Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study.

BACKGROUND: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

Can We Slow Down Biological Age Progression? Study Protocol for the proBNPage Reduction (PBAR) Randomized, Double-Blind, Placebo-Controlled Trial (Effects of 4 "Anti-Aging" Food Supplements in Healthy Older Adults).

Purpose: The availability of a simple and reliable marker of biological age might allow an acceleration of the research in the field of longevity extension. Previous studies suggest that this marker might be the N-terminal of B-type natriuretic peptide precursor (NT-proBNP), from which proBNPage, a biological age surrogate, can be calculated. Objectives of the study: 1) To fine-tune the method of proBNPage progression assessment and 2) To establish whether 4 "anti-aging" treatments, which provided promising results in previous studies, can modify proBNPage progression. Patients and Methods: This is a double-blind randomized placebo-controlled clinical trial on 120 adults aged 65-80 years, free of cardiovascular diseases. Participants will be randomized into 3 groups: A) Coenzyme Q10 100 mg bid + Selenium 100 mcg; B) Resveratrol 350 mg bid + TA-65 (Astragalus Membranaceus extract) 100U; C) Placebo-1 bid + Placebo-2. They will be followed for 2 years and checked 8 times, to assess both proBNPage progression and treatment safety. Secondary variables (handgrip strength, aerobic capacity at the step test and quality of life) will also be assessed. Primary outcome will be the demonstration of significant changes of proBNPage, compared to baseline, in the 3 groups at 6, 12, 18 and 24 months. Secondary outcome will be the demonstration of similar changes of secondary variables. Statistical analyses will be mainly performed by repeated measures ANOVA (both according to intention to treat and per protocol) and paired t tests. The study was approved by the Ethics Committee Area Vasta Emilia Centro, Emilia-Romagna Region, ID: 64/2022/Sper/AOUBo. Trial registration: ClinicalTrials.gov, NCT05500742. Conclusion: The use of proBNPage as a surrogate of biological age may prove an easy method to select anti-aging treatments worthy of further, more complex assessments.

Cancer mortality in Common Mental Disorders: A 10-year retrospective cohort study.

PURPOSE: Individuals with Common Mental Disorders (CMDs) may have a higher cancer mortality. The purpose of this study was to examine cancer-related mortality among patients with CMDs and verify which cancer types are predominantly involved. METHODS: We used the Regional Mental Health Registry of the Emilia-Romagna region, in Northern Italy to identify patients aged ≥ 18 years who received an ICD 9-CM diagnosis of CMDs (i.e., depressive and neurotic disorders) over a 10 year period (2008-2017). Information on cause of death was retrieved from the Regional Cause of Death Registry. Comparisons were made with data from the regional population without CMDs. RESULTS: Among 101,487 patients suffering from CMDs (55.7% depression; 44.3% neurotic disorders), 3,087 (37.8%) died from neoplasms. The total standardized mortality ratio (SMR) was 1.82 (95% CI 1.78-1.86) while the SMR for all neoplasms was 2.08 (95% CI 2.01-2.16). Individuals of both genders, with both depressive and neurotic disorders had a higher risk of death from almost all cancers compared with the regional population. CONCLUSION: Patients with CMDs have considerably higher cancer mortality risk than the general population. Higher mortality was observed for a broad range of cancers associated with different aetiologies. It is imperative to promote cancer awareness, prevention and treatment for people with CMDs.

Emergency Department Visits and Summer Temperatures in Bologna, Northern Italy, 2010-2019: A Case-Crossover Study and Geographically Weighted Regression Methods.

The aim of the study is to evaluate the association between summer temperatures and emergency department visits (EDVs) in Bologna (Italy) and assess whether this association varies across areas with different socioeconomic and microclimatic characteristics. We included all EDVs within Bologna residences during the summers of 2010-2019. Each subject is attributed a deprivation and a microclimatic discomfort index according to the residence. A time-stratified case-crossover design was conducted to estimate the risk of EDV associated with temperature and the effect modification of deprivation and microclimatic characteristics. In addition, a spatial analysis of data aggregated at the census block level was conducted by applying a Poisson and a geographically weighted Poisson regression model. For each unit increase in temperature above 26 °C, the risk of EDV increases by 0.4% (95%CI: 0.05-0.8). The temperature-EDV relationship is not modified by the microclimatic discomfort index but rather by the deprivation index. The spatial analysis shows that the EDV rate increases with deprivation homogeneously, while it diminishes with increases in median income and microclimatic discomfort, with differences across areas. In conclusion, in Bologna, the EDV risk associated with high temperatures is not very relevant overall, but it tends to increase in areas with a low socioeconomic level.

Short-term mortality following COVID-19 vaccination in Bologna, Italy: a one-year study.

The main objective of the study is to assess whether there is an increased risk of mortality in the days following the administration of COVID-19 vaccines in Bologna Health Authority in the first year of COVID-19 vaccination campaign. A secondary objective was to describe causes of deaths occurred in the days after vaccination. We conducted a retrospective observational study on all residents of Bologna Health Authority who received at least one COVID-19 vaccination dose from December 27, 2020 to December 31, 2021 and compared mortality in the 3, 7, 14 30 days after vaccination (risk interval) with the mortality in the period of the same length (3, 7, 14 and 30 days) beyond the 30th day after the last dose of vaccination (control interval). The cohort included 717,538 people. The mortality rate was 2.24 per 100 person-years during the 30 days risk interval vs 2.72 in the control interval with an adjusted incidence rate ratio equal to 0.76 (95% CI: 0.70-0.83, p < 0.001). The risk of mortality is significantly lower (p < 0.001) also in the 3, 7, 14 days risk intervals than in the control intervals. This study shows that there is no increase in mortality in the short-term period after COVID-19 vaccines.

Risk of SARS-CoV-2 infection, hospitalization and death for COVID-19 in people with Parkinson's disease or parkinsonism over a 15-month period: a cohort study.

BACKGROUND: The patterns of long term risk of SARS-CoV-2 infection, hospitalization for COVID-19 and related death are uncertain in people with Parkinson's disease (PD) or parkinsonism (PS). The aim of the study was to quantify these risks compared to a control population cohort, during the period March 2020-May 2021, in Bologna, northern Italy. METHOD: ParkLink Bologna cohort (759 PD; 192 PS) and controls (9,226) anonymously matched (ratio 1:10) for sex, age, district, comorbidity were included. Data were analysed in the whole period and in the two different pandemic waves (March-May 2020 and October 2020-May 2021). RESULTS: Adjusted hazard ratio of SARS-CoV-2 infection was 1.3 (95% CI 1.04-1.7) in PD and 1.9 (1.3-2.8) in PS compared to the controls. The trend was detected in both the pandemic waves. Adjusted hazard ratio of hospitalization for COVID-19 was 1.1 (95% CI 0.8-1.7) in PD and 1.8 (95% CI 0.97-3.1) in PS. A higher risk of hospital admission was detected in PS only in the first wave. The 30-day mortality risk after hospitalization was higher (p=0.048) in PS (58%) than in PD (19%) and controls (26%). CONCLUSIONS: Compared with controls, after adjustment for key covariates, people with PD and PS showed a higher risk of SARS-CoV-2 infection throughout the first 15 months of the pandemic. COVID-19 hospitalization risk was increased only in people with PS and only during the first wave. This group of patients was burdened by a very high risk of death after infection and hospitalization.

COVID-19 vaccine effectiveness among the staff of the Bologna Health Trust, Italy, December 2020-April 2021.

BACKGROUND AND AIM: Randomized controlled trials have shown that mRNA vaccines are highly effective in preventing SARS-CoV2 infection. We conducted a study to assess the real-world effectiveness of mRNA vaccines (Pfizer-BioNTech or Moderna) in preventing all and symptomatic SARS-CoV2 infections and COVID-19 related hospitalizations in the staff of the Bologna Health Trust (HT), Italy Methods: We followed up retrospectively 9839 staff of the Bologna HT from December 27, 2020 to April 3, 2020 and calculated the effectiveness in partially and fully vaccinated subjects by applying a multivariable Cox proportional hazard model. RESULTS: Vaccine effectiveness in preventing SARS-CoV2 infections is 85.5% (95%CI: 75.9-91.3) in the partially vaccinated and 84.8% (95%CI: 73.2-91.4) in the fully vaccinated. In preventing symptomatic infection effectiveness is 81.7% (95%CI: 62.7-91.0) in the partially and 87.1% (95%CI: 69.3-94.6) in the fully vaccinated. There were no COVID-19-related hospitalizations in the partially or fully vaccinated vs 15 hospitalization in the unvaccinated cohort. CONCLUSIONS: Our results confirm the effectiveness of mRNA vaccines in a real-world setting in Northern Italy.

Mortality from cancer in people with severe mental disorders in Emilia Romagna Region, Italy.

OBJECTIVE: To examine cancer-related mortality in patients with severe mental disorders (SMI) in the Emilia Romagna (ER) Region, Northern Italy, during the period 2008-2017 and compare it with the regional population. METHODS: We used the ER Regional Mental Health Registry identifying all patients aged ≥18 years who had received an ICD-9CM system diagnosis of SMI (i.e., schizophrenia or other functional psychosis, mania, or bipolar affective disorders) during a 10-year period (2008-2017). Information on deaths (date and causes of death) were retrieved through the Regional Cause of Death Registry. Comparisons were made with the deaths and cause of deaths of the regional population over the same period. RESULTS: Amongst 12,385 patients suffering from SMI (64.1% schizophrenia spectrum and 36.9% bipolar spectrum disorders), 24% (range 21%-29%) died of cancer. In comparison with the general regional population, the mortality for cancer was about 50% higher among patients with SMI, irrespective if affected by schizophrenia or bipolar disorders. As for the site-specific cancers, significant excesses were reported for stomach, central nervous system, respiratory, and pancreas cancer with a variability according to psychiatric diagnosis and gender. CONCLUSIONS: Patients suffering from SMI had higher mortality risk than the regional population with some differences according to cancer type, gender, and psychiatric diagnosis. Proper cancer preventive and treatment interventions, including more effective risk modification strategies (e.g., smoking cessation, dietary habits) and screening for cancer, should be part of the agenda of all mental health departments in conjunction with other health care organizations, including psycho-oncology.

Mortality in mental health patients of the Emilia-Romagna region of Italy: A registry-based study.

Evidence from previous research demonstrated a gap in mortality between patients with mental disorders and the general population. However, a more exhaustive assessment is required to address this public health issue. The aim of this study was to provide comprehensive analysis of mortality examining all causes of death and all psychiatric diagnoses. We conducted a 10-year retrospective cohort study, including all in and out patients registered in the Mental Health Registry of Emilia-Romagna, Italy. Standardized mortality ratios (SMRs) were calculated. The cohort consisted of 137,351 patients 11,236 of whom died during the study period and the overall SMR was 1.99. 85.9 % of excess mortality was attributable to a broad range of natural causes. Diseases of circulatory and respiratory systems as well as neoplasms were the principal contributors to the mortality gap. All psychiatric conditions led to a higher risk of death. The greatest excess was due to neoplasms in depressed and neurotic patients and to cardiovascular diseases in patients with schizophrenia and personality disorders. Our results highlight the need for close collaboration between mental and primary health care services with the aim of reducing excess mortality as a result of medical diseases among all patients suffering from psychiatric condition.

Mental Health Disorders and Summer Temperature-Related Mortality: A Case Crossover Study.

Identifying the most vulnerable subjects is crucial for the effectiveness of health interventions aimed at limiting the adverse consequences of high temperatures. We conducted a case crossover study aimed at assessing whether suffering from mental health disorders modifies the effect of high temperatures on mortality. We included all deaths occurred in the area of Bologna Local Health Trust during the summers 2004-2017. Subjects with mental disorders were identified by using the local Mental Health Registry. A conditional logistic model was applied, and a z-test was used to study the effect modification. Several models were estimated stratifying by subjects' characteristics. For every 1 °C above 24 °C, mortality among people without mental disorders increased by 1.9% (95% CI 1.0-2.6, p < 0.0001), while among mental health service users, mortality increased by 5.5% (95% CI 2.4-8.6, p < 0.0001) (z-test equal to p = 0.0259). The effect modification varied according to gender, residency and cause of death. The highest probability of dying due to an increase in temperature was registered in patients with depression and cognitive decline. In order to reduce the effects of high temperatures on mortality, health intervention strategies should include mental health patients among the most vulnerable subjects taking account of their demographic and clinical characteristics.

COVID-19 cases before and after the "I Stay at home" decree, Bologna Local Health Authority, Italy.

BACKGROUND AND AIM OF THE WORK: Various measures have been taken by the Italian Government to contain and mitigate the COVID-19 outbreak and on March 11th a decree called "I stay at home" put the whole nation under lockdown. Our aim is to describe sociodemographic and transmission profile of COVID-19 cases that were transmitted before and after the introduction of the decree in the Bologna Local Health Authority. METHODS: Cases were classified as transmitted before or after the decree according to the date of last contact with a COVID-19 case or, if this date was unavailable, we used the date of onset of symptoms considering the incubation period. Sociodemographic, clinical and epidemiological information was collected by using the infectious disease monitoring database, hospital discharge, deprivation index and long term care facility databases. RESULTS: In the period after the publication of the decree, there were more elderly, females, strangers, retired, residents in nursing homes and deprived people than in the first period. There were also more health care personnel and less professionals/managers, sales or office workers. In both phases, family is mentioned as the first community attended although less frequently in the second group. CONCLUSIONS: The profile of the new COVID-19 cases changed during the outbreak suggesting a differential effect of lockdown measures on the population. An equity lens should be used when analyzing the impact of pandemia and the measures taken to curb it.

An ecological study on health inequalities in the city of Bologna (Emilia-Romagna Region, Northern Italy): bridging knowledge and action.

BACKGROUND: since January 2017, a multidisciplinary research group, involving the Local Health Authority, the Municipality, and the University of Bologna, carried out a city-wide action-research project on health inequalities consisting of an ecological study over the years 2011-2015 based on indicators that are routinely available within health and social services. OBJECTIVES: to document existing geographical inequalities in health outcomes and use of healthcare services in the city of Bologna (Emilia-Romagna Region, Northern Italy), with the aim to suggest policy action to tackle them. DESIGN: the results of the first phase of the above-mentioned project were reported: five related to the social determinants of health (exposure) and five related to the social determinants of ill-health (outcomes). For each municipal statistical area, the distribution of the exposures as well as rates and Bayesian Relative Risks of the outcomes were plotted on the city map. To evaluate the association between social determinants and health outcomes, Spearman correlation coefficients were estimated. SETTING AND PARTICIPANTS: residents in the city of Bologna aged >=18 years in the period 2011-2015, grouped into 90 statistical areas. RESULTS: a North-South divide was apparent for most of the socioeconomic and ill-health indicators, with a high concentration of adverse outcomes in the North-Western part of the city. Adherence to cancer screening represented an exception, being greater in the areas with higher proportion of unfavourable health outcomes. An inverse association between education level and health outcomes was found. Low family income was weakly to moderately correlated with health outcomes. Proportion of residents in council houses and of the teenage foreign population showed a moderate to strong association with all outcomes, but mortality and screening adherence. CONCLUSIONS: an ecological analysis based on data that are routinely collected by local health and social institutions can be effective in revealing the geographical patterns of health inequalities. When accompanied by strategic choices aimed at bridging knowledge and action, this approach may facilitate the direct engagement of local actors towards health equity.

[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.

[Development of a predictive model of death or urgent hospitalization to identify frail elderly]. / Sviluppo di un modello predittivo di decesso o ricovero d'urgenza per l'individuazione degli anziani fragili.

OBJECTIVES: to develop and validate a predictive model of mortality or emergency hospitalization in all subjects aged 65 years and over. DESIGN: cohort study based on 9 different databases linked with each other. SETTING AND PARTICIPANTS: the model was developed on the population aged 65 years and over resident at 01.01.2011 for at least two years in the city of Bologna (Emilia-Romagna Region, Northern Italy); 96,000 persons were included. MAIN OUTCOME MEASURES: the outcome was defined in case of emergency hospitalization or death during the one-year follow-up and studied with a logistic regression model. The predictive ability of the model was evaluated by using the area under the Roc curve, the Hosmer-Lemeshow test, and the Brier score in the derivation sample (2/3 of the population). These tests were repeated in the validation sample (1/3 of the population) and in the population of Bologna aged 65 years and over on 01.01.2012, after applying the coefficients of the variables obtained in the derivation model. By using the regression coefficients, a frailty index (risk score) was calculated for each subject later categorized in risk classes. RESULTS: the model is composed of 28 variables and has good predictive abilities. The area under the Roc curve of the derivation sample is 0.77, the Hosmer-Lemeshow test is not significant, and the Brier score is 0.11. Similar performances are obtained in the other two samples. With increasing risk class, the mean age, number of hospitalizations, emergency room service consultations, and multiple drug prescriptions increase, while the average income decreases. CONCLUSION: the model has good predictive ability. The frailty index can be used to support a proactive medicine and stratify the population, plan clinical and preventive activities or identify the potential beneficiaries of specific health promotion projects.

Evaluation of service mammography screening impact in Italy. The contribution of hazard analysis.

12,987 invasive breast cancer cases were diagnosed in women aged 50-69 upto the year 2001 in nine Italian areas where a screening programme was active. Cases were followed up in 2005 for a total of 1921 breast cancer failures. The 10-year survival rates were 85.3% for the invited group against 75.6% for the non-invited. A time dependent analysis was performed using 5-year intervals. Crude hazard ratios for the invited group in comparison to the not invited group were 0.52 and 0.64 respectively in the (0-5) year and [5-10] year time windows. Hazard ratio adjusted for tumour characteristics was 0.96 in the [5-10] year time window, suggesting minimal or any length bias. Consistent with the results of randomised trials, these analyses of service screening data document a mortality reduction of 36% at 5-10 years after diagnosis.

Work-related injuries in young workers: an Italian multicentric epidemiological survey.

Emergency departments records from 33 hospitals were reviewed to disclose work-related injuries occurred in teen-subjects living in 14 Italian cities. During January-June 2000, 317 work-related injuries were reported. Male subjects, 17 year old, working in the industrial field, resulted the most affected, probably due to the fact that among young workers this sex and age class is the most represented one. Cluster analysis identified two groups of work-related injuries: one includes mainly transportation injuries causing lower extremities or multiple body sites traumas. The other is more strictly related to specific working tasks and includes mostly traumas and cut wounds in hand/wrist and head, together with eye lesions. A more intensive supervision on the use of protective equipment, a more appropriate training in hazard recognition and safe work practices, including operation of vehicles in the work site, must be implemented to reduce work-related injuries.