DIET AND OTHER LIFESTYLE FACTORS IN ADULTHOOD AND INCIDENCE OF CHRONIC DISEASES AND MORTALITY: A PASSIVE-CASE FINDING COHORT STUDY.EVALUATION OF THE POSSIBLE USE OF RECORD LINKAGE IN THE ANALYSIS OF WEAK EXPOSURES.

Introduzione e Obiettivi: Sebbene l'uso integrato di dati amministrativi in sanit\ue0 pubblica e nella ricerca epidemiologica sia di crescente interesse, il loro utilizzo nel mettere in relazione dati provenienti da studi epidemiologici con quelli provenienti da fonti amministrative non \ue8 molto frequente. Ad oggi, pochi studi longitudinali hanno valutato gli effetti degli stili di vita, come la dieta, nella mezza et\ue0 su esiti di salute a lungo termine e comunque i principali si sono focalizzati sulla mortalit\ue0. Gli obiettivi di questo progetto di tesi sono stati: i) ricostruire la storia di un gruppo di soggetti che furono visitati e intervistati tra il 1991 e il 1995, ii) stimare l'incidenza delle principali malattie che si sono verificate durante 20 anni di follow-up e la mortalit\ue0 per tutte le cause, e iii) studiare la relazione tra abitudini alimentari e altri stili di vita raccolti nella mezza et\ue0 e il rischio di sviluppare malattie cardiovascolari (CVD) e morte attraverso l\u2019utilizzo di un follow-up passivo. Soggetti e Metodi: Per illustrare la possibile applicazione dell'uso di dati amministrativi in epidemiologia nutrizionale sono stati utilizzati dati provenienti dallo studio di 'Bollate Study Eye', condotto su un campione di popolazione di et\ue0 compresa tra 40 e 74 anni residente nella Regione Lombardia. Al baseline, 1.693 soggetti furono visitati ed intervistati sull\u2019utilizzo di farmaci, su malattie pregresse, e sugli stili di vita; ai soggetti fu inoltre somministrato un questionario alimentare per frequenza (FFQ) per stimare l'assunzione abituale di 158 alimenti durante l\u2019anno precedente. Lo studio si \ue8 avvalso dell'applicazione di algoritmi sviluppati per identificare i soggetti della coorte nei database dei Servizi Sanitari Regionali (RHSD) dell'Azienda Sanitaria Locale (ASL) di Mi1, utilizzando il codice fiscale e regionale come codici identificativi personali. I due endpoints principali di questo lavoro sono stati l'incidenza delle malattie cardiovascolari (CVD) e il decesso per tutte le cause, che sono stati determinati per mezzo di record linkage deterministici (DRL) con i registri di dimissione ospedaliera e di mortalit\ue0. I dati originariamente raccolti al baseline sono stati integrati con quelli di follow-up in un unico dataset utilizzato per la conduzione delle analisi statistiche. Per valutare il ruolo della dieta, i dati nutrizionali raccolti al baseline sono stati elaborati ed analizzati mediante approcci differenti. In primo luogo \ue8 stata calcolata l\u2019energia proveniente dal consumo dei macronutrienti e categorizzata in terzili, poi \ue8 stato calcolato un indice a priori al fine di valutare l'aderenza alla dieta mediterranea (MeDi) ed infine \ue8 stato applicato un approccio esplorativo a posteriori per caratterizzare i soggetti della coorte sulla base delle loro abitudini alimentari. Inoltre, \ue8 stato valutato l'effetto combinato dei diversi fattori legati agli stili di vita, calcolando un punteggio \u2018salutare\u2019. Lo studio della relazione tra le diverse esposizioni (dieta, attivit\ue0 fisica, abitudine al fumo e punteggio salutare) e l\u2019insorgenza di CVD e la morte per tutte le cause \ue8 stata studiata utilizzando modelli di regressione di Cox, che permettono di stimare i rischi relativi (RRs) espressi come hazard ratios (HRs) con i relativi intervalli di confidenza al 95% (95% CI). Risultati e Conclusioni: Da un punto di vista metodologico, si sono presentate e sono conseguentemente state affrontate diverse problematiche relative alla ricostruzione della coorte e alla determinazione degli outcomes. Attraverso il record linkage, il 95% dei soggetti reclutati nel periodo 1991-1995 \ue8 stato recuperato dai registri regionali (n=1604). Escludendo i soggetti con precedenti di malattie croniche al baseline, 530 soggetti hanno sviluppato CVD e 194 persone sono morte durante il follow-up. I risultati confermano che mantenere un corretto stile di vita, consumare alimenti tipici della dieta mediterranea, come ad esempio l'olio d'oliva, non fumare e svolgere regolare attivit\ue0 fisica sono condizioni che riducono il rischio di CVD e garantiscono un prolungamento della vita, soprattutto considerando questi fattori in combinazione tra di loro. Inoltre, questa tesi ha mostrato una possibile applicazione dell'uso dei dati amministrativi, che in Italia vengono utilizzati raramente in combinazione con studi di epidemiologia. L\u2019utilizzo di questa sorgente di informazioni pu\uf2 rivestire un ruolo promettente nella conduzione di studi di coorte osservazionali che dispongano di numerose informazioni al baseline, e risulterebbe molto vantaggioso sia per la riduzione dei tempi e dei costi rispetto agli studi tradizionali sia per il ridotto numero di persi al follow-up e, conseguentemente, per l\u2019elevato numero di soggetti da poter analizzare.Introduction and Aims: Although the integrated use of administrative data in public health and epidemiological research is of increasing interest, the practice of linking data from epidemiological studies to administrative data is not very common. As far as I know, only few longitudinal studies have been carried out combining historical cohort and administrative data for evaluating the effects of life-styles factors collected in mid-life on long term health outcome, and the main evidence are related to mortality. The aims of this thesis project were: i) to reconstruct the history of a cohort of subjects who were visited and interviewed during the period from 1991-1995, ii) to estimate the incidence of major diseases that occurred during 20-years follow-up and mortality for all causes, and iii) to study the relationship between dietary habits and other lifestyles factors in middle age, and risk of cardiovascular diseases (CVD) and death by means of passive follow-up. Subjects and Methods: The data used for illustrating the possible application of the use of administrative data in the nutritional epidemiology field come from the cross-sectional \u2018Bollate Eye Study\u2019, which was carried out in a population sample of people aged 40-74 resident in Lombardy Region. At baseline, the hospital visits were attended by 1693 subjects and included an interview concerning medical and family history, the past or current use of drugs, lifestyle habits, and a food frequency questionnaire (FFQ) for estimating the usual intake of 158 foods during the year preceding the assessment. The study involved the application of algorithms developed to retrieve subjects of the cohort in the Regional Health Services databases (RHSD) of the Local Health Authority (ASL) of Mi1 by using fiscal and regional code as personal identifiers codes. The main outcomes investigated in this work were the incidence of cardiovascular diseases (CVD) and all-causes death, that were determined by means of deterministic record linkage (DRL) with the Regional Hospital discharge forms and the Mortality registries by using an international coding system of diseases. Baseline data were thereafter aggregated into a single dataset to carry out all of the analyses. For evaluating the role of diet on the two endpoints, the dietary data collected at baseline were processed and analyzed with different approaches. First, energy derived from macronutrient intake was calculated and then categorized in tertiles, then an a priori index was computed in order to assess the adherence to Mediterranean Diet (MeDi) and finally an exploratory a posteriori approach was applied to characterize subjects on the basis of their dietary patterns. Furthermore, the combined effect of lifestyle factors was evaluated by calculating a healthy score. The relationship between exposures (diet, physical activity, smoking habits and the healthy score) and fatal and nonfatal CVD and all-causes death was investigated by means of Cox\u2019s regression models that estimated relative risks (RRs) as hazard ratios (HRs) with their 95% confidence intervals (95%CI). Results and Conclusion: From a methodological point of view, several issues related to the reconstruction of the cohort and to the outcomes definition have been focused and then addressed. After the record linkage procedures, 95% of subjects recruited during the period 1991-1995 were retrieved in the registries (n=1604). Excluding subjects with previous chronic diseases at baseline, a total of 530 CVD occurred and 194 persons died for all causes during follow-up. Results support the evidence of a positive effect of a healthy lifestyle, as adherence to a Mediterranean dietary pattern, the intake of specific components of this pattern, such as olive oil, abstinence from smoking and engaging in regular physical activity on the risk of CVD and all-causes death, particularly when these modifiable risk factors were considered in a healthy score. Furthermore, this thesis showed a possible application of the use of administrative data rarely used for epidemiological analytical study in Italy, suggesting their promising role for carrying out observational cohort studies with a large amount of data collected at baseline, guaranteeing a reduction in times and costs compared to traditional studies, ensuring a minimal number of persons lost to follow-up and resulting in a high number of subjects to analyze

Fear of covid-19 for individuals and family members: Indications from the national cross-sectional study of the epicovid19 web-based survey

The study analyzed the association of the fear of contagion for oneself and for family members (FMs) during the first wave of the COVID-19 pandemic, with demographic and socioeconomic status (SES) and health factors. The study was performed within the EPICOVID19 web-based Italian survey, involving adults from April–June 2020. Out of 207,341 respondents, 95.9% completed the questionnaire (60% women with an average age of 47.3 vs. 48.9 years among men). The association between fear and demographic and SES characteristics, contacts with COVID-19 cases, nasopharyngeal swab, self-perceived health, flu vaccination, chronic diseases and specific symptoms was analyzed by logistic regression model; odds ratios adjusted for sex, age, education and occupation were calculated (aORs). Fear for FMs prevailed over fear for oneself and was higher among women than men. Fear for oneself decreased with higher levels of education and in those who perceived good health. Among those vaccinated for the flu, 40.8% responded they had feelings of fear for themselves vs. 34.2% of the not vaccinated. Fear increased when diseases were declared and it was higher when associated with symptoms such as chest pain, olfactory/taste disorders, heart palpitations (aORs > 1.5), lung or kidney diseases, hypertension, depression and/or anxiety. Trends in fear by region showed the highest percentage of positive responses in the southern regions. The knowledge gained from these results should be used to produce tailored messages and shared public health decisions

Missed opportunities of flu vaccination in Italian target categories: Insights from the online EPICOVID 19 survey

We aimed to assess the reported rate of flu vaccination in the 2019/2020 season for respondents to the Italian nationwide online EPICOVID 19 survey. A national convenience sample of volunteers aged 18 or older was assessed between 13 April and 2 June 2020. Flu vaccine rates were calculated for all classes of age. The association between the independent variables and the flu vaccine was assessed by applying a multivariable binary logistic regression model. Of the 198,822 respondents, 41,818 (21.0%) reported having received a flu vaccination shot during the last influenza season. In particular, 15,009 (53.4%) subjects aged 65 years or older received a flu vaccination shot. Being 65 years aged or older (Adjusted Odds Ratios (aOR) 3.06, 95% Confidence Interval (CI) 2.92-3.20) and having a high education level (aOR 1.34. 95%CI 1.28-1.41) were independently associated to flu vaccination. Heart and lung diseases were the morbidities associated with the higher odds of being vaccinated (aOR 1.97 (95%CI 1.86-2.09) and aOR 1.92 (95%CI 1.84-2.01), respectively). Nursing home residents aged ≥ 65 years showed lower odds of being vaccinated (aOR 0.39 (95%CI 0.28-0.54)). Our data indicate the need for an urgent public heath effort to fill the gap of missed vaccination opportunities reported in the past flu seasons

Rapid COVID-19 screening based on self-reported symptoms: Psychometric assessment and validation of the EPICOVID19 short diagnostic scale

Background: Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. Although surveys are widely used for identifying COVID-19 cases, outcomes, and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the general population. Objective: We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. Methods: Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. Results: Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P<.001), loss of taste and smell (365/694, 52.6% vs 239/2009, 11.9%; P<.001), and cough (352/694, 50.7% vs 580/2009, 28.9%; P<.001). With regard to subjects who underwent serological tests, IgG-positive subjects had a higher incidence of fever (65/108, 60.2% vs 43/364, 11.8%; P<.001) and pain in muscles/bones/joints (73/108, 67.6% vs 71/364, 19.5%; P<.001) than IgG-negative subjects. An analysis of self-reported COVID-19 symptom items revealed a 1-factor solution, the EPICOVID19 diagnostic scale. The following optimal scores were identified: 1.03 for respiratory problems, 1.07 for chest pain, 0.97 for loss of taste and smell 0.97, and 1.05 for tachycardia (ie, heart palpitations). These were the most important symptoms. For adults aged 18-84 years, the cutoff score was 2.56 (sensitivity: 76.56%; specificity: 68.24%) for NPS-positive subjects and 2.59 (sensitivity: 80.37%; specificity: 80.17%) for IgG-positive subjects. For subjects aged ≥60 years, the cutoff score was 1.28, and accuracy based on the presence of IgG antibodies improved (sensitivity: 88.00%; specificity: 89.58%). Conclusions: We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics

Self-reported symptoms of SARS-CoV-2 infection in a non-hospitalized population : results from the large Italian web-based EPICOVID19 cross-sectional survey. (Preprint)

Background: Understanding the occurrence of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)-like symptoms in a large non-hospitalized population, when the epidemic peak was occurring in Italy, is of paramount importance but data are scarce. Objective: Aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test in non-hospitalized individuals and to estimate the occurrence of COVID-19-like symptoms in a larger non-tested population. Methods: This is an Italian countrywide self-administered cross-sectional web-based survey on voluntary adults who completed an anonymous questionnaire in the period 13-21 April 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios with 95% confidence intervals (aOR, 95%CI) by means of multiple logistic regression analysis controlling for age, sex, education, smoking habits, and the number of co-morbidities. Thereafter, for each symptom and for their combination, we calculated sensitivity, specificity, accuracy and AUC in a ROC analysis to estimate the occurrence of COVID-19-like infections in the non-tested population. Results: A total of 171,310 responded to the survey (59.9% females, mean age 47.4 years). Out of the 4,785 respondents with known NPS test result, 4,392 were not hospitalized. Among them, the NPS positive respondents (n=856) most frequently reported myalgia (61.6%), olfactory and/or taste disorders (OTDs, 59.2%), cough (54.4%), and fever (51.9%) whereas 7.7% were asymptomatic. Multiple regression analysis showed that OTDs (aOR 10.3, [95%CI 8.4-12.7]), fever (2.5, 95%CI 2.0-3.1), myalgia (1.5, 95%CI 1.2-1.8), and cough (1.3, 95%CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95%CI, 5.6-9.7) to 35.5 (95%CI, 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95%CI 0.795-0.825) in classifying NPS-P, and was applied to the non-hospitalized and non-tested sample (n=165,782). We found that from 4.4% to 12.1% of respondents had experienced symptoms suggestive of COVID-19 infection. Conclusions: Our results suggest that self-reported symptoms may be reliable indicators of SARS-CoV-2 infection in a pandemic context. A not negligible part (up to 12.1%) of the symptomatic respondents were left undiagnosed and potentially contributed to the spread of the infection

Risk factors for bronchiolitis hospitalization during the first year of life in a multicenter Italian birth cohort

BACKGROUND: Respiratory Syncytial Virus (RSV) is one of the main causes of respiratory infections during the first year of life. Very premature infants may contract more severe diseases and 'late preterm infants' may also be more susceptible to the infection. The aim of this study is to evaluate the risk factors for hospitalization during the first year of life in children born at different gestational ages in Italy. METHODS: A cohort of 33-34 weeks gestational age (wGA) newborns matched by sex and age with two cohort of newborns born at 35-37 wGA and > 37 wGA were enrolled in this study for a three-year period (2009-2012). Hospitalization for bronchiolitis (ICD-9 code 466.1) during the first year of life was assessed through phone interview at the end of the RSV season (November-March) and at the completion of the first year of life. RESULTS: The study enrolled 2314 newborns, of which 2210 (95.5 %) had a one year follow-up and were included in the analysis; 120 (5.4 %) were hospitalized during the first year of life for bronchiolitis. Children born at 33-34 wGA had a higher hospitalization rate compared to the two other groups. The multivariate analysis carried out on the entire population associated the following factors with higher rates for bronchiolitis hospitalization: male gender; prenatal treatment with corticosteroids; prenatal exposure to maternal smoking; singleton delivery; respiratory diseases in neonatal period; surfactant therapy; lack of breastfeeding; siblings <10 years old; living in crowded conditions and/or in unhealthy households and early exposure to the epidemic RSV season. When analysis was restricted to preterms born at 33-34 wGA the following variables were associated to higher rates of bronchiolitis hospitalization: male gender, prenatal exposure to maternal smoking, neonatal surfactant therapy, having siblings <10 years old, living in crowded conditions and being exposed to epidemic season during the first three months of life. CONCLUSION: Our study identified some prenatal, perinatal and postnatal conditions proving to be relevant and independent risk factors for hospitalization for bronchiolitis during the first year of life. The combination of these factors may lead to consider palivizumab prophylaxis in Italy

Addressing nanomaterial immunosafety by evaluating innate immunity across living species

The interaction of a living organism with external foreign agents is a central issue for its survival and adaptation to the environment. Nanosafety should be considered within this perspective, and it should be examined that how different organisms interact with engineered nanomaterials (NM) by either mounting a defensive response or by physiologically adapting to them. Herein, the interaction of NM with one of the major biological systems deputed to recognition of and response to foreign challenges, i.e., the immune system, is specifically addressed. The main focus is innate immunity, the only type of immunity in plants, invertebrates, and lower vertebrates, and that coexists with adaptive immunity in higher vertebrates. Because of their presence in the majority of eukaryotic living organisms, innate immune responses can be viewed in a comparative context. In the majority of cases, the interaction of NM with living organisms results in innate immune reactions that eliminate the possible danger with mechanisms that do not lead to damage. While in some cases such interaction may lead to pathological consequences, in some other cases beneficial effects can be identified