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

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

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

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

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

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

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

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

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

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

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

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

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia. The availability of new antidiabetic drugs (ADs) has led to complex treatment patterns and to changes in the patterns of specific drug utilization. The aim of this population-based study was to describe the pattern of antidiabetic drugs (ADs) use in Southern Italy in the years 2011-2017, in relation to the updated type 2 diabetes mellitus (T2DM) therapy guidelines. A retrospective cohort study was conducted on T2DM patients using data from the Palermo Local Health Unit (LHU) claims database and diabetologist registry. The first-line treatment was investigated and incident treatments were identified and characterized at baseline in terms of demographics, complications, comorbidities, concomitant drugs and clinical parameters. Persistence to AD treatment was also evaluated. During the study period, one-third of first ever ADs users started the treatment with ADs other than metformin, in contrast to guideline recommendations. Among 151,711 incident AD treatments, the male to female ratio was 1.0 and the median age was 66 (57-75) years. More than half (55.0%) of incident treatments discontinued the therapy during the first year of treatment. In Italy, general practitioners (GPs) can only prescribe first-generation ADs, while the prescription of more recently marketed ADs, such as GLP-1RA, DPP4i and SGLT2i, is restricted to diabetologists only, based on a therapeutic plan. The role of GPs in the management of T2DM in Italy should be re-evaluated.

Background: Multimorbidity is a growing concern for healthcare systems, with many countries experiencing demographic transition to older population profiles. A simple multisource comorbidity score (MCS) has been recently developed and validated. A very large real-world investigation was conducted with the aim of measuring inequalities in the MCS distribution across Italy., Methods: Beneficiaries of the Italian National Health Service aged 50-85 years who in 2018 were resident in one of the 10 participant regions formed the study population (15.7 million of the 24.9 million overall resident in Italy). MCS was assigned to each beneficiary by categorizing the individual sum of the comorbid values (i.e. the weights corresponding to the comorbid conditions of which the individual suffered) into one of the six categories denoting a progressive worsening comorbidity status. MCS distributions in women and men across geographic partitions were compared., Results: Compared with beneficiaries from northern Italy, those from centre and south showed worse comorbidity profile for both women and men. MCS median age (i.e. the age above which half of the beneficiaries suffered at least one comorbidity) ranged from 60 (centre and south) to 68 years (north) in women and from 63 (centre and south) to 68 years (north) in men. The percentage of comorbid population was lower than 50% for northern population, whereas it was around 60% for central and southern ones., Conclusion: MCS allowed of capturing geographic variability of multimorbidity prevalence, thus showing up its value for addressing health policy in order to guide national health planning., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Although trastuzumab (T) represents the standard of care for the adjuvant treatment of HER2-positive early-stage breast cancer, contrasting results are available about the cardiac toxicity associated to its use. We conducted a multiregional population-based cohort investigation aimed to assess both the short- and long-term cardiovascular (CV) outcomes in women with early breast cancer treated with T-based or standard adjuvant chemotherapy (CT)., Materials and Methods: We used health care use databases of six Italian regions, overall accounting for 42% of the Italian population. The study cohort was made by all women surgically treated for breast cancer who started a first-line adjuvant T-based or CT treatment. Patients treated with T were 1:2 matched to those treated with CT based on date of treatment start, age, and presence of CV risk factors. Short- and long-term CV outcomes (heart failure and cardiomyopathy) were measured, respectively, after 1 year and at the end of follow-up., Results: Among 28,599 women who met the inclusion criteria, 6,208 T users were matched to 12,416 CT users. After a mean follow-up of 5.88 years, short- and long-term cumulative CV risk were 0.8% and 2.6% in patients treated with T and 0.2% and 2.8% in those treated with CT, respectively. Adjusted hazard ratios were 4.6 (95% confidence interval [CI], 2.6-8.0) for short-term and 1.2 (95% CI, 0.9-1.6) for long-term CV risk., Discussion: In our large real-world investigation, T-associated cardiotoxicity was limited to the treatment period. The addition of T to adjuvant CT did not result in long-term worsening of CV events., Implications for Practice: Adjuvant trastuzumab-based chemotherapy represents the backbone therapy in patients with HER2-positive early breast cancer. Although well tolerated, cardiovascular events can manifest during or after therapy because of treatment-related toxicities. In this wide multicenter and unselected cohort, long-term symptomatic cardiotoxicity was low and limited to the treatment period. The findings suggest that developing tools that would be adequately able to predict cardiac toxicity at an early stage remains an important area in which additional research efforts are needed., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

The article compares two of the most followed indices in the monitoring of COVID-19 epidemic cases: the Rt and the RDt indices. The first was disseminated by the Italian National Institute of Health (ISS) and the second, which is more usable due to the lower difficulty of calculation and the availability of data, was adopted by various regional and local institutions.The rationale for the Rt index refers to that for the R0 index, the basic reproduction number, which is used by infectivologists as a measure of contagiousness of a given infectious agent in a completely susceptible population. The RDt index, on the other hand, is borrowed from the techniques of time series analysis for the trend of an event measurement that develops as a function of time. The RDt index does not take into account the time of infection, but the date of the diagnosis of positivity and for this reason it is defined as diagnostic replication index, as it aims to describe the intensity of the development of frequency for cases recognized as positive in the population.The comparison between different possible applications of the methods and the use of different types of monitoring data was limited to four areas for which complete individual data were available in March and April 2020. The main problems in the use of Rt, which is based on the date of symptoms onset, arise from the lack of completeness of this information due both to the difficulty in the recording and to the absence in asymptomatic subjects.The general trend of RDt, at least at an intermediate lag of 6 or 7 days, is very similar to that of Rt, as confirmed by the very high value of the correlation index between the two indices. The maximum correlation between Rt and RDt is reached at lag 7 with a value of R exceeding 0.97 (R2=0.944).The two indices, albeit formally distinct, are both valid; they show specific aspects of the phenomenon, but provide basically similar information to the public health decision-maker. Their distinction lies not so much in the method of calculation, rather in the use of different information, i.e., the beginning of symptoms and the swabs outcome.Therefore, it is not appropriate to make a judgment of preference for one of the two indices, but only to invite people to understand their different potentials so that they can choose the one they consider the most appropriate for the purpose they want to use it for.

Objectives: to evaluate maternal and child healthcare, avoidable hospitalisation, access to emergency services among immigrants in Italy., Design: cross sectional study of some health and health care indicators among Italian and foreign population residing in Italy in 2016-2017., Setting and Participants: indicators based on the national monitoring system coordinated by the Italian National Institute for Health, Migration and Poverty (INMP) of Rome, calculated on perinatal care (CedAP), hospital discharge (SDO), emergency services (EMUR) archives for the years 2016-2017, by of the following regions: Piedmont, Trento, Bolzano, Emilia-Romagna, Tuscany, Umbria, Lazio, Basilicata, Sicily., Main Outcome Measures: number and timeliness of pregnancy visits, number of ultrasounds, invasive prenatal investigations; perinatal mortality rates, birth weight, Apgar score at 5 minutes, need for neonatal resuscitation; standardized rates of avoidable hospitalisation and access to emergency services by triage code., Results: more often than Italians, immigrant women have during pregnancy: less than 5 gynaecological examination (16.3% vs 8.5%), first examination after the 12th week of gestational age (12.5% vs 3.8%), less than 2 ultrasounds (3.8% vs 1.0%). Higher perinatal mortality rates among immigrants compared to Italians (3.6 vs 2.3 x1,000). Higher standardized rates (x1,000) among immigrants compared to Italians of avoidable hospitalisation (men: 2.1 vs 1.4; women: 0.9 vs 0.7) and of white triage codes in emergency (men: 62.0 vs 32.7; women: 52.9 vs 31.4)., Conclusions: study findings show differences in access and outcomes of healthcare between Italians and immigrants. National monitoring system of indicators, coordinated by INMP, represents a useful tool for healthcare intervention policies aimed to health equity.

Objectives: to build an equity profile for assessing the impact of socioeconomic inequalities on the determinants and health outcome in Sicily (Southern Italy)., Design: descriptive study aimed to define an equity profile in Sicily by using a rich list of indicators of structure of the resident population and of distribution of determinants and health outcome, derived from the integration of available information and scientific evidence at regional level with high local detail., Setting and Participants: the equity profile collects available information on the health status of the population in Sicily, on the determinants, and on the use of health and social services. The characteristics of people or population groups have been explored and can produce inequalities on health which included individual and context socioeconomic status., Main Outcome Measures: using available information sources and study results have explored the effects of the disadvantage on health in the region: mortality, morbidity, oncological incidence, reproductive health, and some of their determinants., Results: the Sicilian population tends to aging. Migration flows tend to compensate the reduction in births in Sicily and it increases the proportion of younger people and women in childbearing age. The proportion of large families tends to get smaller, whereas the proportion of single-component ones increases; the population groups with low education, unemployment, poverty, and income increases. Starting from the first thousand days of life, to continue in the other classes of the population, the different distribution of risk factors on health was identified according to different levels of deprivation., Conclusions: the Sicilian equity profile has systematized and consolidated previous experiences on the effects of disadvantage on health. Prevention interventions, oriented towards equity, should be based on the results of this study and should take care of the general aspects of actions and, at the same time, focus on vulnerable population groups.

Objectives: to evaluate the effects of a pre-existing condition of diabetes and of the use of antidiabetic drugs in the Sicilian population on different outcomes of the COVID-19 disease., Design: a retrospective observational study based was used. Data deriving from the COVID-19 epidemic surveillance and from the collection of information on drugs consume by Sicilian residents., Setting and Participants: due to the data availability, the study was calibrated on the Region and included all population distinguishing by gender and age groups., Main Outcome Measures: the risks of cumulative incidence for COVID-19 were investigated in people who had diabetes comorbidities to incur a hospitalization for COVID-19, to be treated within an intensive care unit, and lethality. The role of previous antidiabetic drug treatments with respect to each study outcome was also investigated., Results: in Sicily, from 01.03.2020 to 26.06.2020, a number of 172 cases of COVID-19 disease with diabetes comorbidity were diagnosed. The data did not show any difference in the cumulative incidence for COVID-19 between diabetics (64.2/100,000 inhabitants) and non-diabetics (56.9/100,000 inhabitants) patients. Diabetes increases the risk of hospitalization in the under 80 in both men and women (men: OR 2.62; women OR 4.31), for treatment in intensive care (men: OR 4,41; women: OR 7.74), and for death (men: OR 5.21; women OR 5.92). The analysis of drug using showed risks effect of insulin (OR 2.13) on hospitalization, sulfonylureas/glinides (OR 2.58) on intensive care and protective of metformin on death both in single component (OR 0.44) and in multicomponent (OR 0.43)., Conclusions: data availability made it possible to monitor the occurrence and explore some of the characteristics of the cases with COVID-19 in Sicily. Diabetes does not seem to represent a risk factor for SARS-CoV-2 infection in Sicily, while previous diabetes condition seems to determine greater risk of hospitalization, treatment in intensive care, and lethality among over 80. There are also gender differences with almost double risks in women for hospitalization and intensive care only. Among the antidiabetic drugs investigated, there was a risk for hospitalization and intensive care while protective for deaths. This study represents an important tool for the activation of intervention programmes in the area aimed at populations with greater health risk deriving from the effects of this new pandemic.

Aim: The aim of this study was to measure gender differences among COPD patients' quality of care (QOC) before and after two educational interventions in Southern Italy., Methods: In this prospective cohort study, COPD patients were identified from primary care electronic medical records (EMRs). Twelve process indicators concerning diagnosis, preventative measures and therapeutic processes were developed as a measure of QOC. Educational interventions consisted of clinical seminars and audits on COPD QOC at baseline, and at 12 and 24 months. QOC indicators were stratified by gender: odds ratios (ORs) (males as reference group) of having a good QOC indicator were calculated at baseline, 12 and 24 months, with 95% confidence intervals (CIs) using hierarchical generalised linear models., Results: Of 46 326 people registered in the EMRs, 1463 COPD patients (3.1%) were identified, of which 37% were women. QOC indicators reflecting best practice 24 months after the educational programme were generally not different to baseline, often favouring men. On the other hand, the composite global QOC indicator suggested that while a good overall QOC at baseline was significantly higher in men than women (OR: 0.74; 95% CI: 0.57-0.96), it became nonsignificant at 24 months (OR: 0.96; 95% CI: 0.72-1.29)., Conclusions: Specific QOC indicators among COPD patients often favoured men. However, several gender disparities seen at baseline disappeared at 24 months, suggesting that even general educational interventions which do not target gender can improve the gender disparity in QOC., Competing Interests: Conflict of interest: V. Isgrò has nothing to disclose. Conflict of interest: J. Sultana has nothing to disclose. Conflict of interest: A. Fontana has nothing to disclose. Conflict of interest: V. Ientile has nothing to disclose. Conflict of interest: U. Alecci has nothing to disclose. Conflict of interest: R. Scoglio has nothing to disclose. Conflict of interest: F. Magliozzo has nothing to disclose. Conflict of interest: S. Scondotto has nothing to disclose. Conflict of interest: G. Caramori has nothing to disclose. Conflict of interest: M. Cazzola reports participation in courses sponsored by Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, Cipla, Edmond Pharma, GlaxoSmithKline, Lallemand, Menarini Group, Mundipharma, Novartis, Pfizer, Teva, Verona Pharma and Zambon; and consultancy for ABC Farmaceutici, AstraZeneca, Chiesi Farmaceutici, Edmond Pharma, Lallemand, Novartis, Ockham Biotech, Verona Pharma and Zambon, all outside the submitted work. Conflict of interest: G. Trifirò reports an unconditional grant from Novartis and a pharmacovigilance grant (Evaluating the appropriate use and safety of drugs used for chronic obstructive pulmonary disease in a Sicilian primary care setting) from the Italian Drug Agency/Sicilian Regional during the conduct of the study; participation on advisory boards for Sandoz, Hospira, Sanofi, Biogen, Ibsen and Shire, consultancy for Otsuka, acting as the principal investigator of studies funded by Amgen, AstraZeneca, Daiichi Sankyo and IBSA, and coordinator of a master's degree that received unconditional grants from several pharmaceutical companies, outside the submitted work., (Copyright ©ERS 2020.)

Objectives: to evaluate short-medium term incidence and mortality projections of pleural malignant mesothelioma (PMM) in Sicily Region (Southern Italy) and in its four National Priority Contaminated Sites (NPCSs)., Design: population-based prediction study., Setting and Participants: PMM cases from 1998 to 2016 registered by the Regional Operations Centre of the Sicilian Region., Main Outcome Measures: incidence and mortality trends of PMM were estimated for the period 1998-2016 from the relationships among mortality, incidence, and survival. Projections of incidence and mortality rates were obtained up to 2026., Results: age-standardized incidence rates of PMM in Sicily were estimated to increase in men from 1.4 (x100,000) in 1998 to 2.29 in 2021 and to slightly decrease down to 2.2 in 2026. Women age-standardized rates in the same period are estimated to decrease from 0.52 to 0.27. In Biancavilla, age-standardized incidence rates were estimated to remain stable between 8.1 and 8.0 in men, while crude rates increased from 8.3 in 1998 to 10.7 in 2026. For women, the estimated age-standardized incidence rates are increasing from 3.08 to 6.75. In the three pooled NPCSs of Augusta-Priolo, Gela, and Milazzo, the estimates of age-standardized incidence rates show an initial trend to growth followed by a decreasing trend, both in men and women, down to predicted values in 2016 of 3.0 in men and 0.77 in women. Estimated age-standardized and crude mortality rates show, for both sexes and all areas, similar patterns as those estimated for incidence., Conclusions: in Sicily and in the three NPCSs of Gela, Milazzo, and Priolo, incidence and mortality projections are downward in both sexes. In Biancavilla, mesothelioma occurrence is estimated to increase up to 2026, slightly in males and more significantly in females.

Evidence available on the effectiveness and costs of biological therapies for the initial treatment of metastatic colorectal cancer (mCRC) is scarce and contrasting. We conducted a population-based cohort investigation for assessing overall survival and costs associated with their use in a real-world setting. Healthcare utilization databases were used to select patients newly diagnosed with mCRC between 2010 and 2016. Those initially treated with biological therapy (bevacizumab or cetuximab) added to chemotherapy were propensity-score-matched to those treated with standard chemotherapy alone, and were followed up to June 30th, 2018. Kaplan-Meier survival estimates, restricted mean survival time (RMST) and cumulative costs were compared between the two treatment arms. The study cohort included 1896 mCRC patients treated with biological therapy matched to 5678 patients treated with chemotherapy alone. Median overall survival was 21.8 and 20.2 months, respectively. After 84 months of follow-up, RMSTs were 30.9 and 31.9 months ( p = 0.193), indicating no differences between the average survival time between treatment arms. Patients treated with biological therapy were associated with higher costs. Cumulative per capita costs were €59,663 and €44,399, respectively. In our study, first-line biological therapy did not improve long-term overall survival and was associated with higher costs as compared to standard chemotherapy.

Objectives: to analyse the asbestos-related diseases risk among the former workers of Sacelit asbestos-cement plant, operating in San Filippo del Mela (Sicily: 1958- 1993)., Design: cohort study., Setting and Participants: 228 subjects were employed in Sacelit from 1958 to 1993. Due to the available observation periods, the analyses of the different outcomes were performed for the subjects alive at the beginning of the respective follow up periods: mortality (1986-2018) was analysed for 204 subjects (177 men, 27 women), hospitalization (2001-2016) for 164 workers (139 men, 25 women) and the incidence of mesothelioma (1998-2016) was estimated for 178 subjects (153 men, 25 women)., Main Outcomes Measures: mortality (Standardized Mortality Ratio: SMR) and hospitalization (Standardized Hospitalization Ratio: SHR) from specific diseases were analysed. Incidence (Standardized Incidence Ratio: SIR) of mesothelioma cases was detected, also. SMR (1986-2014), SHR (2001-2016) and SIR (1998-2016), with 95% Confidence Intervals, were computed with respect to the regional rates, with STATA11., Results: in the men cohort, mortality from lung (17 cases, SMR 2.83) and pleural cancers (5 cases, SMR 30) and from asbestosis (15 cases, SMR 1,930) was in excess. The risk of hospitalization was in excess, in both genders, from lung cancer (men: 6 cases, SHR 4.1; women: 2 cases, SHR 8.6) and asbestosis (men: 17 cases, SHR 1,304; women: 6 cases, SHR 2,455). The incidence of mesothelioma was in excess in men (5 cases, SIR 23.9); no female cases of mesothelioma were observed., Conclusions: a high occurrence of asbestos-related diseases in the cohort, particularly among men, was observed. The excess of hospitalization from asbestosis and lung cancer was highlighted also in women. The prosecution of the on-going health surveillance plan is particularly appropriated.

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.

Introduction: Real-world data on the comparative effectiveness and safety of switching among different epoetins (including originators and biosimilars) are limited. In light of current debate about interchangeability, prescribers, some patient groups and decision makers are calling for additional post-marketing evidence on the clinical effects of switching between originator and biosimilar epoetins in chronic kidney disease (CKD) patients., Objective: The objective of this study was to evaluate the effectiveness and safety of switching versus non-switching and of switching from originator/biosimilar epoetin alpha (ESA α) to any other epoetin in CKD patients., Methods: An observational, record-linkage, multi-database, retrospective cohort study was carried out in four Italian geographical areas. All subjects with at least one ESA α dispensing between 1 January 2009 and 31 December 2015 were retrieved. Switching was defined as any transition between originator/biosimilar ESA α to any other epoetin in a series of two consecutive prescriptions up to 2 years. Switchers were matched 1:1 with non-switchers by baseline propensity score and by duration of ESA α treatment. Switchers and non-switchers were followed up from switching date to a maximum of 1 year. Lack of effectiveness and safety of switching versus non-switching were evaluated through Cox regression models (hazard ratio [HR], 95% confidence interval [CI]). A direct comparison between the two switcher categories (switchers from originator/biosimilar ESA α to any other epoetin) was also performed., Results: Overall, 14,400 incident users of ESA α for anaemia due to CKD (61.4% originator, 38.6% biosimilar) were available for analysis. During the follow-up, we found no differences on effectiveness (HR 1.02, 95% CI 0.79-1.31 originators; HR 1.16, 95% CI 0.75-1.79 biosimilars) and safety outcomes (HR 1.08, 95% CI 0.77-1.50 originators; HR 1.20, 95% CI 0.66-2.21 biosimilars) between switchers and non-switchers of ESA α. Cumulative probabilities of recording an adverse event, either in terms of lack of effectiveness or safety issue, were the same for two switching categories CONCLUSIONS: In this large-scale Italian observational multi-database study, switching versus non-switching as well as switching from biosimilar/originator ESA α to any other epoetin in CKD patients is not associated with any effectiveness and safety outcomes.

Despite the advantages of breastfeeding being widely recognized, the economic level can have an influence on breastfeeding rates, with rich women breastfeeding longer than poor in high-income countries. In Italy, socio-economic differences affect breastfeeding start and continuation among most deprived people, such as in Southern Italy. The objective of the study was to evaluate the prevalence of the initiation and continuation of exclusive breastfeeding and its association with the levels of socio-economic deprivation in Sicily. A prospective cohort study with a two-phase survey in three breastfeeding detection times was conducted. Overall, 1,055 mothers were recruited with a mean age of 31 years. Breastfeeding decreased from 86% during hospitalization to 69% at the first month and 42% at the sixth month, yet at the same time, exclusive breastfeeding increased from 34% to 38% during hospitalization to the first month and went down to 20.2% at the sixth month. The adjusted multivariate analysis showed no association with individual inequalities. On the other hand, the context inequalities had a significant association with the risk of not following exclusive breastfeeding in the deprived class (odds ratio (OR): 2.08, confidence interval (CI) 95% 1.01-4.27) and in the very deprived class (OR: 1.83, CI 95% 1.00-3.38) at the six-month survey. These results indicate that the context inequalities begin to emerge from the return home of the mother and the child.

Background: Few epidemiological data about inflammatory bowel disease (IBD) in Italy are available., Aims: To estimate IBD prevalence and incidence in two Italian regions - Sicily and Sardinia - using regional health information systems., Methods: Data from hospital discharges and disease-specific payment exemptions register were retrieved and underwent record-linkage procedures. Standardized prevalence and incidence were calculated as rates per 100,000 inhabitants., Results: In Sicily, during the year 2013, the overall IBD incidence rate was 27 per 100,000 inhabitants, while the incidence rate of Crohn's disease (CD) was 16 for males and 13 for females, and the incidence of ulcerative colitis (UC) was 15 and 11 for males and females, respectively. At the date of December 31st, 2013, the standardized prevalence rate of IBD was estimated at 300 cases per 100,000 inhabitants. In Sardinia, during the period 2008-2010, the average IBD incidence rate per 100,000 was 15, with an incidence rate of 5 per 100,000 for CD, and 10 per 100,000 for UC, while the standardized prevalence rate of IBD was estimated at 187 cases per 100,000 inhabitants., Conclusions: The particularly high incidence of CD in Sicily, and the marked difference of IBD occurrence between the two islands deserve future investigations., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: In response to public health concern about effects of arson at solid waste management plants in July 2012, we analysed vital statistics data to evaluate any potential effect on pregnancies at different gestational ages of pollutants emitted from the landfill on fire., Setting: A community living near the largest landfill plant in Sicily., Participants: The study group comprised 551 births, live births and stillbirths from pregnancies of mothers residing in the extra-urban exposed area, conceived during a 40 week period during which the highest fire's peak might have influenced pregnancy., Primary and Secondary Outcome Measures: Birth outcomes (gestational age <37 and <32 weeks, low birth weight, very low birth weight and small for gestational age) in the study group were compared with the ones of a reference group of women residing in areas of Sicily with similarly low population density and industrial development., Results: Among singleton live births we observed a three-fold increase in risk of very preterm birth between the extra-urban area and the remaining low inhabitants density and unindustrialised areas for births whose pregnancies were in the third trimester (OR adjusted for maternal age and infant gender=3.41; 95% CI 1.04 to 11.16). There was an excess of very low birth weight singleton infants in the study group as compared with the reference group, which was limited to births to mothers exposed during periconception period (OR adjusted for maternal age and infant gender=4.64; 95% CI 1.04 to 20.6) and first trimester (OR adjusted for maternal age and infant gender=3.66; 95% CI 1.11 to 12.1). The association estimates were imprecise due to the small number of outcomes recorded., Conclusions: The study documented an excess of very preterm and very low birth weight among infants born to mothers exposed to the landfill fire emissions during conception or early pregnancy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Orphan drugs are medicines intended to treat, prevent, or diagnose a rare and serious condition. The collection of pre-marketing safety and efficacy data for orphan drugs is very challenging for several reasons related to the rarity of the diseases. This highlights the need for robust post-marketing evidence generation. Real-world data sources, such as claims databases, electronic healthcare records, and disease and drug registers, have an important role in studying orphan drugs. The availability and usefulness of such resources vary from country to country., Areas Covered: A detailed description of the available real-world data sources and their contribution to generating post-marketing evidence on orphan drug benefit-risk profile in Italy is provided., Expert Opinion: Despite their considerable potential for rare disease research, the available Italian data sources are currently under-used and require further harmonization of data collection. The establishment of large structured and integrated nationwide data sources, tailored to respond to both research as well as regulatory requirements, is necessary to provide clinically useful information on orphan drugs as well. Such data sources should also be more accessible at the loco-regional, national and international level.

Objectives: to update the health profile of populations residing in the national priority contaminated sites (NPCSs) in Sicily Region (Southern Italy) through a description of mortality and hospitalization for causes and through cancer incidence. This new profile is part of the implementation of the epidemiological surveillance system within the new Programme of care intervention for health protection in these populations and in the new Regional Prevention Plan., Design: geographic population survey providing, for each NPCS considered in this study, a comparison between the local population and the populations of the neighbouring areas., Setting and Participants: the study population included the residents in the municipalities residing in the NPCSs of Augusta-Priolo, Gela, Milazzo, and Biancavilla., Main Outcome Measures: the standardized mortality ratio (SMR), morbidity (SHR), and tumour incidence (SIR), with the respective 95% confidence intervals, were estimated using the Mortality Registry as source for the mortality index, the database of the hospital discharged as source for the morbidity index, and the data from the Regional Network of Tumour Registers as source for the incidence index., Results: in the local comparison, excess of hospitalization in both sexes was reported in Augusta-Priolo for liver cirrhosis, mental disorders, and digestive tract disease, and an excess of incidence and mortality for leukaemia in women and prostate cancer in men. In the NPCS of Gela, there was an excess of hospitalization in both sexes for blood and hematopoietic diseases, circulatory and nervous system diseases, coupled with the same excess of mortality. Excess of incidence and mortality of stomach tumours in men and incidence of lung cancer in women were observed. The area of ​​Milazzo was characterized by an excess of incidence and mortality for melanoma in men. In the municipality of Biancavilla, there is evidence of excess of hospitalization for respiratory diseases and endocrine glands diseases in both sexes, while a mortality excess for circulatory system diseases was highlighted. The excess of incidence of mesothelioma in both men and women was confirmed., Conclusion: data from the new surveillance system help to define the health profile in the NPCSs of Sicily. Even using the local level of comparison, that was added to the traditional approach in geographic studies for the NPCSs available to date, the particular impact of some chronic diseases in these populations has been confirmed also in recent years.

Introduction and Objectives: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program "Environment and Health". The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings., Methods: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs., Results: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system., Conclusions: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.

Renal Diseases represent almost 6% of all Rare Diseases but are often misdiagnosed. In a survey made in Sicily in 2016, based on cases reported from all public hospitals according to a list of rare kidney diseases, we were able to collect 337 cases (199 males and 138 females). The highest prevalence was detected in children: 13.9 cases in 100.000 children; the mean age was 10, and the median 5 years, at the time of the diagnosis. Comparing our data with those available in the Sicilian Register of Rare Diseases we found that only 141 cases (54%) were present in the register. Promoting regional registries of rare kidney diseases in Italy may be useful for epidemiologic studies., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Background: Increased PM 10 concentrations are commonly observed during Saharan dust advections. Limited epidemiological evidence suggests that PM 10 from anthropogenic and desert sources increase mortality. We aimed to evaluate the association between source-specific PM 10 (non-desert and desert) and cause-specific mortality in Sicily during 2006-2012 period., Methods: Daily PM 10 concentrations at 1-km 2 were estimated in Sicily using satellite-based data, fixed monitors and land use variables. We identified Saharan dust episodes using meteorological models, back-trajectories, aerosol maps, and satellite images. For each dust day, we estimated desert and non-desert PM 10 concentrations. We applied a time-series approach on 390 municipalities of Sicily to estimate the association between PM 10 (non-desert and desert) and daily cause-specific mortality., Results: 33% of all days were affected by Saharan dust advections. PM 10 concentrations were 8 μg/m 3 higher during dust days compared to other days. We found positive associations of both non-desert and desert PM 10 with cause-specific mortality. We estimated percent increases of risk (IR%) of non-accidental mortality equal to 2.3% (95% Confidence Interval [CI]: 1.4, 3.1) and 3.8% (3.2, 4.4), per 10 μg/m 3 increases in non-desert and desert PM 10 at lag 0-5, respectively. We also observed significant associations with cardiovascular (2.4% [1.3, 3.4] and 4.5% [3.8, 5.3]) and respiratory mortality (8.1% [6.8, 9.5], and 6.3% [5.4, 7.2]). We estimated higher effects during April-September, with IR% = 4.4% (3.2, 5.7) and 6.3% (5.4, 7.2) for non-desert and desert PM 10 , respectively., Conclusions: Our results confirm previous evidence of harmful effects of desert PM 10 on non-accidental and cardio-respiratory mortality, especially during the warm season., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: to describe the prevalence of breastfeeding in Sicily Region (Southern Italy) and to analyze the socioeconomic status and other major risk factors on the attitudes towards exclusive breastfeeding., Design: information on the practice of breastfeeding in Sicily have been collected from a Regional survey on Sudden Infant Death Syndrome (SIDS). An index of socioeconomic position was created by using data from the 2011 Census of the Italian National Institute of Statistics., Setting and Participants: in May 2015, a questionnaire was distributed to all mothers accessing to immunization services in Sicily for the first vaccination of their children. Two hundred seventy-three (273) vaccination centres have been involved, and 2,692 questionnaires were administered., Main Outcome Measures: five socio-economic levels were identified and, for each of them, the prevalence of breastfeeding and the risk factors for nonadherence to exclusive breastfeeding were described., Results: the prevalence of exclusive breastfeeding was 30.6%, unevenly distributed in the region, being the lowest in the Province of Messina (21.4%). Nonadherence to exclusive breastfeeding was associated with the disadvantage of the low context culture (χ2: 14.9), and was more common in the areas with higher socioeconomic deprivation index (odds ratio - OR: 1.81). Among other determinants investigated, being premature was a risk factor for not being breastfed (OR: 1.59)., Conclusion: the study confirms a low prevalence of breastfeeding in Sicily and its association with the socioeconomic level, being lower among women living in higher disadvantage areas. Moreover, this study confirms the association with co-sleeping practices (rooming-in and bed-sharing) for preterm babies. However, mother-child bed-sharing is not a guarantee for a successful breastfeeding, indeed being associated with a higher risk of SIDS. Finally, the study suggests the need for appropriate interventions focusing on specific high-risk groups.

Background: Thalassemia minor (Tm) individuals, are generally considered healthy. However, the prognosis of Tm individuals has not been extensively studied. The aim of this study was to evaluate the prognosis of Tm versus controls without β-thalassemia carrier state., Methods: A total of 26,006 individuals seeking thalassemia screening at the AOOR Villa Sofia-V. Cervello, Palermo (Italy) were retrospectively studied. Logistic penalised regression model was used to estimate risk of potential complications and survival techniques were used to study mortality., Results: We identified a total of 4943 Tm and 21,063 controls. Tm was associated with significantly higher risks of hospitalisation for cirrhosis (OR 1·94, 95% CI 1·30 to 2·90, p = 0·001), kidney disorders (OR 2·11, 95% CI 1·27 to 3·51, p = 0·004), cholelithiatis (OR 1·39, 95% CI 1·08 to 1·79, p = 0·010), and mood disorders (OR 2·08, 95% CI 1·15 to 3·75, p = 0·015). No statistically difference in life expectancy between thalassemia minor and control group was found (HR 1·090, 95% CI 0·777 to 1·555, p < 0·590; log-rank test p = .426)., Conclusion: This study shows that Tm affects the prognosis of Tm carriers regarding health expectation. Probably, iron overload and anaemia for several years may be at the basis of these effects., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Purpose: Somatropin [recombinant growth hormone (rGH)] is approved in children and adults for several conditions involving growth disturbances and the corresponding biosimilar is available in Italy since 2006. No population-based data are available on the pattern of rGH use in Italian clinical practice. This study aimed at exploring the pattern of biosimilar and originator rGH use in six Italian centers, where different policy interventions promoted biosimilar use., Methods: This population-based, drug-utilization study was conducted in the years 2009-2014, using administrative databases of Umbria, Tuscany, and Lazio Regions and Local Health Units of Caserta, Treviso, and Palermo. Naïve rGH users were characterized, and prevalence of use and discontinuation were assessed over time., Results: Among 6,785 patients treated with rGH during the study years, 4,493 (66.2%) were naïve users (males/females = 1.3), mostly affected by GH deficiency. The prevalence of rGH use increased from 2009 to 2010, remaining stable thereafter, but it was heterogeneous across centers (twofold higher prevalence of use in center n.2 than centers n.4 and 1 in 2014). Biosimilar rGH uptake increased over time but was low (7.8% in 2014) and heterogeneous as well. Discontinuation of rGH therapy occurred in 54.0% of naïve users, more frequently in females than males (58.1 vs. 50.9%). During the first year of treatment, discontinuation was frequent (39.9%), but no statistically significant differences were observed in treatment persistence for biosimilar vs. originator rGH ( p  > 0.05)., Conclusion: Geographical heterogeneity in the prevalence of rGH use was observed. Similarly, the biosimilar rGH uptake was low and variable across centers. Post-marketing monitoring is required to continuously monitor the benefit-risk profile of rGH, thus guaranteeing greater savings than only promoting lowest cost rGH.

Objectives: to propose a composite indicator for maternity hospital classification., Design: descriptive analysis of maternity hospitals through a composite indicator and analysis of its association with infant readmissions within 30 days from the childbirth., Setting and Participants: 56 maternity units in Sicily, accounting for 44.436 newborns in 2014., Main Outcome Measures: infant readmission rates within 30 days from the childbirth., Results: low-level hospitals show higher infant readmission rates (odds ratio: 1.3) which may be seen as a signal of inappropriateness of maternity care., Conclusions: the proposed indicator allows for a classification of maternity hospitals taking into account for different dimensions of the quality of care; it allows the identification of critical signals related to the considered dimensions.

Aim: Primary endpoint was to report polypharmacy distribution in the general population vs ≥65 years old people and to examine the frequency of drug-drug interactions (DDIs) in the Health Local Unit of Palermo, Italy, in relationship with patients' age., Methods: Drug prescription data for the year 2014 were extracted from the database of the Local Health Unit of Palermo Province, Italy. Patients were divided into five age groups (0-13, 14-64, 65-69, 70-74, and ≥75 year old). The detection of potential DDIs in polypharmacy profiles was performed with NavFarma software (Infologic srl, Padova, Italia), with DDI classification provided by tool Micromedex Drug Reax (Truven Health Analitics, Michigan, USA)., Results: We analyzed data of 1,324,641 patients, and 15,801,191 medical prescription were recorded; of these, 11,337,796 regarded chronic conditions. The drug prescriptions reached the highest values in the 65-69 and 70-74 age groups (p = 0.005 and p = 0.008 vs age 14-64 respectively). An overall amount of 6,094,373 DDIs were detected, of which 47,173 were contraindicated. Median number of DDIs was higher in 65-69 and 70-74 age groups (p = 0.008 and p = 0.012 vs age 14-64, respectively). Regarding contraindicated DDIs a significant difference was detected comparing 14-64 vs ≥65 age groups (p = 0.010 vs 65-69 group, p = 0.005 vs 70-74 group and ≥75 group)., Conclusions: Polypharmacy is a phenomenon acquiring increasing dimensions also in our province. It interests particularly the older subjects, and assumes a dramatic accent when it is put in relationship with the frequency of DDIs. A proactive vigilance about potential life threatening drug interactions is mandatory.

Objective: To develop and validate a novel comorbidity score (multisource comorbidity score (MCS)) predictive of mortality, hospital admissions and healthcare costs using multiple source information from the administrative Italian National Health System (NHS) databases., Methods: An index of 34 variables (measured from inpatient diagnoses and outpatient drug prescriptions within 2 years before baseline) independently predicting 1-year mortality in a sample of 500 000 individuals aged 50 years or older randomly selected from the NHS beneficiaries of the Italian region of Lombardy (training set) was developed. The corresponding weights were assigned from the regression coefficients of a Weibull survival model. MCS performance was evaluated by using an internal (ie, another sample of 500 000 NHS beneficiaries from Lombardy) and three external (each consisting of 500 000 NHS beneficiaries from Emilia-Romagna, Lazio and Sicily) validation sets. Discriminant power and net reclassification improvement were used to compare MCS performance with that of other comorbidity scores. MCS ability to predict secondary health outcomes (ie, hospital admissions and costs) was also investigated., Results: Primary and secondary outcomes progressively increased with increasing MCS value. MCS improved the net 1-year mortality reclassification from 27% (with respect to the Chronic Disease Score) to 69% (with respect to the Elixhauser Index). MCS discrimination performance was similar in the four regions of Italy we tested, the area under the receiver operating characteristic curves (95% CI) being 0.78 (0.77 to 0.79) in Lombardy, 0.78 (0.77 to 0.79) in Emilia-Romagna, 0.77 (0.76 to 0.78) in Lazio and 0.78 (0.77 to 0.79) in Sicily., Conclusion: MCS seems better than conventional scores for predicting health outcomes, at least in the general population from Italy. This may offer an improved tool for risk adjustment, policy planning and identifying patients in need of a focused treatment approach in the everyday medical practice., Competing Interests: Competing interests: GC received research support from the European Community (EC), the Italian Agency of Drug (AIFA) and the Italian Ministry of Education, University and Research (MIUR). GC took part in a variety of projects that were funded by pharmaceutical companies (ie, Novartis, GSK, Roche, AMGEN, BMS). GC also received honoraria as member of Advisory Board from Roche., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

"OBJECTIVES: to investigate the increase of PM10 during Saharan dust outbreaks with adverse health effects in Sicily (Southern Italy), the largest Mediterranean Island., Design: pooled analyses of time series with Poisson regression models to estimate the association between PM10 from different sources (desert and non-desert) and different outcomes., Setting and Participants: the four largest cities of Sicily (Palermo, Catania, Syracuse, and Messina) and three macroareas (North- East, South, and West) Sicily was divided into., Main Outcome Measures: daily count of cause-specific (ICD-9 codes) mortality and hospital admissions: natural (0-799), cardiovascular (390-459), and respiratory causes (460-519)., Results: 962 days affected by Saharan dust (30% of all days: 2,257) were identified. Significant associations between desert PM10 and natural mortality both in the cities and in the macro-areas were found, with increases of risk and 95% confidence intervals equal to 1.1% (95%CI 0.1-2.1) and 1.1% (95%CI 0.8-1.5) per 10 μg/m3 increase in lag 0-1 PM10, respectively. Weaker estimates were found for cardiorespiratory mortality. Desert PM10 displayed an association with respiratory hospitalizations, especially in the three macroareas (0.5%; 95%CI 0.1-1.0). In contrast, cardiovascular hospitalizations were associated only with non-desert PM10 in the four cities (1.3%; 95%CI 0.4- 2.1%). Higher desert PM10-related mortality was found during the warmer months (period: April-September): 2.7% (95%CI 0.8-4.5) in the four cities and 2.5% (95%CI 1.8%-3.2%) in the three macroareas. CONCLUSIONS PM10 originating from desert was positively associated with mortality and hospitalizations in Sicily. Policies should aim to reduce anthropogenic emissions even in areas with large contribution from desert sources."

Background: The aim of this study was to estimate the cost of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (AVR) procedures, together with the cost of the first-year hospitalizations following the index ones, in 4 Italian regions where diffusion level of TAVI and coverage decisions are different., Methods: The cost analysis was performed evaluating 372 patients enrolled consecutively from December 1, 2012 to September 30, 2015. The index hospitalization cost was calculated both from the hospital perspective through a full-costing approach and from the regional healthcare service perspective by applying the regional reimbursement tariffs. The follow-up costs were calculated for one year after the index hospitalization, from the regional healthcare sservice perspective, through the identification of hospital admissions for cardiovascular pathologies after the index hospitalization and computation of the relative regional tariffs., Results: The mean hospitalization cost was € 32 120 for transfemoral TAVI (232 procedures), € 35 958 for transapical TAVI (31 procedures) and € 17 441 for AVR (109 procedures). From the regional healthcare service perspective, the mean transfemoral TAVI cost was € 29 989, with relevant regional variability (range from € 19 987 to € 36 979); the mean transapical TAVI cost was € 39 148; the mean AVR cost was € 32 020. The mean follow-up costs were € 2294 for transfemoral TAVI, € 2335 for transapical TAVI, and € 2601 for AVR., Conclusions: In our study, transapical TAVI resulted more expensive than transfemoral TAVI, while surgical AVR was cheaper than both (less than 40%). Costs of the transfemoral approach showed great variability between participating regions, probably due to different hospital costs, logistics, patients' selection and reimbursement policy. A central level of control would be appropriate to avoid unjustified differences in access to innovative procedures between different Italian regions.

Background: Granulocyte colony-stimulating factors (G-CSFs) are biological products for which the main indication of use is chemotherapy-induced neutropenia. Biosimilars of G-CSFs have been available in Europe since 2007., Objective: The objective of this study was to investigate the prescribing pattern of G-CSFs in five Italian centres using different healthcare policy interventions to promote the use of biosimilars in routine care., Methods: This retrospective, population-based drug utilization study was conducted during the years 2009-2014 using the administrative databases of the Caserta, Treviso and Palermo Local Health Units (LHUs) and the Tuscany and Umbria regions. G-CSF users were characterized and the prevalence of use, proportion of biosimilar users and switching pattern of different G-CSFs were evaluated over time and across centres., Results: Overall, 30,247 patients were treated with G-CSFs in the years 2009-2014, of which 29,083 (96.2 %) were naïve users. The overall prevalence of G-CSF use increased from 0.8 per 1000 inhabitants in 2009 to 1.1 per 1000 in 2014. An increase in the proportion of the use of the biosimilar filgrastim by the total G-CSF users was observed in all centres: from 0.2 % (2009) to 66.2 % (2014). However, heterogeneity across different centres was reported, with the largest increase in Treviso LHU (from 0 to 89.1 % from 2009 to 2014). During the first year of treatment, switching between different G-CSFs was frequent (20.3 %)., Conclusions: Heterogeneity in the use of G-CSF and, in particular, biosimilar filgrastim across different Italian centres was observed, probably due to different regional healthcare policy interventions. During the first year of treatment, switching between different G-CSFs was frequent. Considering the impact of biological drugs on pharmaceutical expenses, it is necessary to harmonize healthcare policies promoting the use of biological drugs with the lowest cost.

Health impact assessment (HIA) is a multidisciplinary method aimed at assessing the health effects of policies, plans, and projects using quantitative, qualitative, and participatory techniques. In many European countries, such as in Italy, there is a lack of implementation of HIA procedures and it would be necessary to develop instruments and protocols in order to improve the specific skills of professionals involved in the assessment process. This article aims to describe the development and implementation of HIA guidelines, promoted by the Italian National Agency for Regional Health Services (AGENAS), in 4 Southern Italian regions. Public health search engine and institutional Web sites were consulted to collect international data existing in this field. Monthly workshops were then organized with regional representatives to discuss the scientific literature and to identify the guidelines' contents: source of data, stakeholders, screening- and scoping-phase checklist tools, priority areas, monitoring, and reporting plans. Four regions (Calabria, Campania, Puglia, and Sicilia) took part in the project. This article describes the methodology of development and implementation of HIA guidelines in the Italian context. The tools created to collect data and assess health consequences (such as screening and scoping grids) are reported. This project represents the first structured initiative proposed and supported by the Ministry of Health aiming to introduce HIA in Italy. HIA should be considered a priority in the public health agenda, as a fundamental instrument in helping decision makers to make choices about alternatives to prevent disease/injury and to actively promote health.