Multimorbidity and SARS-CoV-2-Related Outcomes: Analysis of a Cohort of Italian Patients.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, identifying the main risk factors has been imperative to properly manage the public health challenges that the pandemic exposes, such as organizing effective vaccination campaigns. In addition to gender and age, multimorbidity seems to be 1 of the predisposing factors coming out of many studies investigating the possible causes of increased susceptibility to SARS-CoV-2 infection and adverse outcomes. However, only a few studies conducted have used large samples. OBJECTIVE: The objective is to evaluate the association between multimorbidity, the probability to be tested, susceptibility, and the severity of SARS-CoV-2 infection in the Piedmont population (Northern Italy, about 4 million inhabitants). For this purpose, we considered 5 main outcomes: access to the swab, positivity to SARS-CoV-2, hospitalization, intensive care unit (ICU) admission, and death within 30 days from the first positive swab. METHODS: Data were obtained from different Piedmont health administrative databases. Subjects aged from 45 to 74 years and infections diagnosed from February to May 2020 were considered. Multimorbidity was defined both with the Charlson Comorbidity Index (CCI) and by identifying patients with previous comorbidities, such as diabetes and oncological, cardiovascular, and respiratory diseases. Multivariable logistic regression models (adjusted for age and month of infection and stratified by gender) were performed for each outcome. Analyses were also conducted by separating 2 age groups (45-59 and 60-74 years). RESULTS: Of 1,918,549 subjects, 85,348 (4.4%) performed at least 1 swab, of whom 12,793 (14.9%) tested positive for SARS-CoV-2. Of these 12,793 subjects, 4644 (36.3%) were hospitalized, 1508 (11.8%) were admitted to the ICU, and 749 (5.9%) died within 30 days from the first positive swab. Individuals with a higher CCI had a higher probability of being swabbed but a lower probability of testing positive. We observed the same results when analyzing subjects with previous oncological and cardiovascular diseases. Moreover, especially in the youngest group, we identified a greater risk of being hospitalized and dying. Among comorbidities considered in the study, respiratory diseases seemed to be the most likely to increase the risk of having a positive swab and worse disease outcomes. CONCLUSIONS: Our study shows that patients with multimorbidity, although swabbed more frequently, are less likely to get infected with SARS-CoV-2, probably due to greater attention on protective methods. Moreover, a history of respiratory diseases is a risk factor for a worse prognosis of COVID-19. Nonetheless, whatever comorbidities affect the patients, a strong dose-response effect was observed between an increased CCI score and COVID-19 hospitalization, ICU admission, and death. These results are important in terms of public health because they help in identifying a group of subjects who are more prone to worse SARS-CoV-2 outcomes. This information is important for promoting targeted prevention and developing policies for the prioritization of public health interventions.

[Long-term exposure to air pollution and incidence of coronary heart diseases and stroke in the longitudinal metropolitan studies (LMS) network: the BIGEPI project]. / Esposizione di lungo periodo all'inquinamento atmosferico e incidenza di malattia coronarica acuta e ictus nella rete degli studi longitudinali metropolitani: il progetto BIGEPI.

OBJECTIVES: to assess the potential of using longitudinal metropolitan studies (LMS) to study the association between long-term exposure to air pollution and the incidence of acute coronary events and stroke. DESIGN: closed cohort. SETTING AND PARTICIPANTS: subjects aged >=30 years, who took part in the 2011 census, residents in 5 cities (Turin, Bologna, Rome, Brindisi and Taranto). Annual concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2) and warm-season ozone (O3) (annual O3 in Taranto and Brindisi), estimated through satellite (Turin, Bologna, Rome) or photochemical models (Taranto and Brindisi) with a spatial resolution of 1 km2, were assigned to the census address. MAIN OUTCOME MEASURES: incidence of coronary heart disease (CHD) and stroke until 31.12.2018 (2019 in Bologna). Cohort-specific Hazard Ratios (HRs), estimated using Cox regression models progressively adjusting for individual and contextual covariates, were pooled with random-effect meta-analysis. RESULTS: there were 71,872 incident CHD cases and 43,884 incident cases of stroke in almost 18 million person-years. No association was observed between the exposures studied and incidence of CHD and stroke, except for an increase in the incidence of CHD associated with warm-season O3 exposure (HR 1.034 per 5 µg/m3 increase). Some positive associations were found in specific cities (both outcomes in Brindisi with PM10 exposure and in Taranto with NO2 exposure, stroke in Rome with both PM10 and PM2.5), although estimates were not significant in some instances. CONCLUSIONS: LMS are a high potential tool for the study of comparative medium- and long-term effects of air pollution. Their further development (different definitions of exposure, outcomes, characteristics of the urban areas and extension to other LMS) may make them even more valuable tools for monitoring and planning public health interventions.

[Employment sector and respiratory mortality in Rome and Turin longitudinal metropolitan studies]. / Settore occupazionale e mortalità respiratoria negli studi longitudinali metropolitani di Roma e Torino.

OBJECTIVES: to assess the association between the occupational sector and respiratory mortality in the metropolitan longitudinal studies of Rome and Turin. DESIGN: retrospective cohort study. SETTING AND PARTICIPANTS: the 2011 census cohorts of residents of Rome and Turin aged 30 years and older who had worked for at least one year in the private sector between 1970s and 2011 was analysed. The individuals included in the study were followed from 9 October 2011 to 31 December 2018. Occupational history was obtained from archives of private sector contributions at the National Social Insurance Agency (INPS) and then was linked to data from the longitudinal studies. MAIN OUTCOME MEASURES: the study outcome was non-malignant respiratory mortality. The exposure of interest was whether or not individuals had worked in one of the 25 occupational sectors considered (agriculture and fishing, steel industry, paper and printing, pharmaceuticals, manufacturing, textile, energy and water, food and tobacco industry, non-metal mining, glass & cement industry, metal processing, electrical construction, footwear and wood industry, construction, trade, hotel and restaurants, transportation, insurance, healthcare, services, laundries, waste management, hairdressing, cleaning services, and gas stations). The association between the occupational sector and respiratory mortality, adjusted for potential confounders (age, marital status, place of birth, educational level), was estimated using Cox models. All analyses were stratified by sex and city. RESULTS: a total of 910,559 people were analysed in Rome and 391,541 in Turin. During the eight years of follow-up, 4,133 people in Rome and 2,772 people in Turin died from respiratory causes. The sectors associated with high respiratory mortality in both cities among men were footwear and wood industry (adjusted HR for age: 1.37 (95%CI 1.07-1.76) and 1.48 (95%CI 1.08-2.03) in Rome and Turin, respectively), construction (HR: 1.31 (95%CI 1.20-1.44) in Rome and 1.51 (95%CI 1.31-1.74) in Turin), hotel and restaurant sector (HR: 1.25 (95%CI 1.07-1.46) in Rome and 1.68 (95%CI 1.20-2.33) in Turin), and cleaning services (HR: 1.57 (95%CI 1.19-2.06) in Rome and 1.97 (95%CI 1.51-2.58) in Turin). Some sectors had high respiratory mortality only in one of the two cities: in Rome, the food& tobacco industry, and gas stations, while in Turin, the metal processing industry. Among female workers, the cleaning services sector was associated with higher respiratory mortality in both Rome and Turin (HR: 1.52, 95%CI 1.27-1.82, e 1.58, 95%CI 1.17-2.12, respectively). CONCLUSIONS: the data confirm the previously known associations between occupational sectors and respiratory mortality for exposures characteristic of specific sectors, such as construction, hotel and restaurant sector, and cleaning services. The differences reported between the two cities reflect the different composition of the workforce and the size of the two study populations. Administrative social insurance data can provide helpful information for epidemiological studies of occupational exposure.

Inequalities in the Health Impact of the First Wave of the COVID-19 Pandemic in Piedmont Region, Italy.

(1) Introduction: Several studies observe a social gradient in the incidence and health consequences of SARS-CoV-2 infection, but they rely mainly on spatial associations because individual-level data are lacking. (2) Objectives: To assess the impact of social inequalities in the health outcomes of COVID-19 during the first epidemic wave in Piedmont Region, Italy, evaluating the role of the unequal social distribution of comorbidities and the capacity of the healthcare system to promote equity. (3) Methods: Subjects aged over 35, resident in Piedmont on 22 February 2020, were followed up until 30 May 2020 for access to swabs, infection, hospitalization, admission to intensive care unit, in-hospital death, COVID-19, and all-cause death. Inequalities were assessed through an Index of Socioeconomic Disadvantage composed of information on education, overcrowding, housing conditions, and neighborhood deprivation. Relative incidence measures and Relative Index of Inequality were estimated through Poisson regression models, stratifying by gender and age groups (35-64 years; ≥65 years), adjusting for comorbidity. (4) Results: Social inequalities were found in the various outcomes, in the female population, and among elderly males. Inequalities in ICU were lower, but analyses only on in-patients discount the hypothesis of preferential access by the most advantaged. Comorbidities contribute to no more than 30% of inequalities. (5) Conclusions: Despite the presence of significant inequities, the pandemic does not appear to have further exacerbated health inequalities, partly due to the fairness of the healthcare system. It is necessary to reduce inequalities in the occurrence of comorbidities that confer susceptibility to COVID-19 and promote prevention policies that limit inequalities in the mechanisms of contagion and improve out-of-hospital timely treatment.

Education inequalities in cardiovascular and coronary heart disease in Italy and the role of behavioral and biological risk factors.

BACKGROUND AND AIMS: Behavioral and biological risk factors (BBRF) explain part of the variability in socioeconomic differences in health. The present study aimed at evaluating education differences in incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) in Italy and the role of BBRF. METHODS AND RESULTS: All subjects aged 30-74 years (n = 132,686) who participated to the National Health Interview Surveys 2000 and 2005 were included and followed-up for ten years. Exposure to smoking, physical activity, overweight/obesity, diabetes and hypertension at baseline was considered. Education level was used as an indicator of socioeconomic status. The outcomes were incident cases of CVD and CHD. Hazard ratios by education level were estimated, adjusting for sociodemographic covariates and stratifying by sex and geographic area. The contribution of BBRF to education inequalities was estimated by counterfactual mediation analysis, in addition to the assessment of the risk attenuation by comparing the models including BBRF or not. 22,214 participants had a CVD event and 6173 a CHD event. After controlling for sociodemographic factors, the least educated men showed a 21% higher risk of CVD and a 17% higher risk of CHD compared to the most educated (41% and 61% among women). The mediating effect (natural indirect effect) of BBRF between extreme education levels was 52% for CVD and 84% for CHD among men (16% among women for CVD). CONCLUSIONS: More effective strategies aiming at reducing socioeconomic disparities in CVD and CHD are needed, through programs targeting less educated people in combination with community-wide initiatives.

Use of antipsychotics and long-term risk of parkinsonism.

INTRODUCTION: Few epidemiological studies have assessed the risk of parkinsonisms after prolonged use of neuroleptics. We aimed to examine the long-term risk of degenerative parkinsonisms (DP) associated with previous use of neuroleptics. METHODS: All residents in Piedmont, Northern-west Italy, older than 39 years (2,526,319 subjects), were retrospectively followed up from 2013 to 2017. Exposure to neuroleptics was assessed through the regional archive of drug prescriptions. The development of DP was assessed using the regional archives of both drug prescriptions and hospital admissions. We excluded prevalent DP cases at baseline as well as those occurred in the first 18 months (short-term risk). The risk of DP associated with previous use of neuroleptics was examined through Cox regression, using a matched cohort design. RESULTS: The risk of DP was compared between 63,356 exposed and 316,779 unexposed subjects. A more than threefold higher risk of DP was observed among subjects exposed to antipsychotics, compared to those unexposed (HR = 3.27, 95% CI 3.00-3.57), and was higher for exposure to atypical than typical antipsychotics. The risk decreased after 2 years from therapy cessation but remained significantly elevated (HR = 2.38, 95% CI 1.76-3.21). CONCLUSIONS: These results indicate a high risk of developing DP long time from the start of use and from the cessation for both typical and atypical neuroleptics, suggesting the need of monitoring treated patients even after long-term use and cessation.

Occupational physical activity, mortality and CHD events in the Italian Longitudinal Study.

PURPOSE: Several recent studies have suggested a 'physical activity paradox' whereby leisure-time physical activity benefits health, but occupational physical activity is harmful. However, other studies imply that occupational physical activity is beneficial. Using data from a nationally representative Italian sample, we investigate if the context, or domain, of physical activity matters for mortality and coronary heart disease (CHD) events. METHODS: Among 40,220 men and women aged 40-55 at baseline, we used Cox models to compare associations of occupational, domestic and leisure-time physical activity with risk of mortality and CHD events over a follow-up period of up to 14 years. We accounted for sociodemographic factors, smoking, body mass index (BMI), physical and mental health, and educational qualifications. RESULTS: Occupational physical activity was not significantly associated with risk of mortality or CHD events for women, or with CHD events for men. In crude models, risk of mortality was higher for men in the highest occupational activity group, compared to the lowest (HR 1.26, 95% CI 1.01, 1.57). This attenuated with adjustment for health-related behaviours, health, and education (HR 1.03, 95% CI 0.77, 1.38). In crude models, leisure-time physical activity was significantly associated with decreased mortality and CHD risk only for men. Domestic physical activity was not associated with either outcome for either gender. CONCLUSION: In a large sample of middle-aged Italian workers, we found limited evidence of harmful or beneficial effects of occupational physical activity on mortality or CHD events. However, confidence intervals were wide, and results consistent with a range of effects in both directions.

[Monitoring the trend of occupational injuries: comparison between different indicators]. / Monitorare il trend degli infortuni sul lavoro: confronto tra diversi indicatori.

OBJECTIVES: to compare three injuries indicators to establish which are less affected by underreporting and therefore best suited for the monitoring of the occupational injuries time trend during economic crisis. DESIGN: open cohort. SETTING AND PARTICIPANTS: a national sample of employees in the private sector, blue collars, males aged 15-64 years, extracted from the Work History Italian Panel-Healt archive, which combines data about firms and employee from the National Social Security Institute (Inps) and occupational injuries data from the Italian National Institute for Insurance against Accidents at Work (Inail). MAIN OUTCOME MEASURES: annual injuries rates for the period 2001-2012 classified according to three severity definitions: • serious injuries according to the prognosis (IGP); • serious Injuries according to the type of lesion (IGL); • minor injuries. Time trends and their changes during the economic crisis (2008-2013) were analysed through negative binomial regression models, stratified by country of origin, macroarea of work, firm size, and economic activity. RESULTS: IGP rates decreased more than IGL and minor injuries rates during the economic crisis, highlighting their greater association with the economic cycle. Negatives and significant trend changes were observed in some subgroups: in manufacturing, among workers from high developed countries and Moroccans, in the Northern and Central macroareas of Italy, and in larger firms. CONCLUSIONS: variations in injuries rates were not so much influenced by the underreporting of injuries as by the changes in the working conditions following the economic crisis. To accurately monitor the injuries time trends, it is recommended to report at the same time at least one indicator based on minor injuries and one based on serious injuries.

Potentially avoidable hospitalization for asthma in children and adolescents by migrant status: results from the Italian Network for Longitudinal Metropolitan Studies.

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.

Status inconsistency and mortality in the immigrant population in the Turin and the Emilian Longitudinal Studies.

OBJECTIVES: to compare the educational gradient in mortality between Italians and immigrants and to assess the hypothesis of status inconsistency in the immigrant population, evaluating the relationship between educational qualification and occupational class. DESIGN: multicentre longitudinal study. SETTING AND PARTICIPANTS: subjects aged 30-64 years, resident in Turin, Bologna, Modena, or Reggio Emilia who took part in the 2011 Census and followed up until 31.12.2018. MAIN OUTCOME MEASURES: all-cause mortality by educational qualification and occupational class was compared between Italians and immigrants from High Migratory Pressure countries; analyses were carried out using mortality rate ratios (MRR) and relative index of inequality (RII), applying Poisson models, adjusted for city, calendar period, age, and macroareas of origin, stratified by gender. RESULTS: occupational class among immigrants is evenly distributed across educational qualifications. Compared with Italians, immigrant men and women had a weaker and non-significant inverse educational gradient in mortality, which did not change substantially after the adjustment for occupational class. CONCLUSIONS: the results support the status inconsistency hypothesis, which may be partly responsible for the observed flattening of the educational gradients. The macroarea of origin appears to be a key determinant of mortality inequalities. Therefore, the use of educational qualification in exploring health inequalities among immigrants should be always complemented with other indicators of socioeconomic position and migratory history.

[Immigrants' health and socioeconomic inequalities of overall population residing in Italy evaluated through the Italian network of Longitudinal Metropolitan Studies]. / Salute degli immigrati e disuguaglianze socioeconomiche nella popolazione residente in Italia valutate attraverso la rete degli Studi Longitudinali Metropolitani.

INTRODUCTION: Describing and monitoring socioeconomic inequalities in health are the prerequisite for planning equity policies. In Italy, some cities have integrated personal information from the municipal registries with Census data and with data from healthcare information systems to set up Longitudinal Metropolitan Studies (LMS). Under the coordination of the Italian National Institute for Health, Migration, and Poverty (NIHMP), six cities in the LMS network have contributed to the present monograph: Turin, Venice, Reggio Emilia, Modena, Bologna, and Rome. MORTALITY RESULTS. Significant socioeconomic differences by level of education were seen in all the participating centres. People who live alone or in single-parent households are more likely to die, as are those living in a substandard dwelling. Immigrants resident in the six cities included in the study showed lower all-cause mortality than Italians (males: MRR 0.83; 95%CI 0.78-0.90 - females: MRR 0.70; 95%CI 0.64-0.77). Sub-Saharan Africans experienced a significant higher mortality than Italians (males: MRR 1.33; 95%CI 1.12-1.59 - females: MMR 1.69; 95%CI 1.31-2.17). Immigrants had a neonatal and post-neonatal mortality risk about 1.5 times higher than Italians (neonatal: OR 1.71; 95%CI 1.22-2.39 - post-neonatal: OR 1.63; 95%CI 1.03-2.57). A difference between Italians and immigrants was also observed for mortality in children aged 1-4 years, though less marked (OR 1.24; 95%CI 0.73-2.11). Excesses concerned particularly immigrants from North Africa and from sub-Saharan Africa as well as those residing in Italy for >5 years. HOSPITALISATION RESULTS. Hospitalisation rates are lower for immigrants than for Italians, except when due to infectious diseases, blood disorders, and, among women, for reasons linked to pregnancy and childbirth. Avoidable hospitalisation rates of adults from low migratory pressure Countries are lower than or equal to those of Italians. On the contrary, adults from low migratory pressure Countries show higher avoidable hospitalisation rates compared to Italians in every cohort, with the exception of Rome (RR 0.81; 95%CI 0.78-0.85), with RR ranging from 1.08 (95%CI 0.96-1.22) in Venice to 1.64 (95%CI 1.47-1.83) in Modena. CONCLUSIONS: Maternal and child health is the most critical area of health for immigrant population. Considering the importance that the issue of health equity has taken on in the political agenda, the data presented in this volume are a great asset, particularly in light of the long recession and the social crisis that have impacted the Country.