Drug utilization in patients starting haemodialysis with a focus on cardiovascular and antidiabetic medications: an epidemiological study in the Lazio region (Italy), 2016-2020.

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

Investigating socioeconomic disparities in lung cancer diagnosis, treatment and mortality: an Italian cohort study.

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

Pattern of care of brain tumor patients in the last months of life: analysis of a cohort of 3045 patients in the last 10 years.

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

Trend and determinants of mortality in incident hemodialysis patients of the Lazio region.

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

Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project).

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

SARS-CoV-2 spread and area economic disadvantage in the italian three-tier restrictions: a multilevel approach.

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

Use of inhaled corticosteroids in preschool children and variability among pediatricians: a real-world analysis before and during the SARS-CoV-2 pandemic.

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

Mortality Rate in Breast Implant Surgery: Is an Additional Procedure Worthwhile to Mitigate BIA-ALCL Risk?

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

[How to optimize Audit&Feedback: experience from the EASY-NET programme]. / Come rendere più efficace l'Audit&Feedback: riflessioni dal programma di rete EASY-NET.

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

Effectiveness and safety of gonadotropins used in female infertility: a population-based study in the Lazio region, Italy.

PURPOSE: Infertility is a topic of growing interest, and female infertility is often treated with gonadotropins. Evidence regarding comparative safety and efficacy of different gonadotropin formulations is available from clinical studies, while real-world data are missing. The present study aims to investigate effectiveness and safety of treatment with different gonadotropin formulations in women undergoing medically assisted procreation treatments in Latium, a region in central Italy, through a real-world data approach. METHODS: A retrospective population-based cohort study in women between the ages of 18 and 45 years who were prescribed with at least one gonadotropin between 2007 and 2019 was conducted. Women were enrolled from the regional drug dispense registry, and data on their clinical history, exposure to therapeutic cycles (based on recombinant "REC" or extractives "EXT" gonadotropin, or combined protocol "CMD" (REC + EXT)), and maternal/infantile outcomes were linked from the regional healthcare administrative databases. Multivariate logistic regression models were applied to estimate the association between exposure and outcomes. RESULTS: Overall, 90,292 therapeutic cycles prescribed to 35,899 women were linked to pregnancies. Overall, 15.8% of cycles successfully led to pregnancy. Compared to extractives, recombinant and combined treatments showed a stronger association with conception rate (RRREC adj = 1.06, 95% CI: 1.01-1.12; RRCBD adj = 1.17, 95% CI: 1.11-1.24). Maternal outcomes occurred in less than 5% of deliveries, and no significant differences between treatments were observed (REC vs EXT, pre-eclampsia: RR adj = 1.24, 95% CI: 0.86-1.79, ovarian hyperstimulation syndrome: RR adj = 1.25, 95% CI: 0.59-2.65, gestational diabetes: RR adj = 1.06, 95% CI: 0.84-1.35). Regarding infantile outcomes, similar results were obtained for different gonadotropin formulations (REC vs EXT: low birth weight: RR adj = 0.98, 95% CI: 0.83-1.26, multiple births: RR adj = 1.06, 95% CI: 0.92-1.23, preterm birth: RR adj = 1.03, 95% CI: 0.92-1.26). CONCLUSIONS: Efficacy and safety profiles of REC proved to be similar to those of EXT. Regarding the efficacy in terms of conception rate and birth rate, protocols using the combined approach performed slightly better. Outcomes related to maternal and infantile safety were generally very rare, and safety features were overlapping between gonadotropin formulations.

Long-term exposure to air pollution and risk of venous thromboembolism in a large administrative cohort.

BACKGROUND: Venous thromboembolisms (VTE) are one of the most frequent cause among the cardiovascular diseases. Despite the association between long-term exposure to air pollution and cardiovascular outcomes have been widely explored in epidemiological literature, little is known about the air pollution related effects on VTE. We aimed to evaluate this association in a large administrative cohort in 15 years of follow-up. METHODS: Air pollution exposure (NO2, PM10 and PM2.5) was derived by land use regression models obtained by the ESCAPE framework. Administrative health databases were used to identify VTE cases. To estimate the association between air pollutant exposures and risk of hospitalizations for VTE (in total and divided in deep vein thrombosis (DVT) and pulmonary embolism (PE)), we used Cox regression models, considering individual, environmental (noise and green areas), and contextual characteristics. Finally, we considered potential effect modification for individual covariates and previous comorbidities. RESULTS: We identified 1,954 prevalent cases at baseline and 20,304 cases during the follow-up period. We found positive associations between PM2.5 exposures and DVT, PE and VTE with hazard ratios (HRs) up to 1.082 (95% confidence intervals: 0.992, 1.181), 1.136 (0.994, 1.298) and 1.074 (0.996, 1.158) respectively for 10 µg/m3 increases. The association was stronger in younger subjects (< 70 years old compared to > 70 years old) and among those who had cancer. CONCLUSION: The effect of pollutants on PE and VTE hospitalizations, although marginally non-significant, should be interpreted as suggestive of a health effect that deserves attention in future studies.

The additional value of lung cancer screening program in identifying unrecognized diseases.

BACKGROUND: A systematic examination of low-dose CT (LDCT) scan, beside lung nodules, may disclose the presence of undiagnosed diseases, improving the efficacy and the cost/efficacy of these programs. The study was aimed at evaluating the association between LDCT scan findings and non-oncologic and oncologic diseases. METHODS: The LDCT scan of participants to the "Un Respiro per la vita"® lung cancer screening program were checked and abnormal findings, beside lung nodules, recorded. First admission to the acute care because of cardiovascular (CD), respiratory (RD) and oncological diseases (OD) in the following three years were retrieved. The association of LDCT scan abnormal findings with CD, RD and OD was assessed through univariable and multivariable logistic regression models. RESULTS: Mean age of 746 participants was 62 years (SD:5), 62% were male. 11 (1.5%) received a diagnosis of lung cancer. 16.1% participants were admitted to the acute care in the following three years: 8.6% for CD, 4.3% for RD and 5.2% for OD. Valve calcification (OR 2.02, p:0.02) and mucus plugs (OR 3.37, p:0.04) were positively associated with CD, while sub-pleural fibrosis had a protective role (OR 0.47, p:0.01). Lung nodules > 8 mm (OR 5.54, p: < 0.01), tracheal deviation (OR 6.04, p:0.01) and mucus plugs (OR 4.00, p:0.04) were positively associated with OD admissions. Centrilobular emphysema OR for RD admissions was 1.97 (p:0.06). CONCLUSIONS: The observed association between selected LDCT findings and ensuing CD, RD and OD suggests that the information potential of LCDT goes beyond the screening of lung cancer.

[Incidence of cancer among children and adolescents (0-19 years) in Lazio Region (Central Italy), 2009-2015]. / Incidenza di tumori nella popolazione infantile e adolescenziale (0-19 anni) della Regione Lazio, anni 2009-2015.

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

[Impact of the COVID-19 epidemic on total and cause-specific mortality in Rome (Italy) in 2020]. / Impatto dell'epidemia di COVID-19 sulla mortalità totale e per causa a Roma nel 2020.

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

[Geocoding one million of addresses using API: a semiautomatic multistep procedure]. / Geocodificare un milione di indirizzi mediante l'utilizzo di API: una procedura semiautomatica a più step.

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

School closures and mental health, wellbeing and health behaviours among children and adolescents during the second COVID-19 wave: a systematic review of the literature.

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

[Hospital assistance for COVID-19: a comparison between non-Italian and Italian resident population in five Italian Regions since the beginning of the pandemic until June 2021]. / Un confronto tra italiani e stranieri residenti nell'assistenza ospedaliera per COVID-19 in cinque Regioni italiane da inizio pandemia a giugno 2021.

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

Impact of the COVID-19 pandemic on access to healthcare services amongst patients with multiple sclerosis in the Lazio region, Italy.

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

Impact of antipsychotics in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis.

BACKGROUND: The net health benefit of using antipsychotics in children and adolescents with ASD is unclear. This review was performed to provide the evidence necessary to inform the Italian national guidelines for the management of ASD. METHODS: We performed a systematic review of randomized controlled trials (RCTs) comparing antipsychotics versus placebo for the treatment of ASD in children and adolescents. For efficacy, acceptability and safety we considered outcomes evaluated by the guideline panel critical and important for decision-making. Continuous outcomes were analyzed by using standardized mean difference (SMD), and dichotomous outcomes by calculating the risk ratio (RR), with their 95% confidence interval (95% CI). Data were analyzed using a random effects model. We used the Cochrane tool to assess risk of bias of included studies. Certainty in the evidence of effects was assessed according to the GRADE approach. RESULTS: We included 21 RCTs with 1,309 participants, comparing antipsychotics to placebo. Antipsychotics were found effective on "restricted and repetitive interests and behaviors" (SMD - 0.21, 95% CI - 0.35 to - 0.07, moderate certainty), "hyperactivity, inattention, oppositional, disruptive behavior" (SMD - 0.67, 95% CI - 0.92 to - 0.42, moderate certainty), "social communication, social interaction" (SMD - 0.38, 95% CI - 0.59 to - 0.16, moderate certainty), "emotional dysregulation/irritability" (SMD - 0.71, 95% CI - 0.98 to - 0.43, low certainty), "global functioning, global improvement" (SMD - 0.64, 95% CI - 0.96 to - 0.33, low certainty), "obsessions, compulsions" (SMD - 0.30, 95% CI - 0.55 to - 0.06, moderate certainty). Antipsychotics were not effective on "self-harm" (SMD - 0.14, 95% CI - 0.58 to 0.30, very low certainty), "anxiety" (SMD - 0.38, 95% CI - 0.82 to 0.07, very low certainty). Antipsychotics were more acceptable in terms of dropout due to any cause (RR 0.61, 95% CI 0.48 to 0.78, moderate certainty), but were less safe in terms of patients experiencing adverse events (RR 1.19, 95% CI 1.07 to 1.32, moderate certainty), and serious adverse events (RR 1.07, 95% CI 0.48 to 2.43, low certainty). CONCLUSIONS: Our systematic review and meta-analysis found antipsychotics for children and adolescents with ASD more efficacious than placebo in reducing stereotypies, hyperactivity, irritability and obsessions, compulsions, and in increasing social communication and global functioning. Antipsychotics were also found to be more acceptable, but less safe than placebo.

The impact of in-hospital cardiac rehabilitation program on medication adherence and clinical outcomes in patients with acute myocardial infarction in the Lazio region of Italy.

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