Estimating Overall and Cause-Specific Excess Mortality during the COVID-19 Pandemic: Methodological Approaches Compared.

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.

Excess diabetes-related deaths: The role of comorbidities through different phases of the COVID-19 pandemic.

BACKGROUND AND AIMS: Diabetes confers an excess risk of death to COVID-19 patients. Causes of death are now available for different phases of the pandemic, encompassing different viral variants and COVID-19 vaccination. The aims of the present study were to update multiple causes of death data on diabetes-related mortality during the pandemic and to estimate the impact of common diabetic comorbidities on excess mortality. METHODS AND RESULTS: Diabetes-related deaths in 2020-2021 were compared with the 2018-2019 average; furthermore, age-standardized rates observed during the pandemic were compared with expected figures obtained from the 2008-2019 time series through generalized estimating equation models. Changes in diabetes mortality associated with specific comorbidities were also computed. Excess diabetes-related mortality was +26% in 2020 and +18% in 2021, after the initiation of the vaccination campaign. The presence of diabetes and hypertensive diseases was associated with the highest mortality increase, especially in subjects aged 40-79 years, +41% in 2020 and +30% in 2021. CONCLUSION: The increase in diabetes-related deaths exceeded that observed for all-cause mortality, and the risk was higher when diabetes was associated with hypertensive diseases. Notably, the excess mortality decreased in 2021, after the implementation of vaccination against COVID-19.

Veneto Region dementia-related mortality during the COVID-19 pandemic: multiple causes of death and time series analysis.

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.

Mortality Related to Chronic Obstructive Pulmonary Disease during the COVID-19 Pandemic: An Analysis of Multiple Causes of Death through Different Epidemic Waves in Veneto, Italy.

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.

Diabetes as a cause of death across different COVID-19 epidemic waves.

AIMS: The aim of this study is to assess the role of diabetes as a cause of death through different epidemic waves of COVID-19. METHODS: The annual percentage change in age-standardized rates (APC) was estimated for diabetes as the underlying (UCOD) and as multiple causes of death (MCOD) in 2008-2019. Diabetes-related deaths in 2020 were compared to the 2018-2019 average. SARIMA models were applied to monthly excess in mortality considering seasonality and long-term trends. RESULTS: 2018-2019-Age-standardized mortality rates decreased, especially among females (MCOD: APC -2.49, 95%CI -3.01/-1.97%). In 2020, deaths increased by 19% (95%CI 13-25%) for UCOD, and by 27% (95%CI 24-30%) for MCOD. Diabetes and COVID-19 accounted for 74% of such excess. During the first epidemic wave, the increase in observed rates vs predicted by the model was larger in males (March +39%, April +46%) than in females (+30% and +32%). In the second wave, a huge excess of similar magnitude was observed in the two sexes; rates in December exceeded those predicted by more than 100%. CONCLUSIONS: The COVID-19 pandemic abruptly interrupted a long-term declining trend in mortality associated to diabetes. MCOD analyses are warranted to fully estimate the impact of epidemic waves on diabetes-related mortality.

Parkinson's disease related mortality: Long-term trends and impact of COVID-19 pandemic waves.

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.

The impact of COVID-19 on new mesothelioma diagnoses in Italy.

BACKGROUND: The aim of this work was to evaluate the impact of the restrictions put in place to control the COVID-19 pandemic on new diagnoses of malignant mesothelioma (MM) in Italy. METHODS: Twelve of the 21 Italian malignant mesothelioma CORs (regional operating centres) participated. The study included all cases of MM with microscopic confirmation; cases without microscopic confirmation and death certificate only (DCO) were excluded. For each case, information on sex, date of birth, tumor site, morphology, and date of diagnosis was retrieved. We compared the number of incident cases in 2020 with 2019, looking at the overall picture and for four periods: pre-pandemic (January-February), first wave (March-May), low incidence (June-September), and second wave (October-December). RESULTS: A total of 604 cases were registered: 307 in 2019 and 297 in 2020. In the 2020 pre-pandemic period, the incidence was higher than in the same months in 2019 (+45%); there was no significant change during the first wave (+1%) or in the low-incidence period (-3%), while a decrease was observed during the second wave (-32%). However, the data were not homogeneous across the country: the increase in the pre-pandemic period concerned mostly the regions of northern (+61.5%) and central Italy (+43.5%); during the first wave, MM diagnoses increased in the northern (+38.5%) and central (+11.4%) regions but decreased in the southern regions (-52.9%). All these differences are compatible with random fluctuations. CONCLUSION: The COVID-19 pandemic had little or no impact on new MM diagnoses, and variations were not homogeneous throughout the country.