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Background: Global estimates of sepsis mortality are based on multiple causes of death (MCOD, any mention of the condition on death certificates); however, MCOD data are sparse and mainly referring to the pre-pandemic period., Objectives: To investigate recent trends in sepsis-related mortality, associated sites of infection, and comorbidities in Veneto (Northeastern Italy)., Methods: Mortality records from 2008 to 2022 were extracted, and sepsis-related mortality was assessed based both on the underlying cause of death (UCOD) and on MCOD. The average annual percent change in age-standardised rates was estimated by join point regression through the whole study period. MCOD records were investigated to retrieve infection sites and comorbidities., Results: Sepsis was mentioned in 63,479 death certificates, growing from 4.9% out of all deaths in 2008 to 12.9% in 2022. Age-standardised mortality rates increased yearly by 8.2% (95%CI 2.1-14.7%) based on the UCOD and by 5.9% (95%CI 5.3-6.5%) based on MCOD. Sharp peaks in monthly mortality were observed in correspondence with flu epidemics, COVID-19 pandemic waves, and periods of extreme heat. The percentage of sepsis-related deaths associated to urinary tract infections, and with mention of neurodegenerative disorders and chronic kidney disease increased over time., Conclusion: Raised awareness of physicians, ageing of the population, spread of antimicrobial resistance further fuelled by the COVID-19 pandemic are among reasons of increasing sepsis-related mortality in Italy. Continuous monitoring of sepsis by means of MCOD data and other surveillance tools is warranted.

Background: Traumatic brain injury (TBI) is a severe condition that represents a major global public health concern., Objectives: Provide a comprehensive epidemiological outlook encompassing TBI incidence, healthcare provision and mortality., Methods: Population-based study in Veneto (4.9 million inhabitants), Italy, from 2012 to 2021. Hospital discharge and mortality records were used to assess incidence and mortality. Kaplan-Meier survival estimator and Cox regression models were fitted to investigate determinants of mortality., Results: Between 2012 and 2021, there were 37,487 incident TBI cases, corresponding to an age-standardized rate of 77.30/100,000 people (95% CI 76.52-78.09), higher among males, with an exponential growth after age 70. Leading causes were domestic (33.1%) and traffic accidents (17.7%), the first predominating among the elderly and children, while the latter in males 15-24 and older people. After rates stably declined between 2012 and 2019, the study captured a sharp decrease especially for traffic and occupational accidents in males, due to COVID-19 lockdown in 2020. Overall, 48.9% TBI patients were hospitalized in a specialized trauma center, with 2.6% requiring a transfer after accessing a spoke hospital. Over a 3.7 years median follow-up, 16,145 deaths were recorded, with higher mortality for those undergoing neurosurgical interventions, regardless of their access point. Risks of death increased with age, male gender, and comorbidities., Discussion: TBI incidence is characterized by distinct patterns, affecting particularly older individuals and males. Minimal hospital transfers with comparable survival irrespective of access point suggests an effective patient management within the network. The study underscores the critical need for acute-phase support and prolonged care strategies for older TBI patients., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Patients with hematologic malignancies are at increased risk of adverse COVID-19 outcomes; nonetheless, only sparse population-based data are available on mortality related to hematologic cancers during the pandemic. Number of deaths and age-standardized mortality rates for specific hematologic malignancies selected either as the underlying cause of death (UCOD), or mentioned in death certificates (multiple causes of death-MCOD) were extracted from the US National Center for Health Statistics, CDC WONDER Online Database. Joinpoint analysis was applied to identify changes in mortality trends from 1999 to 2021, and to estimate the annual percent change with 95% Confidence Intervals (CI) across time segments. Among the most common malignancies, chronic lymphocytic leukemia showed marked peaks in the monthly number of deaths attributed to COVID-19 during epidemic waves; acute myeloid leukemia showed the least variation, and non-Hodgkin lymphoma and multiple myeloma were characterized by an intermediate pattern. Age-standardized death rates relying solely on the UCOD did not show significant variations during pandemic years. By contrast, rates based on MCOD increased by 14.0% (CI, 10.2-17.9%) per year for chronic lymphocytic leukemia, by 5.1% (CI, 3.1-7.2%) for non-Hodgkin lymphoma and by 3.2% (CI, 0.3-6.1%) per year for multiple myeloma. Surveillance of mortality based on MCOD is warranted to accurately measure the impact of the COVID-19 pandemic and of other epidemics, including seasonal flu, on patients with hematologic malignancies, and to assess the effects of vaccination campaigns and other preventive measures., (© 2024 UICC.)

Few studies have examined cancer-related mortality overall, never mind select cancer types, during the COVID-19 pandemic. Data on cancer-related mortality (any mention in death certificates, multiple causes of death approach) was extracted from the US Centers for Disease Control and Prevention WONDER database. Changes in trends for age-standardized mortality rates through 1999-2021 were assessed by Joinpoint analysis. In total, 1 379 643 cancer-related deaths were registered in 2020-2021, with cancer selected as the underlying cause in 88%. After 2 decades of decline, age-standardized cancer-related mortality increased from 2019 to 2021 for all cancers (annual percentage change = 1.6%, 95% confidence interval = 0.6% to 2.6%), especially for prostate cancer (annual percentage change = 5.1%, 95% confidence interval = 2.2% to 8.2%) and hematologic cancers (annual percentage change = 4.8%, 95% confidence interval = 3.1% to 6.6%). Sharp peaks in cancer-related deaths for many cancer sites were observed during pandemic waves in both 2020 and 2021, mostly attributed to COVID-19 as the underlying cause. Multiple causes of death analyses are warranted to fully assess the impact of the pandemic on cancer-related mortality., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Purpose: People with multiple sclerosis (MS) suffer from higher infection-related mortality compared to the general population; however, sparse data are available on the increased risk of death associated with coronavirus disease 2019 (COVID-19) and other common types of infections., Methods: All mortality records and multiple-cause-of-death data in 2010-2021 of residents in the Veneto region (northeastern Italy) were extracted. Mention of specific infections was compared between death certificates reporting MS or not. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated by conditional logistic regression matching by age, sex and calendar year. The bimonthly averages of MS-related deaths in 2010-2019 were compared with those registered during the pandemic (2020-2021)., Results: Of 580,015 deaths through 2010-2021, MS was mentioned in 850 cases (0.15%), 59.3% women. Influenza and pneumonia were reported in 18.4% of MS-related compared to 11.0% non-MS-related deaths (OR 2.72, 95% CI 2.28-3.25). The odds of mention of urinary tract infections was significantly greater in MS-related deaths of men (OR 8.16, 95% CI 5.23-12.7) than women (OR 3.03, 95% CI 1.82-5.02). Aspiration pneumonia, pressure ulcers/skin infections and sepsis were also significantly associated with MS-related deaths. Reporting of COVID-19 as a cause of death did not significantly differ between deaths with and without mention of MS (approximately 11% of both). However, compared to 2010-2019, peaks in MS-related deaths were observed during the pandemic waves., Conclusions: Infections continue to play a significant role in MS-related deaths, underlying the need to improve prevention and management strategies., (© 2023 European Academy of Neurology.)

Background/objective: Little is known about the impact of the COVID-19 pandemic on mortality from COPD at the population level. The objective was to investigate COPD-related mortality throughout different epidemic waves in Italy before and after the vaccination campaign, which started in late December 2020 and initially targeted the population aged ≥80 years., Methods: Death certificates of residents in Veneto (Northeastern Italy) aged ≥40 years between 2008 and 2021 were analyzed. Age-standardized morality rates were computed for death certificates with any mention of COPD. Generalized estimating equation (GEE) models were fitted to estimate the expected mortality during the pandemic. The results were stratified by age groups of 40-79 and ≥80 years, main comorbidities, and place of death., Results: COPD was mentioned in 3478 death certificates in 2020 (+14% compared to the 2018-2019 average) and in 3133 in 2021 (+3%). Age-standardized mortality rates increased in all age and sex groups in 2020; in 2021, mortality returned to pre-pandemic levels among the elderly but not in the population aged 40-79 years (+6%). GEE models confirmed this differential trend by age. COPD-related mortality peaks were observed, especially in the first pandemic waves, with COVID-19 identified as the underlying cause of death in a relevant proportion (up to 35% in November 2020-January 2021). Mortality with comorbid diabetes and hypertensive diseases slightly increased during the pandemic., Conclusion: COPD-related mortality increased at the beginning of the pandemic, due to deaths from COVID-19. The start of the vaccination campaign was associated with an important decline in COPD-related mortality, especially among the elderly, who first benefited from COVID-19 vaccines. The study findings show the role of mass vaccination in reducing COPD-related deaths during the later phases of the pandemic., Competing Interests: No potential conflict of interest was reported by all the authors.

Objectives: We aimed at estimating the incidence and prevalence of SLE in northeastern Italy over the period 2012-20., Methods: A retrospective population-based study was conducted in Veneto Region (4.9 million people) using the population registry, an administrative health database where all residents are recorded. Between 2012 and 2020, SLE prevalence was defined by a healthcare co-payment exemption for SLE (national registry code 028) or any hospital diagnosis of SLE (International Classification of Disease , Ninth Revision, Clinical Modification 710.0), whichever came first. Incident SLE was defined from 2013 to 2020 to exclude prevalent cases. Standardized incidence and prevalence rates were reported by age and sex., Results: During the study period, we identified 4283 SLE patients (85% female), with 1092 incident cases. Across the study period, SLE standardized point prevalence increased from 63.5 (95% CI 61.2, 65.8) to 70.6 (95% CI 68.3, 73.0) per 100 000 residents, corresponding to an annual increment of 1.14% (P < 0.0001). The highest prevalence was observed in females aged 60-69 years. SLE incidence corresponded to 2.8 per 100 000 person-years (95% CI 2.6, 2.9), with an annual decline of 7.3% (P < 0.0001). Incidence was 5-fold higher in females (female-to-male incidence rate ratio: 5.00, 95% CI 4.25, 5.87; P < 0.0001), with a peak among women aged 30-39 years. At diagnosis, women were significantly younger (45 years, IQR 33-58) than men (52 years, IQR 38-64)., Conclusions: Over the last decade, SLE prevalence has increased, while incidence has stably declined. In view of the introduction of new high-cost drugs, a clear definition of the epidemiology of SLE is crucial for all healthcare stakeholders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Prepandemic time trends in mortality from chronic liver disease (CLD) differed according to specific cause of death (decreasing for liver cirrhosis, stable or increasing for liver cancer), etiology (increasing for nonalcoholic fatty liver disease, generally decreasing for other etiologies), and world region (decreasing in areas with the highest burden of hepatitis B virus, increasing in Eastern Europe and other countries). The coronavirus disease 2019 (COVID-19) pandemic affected mortality of patients with CLD both directly, with a higher risk for severe illness and death depending on age, stage and etiology of the disease, and indirectly, through social isolation and loss of support, harmful drinking, and difficulties in access to care. Nevertheless, only sparse data are available on variations in CLD as a cause of death during the pandemic. In the USA, in 2020-2021 a growth in mortality was registered for all liver diseases, more marked for alcoholic liver disease, especially among young people aged 25-44 years and in selected ethnic groups. COVID-19 related deaths accounted only for a minor part of the excess. Further data from mortality registers of other countries are warranted, preferably adopting the so-called multiple cause-of-death approach, and extended to deaths attributed to viral hepatitis and liver cancer., Competing Interests: Conflict-of-interest statement: The authors declare they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To assess mortality rates (MRs), standardized mortality ratios, and causes of death in systemic lupus erythematosus (SLE) in a population-based study., Methods: We analyzed linked administrative health databases of the Veneto Region (Italy, 4,900,000 residents). SLE was defined by any hospital diagnosis or healthcare copayment exemption for SLE. We analyzed mortality from January 1st, 2012, until December 31st, 2021. MRs per 1000 were stratified by year, sex, and age group. Standardized mortality ratios were derived by comparing MRs of the general regional population. Causes of death were coded using the ICD-10 coding system and they were grouped in: SLE, infectious diseases, cardiovascular diseases (CVD), cancer, or others., Results: Among 4283 SLE prevalent cases, 603 deaths occurred, corresponding to an average annual standardized MR of 18.6 per 1000 person/year (95% CI 17.0-20.2). Out of 1092 incident SLE patients, 90 died with a peak in the first year after diagnosis (MR 26.5 per 10,000 person/month). Standardized mortality ratio was 2.65 (95% CI 2.13-3.26) overall, and highest among younger patients (<45 years: 5.59, 95% CI 2.05-12.4). Five- and 8-year survival were 91% and 89%, respectively. About half of the deaths had CVD or cancer as underlying cause, whereas infections were less frequently reported., Conclusions: Although the medium-term survival since diagnosis is good, SLE mortality is still higher than that of the general population, especially in youngest patients. Nowadays, CVD seems to be the major cause of deaths in SLE, whereas infections account for a low proportion of deaths, at least in Western countries., Competing Interests: Declaration of Competing Interest All Authors declare they have no competing interests to report., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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

Background: Older individuals with dementia have been severely affected by the COVID-19 pandemic. There is a lack of in-depth evaluation of mortality trends using both the underlying cause of death (UCOD) and the multiple causes of death (MCOD) approaches. The objective of this study was to determine the impact of the COVID-19 pandemic on dementia-related deaths considering comorbidities and the place of death., Methods: This retrospective, population-based study was conducted in Veneto, Italy. All the death certificates of individuals aged ≥65 years issued from 2008 to 2020 were analyzed for dementia-related mortality using age-standardized sex-stratified rates of dementia as UCOD and MCOD. Excess in monthly dementia-related mortality in 2020 was estimated by applying Seasonal Autoregressive Integrated Moving Average (SARIMA) model., Results: Overall, 70 301 death certificates reported dementia (MCOD proportional mortality: 12.9%), and 37 604 cases identified it as UCOD (proportional mortality: 6.9%). In 2020, the MCOD proportional mortality increased to 14.3% whereas that of UCOD remained static (7.0%). Compared to the SARIMA prediction, MCOD increased by 15.5% in males and 18.3% in females in 2020. Compared to the 2018-19 average, deaths in nursing homes increased by 32% in 2020, at home by 26% and in hospitals by 12%., Conclusions: An increase in dementia-related mortality during the first months of the COVID-19 pandemic could only be detected using the MCOD approach. MCOD proved to be more robust, and hence, should be included in future analyses. Nursing homes appeared to be the most critical setting which should guide establishing protective measures for similar situations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Colorectal cancer (CRC) screening programs based on fecal immunochemical tests (FITs) represent the standard of care for population-based interventions. Their benefit depends on the identification of neoplasia at colonoscopy after FIT positivity. Colonoscopy quality measured by adenoma detection rate (ADR) may affect screening program effectiveness., Objective: To examine the association between ADR and postcolonoscopy CRC (PCCRC) risk in a FIT-based screening program., Design: Retrospective population-based cohort study., Setting: Fecal immunochemical test-based CRC screening program between 2003 and 2021 in northeastern Italy., Patients: All patients with a positive FIT result who had a colonoscopy were included., Measurements: The regional cancer registry supplied information on any PCCRC diagnosed between 6 months and 10 years after colonoscopy. Endoscopists' ADR was categorized into 5 groups (20% to 39.9%, 40% to 44.9%, 45% to 49.9%, 50% to 54.9%, and 55% to 70%). To examine the association of ADR with PCCRC incidence risk, Cox regression models were fitted to estimate hazard ratios (HRs) and 95% CIs., Results: Of the 110 109 initial colonoscopies, 49 626 colonoscopies done by 113 endoscopists between 2012 and 2017 were included. After 328 778 person-years follow-up, 277 cases of PCCRC were diagnosed. Mean ADR was 48.3% (range, 23% and 70%). Incidence rates of PCCRC from lowest to highest ADR group were 13.13, 10.61, 7.60, 6.01, and 5.78 per 10 000 person-years. There was a significant inverse association between ADR and PCCRC incidence risk, with a 2.35-fold risk increase (95% CI, 1.63 to 3.38) in the lowest group compared with the highest. The adjusted HR for PCCRC associated with 1% increase in ADR was 0.96 (CI, 0.95 to 0.98)., Limitation: Adenoma detection rate is partly determined by FIT positivity cutoff; exact values may vary in different settings., Conclusion: In a FIT-based screening program, ADR is inversely associated with PCCRC incidence risk, mandating appropriate colonoscopy quality monitoring in this setting. Increasing endoscopists' ADR may significantly reduce PCCRC risk., Primary Funding Source: None.

Background: The success of pediatric COVID-19 vaccination strongly depends on parents' willingness to vaccinate their children. To date, the role of socioeconomic position (SEP) in pediatric COVID-19 vaccination has not been thoroughly examined., Objective: We evaluated the association between COVID-19 vaccination and SEP in a large pediatric cohort., Methods: A case-control study design nested into a pediatric cohort of children born between 2007 and 2017, living in the Veneto Region and followed up to at least January 1, 2022, was adopted. Data on children were collected from the Pedianet database and linked with the regional COVID-19 registry. Each child vaccinated with at least one dose of any COVID-19 vaccine between July 1, 2021, and March 31, 2022, was matched by sex, year of birth, and family pediatrician to up to 5 unvaccinated children. Unvaccinated children with a positive outcome on the swab test within 180 days before the index date were excluded from the analyses. Children were geo-referenced to determine their area deprivation index (ADI)-a social and material deprivation measure calculated at the census block level and consisting of 5 socioeconomic items. The index was then categorized in quintiles based on the regional ADI level. The association between ADI quintiles and vaccination status was measured using conditioned logistic regression models to estimate odds ratios and the corresponding 95% CIs. Quantile-g-computation regression models were applied to develop a weighted combination of the individual items to estimate how much each component influenced the likelihood of vaccination. All analyses were stratified by age at vaccination (5-11 and 12-14 years)., Results: The study population consisted of 6475 vaccinated children, who were matched with 32,124 unvaccinated children. Increasing area deprivation was associated with a lower probability of being vaccinated, with approximately a linear dose-response relationship. Children in the highest deprivation quintile were 36% less likely to receive a COVID-19 vaccine than those with the lowest area deprivation (95% CI 0.59-0.70). The results were similar in the 2 age groups, with a slightly stronger association in 5-11-year-old children. When assessing the effects of the weighted combination of the individual items, a quintile increase was associated with a 17% decrease in the probability of being vaccinated (95% CI 0.80-0.86). The conditions that influenced the probability of vaccination the most were living on rent, being unemployed, and being born in single-parent families., Conclusions: This study has shown a significant reduction in the likelihood of receiving a COVID-19 vaccine among children living in areas characterized by a lower SEP. Findings were robust among multiple analyses and definitions of the deprivation index. These findings suggest that SEP plays an important role in vaccination coverage, emphasizing the need to promote targeted public health efforts to ensure global vaccine equity., (©Erich Batzella, Anna Cantarutti, Nicola Caranci, Carlo Giaquinto, Claudio Barbiellini Amidei, Cristina Canova. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 01.02.2023.)

Organized cervical cancer screening programs to promote the early identification of precancerous lesions have proven to be effective in decreasing the burden associated with cervical cancer, but knowledge regarding screening adherence among migrant women compared to that of native women has not been summarized. A systematic search of the literature on PubMed, Scopus and Embase led to the identification of 772 papers that were published up to July 2022 and reported population-based data regarding adherence to cervical screening. The screening participation rates among migrant women, compared to native women, were pooled using a random-effects meta-analysis. A total of 18 papers were included in the review, with most of them being conducted in Europe (83.3%). Overall, migrants showed a significantly lower participation rate compared to native women (OR for screening adherence: 0.54, 95% CI = 0.42-0.70). This discrepancy was especially evident for migrant women from North Africa and Sub-Saharan Africa (OR = 0.47, 95% CI = 0.35-0.63, and OR = 0.35, 95% CI = 0.24-0.49, respectively). The results of this systematic review emphasize the importance of increasing cervical cancer screening adherence among migrant women. A significant heterogeneity in screening adherence was observed based on the country of origin. Interventions aimed at reducing the disparities in screening participation should specifically consider how to improve the recruitment of migrant women.

Mortality related to chronic obstructive pulmonary disease (COPD) during the COVID-19 pandemic is possibly underestimated by sparse available data. The study aimed to assess the impact of the pandemic on COPD-related mortality by means of time series analyses of causes of death data. We analyzed the death certificates of residents in Veneto (Italy) aged ≥40 years from 2008 to 2020. The age-standardized rates were computed for COPD as the underlying cause of death (UCOD) and as any mention in death certificates (multiple cause of death-MCOD). The annual percent change (APC) in the rates was estimated for the pre-pandemic period. Excess COPD-related mortality in 2020 was estimated by means of Seasonal Autoregressive Integrated Moving Average models. Overall, COPD was mentioned in 7.2% (43,780) of all deaths. From 2008 to 2019, the APC for COPD-related mortality was -4.9% (95% CI -5.5%, -4.2%) in men and -3.1% in women (95% CI -3.8%, -2.5%). In 2020 compared to the 2018-2019 average, the number of deaths from COPD (UCOD) declined by 8%, while COPD-related deaths (MCOD) increased by 14% (95% CI 10-18%), with peaks corresponding to the COVID-19 epidemic waves. Time series analyses confirmed that in 2020, COPD-related mortality increased by 16%. Patients with COPD experienced significant excess mortality during the first year of the pandemic. The decline in COPD mortality as the UCOD is explained by COVID-19 acting as a competing cause, highlighting how an MCOD approach is needed.

Study Design: A retrospective population-based study., Objectives: Describe the incidence of traumatic spinal cord injury (TSCI) and mortality risks, based on the characteristics of the patient, anatomical level of the lesion, setting/cause of the injury, and type of healthcare support received within the regional trauma network (highly specialized trauma center or spoke hospital)., Setting: Between 2011 and 2020, 1303 patients with incident TSCI were identified in a population of 4.9 million inhabitants., Methods: Hospital discharge records and mortality records were used to identify patients and outcomes. Cox regression models were fitted to estimate mortality risks across several subgroups., Results: Over the past decade, age-sex-standardized TSCI incidence rates remained stable with 26.5 cases (95% CI, 25.0-27.9) per 1,000,000 inhabitants (mean age 59.2 years) and most cases were males (68.3%). Incidence was directly associated with age while the male to female ratio was inversely related. Most TSCIs were cervical lesions (52.1%), and the most common cause of injury were traffic crashes (29.9%) followed by occupational accidents (29.8%). Sex, cause of the trauma, or inpatient hospital management were not associated with an increased risk of death. Mortality rates were greater for cervical lesions, and increased with age, remaining stably high among older individuals even 12 months after the accident. One-month mortality risk was significantly higher at ≥75 years compared to <55 years (adjusted HR 9.14 (95% CI, 4.17-20.03))., Conclusion: Public health policies should aim at reducing preventable TSCIs, and special attention should be drawn to long-term management of elderly patients in the attempt to decrease mortality rates., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

Objectives: to examine the differences in SARS-CoV-2 infection and hospitalization rates among migrant populations in Veneto Region (Northern Italy), according to the geographic area of origin., Setting and Participants: all residents in Veneto Region aged <65 years were included in the analyses. All subjects infected by SARS-CoV-2 and hospitalized for COVID-19 were identified by means of the regional biosurveillance system., Main Outcome Measures: age- and gender-specific infection and hospitalization rates were stratified by geographic area of origin and were estimated using the number of incident cases over the resident population in Veneto on 01.01.2021. Incidence rate ratios (IRR) for infection and hospitalization rates were estimated using a Poisson model, adjusted for age and gender, among migrants compared to Italians., Results: compared to Italians, SARS-CoV-2 infection rates were significantly higher among migrants from Central and South America and Central and South Asia, lower among those from North Africa and High-Income Countries (HIC), and were approximately halved for those coming from Other Asian Countries (mainly represented by China). Hospitalization rates were significantly higher for all migrant populations when compared to Italians, with the exception of those coming from HIC. Neither age nor gender seemed to modify the association of the geographic area of origin with SARS-CoV-2 infection and hospitalization rates. IRR for SARS-CoV-2 infection of migrants compared to Italians showed how migrants from Other Asian Countries had the lowest infection rates (-53%), followed by people from HIC (-25%), North Africa (-21%), and Eastern Europe (-10%). Higher infection rates were present for Central and South America and Central and South Asia (+17% and +10, respectively). Hospitalization rates were especially high among migrants from Central and South Asia, Africa, and Central and South America, ranging from 1.84 to 3.14 times those observed for Italians., Conclusions: a significant heterogeneity in SARS-CoV-2 infection and hospitalization rates of migrant populations from different geographic areas of origin were observed. The significantly lower incidence rate ratio for infections, compared to that observed for hospitalizations, is suggestive of a possible under-diagnosis of SARS-CoV-2 infection among migrant populations. Public health efforts should be targeted at increasing support among migrants to contrast the spread of the pandemic by potentiating vaccination campaigns, contact tracing, and COVID-19 diagnostic tests.

Introduction: Parkinson's disease (PD) mortality burden is increasing worldwide, but accurate estimates on the magnitude of the impact of the COVID-19 pandemic are missing. Mortality rates vary largely when considering PD as underlying cause of death (UCOD), or as one among multiple causes reported in death certificates (MCOD). The aim of this study is to assess COVID-19 impact on PD-related mortality trends using the UCOD and MCOD approach., Methods: Mortality records between 01/2008-12/2020 of residents aged ≥45 years in Veneto Region (Northeastern Italy) with any mention of PD were collected. Age-standardized sex-specific mortality rates were estimated for PD-related deaths as UCOD and MCOD to assess time trends. The average annual percentage change in age-standardized rates (AAPC) was estimated by linear regression models. Monthly mortality in 2020, the first year of the pandemic, was plotted against the 2018-2019 average., Results: Overall, 13,746 PD-related deaths (2.3% of all deaths) were identified, 52% males, median age 84 years. Proportional mortality increased from 1.9% (2008) to 2.8% (2020). AAPC through 2008-2019 was +5.2% for males and +5.3% for females in analyses of the UCOD, and +1.4% in both genders based on MCOD. Excess in PD-related mortality during 2020 corresponded to 19% for UCOD and 28% for MCOD, with the latter showing two peaks corresponding to the first (28%) and second (59%) pandemic waves., Conclusion: Age-standardized PD-related mortality rates have steeply increased during COVID-19 pandemic, amplifying a pre-existing long-term trend. Hence, surveillance of mortality associated to PD is warranted in the forthcoming pandemic and post-pandemic years., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Pulmonary embolism is a known complication of coronavirus disease 2019 (COVID-19). Epidemiological population data focusing on pulmonary embolism-related mortality is limited., Methods: Veneto is a region in Northern Italy counting 4,879,133 inhabitants in 2020. All ICD-10 codes from death certificates (1st January 2018 to 31st December 2020) were examined. Comparisons were made between 2020 (COVID-19 outbreak) and the average of the two-year period 2018-2019. All-cause, COVID-19-related and the following cardiovascular deaths have been studied: pulmonary embolism, hypertensive disease, ischemic heart disease, atrial fibrillation/flutter, and cerebrovascular diseases., Results: In 2020, a total of 56,412 deaths were recorded, corresponding to a 16% (n = 7806) increase compared to the period 2018-2019. The relative percentage increase during the so-called first and second waves was 19% and 44%, respectively. Of 7806 excess deaths, COVID-19 codes were reported in 90% of death certificates. The percentage increase in pulmonary embolism-related deaths was 27% (95%CI 19-35%), 1018 deaths during the year 2020, compared to 804 mean annual deaths in the period 2018-2019. This was more evident among men, who experience an absolute increase of 147 deaths (+45%), than in women (+67 deaths; +14%). The increase was primarily driven by deaths recorded during the second wave (+91% in October-December). An excess of deaths, particularly among men and during the second wave, was also observed for other cardiovascular diseases, notably hypertensive disease, atrial fibrillation, cerebrovascular disease, and ischemic heart disease., Conclusions: We observed a considerable increase of all-cause mortality during the year 2020. This was mainly driven by COVID-19 and its complications. The relative increase in the number of pulmonary embolism-related deaths was more prominent during the second wave, suggesting a possible underdiagnosis during the first wave., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Cardiovascular benefits deriving from physical activity are well known, but it is unclear whether physical activity trajectories in late life are associated with different risks of cardiovascular diseases., Methods: Progetto Veneto Anziani (Pro.V.A.) is a cohort study of 3099 Italians aged ≥65 years with baseline assessment in 1995-1997 and follow-up visits at 4 and 7 years. Surveillance was extended to 2018 by linkage with hospital and mortality records. Prevalent and incident cardiovascular diseases (coronary heart disease, heart failure and stroke) were identified through clinical examination, questionnaire, or hospital records. Moderate to vigorous physical activity was considered as a time-varying variable. Physical activity trajectories were categorised as: stable-low, high-decreasing, low-increasing and stable-high. Exposure was also assessed at 70, 75, 80 and 85 years., Results: Overall, physical activity was associated with lower rates of incident cardiovascular diseases. A significant risk reduction was present among men and was stronger earlier in late life (70-75 years). Trajectories of stable-high physical activity were associated with a significantly lower risk of cardiovascular outcomes among men (HR 0.48, 95% CI 0.27 to 0.86) compared with those with stable-low trajectories (p for trend 0.002). No significant association was found with stroke. The greatest cardiovascular risk reduction was observed for >20 min/day of physical activity, and was more marked at 70 years., Conclusion: Increasingly active trajectories of physical activity were associated with lower rates of cardiovascular diseases and overall mortality. Promoting at least 20 min/day of physical activity early in late life seems to provide the greatest cardiovascular benefits., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Per- and poly-fluoroalkyl substances (PFAS) are persistent and widespread environmental pollutants. People living in Veneto Region (Italy) have been exposed from the late 1970s to 2013 to elevated concentrations of PFAS through drinking water. The effect of PFAS on thyroid function is still controversial and studies focusing on thyroid stimulating hormone (TSH) have shown inconsistent results. The aim of this study was to evaluate the association between serum PFAS and TSH levels and its dose-response relationship in a large population of highly exposed individuals., Methods: A cross-sectional study was conducted on 21,424 individuals aged 14-39 living in the contaminated area. In the main analysis, participants with prevalent thyroid disease and pregnant women were excluded. Serum levels of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were measured. Generalized Additive Models were used to evaluate the association between TSH levels and serum PFAS, using thin plate spline smooth terms to model the potential non-linear relationship. Models were stratified by sex and age group and adjusted for potential confounders. A secondary analysis was conducted to evaluate the association between PFAS with prevalent self-reported thyroid disorders., Results: We found no association between TSH and any type of PFAS among adolescents or women. A decrease in TSH concentration was observed in association with an IQR increase in PFHxS and a mild decrease in TSH at low levels of PFOA, PFOS and PFHxS among male adults. Self-reported thyroid disease was more common among women with higher levels of PFNA concentrations, whereas all other PFAS were not associated with thyroid diseases regardless of sex or age., Conclusions: Overall there is no evidence of an association between TSH and PFAS. However, some results are suggestive of a possible inverse association of TSH with PFOA, PFOS and PFHxS among adult males., (Copyright © 2021. Published by Elsevier Inc.)

Across the world, people have avoided seeking medical attention during the coronavirus pandemic, resulting in a marked reduction in emergency department (ED) visits. This retrospective cohort study examines in detail how the present pandemic affects ED use by the elderly. The regional database on ED visits in Veneto (northeastern Italy) was consulted to extract anonymous data on all ED visits during 2019 and 2020, along with details concerning patients' characteristics (access mode, triage code, chief complaint, and outcome). A year-on-year comparison was drawn between 2019 and 2020. There was a 25.3% decrease in ED visits in 2020 compared to the previous year. The decrease ranged from -52.4% in March to -18.4% in September when comparing the same months in the two years. This decrease started in late February 2020, with the lowest numbers of visits recorded in March and April 2020 (during the "first wave" of the COVID-19 pandemic in Italy), and in the autumn (during the "second wave"). The proportion of visits to the ED by ambulance has increased sharply since March 2020, and patients arrived more frequently with severe conditions (red or yellow triage tags) that often required a hospitalization. The greatest decrease was in fact observed for non-urgent complaints. This decreased concerned a wide range of conditions, including chest pain and abdominal pain. The sharp reduction observed in the present study is unlikely to be attributed entirely to the effect of lockdown measures. Individual psychological and media-induced fear of contagion most likely played a relevant role in leading people to avoid seeking medical attention.

Background: COVID-19 pandemic has stretched healthcare system capacities worldwide and deterred people from seeking medical support at Emergency Departments (ED). Nevertheless, population-based studies examining the consequences on children are lacking., Methods: All ED visits from 2019 to 2020 in Veneto, Italy (4.9 million residents) were collected. Anonymized records of pediatric (≤14 years) ED visits included patient characteristics, arrival mode, triage code, clinical presentation, and discharge mode. Year-on-year variation of the main ED visit characteristics, and descriptive trends throughout the study period have been examined., Results: Overall, 425,875 ED presentations were collected, 279,481 in 2019, and 146,394 in 2020 (- 48%), with a peak (- 79%) in March-April (first pandemic wave), and a second peak (below - 60%) in November-December (second pandemic wave). Burn or trauma, and fever were the two most common clinical presentations. Visits for nonurgent conditions underwent the strongest reduction during both pandemic waves, while urgent conditions reduced less sharply. ED arrival by ambulance was more common in 2020 (4.5%) than 2019 (3.5%), with a higher proportion of red triage codes (0.5%, and 0.4% respectively), and hospitalizations following ED discharge (9.1%, and 5.9% respectively)., Conclusion: Since the beginning of the COVID-19 pandemic, pediatric ED presentations underwent a steeper reduction than that observed for adults. Lockdown and fear of contagion in hospital-based services likely deterred parents from seeking medical support for their children. Given COVID-19 could become endemic, it is imperative that public health experts guarantee unhindered access to medical support for urgent, and less urgent health conditions, while minimizing infectious disease risks, to prevent children from suffering direct and indirect consequences of the pandemic., (© 2021. The Author(s).)

Acute healthcare services are extremely important, particularly during the COVID-19 pandemic, as healthcare demand has rapidly intensified, and resources have become insufficient. Studies on specific prepandemic hospitalization and emergency department visit (EDV) trends in proximity to death are limited. We examined time-trend specificities based on sex, age, and cause of death in the last 2 years of life. Datasets containing all hospitalizations and EDVs of elderly residents in Friuli-Venezia Giulia, Italy (N = 411,812), who died between 2002 and 2014 at ≥ 65 years, have been collected. We performed subgroup change-point analysis of monthly trends in the 2 years preceding death according to sex, age at death (65-74, 75-84, 85-94, and ≥ 95 years), and main cause of death (cancer, cardiovascular, or respiratory disease). The proportion of decedents (N = 142,834) accessing acute healthcare services increased exponentially in proximity to death (hospitalizations = 4.7, EDVs = 3.9 months before death). This was inversely related to age, with changes among the youngest and eldest decedents at 6.6 and 3.5 months for hospitalizations and at 4.6 and 3.3 months for EDVs, respectively. Healthcare use among cancer patients intensified earlier in life (hospitalizations = 6.8, EDVs = 5.8 months before death). Decedents from respiratory diseases were most likely to access hospital-based services during the last month of life. No sex-based differences were found. The greater use of acute healthcare services among younger decedents and cancer patients suggests that policies potentiating primary care support targeting these at-risk groups may reduce pressure on hospital-based services., (© 2021. The Author(s).)

Introduction: Gastroesophageal reflux disease (GERD) as well as its treatment with acid-suppressive medications have been considered possible risk factors for the development of asthma, but few studies have disentangled the role of GERD with that of its treatment. The present study aimed at estimating the association of treated and untreated GERD in the first year of life with the risk of asthma., Methods: Retrospective cohort study including all children born between 2004 and 2015 registered in Pedianet, an Italian primary care database. We analyzed the association of children exposed to GERD (both treated and untreated) in the first year of life with the risk of developing clinically assessed asthma (clinical asthma) after 3 years. Secondary outcomes included asthma identified by anti-asthmatic medications (treated asthma) and wheezing after 3 years. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing children with and without GERD, stratifying by treatment with acid-suppressive medications., Results: Out of 86,381 children, 1652 (1.9%) were affected by GERD in the first year of life, of which 871 (53%) were treated with acid-suppressive medications. Compared with controls, children with GERD were at increased risk of clinical asthma (HR: 1.40, 95% CI 1.15-1.70). Risks were similar between treated and untreated GERD ( p = 0.41). Comparable results were found for treated asthma, but no risk increase was seen for wheezing., Discussion: Early-life GERD was associated with subsequent childhood asthma. Similar risks among children with treated and untreated GERD suggest that acid-suppressive medications are unlikely to play a major role in the development asthma.

Importance: Trends in type 2 diabetes show an increase in prevalence along with younger age of onset. While vascular complications of early-onset type 2 diabetes are known, the associations with dementia remains unclear., Objective: To determine whether younger age at diabetes onset is more strongly associated with incidence of dementia., Design, Setting, and Participants: Population-based study in the UK, the Whitehall II prospective cohort study, established in 1985-1988, with clinical examinations in 1991-1993, 1997-1999, 2002-2004, 2007-2009, 2012-2013, and 2015-2016, and linkage to electronic health records until March 2019. The date of final follow-up was March 31, 2019., Exposures: Type 2 diabetes, defined as a fasting blood glucose level greater than or equal to 126 mg/dL at clinical examination, physician-diagnosed type 2 diabetes, use of diabetes medication, or hospital record of diabetes between 1985 and 2019., Main Outcomes and Measures: Incident dementia ascertained through linkage to electronic health records., Results: Among 10 095 participants (67.3% men; aged 35-55 years in 1985-1988), a total of 1710 cases of diabetes and 639 cases of dementia were recorded over a median follow-up of 31.7 years. Dementia rates per 1000 person-years were 8.9 in participants without diabetes at age 70 years, and rates were 10.0 per 1000 person-years for participants with diabetes onset up to 5 years earlier, 13.0 for 6 to 10 years earlier, and 18.3 for more than 10 years earlier. In multivariable-adjusted analyses, compared with participants without diabetes at age 70, the hazard ratio (HR) of dementia in participants with diabetes onset more than 10 years earlier was 2.12 (95% CI, 1.50-3.00), 1.49 (95% CI, 0.95-2.32) for diabetes onset 6 to 10 years earlier, and 1.11 (95% CI, 0.70-1.76) for diabetes onset 5 years earlier or less; linear trend test (P < .001) indicated a graded association between age at onset of type 2 diabetes and dementia. At age 70, every 5-year younger age at onset of type 2 diabetes was significantly associated with an HR of dementia of 1.24 (95% CI, 1.06-1.46) in analyses adjusted for sociodemographic factors, health behaviors, and health-related measures., Conclusions and Relevance: In this longitudinal cohort study with a median follow-up of 31.7 years, younger age at onset of diabetes was significantly associated with higher risk of subsequent dementia.