Sepsis-related mortality: long-term trends in Northeastern Italy, including pandemic years.

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.

Traumatic brain injury incidence and mortality: a large population-based study.

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.

Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study.

BACKGROUND: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

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.

Changes in mortality associated with different hematologic malignancies during the pandemic in the United States.

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.

Changes in cancer-related mortality during the COVID-19 pandemic in the United States.

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.

Mortality related to HCV and other chronic liver diseases in Veneto (Italy), 2008-2021: Changes in trends and age-period-cohort effects.

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.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

Hyperthyroidism incidence in a large population-based study in northeastern Italy.

Objective: An improvement in iodine status in Veneto Region has been documented in the last decade. We aimed at estimating the incidence of hyperthyroidism in the Veneto Region (Italy) over the period 2013-2022. Methods: Retrospective population-based study conducted in Veneto (4.9 million people) using the population registry, an administrative health database. Between 2012 and 2022, hyperthyroidism incidence was defined thank to a health-care co-payment exemption for hyperthyroidism or any hospital diagnosis of hyperthyroidism. Incident hyperthyroidism was defined from 2013 to 2022 to exclude prevalent cases. Standardized incidence rates (IRs) were reported by age, sex, and etiology of thyroid hyperfunction too. Results: We identified 26,602 incident cases (IR of 54.38 per 100,000 person-years, 2.47-fold higher in females than in males). IR decreased from 69.87 (95% CI: 67.49, 72.25) in 2013 to 42.83 (95% CI: 40.99, 44.66) in 2022. In 2020, an out-of-trend decrease in hyperthyroidism incidence was documented, corresponding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic outbreak, with a realignment to the trend in the subsequent years. The annual percentage change according to the cause of hyperthyroidism was as follows: -6.62% (95% CI: 8.47, 4.73) (P < 0.0001) in toxic multinodular goiter, -7.56% in toxic uninodular goiter (95% CI: 10.54, 4.48) (P < 0.001) and -4.70% (95% CI: 6.33, 3.04) in toxic diffuse goiter (Graves' disease) (P < 0.001). Conclusions: We documented a decline in the incidence of hyperthyroidism in Veneto Region, paralleling the improvement of the iodine status, thanks to a long and sustained iodine prophylaxis campaign. SARS-CoV-2 pandemic and vaccination campaign did not change the declining trend of hyperthyroidism incidence in our study region. Significance statement: An improvement in iodine status in the population residing in the Veneto region has been documented in the last decade, thanks to a nationwide voluntary iodine prophylaxis program running since 2005, but its impact on the epidemiology of thyroid disease has never been documented. This is the largest study on the incidence rates of hyperthyroidism carried out in Italy and covers the longest observation period among all regionwide population-based studies of hyperthyroidism in our country. We documented a reduction in the incidence of hyperthyroidism, which was more pronounced in nodular goiter diagnosis but involved also toxic diffuse goiter. The decline in the incidence of hyperthyroidism in Veneto Region shows the efficacy and safety of the iodine prophylaxis campaign.

COPD-Related Mortality before and after Mass COVID-19 Vaccination in Northern Italy.

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.

Trends in hospital volume and operative mortality in hepato-biliary surgery in Veneto region, Italy.

Hepatobiliary resections are among the most complex and technically challenging surgical procedures. Even though robust evidence showed that complex surgical procedures such as hepatobiliary surgery have better short- and long-term outcomes and lower mortality rate when performed in high-volume centers, the minimal criteria of centers that can perform hepatobiliary activity are not clearly defined. We conducted a retrospective population study of patients who underwent hepatobiliary surgery for malignant disease in a single Italian administrative region (Veneto) from 2010 to 2021 with the aim to investigate the hospitals annual surgical volume for hepatobiliary malignant diseases and the effect of hospital volume on in-hospital, 30- and 90-day postoperative mortality. The centralization process of hepatobiliary surgery in Veneto is rapidly increasing over the past 10 years (rate of performed in highly specialized centers increased from 62% in 2010 to 78% in 2021) and actually it is really established. The crude and adjusted (for age, sex, Charlson Index) mortality rate after hepatobiliary surgery resulted significantly lower in centers with high-volume activity compared to them with low-volume activity. In the Veneto region, the "Hub and Spoke" model led to a progressive centralization of liver and biliary cancer treatment. High surgical volume has been confirmed to be related to better outcomes in terms of mortality rate after hepatobiliary surgical procedures. Further studies are necessary to clearly define the minimal criteria and associated numerical cutoffs that can help define the characteristics of centers that can perform hepatobiliary activities.

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 from chronic liver disease: Recent trends and impact of the COVID-19 pandemic.

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.

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.

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.

Trends in radioactive iodine treatment after total thyroidectomy in Italy, 2001-2018.

Objective: A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy. Methods: From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001-2018. Results: Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas. Conclusion: National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.