Association of multiple-sclerosis-related mortality with COVID-19 and other common infections: a multiple causes of death analysis.

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.

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.

Mortality rate related to peripheral arterial disease: A retrospective analysis of epidemiological data (years 2008-2019).

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is one of the most prevalent cardiovascular diseases with more than 230 million people being affected worldwide. As highlighted by the recent European Society of Cardiology guidelines, data on the epidemiology of PAD is urgently needed. METHODS AND RESULTS: We accessed the vital registration data of the Veneto region (Northern Italy, approximately five millions inhabitants) covering the period 2008-2019. We computed annual age-standardized rates for PAD reported as the underlying cause of death (UCOD) or as one of multiple causes of death (MCOD). Age-adjusted odds ratios (OR) served to study the association between PAD and cardiovascular comorbidities. The age-standardized mortality rate for PAD as MCOD slightly declined from 19.6 to 17.8 in men and from 10.8 to 9.1 deaths per 100,000 population-years in women. The age-standardized PAD-specific mortality rate (UCOD) remained stable: 3.1 to 3.7 per 100,000 person-years in women (Average Annual Percent Change 1.3, 95% CI -0.8; 3.4%) and 4.4 to 4.3 per 100,000 person-years (Average Annual Percent Change -0.2, 95% CI -3.6; 3.4%) in men. PAD contributed to 1.6% of all deaths recorded in the region. Ischemic heart disease, diabetes mellitus and neoplasms were the most prevalent UCOD among PAD patients. PAD was associated with diabetes mellitus (OR 3.79, 95%CI 3.55-4.06) and chronic kidney diseases (OR 2.73, 95%CI 2.51-2.97) in men, and with atrial fibrillation (OR 2.26, 95%CI 2.10-2.44) in women. CONCLUSION: PAD remains a substantial cause of death in the general population of this high-income region of Western Europe with marked sex-specific differences.

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.

SARS-CoV-2 and COVID-19 in diabetes mellitus. Population-based study on ascertained infections, hospital admissions and mortality in an Italian region with ∼5 million inhabitants and ∼250,000 diabetic people.

BACKGROUND AND AIMS: Diabetes conveys an increased risk of infectious diseases and related mortality. We investigated risk of ascertained SARS-CoV-2 infection in diabetes subjects from the Veneto Region, Northeastern Italy, as well as the risk of being admitted to hospital or intensive care unit (ICU), or mortality for COVID-19. METHODS AND RESULTS: Diabetic subjects were identified by linkage of multiple health archives. The rest of the population served as reference. Information on ascertained infection by SARS-CoV-2, admission to hospital, admission to ICU and mortality in the period from February 21 to July 31, 2020 were retrieved from the regional registry of COVID-19. Subjects with ascertained diabetes were 269,830 (55.2% men; median age 72 years). Reference subjects were 4,681,239 (men 48.6%, median age 46 years). Ratios of age- and gender-standardized rates (RR) [95% CI] for ascertained infection, admission to hospital, admission to ICU and disease-related death in diabetic subjects were 1.31 [1.19-1.45], 2.11 [1.83-2.44], 2.45 [1.96-3.07], 1.87 [1.68-2.09], all p < 0.001. The highest RR of ascertained infection was observed in diabetic men aged 20-39 years: 1.90 [1.04-3.21]. The highest RR of ICU admission and death were observed in diabetic men aged 40-59 years: 3.47 [2.00-5.70] and 5.54 [2.23-12.1], respectively. CONCLUSIONS: These data, observed in a large population of ∼5 million people of whom ∼250,000 with diabetes, show that diabetes not only conveys a poorer outcome in COVID-19 but also confers an increased risk of ascertained infection from SARS-CoV-2. Men of young or mature age have the highest relative risks.

SARS-CoV-2 serosurvey in health care workers of the Veneto Region.

Objectives The ongoing outbreak of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses formidable challenges to all health care systems. Serological assays may be used for improving disease management when appropriately applied, for investigating the antibody responses mounted against SARS-CoV-2 infection and for assessing its real prevalence. Although testing the whole population is impractical, well-designed serosurveys in selected subpopulations in specific risk groups may provide valuable information. We evaluated the prevalence of SARS-CoV-2 infection in health care workers (HCW) who underwent molecular testing with reverse transcription real-time polymerase chain reaction (rRT-PCR) in the main hospitals of the Veneto Region of Italy by measuring specific antibodies (Abs). Methods Both immunoglobulin (Ig)M and IgG antibodies against SARS-Cov-2 S-antigen and N-protein were measured using a validated chemiluminescent analytical system (CLIA) called Maglumi™ 2000 Plus (New Industries Biomedical Engineering Co., Ltd [Snibe], Shenzhen, China). Results A total of 8,285 HCW were tested. SARS-CoV-2 specific antibodies (IgM, IgG or both) were detectable in 378 cases (4.6%, 95% CI 4.1-5.0%). Seroconversion was observed in 4.4% of women vs. 5.0% of men, but this difference was not significant. Although detectable antibodies were found in all HCW who developed severe COVID-19 infection (100%), lower seropositivity was found in mild disease (83%) and the lowest prevalence (58%) was observed in asymptomatic subjects. Conclusions Seroprevalence surveys are of utmost importance for understanding the rate of population that has already developed antibodies against SARS-CoV-2. The present study defined precisely the circulation of SARS-CoV-2 in a cohort of HCW in the Veneto Region, with its prevalence (4.6%) reflecting a relatively low circulation. Symptomatic individuals or those hospitalized for medical care were 100% antibody positive, whilst Abs were only detectable in 58% of asymptomatic carriers.

Effectiveness of a community care management program for multimorbid elderly patients with heart failure in the Veneto Region.

BACKGROUND: The rapidly growing population of elderly subjects with multimorbidity is at risk of receiving fragmented and uncoordinated care, and have frequent hospitalizations and emergency room (ER) visits. AIMS: The study aims to describe the impact of a care management program (CMP) developed in the Veneto region (Northeastern Italy) for patients affected by chronic heart failure (CHF) and multimorbidity. METHODS: The CMP was provided to 330 patients > 65 years suffering from CHF and multimorbidity. They were compared to a propensity score matched reference group who received usual care. The intervention was provided by care manager nurses and General Practitioners working in the community. The quality of care from the patients' perspective was assessed by means of the Patient Assessment of Chronic Illness Care (PACIC). The effectiveness of the CMP has been evaluated comparing time changes in hospital admissions in the medical area and ER visits between the intervention and the reference group. RESULTS: The median PACIC overall score was 4 out of 5. The intervention group showed a reduction over time by 39% in hospitalization rates and by 33% in ER visits. The recourse to hospital care and ER did not change in the reference group. DISCUSSION: The current results indicate that a CMP can reduce Emergency Room visits and hospital admissions for elderly patients with CHF and multimorbidity. CONCLUSIONS: The CMP by emphasizing prevention, self-management, continuity and coordination of care, is beneficial among older community-dwelling multimorbid persons as compared to usual care.

Cause-specific mortality in a large population-based cohort of patients with rheumatoid arthritis in Italy.

OBJECTIVES: The aim of our study was to investigate cause-specific mortality in rheumatoid arthritis (RA) subjects living in Italy. METHODS: We identified in the electronic archive of the Veneto Region patients aged 20-89 years who were exempt from co-payment for RA in January 2010, and linked them with the archive of causes of deaths of the period 2010-2015. Causes of death were coded according to the International Classification of Diseases, 10th Edition. Standardised mortality ratios (SMRs) with 95% confidence intervals were computed as the ratios between deaths observed in the cohort, and those expected according to age- and gender-specific regional mortality rates. RESULTS: Overall, 16,098 residents diagnosed with RA and aged 20-89 years were enrolled in the cohort. The overall follow-up amounted to 88,599 person-years, with 2,142 registered decedents. The most common causes of death were circulatory diseases (36.6%), neoplasms (24.2%), and respiratory diseases (8.3%). Overall mortality was increased in RA subjects (SMR=1.42, confidence interval 1.36-1.48). Mortality was significantly increased from circulatory (SMR=1.56, 1.45-1.67), respiratory (SMR=1.83, 1.57-2.12), digestive (SMR=1.93, 1.60-2.32), infectious (SMR=2.34, 1.88-2.89), haematological diseases (SMR=3.22, 2.04-4.83), and falls (SMR=1.95, 1.19-3.01). RA was the underlying cause of death in 6.1% of all deaths in the cohort and was mentioned in 25.4% of death certificates. CONCLUSIONS: In our study, a 42% excess risk of death was observed among subjects with RA compared with the general population. Cardiovascular disease is the primary cause of premature death in RA. Adverse effects of therapy and comorbidities should be adequately monitored in RA subjects.

Intensity of integrated cancer palliative care plans and end-of-life acute medical hospitalisation among cancer patient in Northern Italy.

A high hospital utilisation at the end of life (EOL) is an indicator of suboptimal quality of health care. We evaluated the impact of the intensity of different Integrated Cancer Palliative Care (ICPC) plans on EOL acute medical hospitalisation among cancer decedents. Decedents of cancer aged 18-84 years, who were residents in two Italian regions, were investigated through integrated administrative data. Outcomes considered were prolonged hospital stay for medical reasons, 2+ hospitalisations during the last month of life and hospital death. The ICPC plans instituted 90 to 31 days before death represented the main exposure of interest. Other variables considered were gender, age class at death, marital status, recent hospitalisation and primary cancer site. Among 6,698 patients included in ICPC plans, 44.3% presented at least one critical outcome indicator; among these, 76.5% died in hospital, 60.3% had a prolonged (12+ days) medical hospitalisation, 19.1% had 2+ hospitalisations at the EOL. These outcomes showed a strong dose-response effect with the intensity of the ICPC plans, which is already evident at levels of moderate intensity. A well-ICPC approach can be very effective-beginning at low levels of intensity of care-in reducing the percentage of patients spending many days or dying in hospital.

Excess mortality in 2015: a time series and cause-of-death analysis in Northern Italy.

AIMS: To investigate the excess mortality registered in the Veneto Region (Northern Italy) in 2015. METHODS: A Seasonal Autoregressive Integrated Moving Average Model was applied to predict overall mortality expected in 2014-2015 based on that observed in 2000-2013. The annual percent change in age-standardized rates (APC) was estimated for specific causes of death in 2007-2015. RESULTS: Compared to 2014, the number of deaths and the overall age-standardized mortality increased in 2015 by 7.8 and 4.5%, respectively. When accounting for time trends, the observed mortality was lower than expected in 2014 (-4.5%) and slightly higher in 2015 (+1.1%). In 2015, mortality increased especially for causes with an already rising trend: neurologic/psychiatric (APC = 1.2; 95% Confidence Interval 0.3-2.0%) and infectious diseases (APC = 5.9; 3.6-8.2%). CONCLUSIONS: Short-term changes and long-term trends in mortality must be interpreted within the frame of a rapid growth in the population of elderly subjects affected by multiple comorbidities.

Growing burden of sepsis-related mortality in northeastern Italy: a multiple causes of death analysis.

BACKGROUND: Few population-based data are available on mortality due to sepsis. The aim of the study was to estimate sepsis-related mortality rates and to assess the associated comorbidities. METHODS: From multiple causes of death data (MCOD) of the Veneto Region (northeastern Italy), all deaths with sepsis mentioned anywhere in the death certificate were retrieved for the period 2008-2013. Among these deaths the prevalence of common chronic comorbidities was investigated, as well as the distribution of the underlying cause of death (UCOD), the single disease selected from all condition mentioned in the certificate and usually tabulated in mortality statistics. Age-standardized mortality rates were computed for sepsis selected as the UCOD, and for sepsis mentioned anywhere in the certificate. RESULTS: Overall 16,906 sepsis-related deaths were tracked. Sepsis was mentioned in 6.3 % of all regional deaths, increasing from 4.9 in 2008 to 7.7 % in 2013. Sepsis was the UCOD in 0.6 % of total deaths in 2008, and in 1.6 % in 2013. Age-standardized mortality rates increased by 45 % for all sepsis-related deaths, and by 140 % for sepsis as the UCOD. Sepsis was often reported in the presence of chronic comorbidities, especially neoplasms, diabetes, circulatory diseases, and dementia. Respiratory tract and intra-abdominal infections were the most frequently associated sites of infection. CONCLUSIONS: MCOD analyses provide an estimate of the burden of sepsis-related mortality. MCOD data suggest an increasing importance attributed to sepsis by certifying physicians, but also a real increase in mortality rates, thus confirming trends reported in some other countries by analyses of hospital discharge records.

Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test.

OBJECTIVE: Colorectal cancer (CRC) screening programmes based on the guaiac faecal occult blood test (gFOBT) reduce CRC-specific mortality. Several studies have shown higher sensitivity with the faecal immunochemical test (FIT) compared with gFOBT. We carried out an ecological study to evaluate the impact of FIT-based screening programmes on CRC mortality. DESIGN: In the Veneto Region (Italy), biennial FIT-based screening programmes that invited 50-69-year-old residents were introduced in different areas between 2002 and 2009. We compared CRC mortality rates from 1995 to 2011 between the areas where screening started in 2002-2004 (early screening areas (ESA)) and areas that introduced the screening in 2008-2009 (late screening areas (LSA)) using Poisson regression models. We also compared available data on CRC incidence rates (1995-2007) and surgical resection rates (2001-2012). RESULTS: Before the introduction of screening, CRC mortality and incidence rates in the two areas were similar. Compared with 1995-2000, 2006-2011 mortality rates were 22% lower in the ESA than in the LSA (rate ratio (RR)=0.78; 95% CI 0.68 to 0.89). The reduction was larger in women (RR=0.64; CI 0.51 to 0.80) than in men (RR=0.87; CI 0.73 to 1.04). In the ESA, incidence and surgery rates peaked during the introduction of the screening programme and then returned to the baseline (2006-2007 incidence) or dropped below initial values (surgery after 2007). CONCLUSIONS: FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies.

Mortality trend of ischemic heart disease (2008-2022): A retrospective analysis of epidemiological data.

BACKGROUND: Age-sex specific trend analyses of ischemic heart disease (IHD)-related mortality and prevalent risk factors can improve our understanding and approach to the disease. METHODS: We performed a 15-year retrospective epidemiological analysis of acute and chronic IHD-related mortality and prevalent cardiovascular risk factors using administrative data from Veneto, a socio-economically homogeneous Italian region. Standard mortality statistics using the underlying cause of death (UCOD) and deaths with any mention of IHD in death certificates (MCOD) from ICD-10 codes I20-I25 was performed between 2008 and 2022. RESULTS: A total of 134,327 death certificates reported IHD-related deaths, representing 18.6% of all deaths. Proportional mortality decreased from 14.6% in 2008 to 7.8% in 2022 for deaths with IHD as the UCOD and from 23.5% to 14.6% for deaths with IHD among the MCOD. A more pronounced decline of proportionate and case-specific mortality rate was seen in women. The decline in mortality over the whole study period was larger for acute (vs. chronic) IHD. The COVID-19 pandemic led to a marked increase in mortality in 2020 (+12.2%) with a subsequent further decline. IHD-related deaths displayed a typical seasonal pattern with more deaths during winter. The prevalence of cardiovascular risk factors was higher in IHD (vs. no IHD) deaths: this association appeared more pronounced in younger adults. CONCLUSIONS: We provided an analysis of epidemiological trends in IHD-related mortality and prevalence of risk factors. Our findings indicate a change in the pattern of cardiovascular deaths and may suggest a switch in death from acute to chronic conditions.

Descriptive epidemiology of chronic liver disease in northeastern Italy: an analysis of multiple causes of death.

BACKGROUND: The analysis of multiple causes of death data has been applied in the United States to examine the population burden of chronic liver disease (CLD) and to assess time trends of alcohol-related and hepatitis C virus (HCV)-related CLD mortality. The aim of this study was to assess the mortality for CLD by etiology in the Veneto Region (northeastern Italy). METHODS: Using the 2008-2010 regional archive of mortality, all causes registered on death certificates were extracted and different descriptive epidemiological measures were computed for HCV-related, alcohol-related, and overall CLD-related mortality. RESULTS: The crude mortality rate of all CLD was close to 40 per 100,000 residents. In middle ages (35 to 74 years) CLD was mentioned in about 10% and 6% of all deaths in males and females, respectively. Etiology was unspecified in about half of CLD deaths. In females and males, respectively, HCV was mentioned in 44% and 21% and alcohol in 11% and 26% of overall CLD deaths. A bimodal distribution with age was observed for HCV-related proportional mortality among females, reflecting the available seroprevalence data. CONCLUSIONS: Multiple causes of death analyses can provide useful insights into the burden of CLD mortality according to etiology among different population subgroups.

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.

The incidence and risk factors of selected drug prescriptions and outpatient care after SARS-CoV-2 infection in low-risk subjects: a multicenter population-based cohort study.

Background: Knowledge about the dynamics of transmission of SARS-CoV-2 and the clinical aspects of COVID-19 has steadily increased over time, although evidence of the determinants of disease severity and duration is still limited and mainly focused on older adult and fragile populations. Methods: The present study was conceived and carried out in the Emilia-Romagna (E-R) and Veneto Regions, Italy, within the context of the EU's Horizon 2020 research project called ORCHESTRA (Connecting European Cohorts to increase common and effective response to SARS-CoV-2 pandemic) (www.orchestra-cohort.eu). The study has a multicenter retrospective population-based cohort design and aimed to investigate the incidence and risk factors of access to specific healthcare services (outpatient visits and diagnostics, drug prescriptions) during the post-acute phase from day-31 to day-365 after SARS-CoV-2 infection, in a healthy population at low risk of severe acute COVID-19. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the two Italian Regions. The statistical analysis made use of methods for competing risks. Risk factors were assessed separately in the two Regions and results were pooled using random effects meta-analysis. Results: There were 35,128 subjects in E-R and 88,881 in Veneto who were included in the data analysis. The outcome (access to selected health services) occurred in a high percentage of subjects in the post-acute phase (25% in E-R and 21% in Veneto). Outpatient care was observed more frequently than drug prescriptions (18% vs. 12% in E-R and 15% vs. 10% in Veneto). Risk factors associated with the outcome were female sex, age greater than 40 years, baseline risk of hospitalization and death, moderate to severe acute COVID-19, and acute extrapulmonary complications. Conclusion: The outcome of interest may be considered as a proxy for long-term effects of COVID-19 needing clinical attention. Our data suggest that this outcome occurs in a substantial percentage of cases, even among a previously healthy population with low or mild severity of acute COVID-19. The study results provide useful insights into planning COVID-19-related services.

Mortality after esophageal and gastric cancer resection.

BACKGROUND: Contrasting findings on trends and determinants of operative mortality after surgery for esophageal and gastric cancer have been reported from population-based studies. METHODS: Discharge records of residents in the Veneto Region (northeastern Italy) with a diagnosis of esophageal or gastric cancer and intervention codes for esophagectomy or gastrectomy were extracted for the years 2000-2009. In-hospital, 30-day, 90-day, and perioperative (30-day + in-hospital) mortality were computed. The influence of patient and hospital variables on in-hospital mortality was assessed through multilevel models. RESULTS: Overall, 6,500 resections were performed in the period of 2000-2009, with a 10 % decline in the second half of the study period. In-hospital mortality was 4.6 % (5.3 % in 2000-2004 and 3.8 % in 2005-2009) and was higher for extended total gastrectomy and total esophagectomy. In 2005-2009 mortality declined for all resection types except extended total gastrectomy (8.0 %). For esophageal procedures, 30-day mortality was lower than in-hospital or perioperative mortality. A protective effect of procedural volume was found for esophageal but not for gastric resections; among gastric procedures, mortality was higher in male patients and in extended total gastrectomy patients. CONCLUSIONS: Analyses of discharge records allowed investigation at a population level of time trends (downward mainly for esophageal resections) and determinants of perioperative mortality (hospital volume, gender, and procedure type).

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.

Decline in Overall Pulmonary Embolism-Related Mortality and Increasing Prevalence of Cancer-Associated Events in the Veneto Region (Italy), 2008-2019.

BACKGROUND: Despite evidence of ongoing epidemiological changes in deaths from venous thromboembolism in high-income countries, little recent information is available on the time trends in mortality related to pulmonary embolism (PE) as underlying or concomitant cause of death in Europe. METHODS: We accessed the regional database of death certificates of Veneto Region (Northern Italy, population 4,900,000) from 2008 to 2019. We analyzed the trends in crude and age-adjusted annual rates of mortality related to PE (reported either as underlying cause or in any position in the death certificate) using Joinpoint regression; in the contribution of PE to mortality (proportionate mortality); and, using logistic regression, in the association between PE and cancer at death. RESULTS: Between 2008 and 2019, the annual age-standardized mortality rate related to PE in Veneto decreased from 20.7 to 12.6 deaths per 100,000 population for PE in any position of the death certificate, and from 4.6 to 2.2 deaths per 100,000 population for PE as underlying cause of death. PE-related proportionate mortality remained up to twice as high in women. The age- and sex-adjusted odds ratio for cancer in deaths with versus without PE constantly increased from 1.01 (95% confidence interval [CI]: 0.88-1.16) in 2008 to 1.58 (95% CI: 1.35-1.83) in 2019. CONCLUSION: The descending trends in PE-related mortality reported for Europe up to 2015 for both sexes continued thereafter in this high-income region of Northern Italy. However, sex differences in proportionate mortality persist. The increasing strength in the association between cancer and PE may indicate a change in risk factor distribution, calling for tailored management practices in this patient group.

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.