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Background: Standard of Care (SoC) has been used with different significance across Randomized Clinical Trials (RCTs) on the treatment of Covid-19. In the context of a living systematic review on pharmacological interventions for COVID-19, we assessed the characteristics of the SoC adopted in the published RCTs. Methods: We performed a systematic review searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to April 10, 2021. We included all RCTs comparing any pharmacological intervention for Covid-19 against any drugs, placebo, or SoC. All trials selected have been classified as studies with SoC including treatments under investigation for COVID-19 (SoC+); studies with SoC without specifications regarding the potential therapies allowed (SoC-); studies including as control groups Placebo (P) or active controls (A+). Results: We included in our analysis 144 RCTs, comprising 78,319 patients. Most of these trials included SoC (108; 75.0%); some in all arms of the study (69.7%) or just as independent comparators (30.3%). Treatments under investigation for COVID-19 in other trials were included in the SoC (SoC+) in 67 cases (62.0%), Thirty-one different therapeutic agents (alone or in combination) were counted within the studies with SoC+: mostly hydroxychloroquine or chloroquine (28), lopinavir/ritonavir (20) or azithromycin (16). No specification was given regarding treatment allowed in the control groups (SoC-) in 41 studies (38.0%). Conclusion: Our analysis shows that the findings emerging from several clinical trials regarding the efficacy and safety of pharmacological intervention for COVID-19 might be jeopardized by the quality of control arms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Addis, Amato, Cruciani, Saulle, De Crescenzo, Mitrova, Vecchi, Perrone and Davoli.)

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

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

Objective: To conduct a systematic review to evaluate the association between residential or occupational short- and long-term exposure to odour pollution from industrial sources and the health status of the exposed population., Methods: The searches were conducted in Medline, EMBASE and Scopus in April 2021. Exposure to an environmental odour from industrial sources in population resident near the source or in workers was considered. We considered outcomes for which there was a biological plausibility, such as wheezing and asthma, cough, headache, nausea and vomiting (primary outcomes). We also included stress-related symptoms and novel outcomes (e.g. mood states). Risk of bias was evaluated using the OHAT tool. For primary outcomes, when at least 3 studies provided effect estimates by comparing exposed subjects versus not exposed, we pooled the study-specific estimates of odour-related effect using random effects models. Heterogeneity was evaluated with Higgins I 2 ., Results: Thirty studies were eligible for this review, mainly cross-sectional (n = 23). Only one study involved school-age children and two studies involved workers. Only five studies reported odour effects on objective laboratory or clinical outcomes. Animal Feeding Operations and waste were the most common industrial sources. The overall odds ratios in exposed versus not exposed population were 1.15 (95% CI 1.01 to 1.29) for headache (7 studies), 1.09 (95% CI 0.88 to 1.30) for nausea/vomiting (7 studies), and 1.27 (95% CI 1.10 to 1.44) for cough/phlegm (5 studies). Heterogeneity was a moderate concern. Overall, the body of evidence was affected by a definitely high risk of bias in exposure and outcome assessment since most studies used self-reported information., Conclusions: Findings underline the public health importance of odour pollution for population living nearby industrial odour sources. The limited evidence for most outcomes supports the need for high quality epidemiological studies on the association between odour pollution and its effects on human health., (© 2021. The Author(s).)

Background: The factors associated with the inability to start hemodialysis with an arteriovenous fistula (AVF) in chronic kidney disease patients are not fully understood., Aim: Evaluating factors associated with type of vascular access at the first chronic hemodialysis and at 1 year after it., Methods: The study cohort includes patients registered in the Regional Dialysis and Transplant Registry of Lazio undergoing first hemodialysis between 2008 and 2015. Logistic regression models were used to evaluate the association between socio-demographic, clinical and care/organizational factors, and vascular access at first hemodialysis. Cox regression models were used to assess the odds of switching to AVF during the first year of hemodialysis among patients starting dialysis with central venous catheter (CVC)., Results: In the cohort of 6208 incident hemodialysis patients, 52.7% had an AVF and 47.3% had a CVC. Among the 2939 incident patients with CVC, 27.4% switched to FAV after 1 year. A higher probability of starting dialysis with AVF was observed among males (OR = 1.83; 95% CI 1.63-2.06), while a lower probability was observed among patients aged >85 years (OR 0.64; IC 95% 0.51-0.80). Patients with early referral to a nephrologist had a triple probability of start dialysis with AVF. We observed a higher odds of switch to AVF among males (HR = 1.62; 95% CI 1.40-1.89) and a lower odds among patients over 65 years., Conclusion: The observed high rate of AVF at the start of hemodialysis and of the switch from CVC to AVF in the first year, although declining since 2008, is a positive outcome. However, over one-third of patients maintain the CVC as vascular access for the first year because of unmodifiable factors, such as gender, age, comorbidity. The present study suggests that logistics/management and assistance/welfare problems may contribute to the delay or lack of AVF placement in incident hemodialysis patients or within the first year of dialysis.

There is an acute need for research to acquire high-quality information on the use of medicines in pregnancy, both in terms of appropriateness and safety. For this purpose, the Italian Medicines Agency established a Network for Monitoring Medication use in pregnancy (MoM-Net) through the conduction of population-based studies using administrative data available at regional level. This paper aimed to describe the experiences and challenges within the network. MoM-Net currently involves eight regions and several experts from public and academic institutions. The first study conducted aimed to identify drug use before, during and after pregnancy investigating specific therapeutic categories, analysing regional variability and monitoring drug use in specific subpopulations (i.e. foreign women/multiple pregnancies). Aggregated demographic, clinical, and prescription data were analysed using a distributed network approach based on common data model. The study population included all women delivering during 2016-2018 in the participating regions ( n = 449,012), and corresponding to 59% of deliveries in Italy. Seventy-three per cent of the cohort had at least one drug prescription during pregnancy, compared to 57% before and 59% after pregnancy. In general, a good adherence to guidelines for pregnant women was found although some drug categories at risk of inappropriateness, such as progestins and antibiotics, were prescribed. A strong variability in the use of drugs among regions and in specific subpopulations was observed. The MoM-Net represents a valuable surveillance system on the use of medicines in pregnancy, available to monitor drug categories at high risk of inappropriateness and to investigate health needs in specific regions or subpopulations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Belleudi, Fortinguerra, Poggi, Perna, Bortolus, Donati, Clavenna, Locatelli, Davoli, Addis, Trotta and MoM-Net group.)

Importance: Since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic, Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2) infection has been a serious challenge for immune-compromised patients with immune-mediated inflammatory diseases (IMIDs)., Objective: Our aim was to investigate the impact of COVID-19 in terms of risks of infection, hospitalization and mortality in a cohort of patients with rheumatoid arthritis (RA), psoriasis (PSO) or inflammatory bowel disease (IBD). Furthermore, we studied the impact of SARS-CoV-2 infection on the prescribed drug regimen in these patients., Methods: Through the record linkage between health information systems, a cohort of patients, ≥18 years old, assisted in the Lazio region and who had suffered from immune-mediated inflammatory diseases (RA, PSO, IBD) between 2007 and 2019, was identified. The risk of infection, hospitalization or mortality for COVID-19, was assessed by logistic regression models, and reported in an Odds Ratio (ORs; CI 95%), adjusting for sex, age and the Charlson Comorbidity Index. We also estimated these risks separately by IMID and in the subgroup of prevalent biologic drug users. We investigated deferral of biological treatments in the study population by comparing the prevalence of weekly use of biologicals (2019-2020) before and during the pandemic periods., Findings: Within the 65,230 patients with IMIDs, the cumulative incidence for COVID-19 was 303/10,000 ab. In this cohort of patients, we observed a significantly higher risk of SARS-CoV-2 infection than the general population: OR = 1.17 (95% CI 1.12-1.22). The risk was higher even considering separately each disease and in the subgroup of prevalent biologic drug users. This last subgroup of patients showed a higher risk of death related to COVID-19 (OR 1.89; 95% CI 1.04-3.33) than the general population. However, no differences in terms of risks of hospitalization or death related to COVID-19 were recorded in patients with the IMIDs. Comparing the 2019-2020 prevalence of weekly biological drug treatments in prevalent biologic drug users, we found a decrease (-19.6%) during the lockdown, probably due to pandemic restrictions., Conclusions and Relevance: Patients with IMIDs seem to have a higher risk of SARS-CoV2 infection. However, other than for patients with prevalent biologic drug treatment, no significant differences in terms of hospitalization and mortality were reported compared to the general populations; further investigation is warranted on account of unmeasured confounding. In addition, during the lockdown period, the COVID-19 emergency highlighted a lower use of biologic drugs; this phenomenon requires strict pharmacological monitoring as it could be a proxy of forthcoming long-term clinical progression.

Autism spectrum disorders (ASD) are serious, highly variable neurodevelopmental disorders, commonly characterized by the manifestation of specific behavioral abnormalities, such as stereotypic behaviors and deficits in social skills, including communication. Although the neurobiological basis for ASD has attracted attention in recent decades, the role of microglial cells, which are the main resident myeloid cell population in the brain, is still controversial and underexplored. Microglia play several fundamental roles in orchestrating brain development and homeostasis. As such, alterations in the intrinsic functions of these cells could be one of the driving forces responsible for the development of various neurodevelopmental disorders, including ASD. Microglia are highly sensitive to environmental cues. Amongst the environmental factors known to influence their intrinsic functions, the gut microbiota has emerged as a central player, controlling both microglial maturation and activation. Strikingly, there is now compelling data suggesting that the intestinal microbiota can play a causative role in driving the behavioural changes associated with ASD. Not only is intestinal dysbiosis commonly reported in ASD patients, but therapies targeting the microbiome can markedly alleviate behavioral symptoms. Here we explore the emerging mechanisms by which altered microglial functions could contribute to several major etiological factors of ASD. We then demonstrate how pre- and postnatal environmental stimuli can modulate microglial cell phenotype and function, underpinning the notion that reciprocal interactions between microglia and intestinal microbes could play a crucial role in ASD aetiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Davoli-Ferreira, Thomson and McCoy.)

Abstract: Guidelines for the treatment of rheumatoid arthritis (RA) recommend the use of conventional synthetic disease modifying anti-rheumatic drugs (cs-DMARDs) at the onset of the disease and only in the case of therapeutic failure, the addition of a biological drug (b-DMARD) is suggested.The study aimed to evaluate determinants for first-line biological treatment in patients with RA in clinical practice.A cohort of patients with RA, resident in Lazio, a central Italian Region, where Rome is located, and with at least one disease modifying anti-rheumatic drugs (DMARD) prescription between 2010 and 2016 was selected using health information systems linkable with each other by an individual unique anonymous identifier. In particular RA cohort was defined retrieving all patients with at least a RA disease code in regional data claims (hospital discharge, exemption code, emergency department access, or therapeutic plan). Only new users were included and the first-line treatment was identified: cs-DMARD or b-DMARD.Descriptive analysis according to type of DMARD treatment was performed. Through multivariate logistic regression models (odds ratio [OR]; confidence interval [CI95%]) determinants of therapy such as age, comorbidity, and comedication were investigated.Finally, switching during the first year of treatment from cs-DAMARDs to b-DMARDs was analyzed.DMARD-new users with RA were 5641; 7.1% of them with b-DMARD as first-line treatment. Considering the year of dispensing, this percentage ranged from 4.9% (2011) to 8.2% (2015). Among cs-DMARD the most prescribed active agent was methotrexate (59.3%), while among b-DMARD it was etarnecept (37.0%), followed by adalimumab (21.2%). The average age of the cohort was 54 years with 77% of women. Determinants of first-line b-DMARD use were: age (OR<30vs>65 = 3.7; 2.6-5.2, OR[30-45)vs>65 = 1.7; 1.2-2.4, OR[45-55)vs>65 = 1.6; 1.1-2.4, OR[55-65)vs>65 = 1.2; 0.8-1.7), cancers (OR = 2.3; 1.3-4.2), cardio-cerebrovascular disease (OR = 1.4; 1.0-1.9), use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR = 0.6; 0.4-0.7) and corticosteroids (OR = 0.6; 0.5-0.7) in the 6 months preceding diagnosis.In the first year of treatment, we observed a percentage of switch from cs-DMARDs to b-DMARDs of 7.9%.In clinical practice, about 7% of patients with RA are prescribed with a b-DMARD as first-line treatment. This therapeutic option, even if not supported by guide lines, is mostly link to younger age and clinical profile of the patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Percutaneous coronary intervention reduces mortality in acute coronary syndrome patients but the cost-utility of increasing its use in elderly acute coronary syndrome patients is unknown., Methods: We assessed the efficiency of increased percutaneous coronary intervention use compared to current practice in patients aged ≥75 years admitted for acute coronary syndrome in France, Germany, Greece, Italy, Portugal and Spain with a semi-Markov state transition model. In-hospital mortality reduction estimates by percutaneous coronary intervention use and costs were derived from the EUROpean Treatment & Reduction of Acute Coronary Syndromes cost analysis EU project (n = 28,600). Risk of recurrence and out-of-hospital all-cause mortality were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) database from North-Eastern Spain (n = 55,564). In-hospital mortality was modelled using stratified propensity score analysis. The 8-year acute coronary syndrome recurrence risk and out-of-hospital mortality were estimated with a multistate survival model. The scenarios analysed were to increase percutaneous coronary intervention use among patients with the highest, moderate and lowest probability of receiving percutaneous coronary intervention based on the propensity score analysis., Results: France, Greece and Portugal showed similar total costs/1000 individuals (7.29-11.05 m €); while in Germany, Italy and Spain, costs were higher (13.53-22.57 m €). Incremental cost-utility ratios of providing percutaneous coronary intervention to all patients ranged from 2262.8 €/quality adjusted life year gained for German males to 6324.3 €/quality adjusted life year gained for Italian females. Increasing percutaneous coronary intervention use was cost-effective at a willingness-to-pay threshold of 10,000 €/quality adjusted life year gained for all scenarios in the six countries, in males and females., Conclusion: Compared to current clinical practice, broadening percutaneous coronary intervention use in elderly acute coronary syndrome patients would be cost-effective across different healthcare systems in Europe, regardless of the selected strategy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Several pharmacological interventions are now under investigation for the treatment of Covid-19, and the evidence is evolving rapidly. Our aim is to assess the comparative efficacy and safety of these drugs. Methods and Findings: We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We included 96 RCTs, comprising of 34,501 patients. The network meta-analysis showed in terms of all-cause mortality, when compared to SC or placebo, only corticosteroids significantly reduced the mortality rate (RR 0.90, 95%CI 0.83, 0.97; moderate certainty of evidence). Corticosteroids significantly reduced the mortality rate also when compared to hydroxychloroquine (RR 0.83, 95%CI 0.74, 0.94; moderate certainty of evidence). Remdesivir proved to be better in terms of SAEs when compared to SC or placebo (RR 0.75, 95%CI 0.63, 0.89; high certainty of evidence) and plasma (RR 0.57, 95%CI 0.34, 0.94; high certainty of evidence). The combination of lopinavir and ritonavir proved to reduce SAEs when compared to plasma (RR 0.49, 95%CI 0.25, 0.95; high certainty of evidence). Most of the RCTs were at unclear risk of bias (42 of 96), one third were at high risk of bias (34 of 96) and 20 were at low risk of bias. Certainty of evidence ranged from high to very low. Conclusion: At present, corticosteroids reduced all-cause mortality in patients with Covid-19, with a moderate certainty of evidence. Remdesivir appeared to be a safer option than SC or placebo, while plasma was associated with safety concerns. These preliminary evidence-based observations should guide clinical practice until more data are made public., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 De Crescenzo, Amato, Cruciani, Moynihan, D’Alò, Vecchi, Saulle, Mitrova, Di Franco, Addis and Davoli.)

Background: Schools' closure during covid-19 pandemic implemented almost all over the world, together with social distances measures and lockdown to reduce transmission, could have had negative impact on youths' health., Aim: Summarize the most relevant data from a literature systematic review on the impact on youths' physical health of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic., Methods: Authors of the original review searched on 11 international databases up to 1st September 2020 to retrieve cohort studies, cross sectional surveys, uncontrolled pre-post studies and modelling studies. Methodological quality has been assessed with validated checklists., Results: Forty-two studies reporting the impact on physical health have been finally included. They have been conducted in 14 countries, most of which in Italy (30.9%) and UK (30.9%). The majority were cohort studies (40.5%) and the overall methodological quality, irrespective of study designs, was high for the 71.4% of the studies. Twenty-seven studies assessed the impact on health services utilization, whose results showed a relevant reduction of Emergency Departments accesses (64%-89.3%) and hospital admissions (31%-85%); however, an increase of acute cases was observed together with delayed admission. An important reduction of vaccine services utilization was also noted during the first period of lockdown. Domestic accidents and head trauma for suspected domestic violence increased. Health related behaviours worsened, with a relevant increase of screen time (mean of 2.9 hours to 5.1 hours), an important reduction of physical activity (up to 64%). Finally, sleep problems and increase of food consumption, particularly the unhealthy food were reported., Conclusions: Relevant negative effects of school closure and social distances measures have observed. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of closures implemented for relatively short periods. If school closure and rigid social distances measures imposition will extend for a long time, an even more pronounced negative effect can be expected. In the context of health policies, in addition to the potential benefits of school closures and social distancing measures on the containment of infection, the potential damage on the physical health of young people should be taken into account by implementing policies to safeguard their health.

Background: During the first semester 2020 almost all country implemented rigid measures of social distances, including schools closure, to limit the transmission of SARS-CoV-2 infection. Up to now, however, the efficacy of school closure to reduce the spread of the disease in the community still remain unclear and no much is known about the potential negative effects of such measures on physical health and psychological wellbeing of children and adolescents, mainly if protracted for long periods., Objective: To summarize the most relevant data of a systematic review on the impact of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic on youths physical health and psychological wellbeing. In the present paper we describe the review's methodology and the characteristics and methodological quality of the retrieved studies., Methods: We searched on 11 international databases up to 1st September 2020 to retrieve cohort studies, cross sectional surveys, uncontrolled pre-post studies and modelling studies. Methodological quality of included studies has been assessed with validated checklists., Results: Sixty-four studies have been included; 42 assessed the effect of social distances measure of physical health and 27 on psychological wellbeing. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of social distances measures implemented for relatively short periods. The 32.4% of the studies has been conducted in the UK, 20.3% in Italy, 12.5% in China, 10.9% in developing countries and 9.4% in the US. 37.5% of the studies were cohort studies, 40.6% cross sectional surveys, 19.7% uncontrolled studies and 1 was a modeling study. 59.6% of the studies has been rated as high quality. The most important weakness of the cross-sectional surveys and uncontrolled studies was the scarce representativeness of the sample while 96% of the cohort studies were judged as high quality., Conclusions: A large number of acceptable quality studies have been published during the first months of pandemic to assess the impact of school closure and social distances measures on physical health and psychological wellbeing of youths. This highlights the relevance of the topic and the need to assess carefully the balance between harms and benefits of such measures in terms of actual reduction of transmission and youths' psychological and physical harms. Further studies are needed on the long-term effect of social distances measures extended over long periods.

Background: During the first semester 2020 almost all country implemented rigid measures of social distances, including schools closure, to limit the transmission of SARS-CoV-2 infection. Up to now, however, the efficacy of school closure to reduce the spread of the disease in the community still remains unclear and no much is known about the potential negative effects of such measures on physical health and psychological wellbeing of youths, mainly if protracted for long periods., Objective: To summarize the data of a systematic review on the impact of the 2020 school closure and social distances measures implemented in response to covid-19 pandemic on youths' physical health and psychological wellbeing. In the present paper we describe the impact on psychological wellbeing., Methods: We searched 11 international databases up to 1st September 2020 to retrieve cohort studies, cross sectional surveys, uncontrolled pre-post studies and modelling studies. Methodological quality of included studies has been assessed with validated checklists., Results: Sixty-four studies have been included; 27 assessed the impact on psychological wellbeing. All the studies have been conducted during the first wave of pandemic and assessed the short-term effect of social distances measures implemented for relatively short periods. The majority of the studies were conducted in the UK (37,6%) and China (27%). The 42.3% has been judged of high methodological quality. Two studies reported an increase of suicides, while two studies reported a reduction of the access to Psychiatric Emergency Department, Maltreatment allegations decreased substantially, likely due to a reduction in reports rather than actual incidence. Prevalence of anxiety among adolescents ranged between 19% and 64%, depression between 22.3% and 43.7%. Among children 5-12 years old, prevalence of anxiety varied between 19% and 78%, while depression between 6.3% and 22.6%. Among pre-school children, some studies found worsening of behavioural and emotional problems while others did not., Conclusions: Most of the studies reported relevant worsening of the psychological wellbeing, mainly among adolescents. If school closure and rigid social distances measures will extend for a long time, an even more pronounced negative effect can be expected. Further studies are needed on the long-term effect of prolonged social distances measures, as well as a careful harm-benefit analysis of the impact of such measures.

Introduction There is evidence of improvement on mental health and well-being due to contact with green spaces, through various mechanisms and with potentially differential impacts in different populations. Many of these studies have been conducted among adults, while children have not been sufficiently investigated. This study aimed to evaluate the association between residential exposure to greenness and cognitive development at age 7 and to evaluate nitrogen dioxide (NO 2 ) as a potential mediator of this association.Methods This longitudinal study was based on a cohort of newborns enrolled at delivery in two large obstetric hospitals in Rome. We assessed cognitive development at 7 years of age through the Wechsler Intelligence Scale for Children-III edition (WISC-III). We estimated residential surrounding greenness, using satellite derived Normalized Difference Vegetation Index (NDVI), within 300m and 500m buffers around each residential address at birth. We applied weighted multiple linear regression analyses to study the association between NDVI and the WISC-III cognitive scores, using the inverse probability weighting methodology to correct for potential selection bias. We performed a mediation analysis to evaluate the mediating role of NO 2 in the association under study.Results We enrolled 719 children at birth and performed our analyses only on 465 children with data on exposure and outcome. The results were not consistent for the average residential surrounding greenness in 300m buffer. For an IQR increase in greenness within 500m buffer around home addresses at birth we found a progress in Arithmetic subtest (β:0.39; 90% CI: 0.11-0.6), a test concerning with attention, concentration and numerical reasoning, apart from an indication of the positive association with Full scale IQ and Verbal IQ. This association was partly mediated by reduction in NO 2 , since adding this pollutant in our model explained 35% (90% CI: 7%-62%) of our estimate.Conclusions Our findings showed an association between residential surrounding greenness within 500m and better scores on attention tests at 7 years of age. The observed association between Arithmetic subtest and NDVI was mediated, in part, by a reduction in NO 2 . This topic has important public health implications in supporting green urban planning policies and promoting children's well-being., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Background: SARS-CoV-2 is a coronavirus that causes a disease which can leads to a severe form of fatal pneumonia. At december 2020 in Italy, more than 2 million people have contracted the virus and 78,755 people have died. The scientific community is studying and testing numerous compounds that can be effective and safe for treating people with covid-19., Aim: To synthesize and evaluate the quality of evidence of efficacy and safety for the treatment. The available evidence is summarized in a living systematic review, a review that is constantly updated on the basis of the results of the new clinical studies., Methods: A bibliographic search is launched weekly on the electronic databases and on the main clinical trial registers. Two researchers independently select the articles and assess the quality of the studies using the criteria developed by the Cochrane Collaboration, the certainty of the overall quality of the evidence is assessed using the GRADE criteria., Results: At 31/12/2020, 101 randomized controlled studies were included that consider 72 different comparisons and include a total of 55,281 patients. 37 drugs are tested with respect to the standard treatment, 6 are evaluated against placebo and finally 29 compare different drugs with each other. By selecting studies that evaluate the efficacy and safety of a drug compared to standard treatment, which include at least 2 studies and which have low to high certainty of evidence, results show that corticosteroids, remdesivir, favipiravir, immunoglobulins, colchicine, and umbilical cord mesenchymal stem cell infusion could reduce overall mortality. No differences for the risk of any adverse events are observed between convalescent plasma and remdesivir compared to standard treatment. Remdesivir probably reduces the risk of serious adverse events; a similar effect, although less strong, is also noted for tocilizumab and the lopinavir-ritonavir combination. In contrast, hydroxychloroquine, corticosteroids and convalescent plasma transfusion are associated with safety concerns with respect to the risk of serious adverse events., Conclusions: The 101 studies included consider 72 comparisons and numerous outcomes, the results often coming from single studies and of small dimensions, and for 61% with a very low certainty of evidence, are difficult to summarize and the final result is to increase the uncertainty rather than providing useful information to the clinic and research. From all the work carried out it seems to us that the pandemic has highlighted the many shadows of scientific literature as tool to improve knowledge.

In Italy, reimbursement restrictions regarding palivizumab prophylaxis approved in 2016 have been revoked in 2017, restoring use in infants with Gestational Age (GA) >29 weeks. Respiratory Syncytial Virus (RSV) hospitalisations and prevalence of palivizumab use in infants aged <6 months during five seasons (2014-2019), were considered according to different GA. Although RSV hospitalisations rate showed no significant changes, during different seasons in all GA, lower prevalence of palivizumab use in 2016 (0.8% vs 0.3%), returned to a higher level following the revoke of restrictions. Changes in reimbursement criteria were not associated with neonatal RSV hospitalisations rate but with a significant impact on palivizumab use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although sex differences in cardiovascular diseases are recognised, including differences in incidence, clinical presentation, response to treatments, and outcomes, most of the practice guidelines are not sex-specific. Heart failure (HF) is a major public health challenge, with high health care expenditures, high prevalence, and poor clinical outcomes. The objective was to analyse the sex-specific association of socio-demographics, life-style factors and health characteristics with the prevalence of HF and diastolic left ventricular dysfunction (DLVD) in a cross-sectional population-based study., Methods: A random sample of 2001 65-84 year-olds underwent physical examination, laboratory measurements, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiography, and echocardiography. We selected the subjects with no missing values in covariates and echocardiographic parameters and performed a complete case analysis. Sex-specific multivariable logistic regression models were used to identify the factors associated with the prevalence of the diseases, multinomial logistic regression was used to investigate the factors associated to asymptomatic and symptomatic LVD, and spline curves to display the relationship between the conditions and both age and NT-proBNP., Results: In 857 men included, there were 66 cases of HF and 408 cases of DLVD (77% not reporting symptoms). In 819 women, there were 51 cases of HF and 382 of DLVD (79% not reporting symptoms). In men, the factors associated with prevalence of HF were age, ischemic heart disease (IHD), and suffering from three or more comorbid conditions. In women, the factors associated with HF were age, lifestyles (smoking and alcohol), BMI, hypertension, and atrial fibrillation. Age and diabetes were associated to asymptomatic DLVD in both genders. NT-proBNP levels were more strongly associated with HF in men than in women., Conclusions: There were sex differences in the factors associated with HF. The results suggest that prevention policies should consider the sex-specific impact on cardiac function of modifiable cardiovascular risk factors.

Objectives: This study aimed to measure adherence to chronic polytherapy following an acute myocardial infarction (AMI) and to find out associations between adherence and the setting of AMI onset (in vs out of hospital) as well as other determinants., Design: Retrospective follow-up study., Setting: Population living in the Lazio Region, Italy., Participants: This study included 25 779 hospitalised patients with a first diagnosis of AMI in 2012-2016, after the exclusion of those with hospital admission for AMI or related causes in the previous 5 years., Primary and Secondary Outcome Measures: Patients were classified as in-hospital AMI (IH-AMI) or out of hospital AMI (OH-AMI) according to present-on-admission codes. Adherence was measured based on prescription claims during a 6-month follow-up after hospital discharge, using medication possession ratio (MPR). Adherence to chronic polytherapy was defined as MPR ≥75% to at least 3 of the following medications: antithrombotics, betablockers, ACE inhibitors/angiotensin receptor blockers and statins., Results: Among the entire cohort, 1 044 (4%) patients suffered IH-AMI. Overall, 15 440 (60%) patients were deemed adherent to chronic polytherapy. Female gender, older age, mental disorders, renal disease, asthma and ongoing concomitant treatments were factors associated with poor adherence. By contrast, patients with more severe AMI and those already taking evidence-based (E-B) drugs were more likely to be adherent. A strong association between the setting of AMI onset and adherence was observed: IH-AMI patients were 46% less likely to be adherent to E-B medications during their 6-month follow-up as compared with OH-AMI patients (OR 0.54; 95% CI 0.47 to 0.62; p<0.001)., Conclusion: Pharmacotherapy is not consistent with clinical guidelines, especially for IH-AMI patients. Our findings provide evidence on a previously unidentified groups of patients at risk for poor adherence, who might benefit from greater medical attention and dedicated healthcare interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction and Aims: To corroborate protective effects of a range of drug treatment modalities against overdose mortality risk., Design and Methods: Nested case-control study, with incidence density sampling, selecting controls retrospectively at each case event. Cases and controls came from a sub-cohort of opioid-dependent patients (n = 4444) from two Italian regions (Lazio and Piedmont). From 1998 to 2005, there were 91 overdose deaths (cases) matched to 352 controls. The primary outcome was overdose mortality and the primary exposure was drug treatment: opioid agonist treatment (OAT), opioid detoxification, residential community, psychosocial and other pharmacological treatment. Conditional logistic regression models generated intervention effects comparing mortality risk in and out of treatment, adjusting for confounding variables., Results: Overall, drug treatment reduced overdose mortality risk by 80% [adjusted odds ratio (AOR) 0.18, 95% confidence interval (CI) 0.10-0.33, P < 0.001] compared to being out of treatment. There was a particularly strong protective effect of OAT on overdose mortality (AOR 0.08, 95% CI 0.03-0.23, P < 0.001) compared to being out of treatment. There was evidence of a substantially elevated risk of overdose in the first month of leaving treatment (AOR 23.50, 95% CI 7.84-70.19, P < 0.001) compared to being in treatment., Discussion and Conclusions: The nested case-control design strengthened earlier findings that OAT in Italy has strong protective effects on overdose mortality risk, much stronger than has been previously seen in other Western European settings., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

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.

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

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

Background: It is unclear whether the administration of antipsychotics to children and adolescents with autism spectrum disorders (ASD) is acceptable, equitable, and feasible., Methods: We performed a systematic review to support a multidisciplinary panel in formulating a recommendation on antipsychotics, for the development of the Italian national guidelines for the management of ASD. A comprehensive search strategy was performed to find data related to intervention acceptability, health equity, and implementation feasibility. We used quantitative data from randomized controlled trials to perform a meta-analysis assessing the acceptability and tolerability of antipsychotics, and we estimated the certainty of the effect according to the GRADE approach. We extracted data from systematic reviews, primary studies, and grey literature, and we assessed the risk of bias and methodological quality of the published studies., Results: Antipsychotics were acceptable (dropouts due to any cause: RR 0.61, 95% CI 0.48-0.78, moderate certainty of evidence) and well tolerated (dropouts due to adverse events: RR 0.99, 95% CI 0.55-1.79, low certainty of evidence) by children and adolescents with ASD. Parents and clinicians did not raise significant issues concerning acceptability. We did not find studies reporting evidence of reduced equity for antipsychotics in disadvantaged subgroups of children and adolescents with ASD. Workloads, cost barriers, and inadequate monitoring of metabolic adverse events were indirect evidence of concerns for feasibility., Conclusion: Antipsychotics in children and adolescents with ASD were likely acceptable and possibly feasible. We did not find evidence of concern for equity.

Background: The prevalence of opiate use among pregnant women can range from 1% to 2% to as high as 21%. Just in the United States alone, among pregnant women with hospital delivery, a fourfold increase in opioid use is reported from 1999 to 2014 (Haight 2018). Heroin crosses the placenta, and pregnant, opiate-dependent women experience a six-fold increase in maternal obstetric complications such as low birth weight, toxaemia, third trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neuro-behavioural problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. This is an updated version of the original Cochrane Review first published in 2008 and last updated in 2013., Objectives: To assess the effectiveness of any maintenance treatment alone or in combination with a psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions alone for child health status, neonatal mortality, retaining pregnant women in treatment, and reducing the use of substances., Search Methods: We updated our searches of the following databases to February 2020: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs)., Selection Criteria: Randomised controlled trials which assessed the efficacy of any pharmacological maintenance treatment for opiate-dependent pregnant women., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane., Main Results: We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high dropout rate (30% to 40%), and this was unbalanced between groups. Methadone versus buprenorphine: There was probably no evidence of a difference in the dropout rate from treatment (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.37 to 1.20, three studies, 223 participants, moderate-quality evidence). There may be no evidence of a difference in the use of primary substances between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.68, two studies, 151 participants, low-quality evidence). Birth weight may be higher in the buprenorphine group in the two trials that reported data MD;-530.00 g, 95%CI -662.78 to -397.22 (one study, 19 particpants) and MD: -215.00 g, 95%CI -238.93 to -191.07 (one study, 131 participants) although the results could not be pooled due to very high heterogeneity (very low-quality of evidence). The third study reported that there was no evidence of a difference. We found there may be no evidence of a difference in the APGAR score (MD: 0.00, 95% CI -0.03 to 0.03, two studies,163 participants, low-quality evidence). Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, may not differ between groups (RR 1.19, 95% CI 0.87 to1.63, three studies, 166 participants, low-quality evidence). Only one study which compared methadone with buprenorphine reported side effects. We found there may be no evidence of a difference in the number of mothers with serious adverse events (AEs) (RR 1.69, 95% CI 0.75 to 3.83, 175 participants, low-quality evidence) and we found there may be no difference in the numbers of newborns with serious AEs (RR 4.77, 95% CI 0.59, 38.49,131 participants, low-quality evidence). Methadone versus slow-release morphine: There were no dropouts in either treatment group. Oral slow-release morphine may be superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants, low-quality evidence). In the comparison between methadone and slow-release morphine, no side effects were reported for the mother. In contrast, one child in the methadone group had central apnoea, and one child in the morphine group had obstructive apnoea (low-quality evidence)., Authors' Conclusions: Methadone and buprenorphine may be similar in efficacy and safety for the treatment of opioid-dependent pregnant women and their babies. There is not enough evidence to make conclusions for the comparison between methadone and slow-release morphine. Overall, the body of evidence is too small to make firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: The public, policy makers, and science communities are subject to many false, uninformed, overly optimistic, premature, or simply ridiculous health claims. The coronavirus disease 2019 (COVID-19) pandemic and its context is a paramount example for such claims. In this article, we describe why expressing the certainty in evidence to support a decision is critical and why the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach matters now, perhaps more than ever and no matter what the specific topic is in relation to COVID-19. We finally also offer suggestions for how it can be used appropriately to support decision-making at global, national, and local level when emergency, urgent or rapid responses are needed., Study Design and Setting: This is an invited commentary to address the objectives above building on examples from the recent COVID-19 pandemic. This includes an iterative discussion of examples and development of guidance., Results: The GRADE approach is a transparent and structured method for assessing the certainty of evidence and when developing recommendations that requires little additional time. We describe why emergency, urgent, or rapid responses do not justify omitting this critical assessment of the evidence. In situations of emergencies and urgencies, such as the COVID-19 pandemic, GRADE can similarly be used to express and convey certainty in intervention effects, test accuracy, risk and prognostic factors, consequences of public health measures, and qualitative bodies of evidence., Conclusions: Assessing and communicating the certainty of evidence during the COVID-19 pandemic is critical. Those offering evidence synthesis or making recommendations should use transparent ratings of the body of evidence supporting a claim regardless of time that is available or needed to provide this response., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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

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

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

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

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

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

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

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

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

Objectives: to investigate the association between real estate prices, education, and mortality., Design: cohort study., Setting and Participants: residents in Rome at the 2011 Italian Census, not living in institutions, and living in the address reported in the Census survey. People aged 18-99 years were followed from 2011 to 2016 using anonymous record linkage procedures with administrative databases. The Census includes several individual information, such as gender, age, education, residential neighbourhood. Data and cause of death were collected from mortality register. Real estate prices (euros/m2) were available for each neighbourhood., Main Outcome Measures: adjusted Cox regression models (hazard ratios - HRs and 95%CIs) were used to estimate the association among individual education, real estate price in the neighbourhood, and mortality., Results: the subjects selected were 2,051,376 (54% women, 22.5% with high education level). During the follow-up, 127,352 subjects died. Taking into account gender, age, marital status, and real estate prices, education level was strongly associated with all-cause mortality; compared to highly educated the higher mortality, risk was 35% (95%CI 32%-37%) for low education level and 16% (95%CI 14%-19%) for medium education level. Taking into account the same factors and education level, each increase of 1,000 euros in price/m2 was inversely associated with mortality (HR 0.96, 95%CI 0.96-0.97)., Conclusions: there is an independent association between the two indicators and mortality in Rome. A simple indicator such as real estate prices can be used to tackle inequalities.

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

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

Cirrhosis is an advanced liver disease affecting millions of people worldwide, involving high healthcare costs. Despite experimental evidence suggesting a possible role of airborne pollutants in liver diseases, epidemiological studies are lacking. We aimed at investigating the association between exposure to air pollutants and incidence of cirrhosis in a large population-based cohort in Rome., Methods: We used an administrative cohort established from the 2001 census. We included all adults of 30 years of age or older who were free of cirrhosis, resulting in a study population of over 1.2 million subjects. Follow-up of the subjects ended on 31 December 2015. We ascertained incident cases of cirrhosis from regional mortality and hospital discharge registries using a validated algorithm. We assessed exposure of the subjects to PM 10 , PM coarse, PM 2.5 , PM 2.5 absorbance, NO 2 , NOx, and PM metal components at their residential address using Land Use Regression models. We used Cox regression models, adjusted for relevant covariates, to estimate the association between air pollution exposure and cirrhosis incidence., Results: We observed 10,111 incident cases of cirrhosis, with a crude incidence rate of 67 × 100,000 person-years. Long-term exposure to all pollutants tested was significantly associated with cirrhosis, e.g., PM 10 (hazard ratios [HR], 1.05; 95% confidence interval [CI], 1.01-1.09, per 10 µg/m 3 increments), PM coarse (HR, 1.11; 95% CI, 1.05-1.17, per 10 µg/m 3 increments), PM 2.5 (HR, 1.08; 95% CI, 1.03-1.13, per 5 µg/m 3 increments), and NO 2 (HR, 1.03; 95% CI, 1.02-1.05, per 10 µg/m 3 increments). The associations were robust in secondary analyses., Conclusions: Our findings suggest a possible contribution of air pollution to the development of cirrhosis., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report.Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

The inflammatory/immune response at the site of peripheral nerve injury participates in the pathophysiology of neuropathic pain. Nevertheless, little is known about the local regulatory mechanisms underlying peripheral nerve injury that counteracts the development of pain. Here, we investigated the contribution of regulatory T (Treg) cells to the development of neuropathic pain by using a partial sciatic nerve ligation model in mice. We showed that Treg cells infiltrate and proliferate in the site of peripheral nerve injury. Local Treg cells suppressed the development of neuropathic pain mainly through the inhibition of the CD4 Th1 response. Treg cells also indirectly reduced neuronal damage and neuroinflammation at the level of the sensory ganglia. Finally, we identified IL-10 signaling as an intrinsic mechanism by which Treg cells counteract neuropathic pain development. These results revealed Treg cells as important inhibitory modulators of the immune response at the site of peripheral nerve injury that restrains the development of neuropathic pain. In conclusion, the boosting of Treg cell function/activity might be explored as a possible interventional approach to reduce neuropathic pain development after peripheral nerve damage.

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

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

Introduction: The aim of the study was to identify the sociodemographic and clinical factors associated with death after the first lower-extremity amputation (LEA), minor and major separately, using data from regional health administrative databases., Research Design and Methods: We carried out a population-based cohort study including patients with diabetes residing in the Lazio region and undergoing a primary amputation in the period 2012-2015. Each individual was followed up for at least 2 years. Kaplan-Meier analysis was used to evaluate long-term survival; Cox proportional regression models were applied to identify factors associated with all-cause mortality., Results: The cohort included 1053 patients, 72% were male, 63% aged ≥65 years, and 519 (49%) died by the end of follow-up. Mortality rates at 1 and 4 years were, respectively, 33% and 65% for major LEA and 18% and 45% for minor LEA. Significant risk factors for mortality were age ≥65, diabetes-related cardiovascular complications, and chronic renal disease for patients with minor LEA, and age ≥75 years, chronic renal disease and antidepressant drug consumption for subjects with major LEA., Conclusions: The present study confirms the high mortality rates described in patients with diabetes after non-traumatic LEA. It shows differences between minor and major LEA in terms of mortality rates and related risk factors. The study highlights the role of depression as specific risk factor for death in patients with diabetes after major LEA and suggests including its definition and management in strategies to reduce the high mortality rate observed in this group of patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite the increased attention given to the health impact assessment of air pollution and to the strategies to control it in both scientific literature and concrete interventions, the results of the implementations, especially those involving traffic, have not always been satisfactory and there is still disagreement about the most appropriate interventions and the methods to assess their effectiveness. This state-of-the-art article reviews the recent interpretation of the concepts that concern the impact assessment, and compares old and new measurements of attributable risk and attributable fraction. It also summarizes the ongoing discussion about the designs and methods for assessing the air pollution impact with particular attention to improvements due to spatio-temporal analysis and other new approaches, such as studying short term effects in cohorts, and the still discussed methods of predicting the values of attributable risk (AR). Finally, the study presents the more recent analytic perspectives and the methods for directly assessing the effects of not yet implemented interventions on air quality and health, in accordance with the suggestion in the strategic plan 2020-2025 from the Health Effect Institute.

Objectives: Socioeconomic inequalities have a strong impact on population health all over the world. Occupational status is a powerful determinant of health in rich societies. We aimed at investigating the association between occupation and mortality in a large metropolitan study., Design: Cohort study., Setting: Rome, capital of Italy., Participants: We used the Rome Longitudinal Study, the administrative cohort of residents in Rome at the 2001 general census, followed until 2015. We selected residents aged 15-65 years at baseline. For each subject, we had information on sex, age and occupation (occupational status and type of job) according to the Italian General Census recognition., Main Outcome Measures: We investigated all-cause, cancer, cardiovascular and accidental mortality, major causes of death in the working-age population. We used Cox proportional hazards models to investigate the association between occupation and all-cause and cause-specific mortality in men and women., Results: We selected 1 466 726 subjects (52.1% women). 42 715 men and 29 915 women died during the follow-up. In men, 47.8% of deaths were due to cancer, 26.7% to cardiovascular causes and 6.4% to accidents, whereas in women 57.8% of deaths were due to cancer, 19.3% to cardiovascular causes and 3.5% to accidents. We found an association between occupational variables and mortality, more evident in men than in women. Compared with employed, unemployed had a higher risk of mortality for all causes with an HR=1.99 (95% CI 1.92 to 2.06) in men and an HR=1.49 (95% CI 1.39 to 1.60) in women. Compared with high-qualified non-manual workers, non-specialised manual workers had a higher mortality risk (HR=1.68, 95% CI 1.59 to 1.77 and HR=1.30, 95% CI 1.20 to 1.40, for men and women, respectively)., Conclusions: This study shows the importance of occupational variables as social health determinants and provides evidence for policy-makers on the necessity of integrated and preventive policies aimed at improving the safety of the living and the working environment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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

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

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