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Background Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. Objective The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. Methods A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010–2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. Results From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015–2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. Conclusion The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010–2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-021-00498-3.

Objective. Problematic Social Media Use (PSMU) has an addictive potential for young users. The aim of this study was to show the prevalence of PSMU across Italian regions and its association with health complaints. Materials and methods. Data are gathered from the Italian 2018 Health Behaviour in School-aged Children survey using a representative sample of Italian adolescents aged 11, 13 and 15 years (50.6% males). Participants completed self-administered questionnaires assessing PSMU and health complaints. Results. PSMU affects 8.9% adolescents in Italy and the prevalence is quite consistent across regions. 13-year-olds girls showed the highest percentage of PSMU (13%). Problematic users of social media are more likely to report multiple somatic (OR = 1.84 [95% CI 1.82-1.85]) and psychological (OR = 2.60 [95% CI 2.58-2.63]) symptoms. Conclusions. PSMU represents a widespread problem in Italy. National prevention interventions are needed in order to promote a positive use of social media.

Objective. The aim is to describe dietary habits and their association with socio-demographic characteristics in a large nationally representative sample of Italian adolescents aged 11, 13 and 15 years. Materials and methods. Data from the 2018 Italian Health Behaviour in School-aged Children (HBSC) survey on 58,976 adolescents were analysed to determine eating habits. Logistic regression was used to investigate the association between incorrect dietary habits and potential predictors. Results. 38.3% of boys and 48.1% of girls skipped breakfast and 54.1% did not consume fruit and/or vegetables daily. 15.9% of boys and 11.3% of girls drank carbonated-sugary beverages at least once a day. Incorrect dietary habits were more common among boys, adolescents with lower socio-economic conditions, residents in Southern Italy and those spending more time watching TV. Italian adolescents were more likely to have incorrect dietary habits compared with those from most other countries involved in 2018 HBSC. Conclusions. Action is needed to improve dietary habits among adolescents.

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.

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. 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. 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. 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. Electronic supplementary material The online version of this article (10.1007/s40264-019-00845-y) contains supplementary material, which is available to authorized users.

Rare disease registries are a priority at European level and specific actions are being implemented by the European Commission to support their development.In Italy, a National Registry of rare diseases has been established in 2001 as a network of regional registries. The latter have gradually been established and the full coverage of the Italian territory was attained during 2011.Here we describe the basic features of the National Registry of rare diseases; the activities carried out to promote consistent operations in the regional registries; and the overall quality and composition of the records collected.After a validation process, including removal of duplicate records, 110,841 records of patients with rare diseases, single and with group denominations, are stored in the National Registry of rare diseases. They correspond to the overall diagnoses communicated to national registry by regional registries up to 30 June 2012.The quality of the data collected by the the National Registry of rare diseases has been assessed with respect to completeness and consistency of procedures. Variables characterising case and diagnosis showed a very limited number of missing values. Records reported at least one case of 485 rare conditions.To date, the National Registry of rare diseases is a surveillance system with the main objective of producing epidemiologic evidence on rare diseases in Italy, and of supporting policy making and health services planning.Data quality still represents a limitation for any sound epidemiological estimate of rare diseases in Italy. However, improvements of the quality of collected data and the completeness of case notifications should be strengthened.

Protecting children's health from the effects of environmental contamination is a public health priority. In recent years, particular care has been devoted in Italy to the study of the relationship between environmental pollutants and health during infancy. The SENTIERI Project has called attention to increases in infant mortality in National Priority Contaminated Sites (NPCSs). SENTIERI KIDS provides a blueprint for the establishment of a task force charged with establishing multi and inter-disciplinary cooperation between central and regional institutions on the subject of children's health in contaminated sites. SENTIERI KIDS introduces a multiple outcome analytical model based on updated health outcomes (mortality, cancer incidence, hospital discharges) in order to establish a permanent observation system to monitor the state of health of infants residing in contaminated areas. This will pave the way for more in-depth epidemiological enquiries on an individual basis, and support the establishment and continued monitoring of primary prevention projects. Particular attention is devoted to issues of information and communication.

To show how malignant mesothelioma (MM) surveillance not only identifies settings of exposure representing past industrial history, but it may also detect conditions of current exposure relevant for the prevention, if the wide spectrum of asbestos uses is considered.Active search of MM cases and exposure assessment at individual level through a questionnaire; identification of exposure circumstances relevant for prevention.Italy, all the Regions where a Regional Operating Centre (COR) is established to identify all MM cases diagnosed in the population and analyze their occupational, residential, household and environmental histories. Period of diagnosis: 1993-2008.Descriptive analysis of MM cases and of asbestos exposures.ReNaM includes 15,845 cases of MM diagnosed between 1993 and 2008.The male/female ratio is 2.5. Mean age at diagnosis is 69 years. Pleural MMs represent 93% of all cases. Exposures have been investigated in 12,065 cases (76%). The median latency time is 46 years. In addition to clusters of MM cases in activities well known to entail asbestos use, different current exposure circumstances requiring intervention have been evidenced.On the basis of this experience, epidemiological surveillance of all occupational cancers should be implemented to foster synergies with the compensation system and the Local Health Authorities' occupational safety and health services, as required by the Italian Legislative Decree N. 81/2008.

Due to the large scale use of asbestos (more than 3.5 million tons produced or imported until its definitive banning in 1992), a specific national surveillance system of mesothelioma incident cases is active in Italy, with direct and individual anamnestic etiological investigation. In the period between 1993 and 2004, a case-list of 8,868 pleural MM was recorded by the Italian National Register (ReNaM) and the modalities of exposure to asbestos fibres have been investigated for 6,603 of them. Standardized incidence rates are 3.49 (per 100,000 inhabitants) for men and 1.25 for women, with a wide regional variability. Occupational asbestos exposure was in 69.3% of interviewed subjects (N = 4,577 cases), while 4.4% was due to cohabitation with someone (generally, the husband) occupationally exposed, 4.7% by environmental exposure from living near a contamination source and 1.6% during a leisure activity. In the male group, 81.5% of interviewed subjects exhibit an occupational exposure. In the exposed workers, the median year of first exposure was 1957, and mean latency was 43.7 years. The analysis of exposures by industrial sector focuses on a decreasing trend for those traditionally signaled as "at risk" (asbestos-cement industry, shipbuilding and repair and railway carriages maintenance) and an increasing trend for the building construction sector. The systematic mesothelioma surveillance system is relevant for the prevention of the disease and for supporting an efficient compensation system. The existing experience on all-too-predictable asbestos effects should be transferred to developing countries where asbestos use is spreading.

Adverse health effects of particulate matter

ObjectivesTo 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.DesignRetrospective observational cohort study.SettingPopulation-based study using the healthcare utilisation database from five Italian regions.ParticipantsBeneficiaries 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 measureThe 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).ResultsWe 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.ConclusionsA 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.

ObjectiveTo 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.MethodsAn 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.ResultsPrimary 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.ConclusionMCS 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.

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.

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 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., With breast cancer patients experiencing longer survival, emphasizing their overall health through management of late and long‐term treatment effects is becoming increasingly important. This article reports a multiregional real‐world population‐based cohort investigation carried out to compare short‐term and long‐term cardiovascular risk of symptomatic cardiovascular events in women with localized breast cancer treated with trastuzumab‐based or standard adjuvant therapy in clinical practice.

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 β0 /β0 , β0 /β+ , β+ /β+ , β0 /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, β0 and β+ mutations showed similar risk profiles. Upon adjustment for demographics and receipt of conventional therapy, patients with β0 /β0 , β0 /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 β0 mutations in strata of greatest severity.

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

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 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.

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.

Background and aims To validate a set of indicators for monitoring the quality of care of patients with diabetes in ‘real-life’ practice through its relationship with measurable clinical outcomes and healthcare costs. Methods and results A population-based cohort study was carried out by including the 20,635 patients, residents in the Lombardy Region (Italy), who in the year 2012 were newly taken-in-care for diabetes. Adherence with clinical recommendations (i.e., controls for glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine) was recorded during the first year after the patient was taken-in-care, and categorized according whether he/she complied with none or almost none (0 or 1), just some (2) or all or almost all (3 or 4) the recommendations, respectively denoted as poor, intermediate and high adherence. Short- and long-term complications of diabetes, and healthcare cost incurred by the National Health Service, were assessed during follow-up. Compared with patients with poor adherence, those with intermediate and high adherence respectively showed (i) a delay in outcome occurrence of 13 days (95% CI, -2 to 27) and 23 days (9 to 38), and (ii) a lower healthcare cost of 54 € and 77 €. In average, a gain of 18 Euros and 15 Euros for each day free from diabetic complication by increasing adherence respectively from poor to intermediate and from poor to high were observed. Conclusion Close control of patients with diabetes through regular clinical examinations must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes.

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

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.

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&ndash, 4.27) and in the very deprived class (OR: 1.83, CI 95% 1.00&ndash, 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.

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.

Background Infant mortality rate (IMR) is a key public health indicator. Maternal age is a well-known determinant of pregnancy and delivery complications and of infant morbidity and mortality. In Italy the Infant Mortality Rate was 3.7/1000 during 2005, lower than the average IMR for the European Union (4.94/1000). Sicily is the Italian region with the highest IMR, 5/1000, and neonatal mortality rate (NMR), 3.8/1000, with substantial variation among its nine districts. The present study compared a high IMR/NMR district (Messina) with a low IMR/NMR district (Palermo) during the period 2004-2006 to evaluate potential determinants of the IMRs' differences between the two districts and specifically the impact of maternal age. Methods The Death Causes Registers identified all deaths during the first year of life recorded among infants born to residents of the two districts in 2004-2006. For every case, available hospital charts records were abstracted using a standardized form designed to capture information on potential determinants of infant death. For each district and for each year, IMRs and NMRs were computed. Chi-squared statistics tested the significance of differences between district-specific IMRs. A Poisson regression model was used to analyze the relationship between maternal age, district of residence and IMR. Results The 246 death registry-confirmed cases included 143 (58.1%) males and 103 (41.2%) females, with mean age at death of 33.3 days (SD: 64.5, median: 5.5). The average IMR for 2004-2006 was significantly higher for the Messina district than for the Palermo district (p = 0.0001). The IMR ratio was 1.6 (95%CI: 1.2 - 2.1). The IMRs declined from 2004 to 2006. A significant interaction (p = 0.04) between maternal age and district of residence was documented. Conclusion The association between advanced maternal age and infant deaths in the Messina district was due in part to the excess of newborns from advanced age mothers, but also to increased risk of death among such newborns. The significant interaction between district of residence and maternal age indicated that the IMR excess in the Messina district cannot be explained by disproportionately high live birth rates among older mothers and suggested the hypothesis that health care facilities in the Messina district could be less well prepared to provide assistance to the excess of high risk pregnancies and deliveries, as compared to Palermo district.

Background: Despite the widespread use of transcatheter aortic valve implantation (TAVI), the role of sex on outcome after TAVI or surgical aortic valve replacement (AVR) has been poorly investigated. We investigated the impact of sex on outcome after TAVI or AVR. Methods: There were 2108 patients undergoing TAVI or AVR who were enrolled in the Italian Observational Multicenter Registry (OBSERVANT). Thirty-day mortality, major periprocedural morbidity, and transprosthetic gradients were stratified by sex according to interventions. Results: Female AVR patients showed a worse risk profile compared with male AVR patients, given the higher mean age, prevalence of frailty score of 2 or higher, New York Heart Association class of 3 or higher, lower body weight, and preoperative hemoglobin level (P ≤.02). Similarly, female TAVI patients had a different risk profile than male TAVI patients, given a higher age and a lower body weight and preoperative hemoglobin level (P ≤.005), but with a similar New York Heart Association class, frailty score, EuroSCORE (P = NS), a better left ventricular ejection fraction and a lower prevalence of left ventricular ejection fraction less than 30%, porcelain aorta, renal dysfunction, chronic obstructive pulmonary disease, arteriopathy, and previous cardiovascular surgery or percutaneous coronary intervention (P ≤.01). Women showed a smaller aortic annulus than men in both populations (P