Estimating Overall and Cause-Specific Excess Mortality during the COVID-19 Pandemic: Methodological Approaches Compared.

During the COVID-19 pandemic, excess mortality has been reported worldwide, but its magnitude has varied depending on methodological differences that hinder between-study comparability. Our aim was to estimate variability attributable to different methods, focusing on specific causes of death with different pre-pandemic trends. Monthly mortality figures observed in 2020 in the Veneto Region (Italy) were compared with those forecasted using: (1) 2018-2019 monthly average number of deaths; (2) 2015-2019 monthly average age-standardized mortality rates; (3) Seasonal Autoregressive Integrated Moving Average (SARIMA) models; (4) Generalized Estimating Equations (GEE) models. We analyzed deaths due to all-causes, circulatory diseases, cancer, and neurologic/mental disorders. Excess all-cause mortality estimates in 2020 across the four approaches were: +17.2% (2018-2019 average number of deaths), +9.5% (five-year average age-standardized rates), +15.2% (SARIMA), and +15.7% (GEE). For circulatory diseases (strong pre-pandemic decreasing trend), estimates were +7.1%, -4.4%, +8.4%, and +7.2%, respectively. Cancer mortality showed no relevant variations (ranging from -1.6% to -0.1%), except for the simple comparison of age-standardized mortality rates (-5.5%). The neurologic/mental disorders (with a pre-pandemic growing trend) estimated excess corresponded to +4.0%/+5.1% based on the first two approaches, while no major change could be detected based on the SARIMA and GEE models (-1.3%/+0.3%). The magnitude of excess mortality varied largely based on the methods applied to forecast mortality figures. The comparison with average age-standardized mortality rates in the previous five years diverged from the other approaches due to the lack of control over pre-existing trends. Differences across other methods were more limited, with GEE models probably representing the most versatile option.

[Residential cohort study to assess the impact of emissions released by a cement plant on the health status of the population residing in Pederobba (Veneto Region, Northern Italy)]. / Studio di coorte residenziale per valutare l'impatto delle emissioni di un cementificio sullo stato di salute della popolazione di Pederobba (Treviso).

OBJECTIVES: to assess the impact of a cement plant emissions on mortality, hospitalizations, and cancer incidence in the residents of the municipality of Pederobba (Veneto Region, Northern Italy). DESIGN: retrospective residential cohort study. SETTING AND PARTICIPANTS: the study was conducted in Pederobba and in 7 neighbouring municipalities (Cavaso Del Tomba, Cornuda, Crocetta del Montello, Monfumo, Segusino, Valdobbiadene, Vidor). The cohort included 12,116 residents in Pederobba (151,784 person-years) and 49,004 residents in the neighbouring municipalities (660,268 person-years) in the period 1996-2017. On the basis of the model estimate of the annual average concentration of nitrogen dioxide (NO2), the municipality of Pederobba was divided into an area with higher exposure of NO2 and another one at lower exposure of NO2. Two comparisons were made: the first between the residents in Pederobba and residents in the neighbouring municipalities; the second between people residing in Pederobba in the higher and in the lower exposure areas. MAIN OUTCOME MEASURES: analysis of cause-specific mortality and hospitalization and cancer incidence, with particular attention to the diseases for which there is evidence of association with exposure to air-pollutants. For cancer incidence, available data were limited to the municipalities of Pederobba, Cavaso Del Tomba, Cornuda, Crocetta del Montello, and Monfumo for the period 1996-2015. RESULTS: the comparison among Pederobba and the 7 neighbouring municipalities showed that within Pederobba residents there was:ʉۢ a slight increase in the risk of death from all causes in women, due to circulatory diseases (HR 1.29; 95%CI 1.15-1.45), in particular ischaemic heart disease (HR 1.55; 1.27-1.89) and cerebrovascular diseases (HR 1.35; 1.06-1.72);ʉۢ a moderate increase in hospitalizations for circulatory diseases, such as heart failure (HR 1.17; 1.00-1.37) and cerebrovascular diseases (HR 1.41; 1.17 -1.70), especially in elderly women;ʉۢ a slight increase in hospitalizations for respiratory diseases, especially in older women (HR 1.19; 1.04-1.37);ʉۢ no difference were observed in cancer incidence, neither for all nor for single cancer sites, in both genders.The comparison between residents in the higher exposure area and those in the lower exposure area showed no difference in mortality, hospitalizations, and cancer incidence. CONCLUSIONS: higher mortality and hospitalization rates from circulatory and respiratory causes detected in Pederobba compared to the neighbouring municipalities were not confirmed by the comparison between residents in the higher and in the lower exposure area. Overall, data did not show a clear, well-characterized relationship between the exposure to pollutants emitted by the cement plant and the onset of chronic diseases. The excess of mortality and hospitalization for cardiovascular and cerebrovascular diseases, reported especially in older women, deserves further investigation, because of the complex cause-effect relations of these diseases.

[Effects of high temperature and air pollution on the risk of preterm births. Analysis in six Italian cities, 2001-2010]. / Effetti delle alte temperature e dell'inquinamento atmosferico sul rischio di nascita pretermine. Analisi in sei città italiane, 2001-2010.

OBJECTIVES: to evaluate the association between short term maternal exposure to high temperature and air pollution on preterm births (PBs), which represent the first cause of perinatal mortality and morbidity in developed Countries, and to identify maternal risk factors enhancing individual susceptibility. DESIGN: time series. SETTING E PARTICIPANTS: all singleton live-births occurred in six Italian cities between 1st April and 31st October of each year in the period 2001-2010 were identified through the Certificate of Delivery Care Registry (CedAP). MAIN OUTCOME MEASURES: births occurred between 22nd and 36th week of gestation were defined as preterm births. Daily values were obtained for maximum apparent temperature (MAT), PM10, NO2, and O3. Exposures-preterm births association was estimated using a generalized additive model (GAM) with a Poisson distribution. Exposure and city-specific lag structure were computed using a non-linear distributed lag model (DLNM). RESULTS: 121,797 newborns were enrolled, 6,135 (5.0%) of which were PBs. For MAT, a linear relationship was observed for Turin (Piedmont Region, Northern Italy), Trieste (Friuli Venezia Giulia Region, Northern Italy), Rome (Lazio Region, Central Italy), and Palermo (Sicily Region, Southern Italy), while non-linear relationship was found for Bologna (Emilia-Romagna Region, Northern Italy) and Venice (Veneto Region, Northern Italy). The relative risks (RR) for MAT, computed comparing the 90th vs. the 75th percentile, vary from 1.02 (95%CI 0.95-1.09; lag 0-2) in Palermo to 1.94 (95%CI 1.32-2.85; lag 0-3) in Venice. For pollutants, a significant effect for 10 µg/m3 (IQR) increase of PM10 in Rome (RR: 1.07; 95%CI 1.02-1.12; lag 12-22) and for 16 µg/m3 (IQR) increase of O3 in Palermo (RR: 1.29; 95%CI 1.03-1.62; lag 2-9) was detected. In Rome, a significant effect modification by age and education level of the MAT-PB relationship and by education level and clinical conditions of PM10-PB was found. CONCLUSIONS: results showed a clear positive association between MAT and the risk of NP and a lower and variable effect of pollutants. It is important and necessary to limit the impact of these risk factors on the probability of NP with appropriate prevention programmes.

The effect of job loss on pharmaceutical prescriptions.

We estimate the effect of job loss on the probability that long-tenured workers are prescribed anti-hypertensive and psychotropic drugs. We exploit two administrative data sources from the Veneto region in Italy and estimate an event-study model. Our results indicate that the probability of drug prescription increases among under-40 males but not among older males or female workers. We suggest that the effect on younger male workers is the combined result of their typical role as breadwinners, limited wealth buffers in case of layoff, and unfavourable employment legislative protection.

Cohort profile: the Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS), a multicentre cohort for socioeconomic inequalities in health monitoring.

PURPOSE: The Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS) is a system of integrated data on health outcomes, demographic and socioeconomic information, and represents a powerful tool to study health inequalities. PARTICIPANTS: IN-LiMeS is a multicentre and multipurpose pool of metropolitan population cohorts enrolled in nine Italian cities: Turin, Venice, Reggio Emilia, Modena, Bologna, Florence, Leghorn, Prato and Rome. Data come from record linkage of municipal population registries, the 2001 population census, mortality registers and hospital discharge archives. Depending on the source of enrolment, cohorts can be closed or open. The census-based closed cohort design includes subjects resident in any of the nine cities at the 2001 census day; 4 466 655 individuals were enrolled in 2001 in the nine closed cohorts. The open cohort design includes subjects resident in 2001 or subsequently registered by birth or immigration until the latest available follow-up (currently 31 December 2013). The open cohort design is available for Turin, Venice, Reggio Emilia, Modena, Bologna, Prato and Rome. Detailed socioeconomic data are available for subjects enrolled in the census-based cohorts; information on demographic characteristics, education and citizenship is available from population registries. FINDINGS TO DATE: The first IN-LiMeS application was the study of differentials in mortality between immigrants and Italians. Either using a closed cohort design (nine cities) or an open one (Turin and Reggio Emilia), individuals from high migration pressure countries generally showed a lower mortality risk. However, a certain heterogeneity between the nine cities was noted, especially among men, and an excess mortality risk was reported for some macroareas of origin and specific causes of death. FUTURE PLANS: We are currently working on the linkage of the 2011 population census data, the expansion of geographical coverage and the implementation of the open design in all the participating cohorts.

Ethnic inequalities in acute myocardial infarction hospitalization rates among young and middle-aged adults in Northern Italy: high risk for South Asians.

The knowledge of ethnic-specific health needs is now essential to design effective health services and population-based prevention strategies. However, data on migrant populations living in Southern Europe are limited. The study is designed to investigate ethnic inequalities in hospitalization for acute myocardial infarction (AMI) in the Veneto region (Italy). Hospital admissions for AMI in Veneto for the whole resident population aged 20-59 years during 2008-2013 were studied. Age and gender-specific AMI hospitalization rates for immigrant groups (classified by country of origin according to the United Nations geoscheme) and Italians were calculated. The indirect standardization method was used to estimate standardized hospitalization ratios (SHR) for each immigrant group, with rates of Italian residents as a reference. Overall, 8200 AMI events were retrieved, 648 among immigrants. The highest risk of AMI is seen in South Asians males (SHR 4.2, 95% CI 3.6-4.9) and females (SHR 2.5, 95% CI 1.4-4.5). AMI rates in South Asian males sharply increase in the 30-39 years age class. Other immigrant subgroups (Eastern Europe, North Africa, Sub-Saharan Africa, other Asian countries, Central-South America, high-income countries) displayed age- and gender-adjusted hospitalization rates similar to the native population. Present findings stress the urgent need for implementation of ethnic-specific health policies in Italy. The awareness about the high cardiovascular risk in subjects from South Asia must be increased among general practitioners and immigrant communities.

Socioeconomic factors influencing childhood vaccination in two northern Italian regions.

BACKGROUND: Infant vaccination rates have been declining in Italy over the past 5-7years. The aims of this study were to assess the trend in the proportions of children unvaccinated at 24months old, to identify sociodemographic factors associated with non-vaccination; and to examine changes in parental attitudes to vaccination over time. METHODS: We conducted a population-based birth cohort study by combining existing electronic data sets. The study population consisted of children born from 1995 to 2010 in the Friuli-Venezia Giulia (FVG) region, and from 2007 to 2011 in part of the Emilia Romagna (ER) region, in north-eastern Italy. The immunization registers were linked with the medical birth registers, which contain sociodemographic data on both parents and the newborn. Unconditional logistic regressions were used to identify associations between vaccine uptake at 24months and maternal sociodemographic variables. RESULTS: Of 145,571 babies born in FVG and 75,308 in ER, there were 4222 (1.9%) who had not been vaccinated at all, and 23,948 (11.0%) without the optional measles, mumps and rubella (MMR) vaccination. The number of unvaccinated infants increased over time. Mothers who were over 35 or under 25years old, unmarried, with a higher formal education, and citizens of highly-developed countries were less compliant with vaccination recommendations in both the regions. A cohort effect was observed in FVG, for both educational level and citizenship: babies born between 1995 and 2000 to mothers without an Italian citizenship and with a lower formal education were more likely to refuse vaccination for their offspring, while this association was reversed between 2006 and 2010. CONCLUSIONS: Mothers who are Italian citizens and have a good formal education have begun to refuse vaccination for their children in recent years. Future public health action in this setting should target highly educated parents.

Differences in mortality by immigrant status in Italy. Results of the Italian Network of Longitudinal Metropolitan Studies.

Despite a rapid increase in immigration from low-income countries, studies on immigrants' mortality in Italy are scarce. We aimed to describe differences in all and cause-specific mortality among immigrants and Italians residing in Turin and Reggio Emilia (Northern Italy), two cities participating in the Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS). We used individual data from the municipal population registers linked to the cause of death registers. All people aged 1-64 years residing between 2001 and 2010 were enrolled (open cohort) and followed up until 2013. The mortality of citizens from high migratory pressure countries (as a whole, and for each macro-area group) was compared with that of Italians; differences were estimated by Poisson regression adjusted by age and calendar year mortality rate ratios (MRRs), and by age-standardized mortality ratios for the analysis of cause-specific mortality. Compared with Italians, immigrants had lower overall mortality (MRR for men: 0.82, 95 % CI: 0.75-0.90; for women: 0.71, 95 % CI: 0.63-0.81). Sub-Saharan Africans experienced a significant higher mortality than Italians (MRR for men 1.29, 95 % CI: 1.03-1.61; for women: 1.70, 95 % CI: 1.22-2.36). Higher mortality for immigrants compared to Italians was observed for infectious diseases, congenital anomalies, some site-specific tumours and homicide mortality. Our study showed heterogeneity in mortality across the macro-areas of origin, and in particular Sub-Saharan Africans seemed to be a vulnerable population. The extension to other cohorts of IN-LiMeS will allow the health status of immigrants and vulnerable groups to be studied and monitored in more depth.

[Investigation on the health effects of traffic-related air pollution from Mestre motorway (Veneto Region, Northern Italy)]. / Studio degli effetti sulla salute da esposizione all'inquinamento della tangenziale di Mestre.

OBJECTIVES: to evaluate whether living near motorway A57 (Mestre motorway, Veneto Region, Northern Italy) might have affected the residents' health status. DESIGN: longitudinal cohort study. SETTING AND PARTICIPANTS: 148,673 residents on the mainland in the Municipality of Venice (Mestre) who never changed their residence during the follow- up period (2002-2009). MAIN OUTCOMES MEASURES: the 2001 Italian census data were linked with the data sources of the epidemiological integrated system which includes: population registry, death certificates, hospital discharges, drug prescriptions, and tax exemption. Mortality and incidence for several subgroups of causes, incidence of acute myocardial infarction and stroke, and prevalence of asthma, chronic obstructive pulmonary disease, ischemic cardiopathy and diabetes were estimated. The ADMS-Urban model was adopted to define three different exposure areas based on PM10 emissions from the motorway: A (highly exposed), B (moderately exposed) used as a comparison for the analysis, C (unexposed). Hazard ratios (HR) for incidence and mortality were estimated from Cox proportional hazard models adjusted for calendar period, age, gender, and instruction level. The relationship between the exposure area and prevalence was investigated by multiple logistic regression analysis adjusted for the same covariates. RESULTS: compared with B area (23.25%of the population under study), people living in A area (3.16% of the population under study) had an increased incidence of acute myocardial infarction (HR: 1.43; 95%CI 1.03-1.97) in females, and prevalence of ischemic cardiopathy (odds ratio - OR: 1.12; 95%CI 1.01-1.26) in both genders. Results were borderline for COPD in males (OR: 1.17; 95%CI 0.97-1.41). Positive but nonsignificant associations were found with pneumonia and respiratory recoveries. CONCLUSIONS: this study showed that residents who live near Mestre motorway had an increased prevalence of some cardiorespiratory diseases, particularly ischemic cardiopathy.

[Health impact assessment of airport noise on people living nearby six Italian airports]. / Valutazione dell'impatto del rumore aeroportuale sulla salute della popolazione residente nelle vicinanze di sei aeroporti italiani.

BACKGROUND: aircraft noise has been associated with several health effects. Because of the great success of low-cost flights, small airports have been turned into international airports thus exposing nearby residents to an increase in noise levels and potential disturbances and health disorders. OBJECTIVE: to estimate the exposure levels and evaluate the health impact of aircraft noise on residents nearby six airports in Italy (Rome: Ciampino; Milan: Linate and Malpensa; Pisa; Turin; Venice) focusing on hypertension, acute myocardial infarction (AMI), annoyance and sleep disturbances. METHODS: residents in the local Municipalities considered at 31.12.2010 were included in the study and their addresses were geocoded. Aircraft noise exposure in 2011 was defined using the Integrated Noise Model linked to each participant's address. Lden (<55, 55-60, 61-65, 65-70 dB), Lnight, Leq (day and night) were calculated. Available exposure-response relationships were used to estimate the number of additional cases of hypertension, AMI, annoyance and sleep disturbances in the local population. RESULTS: 73,272 persons exposed to aircraft noise levels >55dB were considered: 55,915 (76.3%) were exposed to 55-60 dB; 16,562 (22.6%) to 60-65 dB; 795 (1.2%) to 65-70 dB. Exposure to aircraft noise levels above 55 dB was estimated to be responsible each year of 4,607 (95%CI 0-9,923) additional cases of hypertension; 3.4 (95%CI 0-10.7) cases of AMI; 9,789 (95%CI 6,895-11,962) cases of annoyance; 5,084 (95%CI 1,894-10,509) cases of sleep disturbances. CONCLUSIONS: a significant impact of airport noise on the health of residents nearby six Italian airports was estimated. Epidemiological evaluation and noise mitigation measures should be introduced to protect the health of residents.