, Rosa, Finocchietti, Bellini, Poggi, Massari, Alegiani, Masiero, Ricci, Bedeschi, Puoti, Cardillo, Pierobon, Nordio, Ferroni, Zanforlini, Piccolo, Leoni, Ledda, Carta, Garau, Lucenteforte, Davoli, Addis and Belleudi.)

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.

Audit and Feedback (A&F) is an effective multidimensional strategy for improving the quality of care. The optimal methods for its implementation remain unclear. This study aimed to map the state of art of A&F strategies in the hospitals involved in a time-dependent emergency network. For these purposes, a structured questionnaire was defined and discussed within the research group. This consists of 29 questions in three sections: (1) characteristics of the structure, (2) internal feedback systems, and (3) external feedback systems. All structures involved in the network were invited to participate in the e-survey by indicating a Health Management representative and a clinical representative for the Cardiovascular (CaV) and/or for the Cerebrovascular area (CeV). Of 20 structures invited, a total of 13 (65%) responded to the survey, 11 for the CaV area and 8 for the CeV area. A total of 10 of 11 (91%) facilities for the CaV area and 8/11 (75%) for the CeV area reported that they perform A&F activities. All facilities perform at least one of the activities defined as "assimilating A&F procedures." The most frequent is the presentation and discussion of clinical cases (82% CaV and 88% CeV) and the least is the identification of responsible for improvement actions (45% CaV and 38% CeV). In 4/10 (40%) facilities for the CaV area and 4/8 (50%) for the CEV area, corrective actions are suggested or planned when the feedback is returned. These results confirm the need to define, in a synergistic way with the relevant stakeholders, an effective and agreed A&F intervention to improve the level of implementation of A&F strategies.

Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO1-expressing dendritic cells (DCs) accumulated in the dorsal root leptomeninges and led to an increase in kynurenine levels in the spinal cord. In the spinal cord, kynurenine was metabolized by kynurenine-3-monooxygenase-expressing astrocytes into the pronociceptive metabolite 3-hydroxykynurenine. Ultimately, 3-hydroxyanthranilate 3,4-dioxygenase-derived quinolinic acid formed in the final step of the canonical KYNPATH was also involved in neuropathic pain development through the activation of the glutamatergic N-methyl-D-aspartate receptor. In conclusion, these data revealed a role for DCs driving neuropathic pain development through elevation of the KYNPATH. This paradigm offers potential new targets for drug development against this type of chronic pain.