Are autopsies on minors a taboo?: The experience of Milan in a 19-year retrospective study.

Forensic autopsy is an important tool for the proper management of non-natural deaths in minors. However, it seems that autopsy in minors is a practice which may not be performed routinely. In this framework, we conducted a study analyzing autopsies of minors (under 18 years of age in Italy) performed at the Institute of Forensic Medicine in Milan in the period 2001-2019. For the period 2015-2019, we extrapolated all deaths due to non-natural causes in minors to investigate how many and which of these deaths were not subjected to forensic autopsy. Of the total, 344 minors (235 males and 109 females) underwent autopsies, with an overall downward trend of about 80% since 2004. Most autopsies occurred between the ages of 0 and 1 year, and the fewest between the ages of 5 and 9 years. The place of death was home in most cases, and accidental death was most common, followed by natural death, suicide, and homicide, with prevalence varying by age group. Blunt force trauma predominated among accidental death in all age groups, followed by asphyxia. Similar findings were observed for suicides, although there was a more differentiated pattern for suicides between the ages of 15 and 17 years. Among homicides, blunt force trauma, asphyxia, and gunshot wounds were fairly evenly distributed across all age groups. Between 2015 and 2019, a total of 86 minors died of a non-natural cause, and a forensic autopsy was performed in only 33 cases (38%). Our data shows that fewer and fewer autopsies are being performed over the last years, which indicates a dangerous lack of forensic investigation of children and adolescent deaths, with enormous implications for prevention of child abuse.

Estimated number of deaths attributable to NO2, PM10, and PM2.5 pollution in the Municipality of Milan in 2019.

BACKGROUND: there is growing evidence that exposure to environmental pollutants affects health, including mortality, chronic diseases, and acute diseases. The World Health Organisation has recently revised downwards the safety thresholds for exposure to environmental pollutants. The City of Milan (CoM) has particularly high levels of pollution; this is due both to the presence of various emission sources and to climatic and orographic conditions. OBJECTIVES: to describe the health effects of exposure to pollutants, measured by deaths due to environmental exposure to NO2, PM10, and PM2.5 in 2019. DESIGN: observational study. Using a pollutant concentration estimation model, annual mean values of NO2, PM10, and PM2.5 were estimated for the CoM in 2019. The number of deaths attributable to each exposure was estimated using risk functions available in the literature; the values recommended by the new World Health Organisation guidelines were used as counterfactual exposure limits. SETTING AND PARTICIPANTS: the population assisted by the Agency for Health Protection of Milan and resident in the CoM on 01.01.2019, aged 30 years or older. The place of residence was georeferenced and the population was followed up until 31.12.2019. Deaths and their causes were obtained from the Causes of Death Registry. MAIN OUTCOME MEASURES: deaths attributable to exposure from non-accidental causes, cardiovascular diseases, respiratory diseases, and lung cancer were estimated. RESULTS: in 2019, the estimated annual average level of NO2 was 36.6 µg/m3, that of PM10 was 24.9 µg/m3, and that of PM2.5 was 22.4 µg/m3, with levels varying across the city area. Concerning exposure to NO2, in 2019 10% of deaths for natural causes were estimated to be attributable to annual mean levels of NO2 above 10 µg/m3. As regard PM2.5, 13% of deaths for natural causes and 18% of deaths from lung cancer were attributable to an annual mean level above 5 µg/m3. The impact of exposure to particulate matter on mortality does not seem to be the same in all the areas of the CoM. CONCLUSIONS: the health impact of exposure to airborne particulate matter in the CoM population is high. It is important that citizens, policy-makers, and stakeholders address this issue, because of its impact on both health and healthcare costs.

[Analysis of predictive factors for non-adherence to organized screening for colorectal and breast cancers in the pre-pandemic period (2018-2019) in Lombardy Region (Northern Italy)]. / Analisi dei fattori predittivi della mancata adesione allo screening organizzato per i tumori del colon retto e della mammella nel periodo pre-pandemico (2018-2019) in Lombardia.

BACKGROUND: according to the International Agency for Cancer Research on Cancer, in 2022, breast cancer is the most common cancer in the Italian population, followed by colorectal cancer. Oncological screenings represent an effective secondary prevention strategy to counteract colorectal and breast cancers, significantly reducing mortality. In Lombardy Region (Northern Italy), screening programmes have been active since 2007, but adherence, especially in specific population subgroups, remains lower than expected. OBJECTIVES: to analyse potential predictors of non-adherence to colorectal and breast cancer screening in the Lombardy Region during the pre-pandemic period of 2018-2019. DESIGN: a retrospective cohort study aimed at investigating the role of sociodemographic variables, health status, and access to the healthcare system on non-adherence to colorectal and breast cancer screening. Statistical analyses were conducted separately by each Agency for Health Protection (ATS). The results of the models were synthesized across the Lombardy region through random-effects meta-analysis. SETTING AND PARTICIPANTS: residents within the territory of each ATS in Lombardy as of 01.01.2018 and aged between 49 and 69 years at the beginning of the follow-up. MAIN OUTCOMES MEASURES: adherence to colorectal and breast cancer screenings. RESULTS: during the study period, across the Lombardy Region, 2,820,138 individuals were eligible to participate in colorectal cancer screening, and 1,357,344 women were eligible to participate in breast cancer screening, with an invitation coverage of 87% and 86%, respectively.For breast cancer screening, older age, cardiopathy, chronic obstructive pulmonary disease (COPD), inflammatory bowel diseases (IBD), autoimmune diseases, and presence of a rare disease are associated with a reduced risk of non-adherence. Conversely, foreign citizenship, oncological diagnosis, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, and presence of a neurological diagnosis are associated with significant excess risks of non-participation. For colorectal cancer screening, factors favouring adherence include female gender, older age, cardiopathy, COPD, autoimmune diseases, and having access/utilization of primary care. Non-adherence is associated with foreign citizenship, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, IBD, neurological diseases, residence in assisted living facilities, use of integrated home care, and presence of disability. CONCLUSIONS: this is the first study conducted in the Lombardy Region which explores the theme of equity of access to organized screenings. This analysis highlights how sociodemographic determinants, chronic conditions, and access to the healthcare and social healthcare system constitute significant risk factors for non-adherence to screening programmes. Based on the results of this analysis, communication and/or organizational change interventions will be developed to counteract inequalities in access to effective prevention procedures.

Trends in mortality from non-natural causes in children and adolescents (0-19 years) in Europe from 2000 to 2018.

BACKGROUND: Non-natural mortality in children and adolescents is a global public health problem that varies widely from country to country. Data on child and adolescent maltreatment are not readily available, and mortality due to violent causes is also underestimated. METHODS: Injury-related mortality rates (overall and by specific causes) from 2000 to 2018 in selected European countries were analysed to observe mortality patterns in children and adolescents using data from the Eurostat database. Age-standardized mortality rates per 100,000 person-years were calculated for each country. Joinpoint regression analysis with a significance level of 0.05 and 95% confidence intervals was performed for mortality trends. RESULTS: Children and adolescent mortality from non-natural causes decreased significantly in Europe from 10.48 around 2005 to 5.91 around 2015. The Eastern countries (Romania, Bulgaria, Poland, Slovakia, Czech Republic) had higher rates; while Spain, Denmark, Italy, and the United Kingdom had the lowest. Rates for European Country declined by 5.10% per year over the entire period. Larger downward trends were observed in Ireland, Spain and Portugal; smaller downward trends were observed for Eastern countries (Bulgaria, Czech Republic, Poland, Slovakia) and Finland. Among specific causes of death, the largest decreases were observed for accidental causes (-5.9%) and traffic accidents (-6.8%). CONCLUSIONS: Mortality among children and adolescents due to non-natural causes has decreased significantly over the past two decades. Accidental events and transport accidents recorded the greatest decline in mortality rates, although there are still some European countries where the number of deaths among children and adolescents from non-natural causes is high. Social, cultural, and health-related reasons may explain the observed differences between countries.

[Reduction of adverse outcome due to COVID-19 infection in a high-risk population: evaluation of an informative intervention through active call by General Practitioners]. / Riduzione degli outcome sfavorevoli dovuti all'infezione da COVID-19 su una popolazione ad alto rischio: valutazione di un intervento informativo mediante chiamata attiva da parte dei medici di medicina generale.

BACKGROUND: currently, individuals at risk of adverse outcomes for COVID-19 can access to vaccination and pharmacological interventions. But, during the first epidemic wave, there were no treatments or therapeutic strategies available to reduce adverse outcomes in patients at risk. OBJECTIVES: to assess the impact of an intervention at 15-month follow-up developed by the Agency for Health Protection of the Metropolitan Area of Milan (ATS Milan) based on telephone triage and consultation by the General Practitioners (GPs) for patient with high-risk for adverse outcomes. DESIGN: intervention on population. SETTING AND PARTICIPANTS: a total of 127,292 patients in the ATS aged ≥70 years and with comorbidities associated with an increased risk of dying from COVID-19 infection were identified. Using a specific information system, patients were assigned to their GPs for telephone triage and consultation. GPs inform them about the risks of the disease, non-pharmacological prevention measures, and precautions in contacts with family members and other persons. No specific clinical intervention was carried out, only an information/training intervention was performed. MAIN OUTCOME MEASURES: by the end of May 2020, 48.613 patients had been contacted and 78.679 had not been contacted. Hazard Ratios (HRs) of infection hospitalisation and death at 3 and 15 months were estimated using Cox regression models adjusted by confounder. RESULTS: no differences in gender, age class distribution, prevalence of specific diseases, and Charlson Index were found between the two groups (treated such as called patients and not called). Called patients had a higher propensity for influenza and antipneumococcal vaccination and have more comorbidities and greater access to pharmacological therapies. Non-called patients have a greater risk for COVID-19 infection: HR was 3.88 (95%CI 3.48-4.33) at 3 months and 1.28 (95%CI 1.23-1.33) at 15 months; for COVID-19 hospitalization HR was 2.66 (95%CI 2.39-2,95) at 3 months and 1.31 (95%CI 1.25-1.37) at 15 months; for overall mortality HR was 2,52 (95%CI 2.35-2:72) at 3 months and 1.23 (95%CI 1.19-1.27) at 15 months. CONCLUSIONS: the results of this study show a reduction in hospitalization and deaths and support, in case of pandemic events, the implementation of new care strategies based on adapted stratification systems in order to protect the population's health. This study presents some limits: it is not randomized; a selection bias is present (called patients were those most in contact with the GPs); the intervention is indication-based (on march 2020, the actual benefit of protection and distancing for high-risk groups was unclear), and the adjustment is not able to fully control for confounding. However, this study points out the importance to develop information systems and improve methods to best protect the health of the population in setting of territorial epidemiology.

Exploring gender differences in medication consumption and mortality in a cohort of hypertensive patients in Northern Italy.

BACKGROUND: This paper aims to assess the presence of gender differences in medication use and mortality in a cohort of patients affected exclusively by hypertension, in 193 municipalities in the Lombardy Region (Northern Italy), including Milan's metropolitan area. METHODS: A retrospective cohort study was conducted (N = 232,507) querying administrative healthcare data and the Register of Causes of Death. Hypertensive patients (55.4% women; 44.6% men) in 2017 were identified; gender differences in medication use (treatment, 80% compliance) and deaths (from all causes and CVDs) were assessed at two-year follow-ups in logistic regression models adjusted for age class, census-based deprivation index, nationality, and pre-existing health conditions. Models stratified by age, deprivation index, and therapeutic compliance were also tested. RESULTS: Overall, women had higher odds of being treated, but lower odds of therapeutic compliance, death from all causes, and death from CVDs. All the outcomes had clear sex differences across age classes, though not between different levels of deprivation. Comparing patients with medication adherence, women had lower odds of death from all causes than men (with a narrowing protective effect as age increased), while no gender differences emerged in non-compliant patients. CONCLUSIONS: Among hypertensive patients, gender differences in medication consumption and mortality have been found, but the extent to which these are attributable to a female socio-cultural disadvantage is questionable. The findings reached, with marked age-dependent effects in the outcomes investigated, suggest a prominent role for innate sex differences in biological susceptibility to the disease, whereby women would take advantage of the protective effects of their innate physiological characteristics, especially prior to the beginning of menopause.

[Identifying deaths due to or involving COVID-19 in absence of the death certificate]. / Identificare i decessi riconducibili al COVID-19 in assenza del certificato di morte.

BACKGROUND: during 2020, Italy was one of the first nation hit by SARS-CoV-2, but it was not the hardest-hit country in terms of deaths. In absence of the death certificate, the burden of COVID-19 on mortality is usually calculated from overall deaths or from deaths of patients tested positive for COVID-19. However, these measures do not express the real burden of the disease on the population. OBJECTIVES: identify deaths due to or involving COVID-19 in absence of the death certificates. DESIGN: deaths for all causes, cause-specific deaths, COVID-19 hospitalization and COVID-19 confirmed cases between 01.01.2020 and 31.12.2021 observed in subjects residing in the territory of the ATS of Milan. Potential deaths due to or involving COVID-19 as those occurring in an optimal time period between the date of death and the date of positive swab and/or COVID-19 hospitalization, were identified. Optimal time period was defined maximizing sensitivity and specificity, comparing potential COVID-19 deaths with 2020 cause-specific mortality as gold standard, stratifying results by time of deaths, age, and number of comorbidities. Then, this method was further validated using a time-series approach to estimate the excess mortality during the COVID-19 outbreak in comparison with the pre-outbreak period 2015-2019. Accuracy of predictions was evaluated with the Root Mean Square Error (RMSE) between observed and predicted values. SETTING AND PARTICIPANTS: 78,202 deaths for all causes, of which 8,815 due to or involving COVID-19 as classified by the Milan Register of Death Causes for 2020. MAIN OUTCOME MEASURES: all-cause mortality, cause-specific mortality. RESULTS: from the beginning of the epidemic, 30% (23,495) died in the first semester of 2020, 26% (19,988) in the second semester of 2020, 23% (18,189) in the first semester of 2021, and 21% (16,530) in the second semester of 2021. COVID-19 hospitalizations were 13.826 (17%), while confirmed COVID-19 cases were 17,548 (22%). The optimal time intervals capable to identify a potential death due to or involving COVID-19 were 0-61 between the date of death and the date of positive swab and 0-11 between the date of death and the date of COVID-19 hospitalization, with an overall sensitivity of 90%, a specificity of 95%, and a RMSE of 3.6. Comparing the method proposed with the time-series approach, a RMSE in 2021 of 15.8 was found. Results showed different optimal time intervals for 2021 vs 2020 and by years of age and comorbidities. CONCLUSIONS: this study found that deaths due to or involving COVID-19 could be sensitively identified from the date of positive swab and/or COVID-19 hospitalization. This method can be used for public health interventions which provided so far measures in terms of total deaths instead of real numbers of COVID-19 death, in particular those involving the effective reproduction number usually calculated from overall mortality.

[Description of excess of overall and cause-specific mortality in the Agency for Health Protection of the Metropolitan Area of Milan (Lombardy Region, Northern Italy) in 2020]. / Descrizione degli eccessi di mortalità per tutte le cause e specifici per causa nell'ATS di Milano nel 2020.

BACKGROUND: as a result of the SARS-CoV-2 pandemic, a generalised mortality excess was recorded in 2020. However, the mortality for COVID-19 cannot fully explain the observed excesses. The analysis of cause-specific mortality could contribute to estimate the direct and indirect effects of the SARS-CoV-2 outbreak and to the monitoring mortality trends. OBJECTIVES: to describe the impact of the SARS-CoV-2 epidemic in overall and cause-specific mortality in population residing in the Agency for Health Protection (ATS) of Milan. Descriptive analysis of cause-specific mortality within thirty days of SARS-COV-2 infection. DESIGN: descriptive analysis of overall and cause-specific mortality in the ATS of Milan area in 2020 and comparison with a reference period (2015-2019). SETTING AND PARTICIPANTS: overall deaths in ATS of Milan in 2020 were collected, using the Local Registry of Causes of Death, and were classified according to the ICD-10 codes. MAIN OUTCOME MEASURES: total and weekly overall and cause-specific mortality, by age. RESULTS: in 2020, 44,757 deaths for all causes were observed in people residing in the ATS of Milan with percentage change of 35%. The leading cause of death in 2020 were cardiovascular disease and neoplasm; COVID-19 infection was the third cause. An excess of mortality was observed for most of all causes of deaths. Starting from 40-49-year age group, an increase of mortality was observed; the largest increase was observed in the group 70+ years. The largest increases were observed for endocrine, respiratory, and hypertensive diseases. On the contrary, for neoplasm, infectious (not COVID-19) diseases, traffic-related mortality, and cerebrovascular disease and ictus, a decrease of mortality was observed. The greater mortality increase was observed during the first pandemic wave. The leading cause of death after positive swab was COVID-19 infection, with little variation with age class. Other frequent causes of death were respiratory diseases, cardiovascular diseases, and neoplasm. CONCLUSIONS: the study showed a generalised increase for most causes of death; observed mortality trends may indicate delay in access to health care system, in diagnosis and treatment.

Boosters and time from the last anti-COVID-19 vaccine dose: lead public health choices by real-time epidemiological assessment.

BACKGROUND: the levels of anti-SARS-CoV-2 antibodies after the second vaccine dose decline in the following months; the administration of an additional vaccine dose (booster) is able to restore the immune system in the short period significantly reducing the risk of a severe disease. In the winter of 2021, a new particularly infectious variant caused the urgent need to increase the coverage of the booster dose. OBJECTIVES: to present, using real data, an evaluation of the efficacy of the booster dose in reducing the severe disease of SARS-CoV-2 infection in terms of hospital admissions, intensive care and death from all causes. DESIGN: descriptive study of vaccine adherence; associative study of the factors linked with adherence of vaccination and COVID-19 symptoms; associative study of vaccine effectiveness against hospital admission and mortality. SETTING AND PARTICIPANTS: population-based study in the Milan and Lodi provinces (Lombardy Region, Northern Italy) with subjects aged >=19 years alive at 01.10.2021, not residing in a nursery home, followed up to 31.12.2021. MAIN OUTCOME MEASURES: COVID-19 symptoms, hospitalization for COVID-19, intensive care hospitalization, and all-cause mortality in the period 01.10.2021-31.12.2021. RESULTS: the cohort included 2,936,193 patients at 01.10.2021: at the end of the follow-up period (31.12.2021), 378,616 (12.9%) had no vaccine, 128,879 (4.3%) had only 1 dose, 412,227 (14.0%) had a 2nd dose given since less than 4 months, 725. 806 (25%) had a 2nd dose given since 4-7 months, 74,152 (2.5%) had a 2nd dose given since 7+ months, 62,614 (2.1%) had a 2nd dose and have had the disease, and 1,153,899 (39.3%) received the booster. In the study period (01.10.2021-31.12.2021), characterized by a very high prevalence of the omicron variant, 121,620 cases (antigenic/molecular buffer positive), 3,661 hospitalizations for COVID-19, 162 ICU hospitalizations, and 7,508 deaths from all causes were identified. Compared to unvaccinated people, subjects who had the booster dose had half the risk of being symptomatic, in particular for asthenia, muscle pain, and dyspnoea which are the most commons COVID-19 symptoms. In comparison with the subjects who had the booster dose, the unvaccinated had a 10-fold risk of hospitalization for COVID-19, a 9-fold risk of intensive care, and a 3-fold risk of dying. CONCLUSIONS: this work highlights the vaccination efficacy in reducing serious adverse events for those who undergo the booster and the need to implement specific engagement policies to bring to a booster those who had taken the second dose since the longest time.

First SARS-CoV-2 vaccine booster and influenza vaccination: risk assessment of COVID-19 hospitalisation and death.

BACKGROUND: the influenza and SARS-CoV-2 viruses share a common respiratory symptomatology and transmission mode. COVID-19 and influenza R0 overlapped in the first epidemic wave. In autumn 2021-winter 2022, the influenza epidemic had a delayed onset compared to pre-COVID-19 years and lower incidence rates than in the pre-pandemic period. The SARS-CoV-2 and influenza vaccination campaign overlapped in 2021-2022. OBJECTIVES: to evaluate in the SARS-CoV-2 vaccinated cohort the effect of different timing of influenza vaccination on hospitalisations for COVID-19 and overall mortality. DESIGN: prospective cohort study. SETTING AND PARTICIPANTS: subjects aged 65 years or older who were administered the first booster dose of SARS-COV-2 vaccine between 01.10.2021 and 01.03.2022. Based on the date of influenza vaccination, subjects were divided into the following 4 different mutually exclusive groups: 1. two vaccinations in the same vaccination session; 2. influenza vaccination following SARS-CoV-2 vaccination; 3. influenza vaccination preceding SARS-CoV-2 vaccination; 4. no influenza vaccination. Using Cox regression models, hazard ratio (HR) and corresponding 95% confidence intervals (95% CI) of hospitalisation and death were estimated for the influenza-vaccinated subjects compared to influenza-unvaccinated subjects. MAIN OUTCOME MEASURES: ordinary hospital admissions for COVID-19 and general mortality. RESULTS: the cohort included 618,964 subjects: 16.3% received two vaccinations in the same vaccination session, 8.5% received the influenza vaccination after SARS-CoV-2 vaccination, 33.9% received it before and 41.1% did not receive an influenza vaccination. Those vaccinated against both SARS-CoV-2 and influenza had a combined HR of 0.73 (0.62-0.86) of hospitalisation for COVID-19 and 0.55 (0.49-0.62) of overall mortality compared to those vaccinated against SARS-CoV-2 only. CONCLUSIONS: influenza vaccination combined with SARS-CoV-2 vaccination increases the protective effect against hospitalisations and overall mortality compared to SARS-CoV-2 vaccination alone. Both organisational and communication actions aimed to promote and encourage vaccination are required.

Metabolic syndrome and risk of COVID-19-related hospitalization: a large, population-based cohort study carried out during the first European outbreak of SARS-CoV-2 infection in the Metropolitan area of Milan (Lombardy Region, Northern Italy).

BACKGROUND: since the beginning of the COVID-19 pandemic, specific characteristics of the infected subjects appeared to be associated with a severe disease, leading to hospitalization or death. OBJECTIVES: to evaluate the association between three components of the metabolic syndrome (diabetes mellitus, dyslipidaemia, and hypertension), alone and in combination, and risk of hospitalization in subjects with nasopharyngeal swab-confirmed COVID-19. DESIGN: cohort study. SETTING AND PARTICIPANTS: the study subjects were all COVID-19 cases diagnosed in the area of the Agency for Health Protection of the Metropolitan Area of Milan (Lombardy Region, Northern Italy) between 10.02.2020 and 25.04.2020, whose data were gathered with an ad hoc information system developed at the beginning of the pandemic. MAIN OUTCOME MEASURES: the association between metabolic syndrome components (alone and in combination) and hospitalization (both in any ward and in intensive care unit) was measured by means of cause-specific Cox models with gender, age, and comorbidities as potential confounders. RESULTS: the cohort included 15,162 subjects followed from diagnosis up to 20.07.2020. Adjusted hazard ratios (HRs) of hospitalization in any ward estimated by the Cox model were 1.26 for uncomplicated diabetes mellitus (95%CI 1.18-1.34); 1.21 for complicated diabetes mellitus (95%CI 1.05-1.39); 1.07 for dyslipidaemia (95%CI 1.00-1.14); and 1.11 for hypertension (95%CI 1.05-1.17). When all components coexisted in the same subject, the HR was 1.46 (95%CI 1.31-1.62). A significant increase in risk of hospitalization in intensive care unit was found for uncomplicated diabetes mellitus (HR 1.38; 95%CI 1.15-1.66). CONCLUSIONS: this population-based study confirms that metabolic syndrome components increase the risk of hospitalization for COVID-19. The HR increases in an additive manner when the three components are simultaneously present.

Validazione di un nuovo algoritmo per identificare le anomalie cromosomiche utilizzando i flussi sanitari correnti: il Registro delle malformazioni congenite di Milano.

OBJECTIVES: to assess the potential of a new algorithm based on current healthcare databases to identify potential cases of malformation, particularly chromosomal anomalies associated with terminations of pregnancy. DESIGN: retrospective observational study. SETTING AND PARTICIPANTS: Registry of Congenital Anomalies of Milan, live births, still births, and termination of pregnancies for fetal anomalies from 2012 to 2016, detected by using current healthcare data. MAIN OUTCOME MEASURES: prevalence between 2012 and 2016 of congenital malformations recorded by Milan's Registry of Congenital Anomalies, with particular regard to chromosomal anomaly trends. Variation in the percentage of malformations detected from terminations of pregnancy. RESULTS: prevalence of malformations increased from 270 in 2012 to 283 per 10,000 in 2016; specifically, chromosomal abnormalities increased from 35 to 51 per 10,000 births. The algorithm detected a greater proportion of anomalies associated with therapeutic abortion, especially with respect to chromosomal anomalies, with an increase from 57.7% in 2012 to 75.8% in 2016 (test for trend p=0.002). CONCLUSIONS: the proposed algorithm identified a greater number of chromosomal anomalies that caused termination of pregnancy and may be applied to existing Italian registries to evaluate the quality of healthcare services, in particular with regard to the effectiveness of prenatal trisomy screening policies. The algorithm may also be used where no active surveillance systems are present, as well as in epidemiological studies, to assess environmental impact on congenital anomalies.

Evaluation of the anti-COVID-19 vaccination campaign in the Metropolitan Area of Milan (Lombardy Region, Northern Italy).

OBJECTIVES: to present an evaluation of the campaign for vaccination against COVID-19 in the territory covered by the Agency for Health Protection of the Metropolitan Area of Milan from 01.01.2021 to 30.09.2021. DESIGN: descriptive study of vaccine adherence; predictive study of the factors associated with vaccine adherence, efficacy of vaccination in terms of hospitalization and mortality, and factors that increase the risk of hospital admission following full vaccination. SETTING AND PARTICIPANTS: population-based study with subjects aged >18 years eligible for vaccination (N. 2,981,997). An information system obtained by integrating various administrative healthcare sources made it possible to analyse socioeconomic characteristics, COVID-19 related hospitalizations, and general mortality in subjects eligible for vaccination. MAIN OUTCOME MEASURES: full vaccination (2 doses); COVID-19-related hospitalizations, COVID-19-related hospitalizations occurring more than 15 days after the second dose, general mortality. RESULTS: in the first nine months of the vaccination campaign, 74.7% of the subjects (N. 2,228,915) was fully vaccinated, whereas 15.6% (N. 465,829) did not even receive one dose. Women have a lower probability of getting vaccinated than men; the 50-59 years and 70+ years age groups emerge as the most problematic to reach, while the younger one (<40) is the most adherent. A social gradient emerged, with residents of more disadvantaged areas progressively less incline to get vaccinated than those living in more affluent areas. Adherence is greater in Italian citizenship and is likely to increase with an increase in the number of chronic conditions. Hospitalizations amounted to 1.22% (N. 5,672) in the unvaccinated population compared to 0.05% (N. 1,013) in the vaccinated population; general mortality was 4.51% (N. 15,198) in the unvaccinated population against 0.32% (N. 8.733) in the vaccinated population. Sociodemographic factors and the presence of previous health conditions are important predictors of hospitalization outcomes even within the fully vaccinated population. Specifically, the highest hazard ratios are found in subjects with heart failure (HR 2.15; 95%CI 1.83-2.53), in immunocompromised patients (HR 2.02; 95%CI 1.52-2.69), and in transplant recipients (HR 1.92; 95%CI 1.10-3.33). CONCLUSIONS: vaccination campaign adherence is affected by the sociodemographic characteristics of the population and is a determining factor in preventing hospitalizations for COVID-19 and death. The persistent higher risk of hospitalization in chronic subjects following the second dose emphasizes the need to direct booster doses to the more vulnerable. Information systems proved to be effective monitoring tools in the absence of specific trials.

Development of a multivariable model predicting mortality risk from comorbidities in an Italian cohort of 18,286 confirmed COVID-19 cases aged 40 years or older.

OBJECTIVES: to develop a risk prediction model for 30-day mortality from COVID­19 in an Italian cohort aged 40 years or older. DESIGN: a population-based retrospective cohort study on prospectively collected data was conducted. SETTING AND PARTICIPANTS: the cohort included all swab positive cases aged 40 years older (No. 18,286) among residents in the territory of the Milan's Agency for Health Protection (ATS-MI) up to 27.04.2020. Data on comorbidities were obtained from the ATS administrative database of chronic conditions. MAIN OUTCOME MEASURES: to predict 30-day mortality risk, a multivariable logistic regression model, including age, gender, and the selected conditions, was developed following the TRIPOD guidelines. Discrimination and calibration of the model were assessed. RESULTS: after age and gender, the most important predictors of 30-day mortality were diabetes, tumour in first-line treatment, chronic heart failure, and complicated diabetes. The bootstrap-validated c-index was 0.78, which suggests that this model is useful in predicting death after COVID-19 infection in swab positive cases. The model had good discrimination (Brier score 0.13) and was well calibrated (Index of prediction accuracy of 14.8%). CONCLUSIONS: a risk prediction model for 30-day mortality in a large COVID-19 cohort aged 40 years or older was developed. In a new epidemic wave, it would help to define groups at different risk and to identify high-risk subjects to target for specific prevention and therapeutic strategies.

Emergency attendance for acute hyper- and hypoglycaemia in the adult diabetic population of the metropolitan area of Milan: quantifying the phenomenon and studying its predictors.

BACKGROUND: We quantified, among diabetic adults, the frequency, costs, and factors associated with visits to the emergency department (EDs) and subsequent hospitalizations for acute hypoglycaemic and hyperglycaemic events. METHODS: We included adults with diabetes residing in the Milan Agency for Health Protection between 2015 and 2017. From healthcare databases, we identified demographic variables, comorbidities, type of treatment, insulin treatment duration, previous ED attendances for acute glycaemic events, and two indicators of glycaemic monitoring. Using a validated ICD-9-CM coding algorithm, we identified all ED attendances for acute glycaemic events from the ED database and calculated their incidence. We computed the direct costs from health databases and presented them as average annual mean costs for those having had at least an ED attendance. The analysis of the association between the number of ED attendances and potential determinants was performed using zero-inflated negative binomial regression models. These two-part models concomitantly estimate two sets of parameters: the odds-ratios (ORs) of having no attendances and the incidence rate ratios (IRRs) of attendance. RESULTS: The cohort included 168,285 subjects, 70% of subjects were older than 64 years, 56% were males, and 26% were treated with insulin. The incidence of acute glycaemic events for those attending the ED was 7.0 per 1000 patient-years, followed by hospitalization 26.0% of the time. The total annual direct cost for ED attendances due to acute glycaemic events was 174,000 €. Type of antidiabetic treatment had the strongest association with ED attendances for hypoglycaemia. Patients assuming insulin only had a lower probability of having no attendances (OR compared to those who assumed non-insulin antidiabetic drugs =0.01, 95% CI = 0.00-0.02). These patients also had the highest rate of hyperglycaemic episodes (IRR = 7.7, 95% CI = 5.1-11.7 for insulin only vs. non-insulin antidiabetic drugs). Subjects having had a previous episode of the same type leading to an ED visit had a higher rate of subsequent attendances (IRR for hypoglycaemia = 5.3, 95% CI = 3.9-7.3 and IRR for hyperglycaemia = 3.7, 95% CI = 1.3-10.2). CONCLUSION: Insulin treatment and having had a prior acute glycaemic event leading to an ED visit were major predictors of ED attendance for hyper and hypoglycaemia in a population of adults with diabetes.

Large community-acquired Legionnaires' disease outbreak caused by Legionella pneumophila serogroup 1, Italy, July to August 2018.

In July 2018, a large outbreak of Legionnaires' disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case-control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5-6 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case-control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic.

Describing the epidemic trends of COVID-19 in the area covered by Agency for Health Protection of the Metropolitan Area of Milan.

OBJECTIVES: to describe the epidemic trends of COVID-19 over time and by area in the territory covered by Milan's Agency for Health Protection (ATS-MI) from February to May 2020. DESIGN: descriptive study of COVID-19 cases. SETTING AND PARTICIPANTS: a new information system was developed to record COVID-19 cases with positive nasopharyngeal swab. Patients resident in the area covered by ATS-MI with symptom onset between February and May 2020 were selected. Different epidemic periods were considered based on the timeline of the various regional and national containment measures. MAIN OUTCOME MEASURES: case fatality ratios, incidence rates, and reproduction number by epidemic period and sub-area of ATS-MI. RESULTS: a total of 27,017 swab-positive COVID-19 cases were included. Mean age was 65 years and males were 45%. Incidence in the ATS-MI area was 776 per 100,000 population. The number of deaths was 4,660, the crude case fatality ratio was 17.3%, higher in males (21.2%) than in females (14.0%). The estimated reproduction number registered its peak (3.0) in the early stages of the epidemic and subsequently decreased. Territorial differences were observed in the epidemic spread, with a higher incidence in the Lodi area. CONCLUSIONS: estimated incidence and case fatality ratios were higher than national estimates for Italy. Each ATS-MI area had different epidemic spread patterns.

Assessment of the Overall Mortality during the COVID-19 Outbreak in the Provinces of Milan and Lodi (Lombardy Region, Northern Italy).

OBJECTIVES: to describe the overall mortality increase in the provinces of Milan and Lodi - area covered by the Agency for Health Protection of Milan - during the COVID-19 epidemic in the first four months of 2020, compare it with the same time period in the years 2016-2019, and evaluate to what extent the mortality can be directly attributed to the outbreak. DESIGN: cohort study. SETTING AND PARTICIPANTS: using a new information system developed during the pandemic, we gathered data on the number of daily deaths in the population residing in the provinces of Milan and Lodi by Local Health Unit (ASST) and age groups. To describe the case fatality of COVID-19, we performed a record linkage with a database specially constructed during the epidemic to identify deaths that occurred in confirmed cases. MAIN OUTCOME MEASURES: mortality and excess mortality were analysed by comparing the number of observed deaths in the first 4 months of 2020 with the average deaths of the years 2016-2019 in the same calendar period and with expected deaths, estimated using a Poisson model. Furthermore, a measure of relative risk was calculated as observed/expected ratio with a 95% confidence interval. RESULTS: the increase in mortality for all causes occurring in the study population in the first 4 months of 2020 was 48.8%, 30.8% for ages between 60 and 69, 43.9% for ages between 70 and 79, and 56.7% for subjects above 80 years of age. Focusing on the epidemic period, from 1 March to 30 April, the excess is quantifiable as more than 2-fold and mainly concerns the population over 60 years of age. The excess mortality was observed in all local health units (ASSTs). The highest increments were in the province of Lodi and the North-East of Milan (ASST Nord). In the ASSTs of Lodi and Melegnano-Martesana the mortality excess was detectable from March 15th, while for the other ASSTs the increase began in the first week of April. CONCLUSIONS: evaluation of overall mortality in the provinces of Milan and Lodi during the first wave of the Covid-19 epidemic showed a significant excess compared to the first 4 months of the years 2016-2019, mainly in the population over 60 years of age. However, this excess cannot be completely attributed directly to COVID-19 itself. This phenomenon was more intense in the Lodi ASST, with daily deaths up to 5 times higher than expected.

Effects of pollution, low temperature and influenza syndrome on the excess mortality risk in 2016-2017.

BACKGROUND: In the winter of 2016-2017, the number of deaths recorded in the north-west Europe was significantly higher than that in previous years. This spike in mortality was attributed principally to an influenza epidemic, but the contribution of air pollution and cold temperature has not been investigated. Information on the combined effect of low temperatures, influenza epidemic, and air pollution on mortality is inadequate. The objective of this study was to estimate the excess mortality in the winter of 2016-2017 in the metropolitan area of Milan, and to evaluate the independent short-term effect of 3 risk factors: low temperatures, the influenza epidemic, and air pollution. METHODS: We used a case-crossover, time-stratified study design. Mortality data were collected on all people aged > 65 years who died of natural causes, due to respiratory diseases or cardiovascular diseases, between December 1, 2016 and February 15, 2017. Environmental data were extracted from the Regional Environmental Protection Agency. The National Surveillance Network provided data on influenza epidemic. RESULTS: Among the 7590 natural deaths in people aged > 65 years, 965 (13%) were caused by respiratory conditions, and 2688 (35%) were caused by cardiovascular conditions. There were statistically significant associations between the minimum recorded temperature and deaths due to natural causes (OR = 0.966, 95% CI: 0.944-0.989), and cardiovascular conditions (OR = 0.961, 95% CI: 0.925-0.999). There were also statistically significant association between the influenza epidemic and deaths due to natural causes (OR = 1.198, 95% CI: 1.156-1.241), cardiovascular conditions (OR = 1.153, 95% CI: 1.088-1.223), and respiratory conditions (OR = 1.303, 95% CI: 1.166-1.456). High levels of PM10 (60 and 70 µg/m3) were associated with a statistically significant increase in natural and cause-specific mortality. There were statistically significant interactions between PM10 and influenza for cardiovascular-related mortality, and between influenza and temperature for deaths due to natural causes. CONCLUSIONS: Excess of mortality in Milan during winter 2016-2017 was associated with influenza epidemic and concomitant environmental exposures, specifically, the combined effect of air pollution and low temperatures. Policies mitigating the effects of environmental risk factors should be implemented to prevent future excess mortality.

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020.

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n = 305,044), while 42% of prevalent women had breast cancer (n = 604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since ≥15 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+ 37% vs 2010). The largest 10-year increases are foreseen for prostate (+ 85%) and for thyroid cancers (+ 79%), and for long-term survivors diagnosed since 20 or more years (+ 45%). Among the population aged ≥75 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation needs.