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Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15–64 years) diagnosed in 2000–2006 vs. 2007–2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.

Objectives: The Seveso accident (1976) caused the contamination with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in an area north of Milan, Italy. We report the results of the update of mortality and cancer incidence in the exposed population through 2013., Methods: The study cohort includes subjects living in three contaminated zones with decreasing TCDD soil concentrations (zone A, B and R) and in a surrounding uncontaminated territory (reference). Poisson models stratified/adjusted for gender, age and period were fitted to calculate rate ratios (RRs) and 95% CIs., Results: In zone A in males, we found elevated mortality from circulatory diseases in the first decade after the accident (17 deaths, RR 2.00, 95% CI 1.24 to 3.23). In females, mortality from diabetes mellitus was increased, with a positive trend across zones. Incidence of soft tissue sarcoma was increased in males in zone R in the first decade (6 cases, RR 2.62, 95% CI 1.01 to 6.83). In females in zone B, there was an excess of non-Hodgkin's lymphoma after 30 years (6 cases, RR 2.87, 95% CI 1.14 to 7.23). Multiple myeloma was increased in the second decade in females in zone B (4 cases, RR 5.09, 95% CI 1.82 to 14.2) and in males in zone R (11 cases, RR 2.15, 95% CI 1.08 to 4.26). In males in zone R, there was a leukaemia excess after 30 years (23 cases, RR 2.02, 95% CI 1.04 to 3.93)., Conclusions: Although with different patterns across gender, zone and time, we confirmed previous results of increased cardiovascular diseases, diabetes, soft tissue sarcoma, and lymphatic and haematopoietic cancers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Few studies have focused on changes in health and social services access due to the COVID-19 pandemic. We aimed to describe changes in the use of selected health and social home services due to the pandemic and to investigate potential associated factors, including socio-demographic characteristics, number of chronic diseases and mental health indicators, among older Italian individuals., Methods: We analysed data from the LOST in Lombardia cross-sectional study conducted in November 2020 on a large representative sample of 4400 individuals aged ⩾65 years. To identify potential factors associated with the increased use of three selected health and social home services, we estimated odds ratios (OR) and confidence intervals (CI) using multivariable logistic regression models., Results: Compared to the year before, 5.0% of older adults increased help from domestic workers (vs. 6.9% reducing) during the pandemic, 4.4% increased help from non-familiar caregivers (vs. 1.3% decreasing) and 4.7% increased medical home visits (vs. 1.0% decreasing). An increase in the use of these services was more frequent among participants with co-morbidities ( p for trend <0.001), especially with diabetes (for caregivers: OR=12.2, 95% CI 6.0-24.8), and worse mental health (for caregivers and for those with a GAD-2 score ⩾3 vs. <3: OR=10.6, 95% CI 5.8-19.4). Conversely, people living in more crowded households less frequently increased health and social services use during the pandemic., Conclusions: Our results should inform targeted interventions for the identified vulnerable groups to close the gap in health and social inequities., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

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

Background: People who reach old age enjoying good physical and mental health can be defined as (health) "superheroes", given their relatively low impact on healthcare expenditure and the desirable model they represent., Aim: To evaluate prevalence and possible determinants of being "physical superheroes" (i.e., free from the ten major chronic conditions, plus obesity), "mental superheroes" (i.e., free from major mental symptoms), and "superheroes" (i.e., both mental and physical superheroes)., Methods: A telephone-based cross-sectional study (LOST in Lombardia) was conducted in November 2020 (i.e., during the COVID-19 pandemic) on a representative sample of 4,400 adults aged ≥ 65 years from Lombardy region, northern Italy. All participants provided both current data and data referring to one year before., Results: Mental and physical superheroes were 59.0% and 17.6%, respectively. Superheroes were 12.8% overall, 15.1% among men, and 11.1% among women; 20.2% among individuals aged 65-69 years, 11.3% among 70-74, 10.0% among 75-79, and 8.3% among ≥ 80 years. Multivariable analysis showed that female sex, higher age, disadvantaged socio-economic status, and physical inactivity (p for trend < 0.001) were inversely related to being superheroes. People not smoking (adjusted odds ratio, aOR = 1.40), alcohol abstainers (aOR = 1.30), and those free from feelings of hopelessness (aOR = 5.92) more frequently met the definition of superheroes. During COVID-19 pandemic, the proportion of superheroes decreased by 16.3%., Conclusions: Differences in the older adults' health status are largely attributable to their lifestyles but are also likely due to gender, educational, and socio-economic disparities, which should be properly addressed by public health policies., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The COVID-19 pandemic and associated lockdown measures posed an unprecedented challenge to the crucial role of grandparenting in family-oriented cultures, such as Italy. Reduced contact with grandchildren during this period potentially threatened grandparents' mental health and well-being., Methods: We analysed data from the LOckdown and lifeSTyles in Lombardia cross-sectional study conducted in November 2020. The study included a representative sample of 4400 older adults from Lombardy, Italy, of which 1289 provided childcare to their grandchildren., Results: A decrease in self-reported grandparenting was associated with an increased likelihood of experiencing depressive symptoms among grandparents (OR 1.50, 95% CI 1.01-2.24). Conversely, an increase in grandparenting was linked to poorer sleep quality (OR 11.67, 95% CI 5.88-23.17) and reduced sleep quantity (OR 2.53, 95% CI 1.45-4.41)., Conclusions: Despite the barriers posed by the pandemic, grandparenting played a beneficial role in maintaining the mental health and well-being of older adults. However, it is crucial to recognise specific vulnerabilities, such as gender, feelings of hopelessness and overcrowding, which can have detrimental effects during and beyond emergency situations. Careful attention to these factors is essential for developing targeted support systems and interventions aimed at safeguarding the mental health of older adults and enhancing their resilience in crises., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To assess the survival predictivity of baseline blood cell differential count (BCDC), discretised according to two different methods, in adults visiting an emergency room (ER) for illness or trauma over 1 year., Design: Retrospective cohort study of hospital records., Setting: Tertiary care public hospital in northern Italy., Participants: 11 052 patients aged >18 years, consecutively admitted to the ER in 1 year, and for whom BCDC collection was indicated by ER medical staff at first presentation., Primary Outcome: Survival was the referral outcome for explorative model development. Automated BCDC analysis at baseline assessed haemoglobin, mean cell volume (MCV), red cell distribution width (RDW), platelet distribution width (PDW), platelet haematocrit (PCT), absolute red blood cells, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets. Discretisation cut-offs were defined by benchmark and tailored methods. Benchmark cut-offs were stated based on laboratory reference values (Clinical and Laboratory Standards Institute). Tailored cut-offs for linear, sigmoid-shaped and U-shaped distributed variables were discretised by maximally selected rank statistics and by optimal-equal HR, respectively. Explanatory variables (age, gender, ER admission during SARS-CoV2 surges and in-hospital admission) were analysed using Cox multivariable regression. Receiver operating curves were drawn by summing the Cox-significant variables for each method., Results: Of 11 052 patients (median age 67 years, IQR 51-81, 48% female), 59% (n=6489) were discharged and 41% (n=4563) were admitted to the hospital. After a 306-day median follow-up (IQR 208-417 days), 9455 (86%) patients were alive and 1597 (14%) deceased. Increased HRs were associated with age >73 years (HR=4.6, 95% CI=4.0 to 5.2), in-hospital admission (HR=2.2, 95% CI=1.9 to 2.4), ER admission during SARS-CoV2 surges (Wave I: HR=1.7, 95% CI=1.5 to 1.9; Wave II: HR=1.2, 95% CI=1.0 to 1.3). Gender, haemoglobin, MCV, RDW, PDW, neutrophils, lymphocytes and eosinophil counts were significant overall. Benchmark-BCDC model included basophils and platelet count (area under the ROC (AUROC) 0.74). Tailored-BCDC model included monocyte counts and PCT (AUROC 0.79)., Conclusions: Baseline discretised BCDC provides meaningful insight regarding ER patients' survival., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A prognostic stratification of mortality risk in older patients with sepsis admitted to medical wards is often challenging., Aims: To evaluate the ability of the Sequential Organ Failure Assessment (SOFA) score, serum biomarkers (lactate and C-Reactive Protein, CRP), and measures of comorbidity and frailty in predicting in-hospital and 6-month mortality in a cohort of older patients admitted to an Acute Geriatric Unit (AGU) with a diagnosis of sepsis., Methods: All patients aged 70 years and over consecutively admitted to our AGU with sepsis in the study period were included. At admission, a Comprehensive Geriatric Assessment including two measures of frailty (Clinical Frailty Scale [CFS], Frailty Index [FI]) was obtained. To assess the predictivity of candidate prognostic markers, the Area Under the Receiver-Operating Characteristic (AUROC) curves were analyzed. A multivariate logistic regression analysis was also performed., Results: We included 240 patients (median age = 85, IQR = 80-89, 40.8% women), of whom 33.8% died before discharge, and 60.4% at 6 months. The SOFA score (AUROC = 0.678, 95% CI 0.610-0.747) and CRP serum levels (AUROC = 0.606, 95% CI 0.532-0.680) were good predictors of in-hospital mortality. The CFS (AUROC = 0.703, 95% CI 0.637-0.768) and the FI (AUROC = 0.677, 95% CI 0.607-0.746) better predicted 6-month mortality. Results of the regression analysis confirmed the findings of the AUROC study. The combined assessment of SOFA and measures of frailty improved the performance of the model both in the short and the long term., Conclusions: Both the severity of organ dysfunction and frailty scores should be addressed on AGU admission to establish the short- and long-term outcomes of older patients with sepsis., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The COVID-19 pandemic disproportionally affected older people in terms of clinical outcomes and care provision. We aimed to investigate older adults' changes in access to care during the pandemic and their determinants. We used data from a cross-sectional study (LOST in Lombardia) conducted in autumn 2020 on a representative sample of 4400 older adults from the most populated region in Italy. Lifestyles, mental health, and access to healthcare services before and during the pandemic were collected. To identify factors associated with care delays, reduction in emergency department (ED) access, and hospitalisations, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) using multivariable log-binomial regression models. During the pandemic, compared to the year before, 21.5% of the study population increased telephone contacts with the general practitioner (GP) and 9.6% increased self-pay visits, while 22.4% decreased GP visits, 12.3% decreased outpatient visits, 9.1% decreased diagnostic exams, 7.5% decreased ED access, and 6% decreased hospitalisations. The prevalence of care delays due to patient's decision (overall 23.8%) was higher among men (PR 1.16, 95% CI 1.05-1.29), subjects aged 75 years or more (PR 1.12, 95% CI 1.00-1.25), and those with a higher economic status ( p for trend < 0.001). Participants with comorbidities more frequently cancelled visits and reduced ED access or hospitalisations, while individuals with worsened mental health status reported a higher prevalence of care delays and ED access reductions. Access to care decreased in selected sub-groups of older adults during the pandemic with likely negative impacts on mortality and morbidity in the short and long run.

Little is known on potential socioeconomic and gender disparities in dietary changes during the COVID-19 pandemic. We conducted a telephone-based survey during fall 2020 on 4400 participants representative of the population aged 65-99 years living in Lombardy, Italy. Changes in a Mediterranean lifestyle were assessed retrospectively by scoring modifications in the consumption of nine food groups and five diet-related behaviours compared to 2019. A Mediterranean COVID-19 Pandemic Score (MedCovid-19 Score) was computed, reflecting changes during pandemic, with increasing values indicating improvements in line with a Mediterranean lifestyle. Predictors of favourable dietary changes (MedCovid-19 Score ≥ 1) were education (odds ratio [OR] = 1.52; 95% confidence interval 1.19-1.95 for postgraduate vs. lower), wealth (OR = 1.52; 1.14-2.02 for high vs. low) and skilled manual occupations (OR = 1.57; 1.28-1.92 vs. white collars). Women were more likely than men to move away from a Mediterranean lifestyle (OR = 1.86; 1.58-2.21). In conclusions, changes towards a Mediterranean lifestyle were disproportionately distributed across gender and socioeconomic strata.

Objectives: to evaluate immunogenicity and effectiveness of BNT162b2 COVID-19 vaccine in a cohort of healthcare workers (HCWs)., Design: cohort study., Setting and Participants: in a hospital in Milan (Lombardy Region, Northern Italy) HCWs without ("negative cohort") and with ("positive cohort") history of SARS-CoV-2 infection or elevated serum antibody before the vaccination campaign (27.12.2020) were included. Data collection and follow-up covered the period 27.12.2020-13.05.2022., Main Outcomes Measures: 1. serum anti-spike-1 (anti-S1) antibody levels after vaccination; 2. vaccine effectiveness (VE) against SARS-CoV-2 infections (either symptomatic or not) in the negative cohort. Data on infections were extracted from multiple sources (laboratory, accident reports, questionnaires). Vaccination was treated as a time-dependent variable. Using unvaccinated person-time as reference, hazard ratios (HR) of infections and 95% confidence intervals (95%CI) were calculated with a Cox regression model adjusted for gender, age, and occupation. VE was calculated as (1 - HR)×100., Results: 5,596 HCWs were included, 4,771 in the negative and 825 in the positive cohort. In both cohorts, serum anti-S1 antibodies were high one months after the second dose, halved after six months, and returned to high levels after the third dose. In the negative cohort, 1,401 SARS-CoV-2 infections were identified. VE was 70% (95%CI 54-80; 46 infected) in the first four months after the second dose and later declined to 16% (95%CI 0-43; 97 infected). After the third dose, VE increased to 57% (95%CI 35-71; 61 infected) in the first month but rapidly declined over time, particularly after three months (24% in the fourth month and 1% afterwards). The number of infections avoided by vaccination was estimated to be 643 (95%CI 236-1,237)., Conclusions: in spite of rapidly declining effectiveness, vaccination helped to avoid several hundred infections in the considered hospital.

Most COVID-19 fatalities have occurred among older adults; however, evidence regarding the determinants of SARS-CoV-2 infection in this population is limited. Telephone interviews were conducted in November 2020 with a representative sample of 4400 Italians aged ≥65 years from the Lombardy region. We determined the prevalence of a history of SARS-CoV-2 infection. Through unconditional multiple logistic regression models, we estimated the odds ratios (ORs) of infection and the corresponding 95% confidence intervals (CIs). We further evaluated whether infection was related to a reduction in mental wellbeing. Of the participants, 4.9% reported a previous infection. No significant relationship between sex and infection was observed. Prior infection was less frequently reported in subjects aged ≥70 (OR = 0.55; 95% CI: 0.41-0.74) compared to 65-69 years, with no trend after 70 years of age. Those with at least one chronic condition reported a lower infection rate compared to healthy subjects (OR = 0.68; 95% CI: 0.49-0.93). Participants who lived alone more frequently reported infection than those who cohabited (OR = 2.33; 95% CI: 1.29-4.20). Prior infection was related to increased depressive symptoms (OR = 1.57; 95% CI: 1.17-2.10). This representative study of people aged ≥65 years suggests that in Italy, the oldest subjects and chronic patients less frequently exposed themselves to SARS-CoV-2 infection.

Background: Evidence showed that mental health problems have risen markedly during COVID-19. It is unclear if part of the mental sufferings relates to the climate of uncertainty and confusion originated from rough communication by health officials and politicians. Here, we test the impact of unanticipated policy announcements of lockdown policies on mental health of the older population., Methods: We used a representative telephone-based survey of 4400 people aged 65 years or older in Italy's Lombardy region to compare information on self-reported symptoms of anxiety, depression and poor-quality sleep of subjects interviewed on the days of the policy announcement with that of subjects interviewed on other days. We used regression models adjusting for potential socio-demographic confounders as well study design with inverse probability weighting., Results: On days when policymakers announced to extend the lockdown, mental health deteriorated on average by 5.5 percentage points [95% confidence interval (CI): 1.1-9.8] for self-reported anxiety symptoms and 5.1 percentage points (95% CI: 2.7-7.4) for self-reported depressive symptoms. The effect of the announcement to shorten the lockdown is more moderate but statistically significant. These associations were short term in duration; after just 1 day, self-reported mental health and sleep quality return to levels better than pre-announcement until a new policy change., Conclusions: Our research shows that lockdown policy announcements are associated with short-term worsening in mental distress, highlighting the importance of appropriate communication strategies and political determinations in crisis times., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Objectives: assessment of the health effects on the resident population around the incinerator for municipal solid waste in Valmadrera (Lombardy Region, Northern Italy) in relation to the exposure level to the pollutants produced by the plant., Design: historical cohort study, based on the resident population from 2003 to 2016 in the study area. With a dispersion model, based on PM10 emitted by the plant, three areas of exposure (high, medium, low) were defined and, on the basis of the residence of the cohort, different exposure levels were attributed to the subjects. The association between level of exposure and health effects were estimated by comparing the high and medium exposure levels with the low exposure level, using a Cox model, adjusted for age and socioeconomic deprivation index., Main Outcome Measures: mortality rates, hospitalization rates, cancer incidence rates, and perinatal outcomes were analysed for the main causes potentially associated with exposure to incineration plants., Results: the subjects enrolled in the cohort were 106,056 (1,000,242 person-years). There were no statistically significant excesses of risk for almost all the outcomes investigated. Excessive mortality and hospitalization were found for liver/biliary cancers (HR women: 2.57; 95%CI 1.15-2.79; HR men: 2.22; 95%CI 1.10-4, 84). In the municipality where the plant is located, an excess prevalence (OR 1.78; 95%CI 1.43-2.21) of hepatitis C was found., Conclusions: the results suggest the absence of a relationship between residence in areas with different levels of pollutants emitted by the plant and the onset of almost all diseases. The associated causes do not have aetiological plausibility with exposure to pollutants from waste incineration. In particular, for liver/liver and biliary cancer, the association with infectious causes rather than exposure to environmental pollutants is more plausible.

Background & Aims: COVID-19 containment measures significantly impacted lifestyle of the general population, including physical activity. Although the older adults are particularly susceptible to the potential consequences of sedentary lifestyle and inactivity, few studies investigated pandemic effects in this segment of the population. We aimed to evaluate COVID-19 pandemic effects on weight gain and physical activity in the Italian older adults, and assess the impact of possible changes in physical activity on mental health wellbeing., Methods: In November 2020, a cross-sectional survey was conducted on a representative sample of 4400 older adults (aged 65 or more) from the Lombardy region, Northern Italy. Changes in body mass index (BMI) and physical activity were assessed, compared to the previous year. Using unconditional multiple logistic models, we estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) of a decrease in physical activity during COVID-19 pandemic and we evaluated if decreased physical activity was a determinant of a worsening in psychological wellbeing., Results: Neither weight gain nor increase in obesity prevalence occurred during the pandemic. Mean time spent in physical activity significantly decreased, with 43.8% of participants reporting a decrease of 1 h/week or more during COVID-19 pandemic. A decreased physical activity was determinant of a worsening of selected mental health outcomes, such as: sleep quality (OR = 2.45; 95% CI: 1.91-3.15) and quantity (OR = 1.54; 95% CI: 1.18-2.02), anxiety (OR = 1.31; 95% CI: 1.14-1.52) and depressive symptoms (OR = 1.61; 95% CI: 1.38-1.88)., Conclusion: During the COVID-19 pandemic, while no major changes in BMI were observed, physical activity significantly declined in the older adults. In this population, the lack of physical activity might have contributed to the observed worsening in mental health. During emergency periods, encouraging physical activity might be effective also to preserve psychological wellbeing., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Although a direct relationship between tinnitus or hearing difficulties and COVID-19 has been suggested, current literature provides inconsistent results, and no research has been undertaken in older adults., Methods: In November 2020, we conducted the LOST in Lombardia survey, a telephone-based cross-sectional study on a sample of 4,400 individuals representative of the general population aged ≥65 years from Lombardy region, Northern Italy. Individuals with diagnosed tinnitus and/or hearing loss were asked whether their conditions had improved or deteriorated in 2020 compared to 2019., Results: Overall, 8.1% of older adults reported a diagnosis of tinnitus and 10.5% of hearing loss. In 2020 compared to 2019, among individuals with tinnitus, those with increasing severity (5.0%) were similar to those decreasing it (5.3%). Among individuals with hearing loss, more people reported an increase (13.6%) than a decrease (3.2%) in their disease severity. No individual with a diagnosis in 2020 of tinnitus ( n = 6) or hearing loss ( n = 13) had COVID-19. The incidence of tinnitus was lower in 2020 (rate: 14.8 per 10,000 person-years) than in previous years (rate in 1990-2019: 36.0 per 10,000 person-years; p = 0.026). There was no change in the incidence of hearing loss ( p = 0.134)., Conclusions: In this large representative sample of older adults, on average neither COVID-19 confinement nor SARS-CoV-2 infection appeared to increase the severity or incidence of tinnitus. The increased severity of hearing difficulties may totally or partially be explained by physiologic deterioration of the condition, or by a misperception due to the use of face-masks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jarach, Lugo, Stival, Bosetti, Amerio, Cavalieri d'Oro, Iacoviello, Odone, Stuckler, Zucchi, van den Brandt, Garavello, Cederroth, Schlee, Gallus and the LOST in Lombardia Study Investigators.)

Background: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care., Methods: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs., Results: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males., Conclusions: These results highlight the need to personalize follow-up strategies for AYA cancer survivors., (© 2021 American Cancer Society.)

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

Introduction: Data on medium- and long-term prognostic factors for death in elderly patients with acute Pulmonary Embolism (APE) are lacking. The present study aimed to assess sPESI score and the Charlson Comorbidity Index (CCI) as medium- and long-term predictors of mortality in elderly patients with haemodinamically stable APE., Methods: All consecutive patients aged≥65 years old, evaluated at the emergency department (ED) of our hospital from 2010 through 2014, with a final diagnosis of APE, were included in this retrospective cohort study., Results: Study population:162 patients, female:36.5%, median age:79 years old, 74% presented a sPESI score>0, and 61% a CCI≥ 1. All causes mortality: 19.8%, 23.5%, 26.5%, 32.1% and 48.2% at 3, 6 months, 1, 2 and 5 years after APE. Univariate regression analysis: CCI≥1 was associated with a higher mortality at 3, 6 months, 1, 2 and 5 years. Multivariate Cox analysis: CCI≥1 associated with increased mortality at 3 months (HR:4.29; IC95%:1.46-12.59), 6 months (HR:5.33; IC95%:1.84-15.44), 1 year (HR:4.87; IC95%:1.87-12.70), 2 years (HR:3.78; IC95%:1.74-8.25), and 5 years (HR:2.30; IC95%:1.33-3.99). sPESI score≥1 was not found to be related to an increased medium-or long-term mortality. Negative predictive values (IC95%) of CCI≥1 were 93.65% (87.61-99.69), 93.65% (87.61-99.69), 92.06% (85.37-98.76), 87.3% (79.05-95.55) and 71.61% (60.13-83.1) for mortality at 3, 6 months, 1, 2 and 5 years., Conclusion: In elderly patients with a confirmed normotensive APE, unlike sPESI score, CCI showed to be an independent prognostic factor for medium- and long-term mortality. In these patients, after the acute phase following a PE event, the assessment of the comorbidities burden represents the most appropriate approach for predicting medium- and long-term mortality., (© 2020 The Author(s).)

Background: The epidemiology of aortic stenosis (AS) in older patients admitted to non-cardiologic acute hospital wards and the effect of AS on mid-term survival are incompletely reported. In a cohort of very old patients admitted to an acute geriatric unit (AGU), we aimed to assess: (1) the prevalence of newly and previously diagnosed AS; and (2) the association between AS severity and patients' 6-month mortality., Methods: The patients consecutively admitted in two AGU rooms from February 2016 to February 2018 were assessed with echocardiography and AS severity was defined according to standard criteria. We assessed frailty using a 34-item Frailty Index (34-FI), which was operationalized using health variable information, and the Clinical Frailty Scale (CFS). Vital status at 6 months was extracted from Regional Register of Birth and Death., Results: Two hundred and three patients (mean age 84.5 ± 6.0 SD, female gender 56.1%) were included. Of these, 57 (28.1%) had AS, mild in 9 (4.5%), moderate in 32 (16.1%) and severe in 16 (8.1%). A new diagnosis of AS was obtained in 42 (73.7%) patients, of whom 33 (78.6%) had moderate or severe AS. At 6 months, 61 (28.9%) patients died. In multiple regression models, after adjusting for covariates, frailty, as assessed with both FI and CFS, was independent predictor of 6-month mortality whereas AS was not., Conclusions: Among older patients admitted to non-cardiologic acute hospital wards, AS was common and frequently underdiagnosed. The severity of AS was not associated with increased 6-month mortality, whereas frailty was the most important predictor.

In March 2020, when the Government imposed nation-wide lockdown measures to contrast the COVID-19 outbreak, the life of Italians suddenly changed. In order to evaluate the impact of lockdown on lifestyle habits and behavioral risk factors of the general adult population in Italy, we set up the Lost in Italy (LOckdown and lifeSTyles IN ITALY) project. Within this project, the online panel of Doxa was used to conduct a web-based cross-sectional study during the first phase of the lockdown, on a large representative sample of adults aged 18-74 years (N=6003). The self-administered questionnaire included information on lifestyle habits and perceived physical and mental health, through the use of validated scales. As we are working within the Lost in Italy project, we got two additional grants to further research on the medium-term impact of lockdown, a topic of great interest and with anticipated large socio-economic and public health implications. In details: we obtained by the AXA Research Fund support to evaluate the impact of COVID-19 lockdown on physical, mental, and social wellbeing of elderly and fragile populations in the Lombardy region, the area most heavily hit by the pandemic in the country. Moreover, as a fruitful integration, we obtained support by the Directorate General for Welfare of the region to assess health services delivery and access to healthcare in the same study population, combining an analysis of administrative databases with an economic analysis. We are confident that the solid background of our partners, the multi-disciplinary competencies they bring, together with appropriate funding and access to rich data sources will allow us to fulfill our research objectives.

Introduction: Most patients evaluated for suspected pulmonary embolism(PE) conclude the Emergency Department(ED) work-up with a diagnosis of PE not confirmed(PE excluded;PE-E). We aimed to investigate the clinical features, short and long-term mortality, and prognostic factors for death in elderly with PE-E, and to compare these figures with those of patients with PE confirmed(PE-C)., Methods: Consecutive patients ≥65 years old evaluated in the ED for clinically suspected hemodynamically stable acute PE were included in this retrospective cohort study., Results: Study population: 657 patients with suspected PE, PE-C:162(24.65%). When compared with PE-C, patients with PE-E presented a higher prevalence of chronic cardiopulmonary disease (17.37% vs 8.02%, p = 0.003), a lower prevalence of pulse rate >110 (13.13% vs 25.93%; p<0.001), of arterial oxygen saturation <90% (16.16% vs. 25.93%; p = 0.007) and of hospitalized patients (52.93% vs 98.15%; p < 0.001). Thirty-day, 90-day, 1-year, 2-year and 5-year overall mortality was 8.83%, 15.98%, 23.59%, 29.68%, and 51.09%, respectively, differences between PE-E and PE-C non statistically significant. Among patients with PE-E, multivariate analysis showed that simplified Pulmonary Embolism Severity Index score>0 was associated with higher short and long-term mortality (30-day:HR:5.31,p = 0.029; 5 year:HR:2.18, p < 0.001), meanwhile comorbidity (Charlson Comorbidity Index>0) only with higher long-term mortality (30-day: HR:1.60, p = 0.342; 5 year: HR:1.41, p = 0.038)., Conclusion: In real world haemodinamically stable elderly patients evaluated in the ED for suspected PE, short and long-term mortality was markedly high regardless whether PE was confirmed or excluded. At the time to set management and follow up strategies, elderly patients with PE excluded should not be considered a low-risk population., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: To generate and validate algorithms for the identification of individuals with dementia in the community setting, by the interrogation of administrative records, an inexpensive and already available source of data., Methods: We collected and anonymized information on demented individuals 65 years of age or older from ten general practitioners (GPs) in the district of Brianza (Northern Italy) and compared this with the administrative data of the local health protection agency (Agenzia per la Tutela della Salute). Indicators of the disease in the administrative database (diagnosis of dementia in the hospital discharge records; use of cholinesterase inhibitors/memantine; neuropsychological tests; brain CT/MRI; outpatient neurological visits) were used separately and in different combinations to generate algorithms for the detection of patients with dementia., Results: When used individually, indicators of dementia showed good specificity, but low sensitivity. By their combination, we generated different algorithms: I-therapy with ChEI/memantine or diagnosis of dementia at discharge or neuropsychological tests (specificity 97.9%, sensitivity 52.5%); II-therapy with ChEI/memantine or diagnosis of dementia at discharge or neuropsychological tests or brain CT/MRI or neurological visit (sensitivity 90.8%, specificity 70.6%); III-therapy with ChEI/memantine or diagnosis of dementia at discharge or neuropsychological tests or brain CT/MRIMRI and neurological visit (specificity 89.3%, sensitivity 73.3%)., Conclusions: These results show that algorithms obtained from administrative data are not sufficiently accurate in classifying patients with dementia, whichever combination of variables is used for the identification of the disease. Studies in large patient cohorts are needed to develop further strategies for identifying patients with dementia in the community setting.

Elderly patients presenting with acute pulmonary embolism (PE) frequently have significant underlying comorbidities which may condition the prognosis. The current study aimed to determine the ability of Charlson comorbidity index (CCI) score to predict short and long-term mortality in elderly patients with hemodynamically stable acute PE. All hemodynamically stable patients aged >65 years with acute PE, evaluated in the Emergency Department since 2010 through 2014, were included in this retrospective cohort study. CCI, simplified pulmonary embolism severity index (sPESI) scores and vital status were recorded. Were included 162 patients with confirmed PE, out of 657 suspected cases (24.7%). Median age: 79.2 years, 74.1% presented an sPESI > 1 and 61.1% a CCI > 1. The overall 30, 90-day and 2-year mortality was 11.7% (95%CI 6.6-16.6), 19.8% (95%CI 13.4-25.7) and 31.8% (95%CI 24.1-38.8). For 30-day mortality sPESI showed an AUC 0.642 (95%CI 0.511-0.772) and adding CCI as covariate did not increase its prognostic performance. For 90-day mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.282 (95%CI 1.151-1.429, p-value < 0.001), and sPESI a HR = NS(p-value = 0.267). For 2-year mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.295 (95%CI 1.180-1.421, p-value < 0.001) and sPESI a HR = NS(p-value = 0.353). In elderly patients with hemodynamically stable PE, the CCI score was found to be an independent predictor of mortality. CCI shows a significantly better ability to predict 90-day and 2-year mortality than sPESI. The assessment of comorbidity burden by using the CCI score may be proposed as an useful tool to predict mortality in these patients.

In a general population with acute Pulmonary Embolism (PE) elevated D-dimer concentrations associate with increased mortality. The aim of the study was to assess the ability of D-dimer to predict 30 and 90-days mortality in elderly patients with acute PE. Hemodynamically stable patients aged ≥65 years old with confirmed PE were included in this retrospective cohort study. A pulmonary computerized tomography angiography scan, D-dimer concentrations, simplified Pulmonary Embolism Severity Index (sPESI) variables and vital status were available for all patients. The study included 154 confirmed cases of PE (23.5 % of suspected), median age 79.1 years. D-dimer was higher in patients dead than in those alive at 30 (median 14,547 vs. 8340 ng/mL, p = 0.05) and 90 days (13,604 vs. 7973 ng/mL, p = 0.013). When adding D-dimer to sPESI, the discriminant capacity to predict mortality within 30 and 90 days was increased by 0.080 and 0.089, respectively. The contribution of D-dimer to the discriminating ability was NRI = 0.286 (95 % CI -0.198 to 0.770, p value: 0.247) at 30 days and NRI = 0.605 (95 % CI 0.223-0.988, p-value: 0.002) at 90 days.D-dimer concentration was associated with 30 and 90-days mortality and showed a higher discriminant capacity than sPESI alone to predict 90-days mortality. Adding D-dimer concentrations to sPESI score seems to improve its prognostic ability, supporting multivariable risk models as the best approach to estimate prognosis in elderly patients with PE.

Rationale, Aims and Objectives: Assuring the best standards of care - in a sustainable way - in chronic diseases as breast cancer is nowadays an important challenge for any health system. The aim of this study was to present the methodology used to define a set of quality indicators, computable from administrative data for the pathway of care of breast cancer, and its application at a population level., Method: The cohort of 2007-2009 incident cases of breast cancer was identified through a network of six cancer registers in Northern Italy. Cases of sarcoma and lymphoma, patients with multiple primary cancers and those metastatic at diagnosis were excluded; 9614 women were retained for the analysis. For each indicator, the sub-cohort of women eligible for the diagnostic/therapeutic procedures was identified and calculations were performed through record linkage between the cohort and sources of health information. Data on potential available confounders or prognostic factors were also collected., Results: For a few indicators, such as cyto-histological assessment before surgery (62%) and intensive follow-up (79%), deviation from recommendations was evident. Younger patients (≤50 years) more frequently needed a short term re-intervention, while older patients less frequently underwent reconstructive surgery and received palliative care. Several indicators had a great variability across hospitals. In some cases, this heterogeneity appeared to be related to the hospital size, with high-volume hospitals being more compliant to guidelines., Conclusion: It is possible to evaluate the quality of cancer care delivered in clinical practice in recent years, in order to implement interventions aimed to improve adherence to international standards of care., (© 2015 John Wiley & Sons, Ltd.)

Pulmonary Embolism (PE) incidence increases with age. Data on mortality and prognosis in elderly patients with suspected PE are lacking. (1) To assess 30- and 90-day mortality in subjects with PE from an elderly population seen in the emergency department (ED); (2) to test the prognostic accuracy of a simplified Pulmonary Embolism Severity Index (sPESI) coupled to a highly sensitive cardiac Troponin T (hs-cTnT) level. A retrospective cohort study was performed, including patients evaluated in the ED of Vimercate Hospital for clinically suspected PE from 2010 to 2012. Study population: n = 470, 63.4% women, mean age ± SD 73.06 ± 16.0 years, 40% aged ≥80 and 77.7% ≥65 years old, confirmed PE: 22.6% (106 cases). Within 30 and 90 days, mortality among patients with confirmed PE was 14.2% (8.8-22.0) and 20.8% (16.5-41.7). In subjects aged ≥80 years, 30-day mortality was 18.9% among patients with confirmed PE, and 12.6% among those with PE excluded (p = 0.317). Ninety-day mortality rates were 29.7 and 19.9%, respectively (p = 0.193). In patients with confirmed PE, Negative Predictive Value of sPESI was 94.1% (80.3-99.3) for 30 days and 88.2% (72.3-96.7) for 90-day mortality. Adding the hs-cTnT level to sPESI did not improve its performance. (1) In an elderly population referring to the ED with clinically suspected PE, mortality was high both in subjects with and without confirmed PE; (2) the ability of sPESI and hs-cTnT to predict PE mortality seems to be lower than reported in studies based on data from younger populations. Better risk stratification tools will be necessary to improve clinical management in this setting.

Objectives: to present a set of indicators developed from six Local Health Authorities of the Lombardy Region to monitor the diagnostic and therapeutic pathway of breast cancer patients, applied to 2007-2009 incident cases., Design: retrospective cohort study., Setting and Participants: all subjects with primary breast cancer, incident in the period 2007-2009, and collected by cancer registries of Milano 1, Bergamo, Cremona, Milano, Milano 2 and Monza-Brianza (5,320,272 inhabitants) were included., Main Outcome Measures: through the use of combined current health databases (health registry, hospitalizations, outpatient, pharmaceutical prescription and specific database for anticancer drugs), for each incident case 34 different indicators have been developed to measure the appropriateness of the procedures provided for diagnosis, treatment (surgical and medical) and follow-up. For each indicator, we analyzed the relationship with age, stage, deprivation index, type of treatment, volume of the specific procedure of the hospital where primary surgery was performed. Estimates were adjusted using multilevel regression models., Results: 12,988 incident cases, without metastatic diseases and other cancers, were included in the cohort: 62% were localized to the breast, 33% to the axillary lymph-nodes, 3% metastatic ab initio, and 2% with unknown stage. Deviations from the expected value of different magnitude depending on the type of indicator were observed: the most important differences were detected for the follow-up indicators. There was, in fact, an excess of several procedures in the first year of follow-up: 75% of the cases performed a dosage of a tumor marker, 67% an ecography or a CT scan or an MR, and 37% a bone scan. On the other hand, the access to neoadjuvant and adjuvant treatments in older women was far below the expected values., Conclusions: the study presents data derived from a large cohort of population cases; the set of indicators was validated by a board of oncologists. The use of indicators calculated by linking the cancer registries (that provide staging) and administrative databases allows the assessment of compliance to the guidelines for diagnosis and treatment of tumours. This experience shows that it is possible to develop a methodology, shared with clinicians, to define indicators that measure the distance between guidelines and current clinical practice in order to decrease variability, to limit inappropriateness, and to reduce unnecessary diagnostic tests for patients (and, consequently, hospitals organizational overload). In order to be sustainable and equitable, a health care system must be able to ensure implementation of protocols/procedures based exclusively on the best available scientific evidences.

Background: Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed., Aim: To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases., Methods: A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty., Results: The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations., Conclusions: No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.

The relationship between liver cirrhosis and hepatocellular carcinoma is recognized, but quantification of risk is still uncertain. Therefore, we analysed data from a case-control study conducted in Italy between 1984 and 1997 on 499 cases of incident, histologically confirmed hepatocellular carcinoma and 1,552 controls in hospital with acute, non-neoplastic disease. Overall, 87 (17.4%) cases vs 10 (0.6%) controls reported clinical history of liver cirrhosis. The corresponding odds ratio (OR) was 27.5 (95% confidence interval (CI), 14.3-15.2) after allowance for sociodemographic factors, and 16.2 (95% CI, 7.9-32.9) after simultaneous allowance for all identified confounding factors, including alcohol consumption and clinical history of hepatitis. The association was of similar magnitude for subjects whose cirrhosis was diagnosed < 55 years (OR = 14.8) or at age 55 or over (OR = 20.0), and the multivariate OR was 33.7 < 5 years after diagnosis of cirrhosis, 37.3 between 5 and 9 years, and 7.6 (95% to 2.7-21.3) > or = 10 years since diagnosis of cirrhosis. The association was stronger in males (OR = 23.4) than in females (OR = 5.9), similar in various age groups, and somewhat stronger in more educated subjects (OR = 53.7), with history of hepatitis (OR = 33.1), reporting heavy alcohol consumption (OR = 24.9) or high body mass index (OR = 58.1), although the interaction term was significant only for sex. In terms of population attributable risk, 17% of hepatocellular carcinomas in this population can be attributed to clinical history of liver cirrhosis.

Background: The protein equivalent of nitrogen appearance is an indirect index commonly used to assess dietary protein intake in patients on CAPD. Moreover it has been suggested that the ratio between nitrogen appearance and dietary nitrogen intake (fractional urea synthesis) can predict nitrogen balance in uraemic patients. Several formulae to directly calculate the protein equivalent of nitrogen appearance have been published. It has not been established, however, what formulae give the most appropriate estimate of protein intake and nitrogen appearance., Study Design: Nitrogen balance studies were carried out in seven stable patients on CAPD. All of the patients were receiving a diet whose protein content (1.2 g/kg/body wt/day) and calorie content (35 kcal/kg/body wt/day) were rigorously controlled. Six formulae for calculating protein equivalent of nitrogen appearance and nitrogen appearance were tested and the agreement of the estimating formulae was evaluated by means of the Bland and Altman method., Result: Net nitrogen balance was 1.68 +/- 0.9 g/N day, protein intake (g/day) 81 +/- 19, protein intake (g/kg) 1.05 +/- 0.17. Differences in protein equivalent of nitrogen appearance of up to about 20% were found. The smallest differences between protein equivalent of nitrogen appearance and protein intake were obtained by the formulae of Bergstrom (1 +/- 7 g, limits of agreement -12 and +15 g) and Blumenkrantz (-2 +/- 5 g, limits of agreement -11 and +7 g). The formula of Bergstrom most closely estimated nitrogen appearance (-0.35 +/- 0.89 g). Using such formula, the fractional urea synthesis was 54 +/- 12%, giving evidence of positive nitrogen balances., Conclusion: For the routine monitoring of protein equivalent of nitrogen appearance in CAPD patients, we recommend Bergstrom's formula with the determination of dialysate protein losses.