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Ugo Fedeli,1 Alfredo De Giorgi,2 Nicola Gennaro,1 Eliana Ferroni,1 Massimo Gallerani,3 Dimitri P Mikhailidis,4 Roberto Manfredini,2 Fabio Fabbian2 1Epidemiological Department, Veneto Region, 2Department of Medical Sciences, Clinica Medica Unit, School of Medicine, University of Ferrara, 3Department of Internal Medicine, University Hospital of Ferrara, Ferrara, Italy; 4Department of Clinical Biochemistry (Vascular Disease Prevention Clinic), University College London Medical School, London, UK Background: COPD is among the major causes of death, and it is associated with several comorbid conditions. Chronic kidney disease (CKD) is frequently diagnosed in older people living in Western societies and could impact COPD patients’ mortality. We evaluated the relationship between burden of comorbidities, CKD, and mortality in a population-based cohort of patients discharged with a diagnosis of COPD.Methods: A longitudinal cohort study was conducted evaluating 27,272 COPD patients. Recruitment of COPD subjects and identification of CKD and other comorbidities summarized by the Charlson comorbidity index (CCI) were based on claims data coded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Severity of COPD was classified by hospital diagnosis or exemption from medical charges due to respiratory failure or previous hospitalizations for COPD. The impact of comorbidities on survival was assessed by Cox regression.Results: Less than 40% of patients were still alive at the end of a median follow-up of 37 months (17 months for patients who died and 56 months for those alive at the end of follow-up). After adjustment for age, gender, and severity score of COPD, CKD (hazard ratio =1.36, 95% confidence interval 1.30–1.42) independently from comorbidities summarized by the CCI was a significant risk factor for mortality.Conclusion: In spite of limitations due to the use of claims data, long-term survival of COPD patients was heavily affected by the presence of CKD and other comorbidities. Keywords: COPD, chronic kidney disease, Charlson comorbidity index, mortality, comorbidity

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. 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. 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. • Diabetes-related mortality was strongly increased during the COVID-19 pandemic. • Further excess mortality was observed for diabetes plus hypertensive diseases. • A vaccination campaign was followed by a reduction of excess diabetes-related deaths. [ABSTRACT FROM AUTHOR]

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. 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. PAD remains a substantial cause of death in the general population of this high-income region of Western Europe with marked sex-specific differences. • PAD is one of the most prevalent cardiovascular diseases with 230 million patients affected worldwide, but mortality data is urgently needed. • In the Veneto region, the age-standardized mortality rate for PAD as multiple cause of death slightly declined in men and women over the past decade. • The age-standardized mortality rate for PAD as underline cause of death declined in men, but increased in women. • Ischemic heart disease, diabetes mellitus, and cancer were the most prevalent underline causes of death among PAD patients. • PAD remains a substantial cause of death in the general population of this high-income European region with marked sex-specific differences. [ABSTRACT FROM AUTHOR]

Background. Despite massive immigration towards Southern Europe in the last two decades, data on mortality by cause among immigrants in Italy are scarce. The aim of this study was to investigate mortality from all and from specific causes of death among immigrants residing in the Veneto Region (Northeastern Italy).Methods. Mortality records for the period 2008–2013 were extracted from the regional archive of causes of death, whereas population data were obtained from the 2011 Italian census. Immigrants were grouped by area of provenience based on the information on country of citizenship available both in mortality and census data. Standardized Mortality Ratios (SMR) with 95% Confidence Intervals (CI) were computed for the period 2008–2013 in subjects aged 20–59 years, with rates of Italian citizens as a reference.Results. Overall mortality was reduced both in male (SMR 0.86, CI [0.80–0.92]) and female immigrants (SMR 0.72, CI [0.65–0.78]), although an increased risk was observed for subjects from Sub-Saharan Africa. Significantly raised SMR for circulatory diseases were found among Sub-Saharan Africans and Southern Asians in both genders. Sub-Saharan Africans experienced a higher risk of death, especially from cerebrovascular diseases: SMR 4.78 (CI [2.67–7.89]) and SMR 6.09 (CI [1.96–14.2]) in males and females, respectively. Among Southern Asians, the increase in mortality from ischemic heart diseases reached statistical significance in males (SMR 2.53, CI [1.42–4.18]). In spite of a lower risk of death for all neoplasms combined, mortality from cancer of cervix uteri was increased among immigrants (SMR 2.61, CI [1.35–4.56]), as well as for other cancer sites in selected immigrant groups. A raised mortality was found for infectious diseases in Sub-Saharan Africans (both genders), and for transport accidents among females from Eastern Europe.Conclusion. Our study showed great variations in mortality by cause and area of provenience among immigrants resident in the Veneto Region and highlighted specific health issues that should be addressed through tailored efforts in chronic diseases prevention.

Purpose: to assess the burden of epilepsy as the underlying or contributory cause of death, to investigate time trends in mortality with epilepsy, and to examine the main associated comorbidities.Methods: All deaths from January 1, 2008 to December 31, 2019 with any mention of epilepsy were retrieved from the mortality register of the Veneto Region (Italy). The average annual percent change (AAPC) in age-standardized mortality rates was estimated by log-linear models. The association between mention of epilepsy and of selected disease categories in death certificates was assessed by conditional logistic regression.Results: Any mention of epilepsy was reported in 5,907 death certificates; of these, epilepsy was selected as the underlying cause in 1,020 decedents. Deaths with epilepsy represented 0.8% of total mortality in 2008-2011, increasing to 1.3% in 2016-2019. The AAPC was 4.7% for males (95% CI 3.0-6.4, p<0.001) and 6.2% for females (95% CI 4.5-7.9, p<0.001). A strong association was found between mention of epilepsy and meningitis/encephalitis, congenital anomalies/cerebral palsy and other paralytic syndromes, central nervous system tumours, cerebrovascular diseases, and dementia/Alzheimer.Conclusions: The present analysis from Southern Europe confirms recent reports limited to the UK and the US on increasing epilepsy-related mortality rates. aging of the population and the growing prevalence of neurological disorders are among long-term causes of this unfavorable trend; further studies on mortality data and other health archives are warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the study is to assess the impact of the COVID-19 pandemic on causes of mortality through multiple methodological approaches. MATERIALS AND METHODS: The causes of mortality in the Veneto region (Italy) during the first epidemic wave, March-April 2020, were compared with the corresponding months of the previous two years. Both the underlying cause of death (UCOD), and all diseases reported in the death certificate (multiple causes of death) were investigated; a further analysis was carried out through a simulation where the UCOD was selected after substituting ICD-10 codes for COVID with unspecified pneumonia. RESULTS: Overall 10,222 deaths were registered in March-April 2020, corresponding to a 24% increase compared to the previous two years. COVID-19 was mentioned in 1,444 certificates, and selected as the UCOD in 1,207 deaths. Based on the UCOD, the increases in mortality were observed for COVID and related respiratory conditions, diabetes mellitus, hypertensive heart diseases, cerebrovascular diseases, and ill-defined causes. Multiple causes of death and the simulation analysis demonstrated further increases in mortality related to dementia/Alzheimer and chronic lower respiratory diseases. CONCLUSIONS: This first report demonstrates an increase of several causes of death during the pandemic, underlying the need of a continuous surveillance of mortality records through different analytic strategies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare different methods assessing the burden of cardiovascular mortality in diabetes mellitus, which is usually underestimated by standard mortality statistics based on the underlying cause of death. PATIENTS AND METHODS: All residents in the Veneto Region (Italy) aged 30-89 years with co-payment exemption for diabetes in January 2010 (n=185,341) were identified and linked with mortality records (2010-2015). The underlying causes of death, as well as all the diseases mentioned in the death certificate (multiple causes), were extracted. The standardized mortality ratios (SMR) were computed with regional rates as a reference. RESULTS: After grouping diabetes and circulatory diseases as the underlying cause of death, the mortality rates were highly increased, especially among patients aged 30-54 years: SMR 4.24 (95% confidence interval 3.57-5.00) and 9.84 (7.47-12.72) in males and females, respectively. After re-assignment of the underlying cause in deaths from diabetes, the percentage of overall mortality caused by circulatory diseases increased from 33.8% to 41.7%. Based on multiple causes, the risk of death was increased for several cardiovascular diseases, including causes rarely emerging from standard mortality statistics such as atrial fibrillation/ flutter. CONCLUSIONS: The re-assignment of the underlying cause and the analyses of the multiple causes of death allowed to estimate the whole burden of mortality associated with cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background and Aims: To investigate the risk of mortality from infections by comparing the underlying causes of death versus the multiple causes of death in known diabetic subjects living in the Veneto region of Northern Italy.Methods and Results: A total of 185,341 subjects with diabetes aged 30-89 years were identified in the year 2010, and causes of death were assessed from 2010 to 2015. Standardized Mortality Ratios (SMRs) with 95% confidence intervals (CIs) were computed with regional mortality rates as reference. The underlying causes of death and all the diseases reported in the death certificates were scrutinized. At the end of the follow-up, 36,382 subjects had deceased. We observed an increased risk of death from infection-related causes in subjects with diabetes with a SMR of 1.83 (95% CI, 1.71-1.94). The SMR for death from septicemia was 1.91 (95% CI, 1.76-2.06) and from pneumonia was 1.47 (95% CI, 1.36-1.59). The use of the multiple causes of death approach emphasized the association of infectious diseases with mortality.Conclusion: The results of the present study demonstrate an excess mortality due to infection-related diseases in patients with diabetes; more interestingly, by routine mortality analyses, the results show a possible underestimation of the effect of these diseases on mortality. [ABSTRACT FROM AUTHOR]

Purpose: We describe nationwide treatment patterns of muscle invasive bladder cancer, investigated determinants of cystectomy and provide contemporary trends in process of care measures in patients undergoing cystectomy. Materials and Methods: We selected 40,388 patients 18 to 99 years old diagnosed with muscle invasive (stages II to IV) bladder cancer in 2003 to 2007 from the National Cancer Database. Treatment included cystectomy, neoadjuvant and adjuvant chemotherapy, chemotherapy without surgery and radiation therapy. In patients undergoing cystectomy we retrieved the procedure type (partial vs radical), lymphadenectomy extent and 30-day followup. Cystectomy determinants were assessed by Poisson regression with robust error variance. Perioperative mortality was analyzed by multilevel logistic regression. Results: The proportion of patients treated with cystectomy (42.9%) and radiation therapy (16.6%) remained stable with time while the incidence of those who received chemotherapy increased from 27.0% in 2003 to 34.5% in 2007 due to an increase in neoadjuvant chemotherapy and chemotherapy without surgery. The cystectomy rate decreased with age and was lower in racial/ethnic minorities (especially black patients), uninsured or Medicaid patients, patients residing in the South and Northeast, and those treated at nonteaching/research hospitals. The partial cystectomy rate decreased and lymphadenectomy extent increased with time. The perioperative mortality rate was 2.6% and it was higher at low vs very high volume hospitals (OR 1.71, 95% CI 1.26–2.32). Conclusions: Recent nationwide data confirm ongoing improvements in process of care measures in patients who undergo cystectomy but also show marked differences in treatment patterns for muscle invasive bladder cancer by patient age, race, insurance status, geographic area and facility type. [ABSTRACT FROM AUTHOR]