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Background and Aims: The objective of this study was to assess the impact of the COVID-19 pandemic and direct-acting antiviral (DAA) agents on mortality related to chronic liver diseases (CLD). Methods: Age-standardized mortality rates were computed based on CLD as the underlying cause of death (UCOD) and as any mention in death certificates (multiple causes of death-MCOD). Time trends in age-standardized mortality rates were investigated using generalized estimation equation models. Additionally, we conducted age, period, and birth cohort (APC) analyses on CLD-related mortality associated with alcohol and hepatitis C virus (HCV). Results: Between 2008 and 2021, among residents in the Veneto region (Northeastern Italy) aged ≥35 years, there were 20 409 deaths based on the UCOD and 30 069 deaths based on MCOD from all CLD. We observed a 4% annual decline in age-standardized MCOD-based mortality throughout 2008--2021, with minor peaks corresponding to COVID-19 epidemic waves. Starting in 2016, the decline in HCV-related mortality accelerated further (p < .001). A peak in HCV-related mortality in the 1963--1967 birth cohort was observed, which levelled off by the end of the study period. Mortality related to alcoholic liver disease declined at a slower pace, becoming the most common aetiology mentioned in death certificates. Conclusions: The study demonstrates a significant decrease in HCV-related mortality at the population level in Italy with the introduction of DAAs. Continuous monitoring of MCOD data is warranted to determine if this favourable trend will continue. Further studies utilizing additional health records are needed to clarify the role of other CLD etiologies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Off-label, under-, and overdosed direct oral anticoagulants (DOACs) are commonly prescribed to patients with atrial fibrillation (AF), but real-world evidence on their effectiveness and safety is limited. Methods: MEDLINE, Embase, and Cochrane Library databases were systematically searched from 01 July 2020 to 28 February 2022 to update a previous systematic review with the same search strategy from the inception to 30 June 2020. Eligible studies were those that reported effectiveness (stroke/systemic embolism and myocardial infarction) or safety (gastrointestinal or major bleeding and death) outcomes of off-label doses of DOACs compared to on-label doses in AF patients. A random-effects metaanalysis was performed to estimate the pooled hazard ratio (HR) and 95% confidence interval (CI). Subgroup analyses were performed by specific DOACs and geographic regions. Results: Twenty-two studies were included. Off-label, underdosed DOACs, compared to on-label doses, were not associated with an increased risk of stroke (HR 1.03, 95%CI: 0.88-1.17) but were associated with an increased risk of death (HR 1.26, 95% CI: 1.09-1.43). However, risk varied depending on the active ingredient. No other safety outcomes were associated with underdosed DOACs. No significant differences were observed by geographic regions. Compared to on-label DOACs, overdosing increased the risk of stroke (HR 1.17, 95%CI: 1.04-1.31), major bleeding (HR 1.18, 95%CI: 1.05-1.31), and death (HR 1.19, 95%CI: 1.03-1.35). Risk varied between geographical regions. Conclusions: Off-label underdoses, compared to on-label dosing of DOACs, did not increase the risk of stroke but did increase overall mortality. Overdosed DOACs, compared to on-label doses, were associated with an increased risk of stroke, major bleeding, and death. Future studies must examine these associations, focusing on specific active ingredients and geographic settings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the associations between exercise habit changes following an incident cardiovascular event and mortality in older adults.Methods: We analysed the relationship between exercise habit change and all-cause, cardiovascular and non-cardiovascular deaths in adults aged ≥60 years between 2003 and 2012 who underwent two consecutive health examinations within 2 years before and after diagnosis of cardiovascular disease (CVD). They were categorised into four groups according to exercise habit changes: persistent non-exercisers, exercise dropouts, new exercisers and exercise maintainers. Differences in baseline characteristics were adjusted using inverse probability of treatment weighting.Results: Of 6076 participants, the median age was 72 (IQR 69-76) years and men accounted for 50.6%. Compared with persistent non-exercisers (incidence rate (IR) 4.8 per 100 person-years), new exercisers (IR 3.5, HR 0.73, 95% CI 0.58 to 0.91) and exercise maintainers (IR 2.9, HR 0.53, 95% CI 0.38 to 0.73) were associated with reduced risk of all-cause death. The rate of non-cardiovascular death was significantly lower in new exercisers (IR 2.3, HR 0.73, 95% CI 0.56 to 0.95) and exercise maintainers (IR 2.3, HR 0.61, 95% CI 0.42 to 0.90) than in persistent non-exercisers (IR 3.2). Also, trends towards reduced cardiovascular death in new exercisers and exercise maintainers were observed (p value for trend <0.001).Conclusions: More virtuous exercise trajectories in older adults with CVD are associated with lower mortality rates. Our results support public health recommendations for older adults with CVD to perform physical activity. [ABSTRACT FROM AUTHOR]