From mono to multi-causality: Towards a comprehensive perspective on understanding death.

Cause-of-death statistics are an age-old source of information for health policy and medical research. In these statistics, the presentation of data is based on the idea of an underlying cause of death, i.e. one ("the") cause of death per deceased. This idea reflects an 18th Century causal thinking and is less and less applicable to contemporary patterns of dying in high income countries with an aging population suffering from chronic diseases and multi- or comorbidity at the end of life. Therefore, today's clinical reality calls for an innovation of cause-of-death statistics. For this, I will consider contemporary philosophical ideas on causality and their application to death. I will argue multi-causality is a more comprehensive way to understand death than mono-causality, implying a change of perspective with regard to current cause-of-death statistics.

Assessing the Quality of Cause-of-Death Reporting Before and During the COVID-19 Pandemic.

This study assessed the quality of cause-of-death reporting in the US before and during the COVID-19 pandemic. We used the selection rate and the adjusted odds ratio (aOR) to analyze each cause identified by the National Center for Health Statistics as unsuitable for the underlying cause of death (UCOD). The selection rate was defined as the proportion of deaths with mention of a particular unsuitable UCOD on the death certificate where that cause was ultimately selected as the UCOD. Out of 36 unsuitable UCODs, 33 exhibited a significant decline in selection rates from 2019 to 2021. However, when deaths with mention of COVID-19 on the death certificate were excluded, only 19 causes revealed a significant decline. In analyses that controlled for the age of decedents, aORs in 2021 were significantly lower compared with 2019 for 26 causes, and this number decreased to 17 causes in analyses that excluded COVID-19-related deaths. In conclusion, the overall quality of COD reporting improved during the COVID-19 pandemic, attributable mainly to the fact that over one-tenth of the deaths were related to COVID-19. Yet, for deaths that did not involve COVID-19, improvements in the quality of COD reporting were less prominent for certain causes.

Advancing Underlying Cause of Death Inference Through Wide and Deep Model.

Introduction: Accurately filling out death certificates is essential for death surveillance. However, manually determining the underlying cause of death is often imprecise. In this study, we investigate the Wide and Deep framework as a method to improve the accuracy and reliability of inferring the underlying cause of death. Methods: Death report data from national-level cause of death surveillance sites in Fujian Province from 2016 to 2022, involving 403,547 deaths, were analyzed. The Wide and Deep embedded with Convolutional Neural Networks (CNN) was developed. Model performance was assessed using weighted accuracy, weighted precision, weighted recall, and weighted area under the curve (AUC). A comparison was made with XGBoost, CNN, Gated Recurrent Unit (GRU), Transformer, and GRU with Attention. Results: The Wide and Deep achieved strong performance metrics on the test set: precision of 95.75%, recall of 92.08%, F1 Score of 93.78%, and an AUC of 95.99%. The model also displayed specific F1 Scores for different cause-of-death chain lengths: 97.13% for single causes, 95.08% for double causes, 91.24% for triple causes, and 79.50% for quadruple causes. Conclusions: The Wide and Deep significantly enhances the ability to determine the root causes of death, providing a valuable tool for improving cause-of-death surveillance quality. Integrating artificial intelligence (AI) in this field is anticipated to streamline death registration and reporting procedures, thereby boosting the precision of public health data.

Deaths caused by osteoporotic fractures in Japan: An epidemiological study.

BACKGROUND: Osteoporosis is a global issue with a worldwide prevalence of 18.3%, and the presence of coexisting fragility fractures can reduce the survival rate by approximately 20%. In Japan, the prevalence of osteoporosis is estimated to be 12.8 million, and the annual occurrence of hip fractures is approximately 193,400. Remarkably, coexisting hip or spinal fragility fractures caused by slight external force meet the Japanese diagnostic criterion for osteoporosis regardless of bone mineral density. However, only 191 deaths due to osteoporosis were published in 2021 in Japan. With the concern that some cases of hip and spinal fragility fractures were assigned an underlying cause of death of traumatic fracture instead of osteoporosis, this study aimed to elucidate the actual number of deaths due to osteoporosis in Japan. METHODS: We used the data from Japan in 2018. First, the number of deaths due to osteoporosis and hip or spinal fractures was reviewed using published vital statistics. Second, we calculated the number of elderly deaths (age ≥80 years) resulting from hip or spinal fractures caused by falls on the same level using data from approximately 1.4 million annual individual death certificates. Combining the above data, the actual number of deaths due to osteoporosis was estimated. RESULTS: Only 190 deaths due to osteoporosis were reported in the published data. The individual certificate data revealed 3437 elderly deaths due to hip or spinal fractures caused by falls on the same level, which could meet the criteria of osteoporotic fragility fractures. Accordingly, the estimated number of deaths caused by osteoporosis was calculated as 3,627, approximately 19 times the published value. CONCLUSIONS: After researching the individual death certificate data focusing on the coexisting hip or spinal fragility fracture, it was implied that osteoporosis may have a higher mortality rate in Japan than what is published.

Mortality and causes of death in systemic lupus erythematosus in New Zealand: A population-based study.

OBJECTIVES: This study aims to assess the mortality of systemic lupus erythematosus (SLE) patients and examine whether there are variations by subgroup. METHODS: SLE patients from 2005-2021 were identified from the national administrative datasets. The underlying causes of death were examined. Standardised mortality ratio (SMR) was estimated to compare the relative rate of observed deaths in SLE patients to expected deaths in the general population. The hazard ratios (HR) and 95% confidence intervals (CI) of all-cause mortality and SLE specific mortality by ethnicity were estimated after adjustment for age using a Cox proportional hazards model. RESULTS: Of the 2,802 patients included for analysis, 699 (24.9%) died with 209 (29.9%) SLE deaths. The age-standardised mortality rate of SLE was 0.29 per 100 000 for women and 0.05 for men. The mean age at death was 65.3 ± 17.1 years. Younger patients were more likely to have SLE as the underlying cause of death, from 78.9% for those under 20 years old to 18.7% for those aged 70-79 years. Compared with the general population, SLE patients were four times more likely to die (SMR: 4.0; 95% CI: 3.7-4.3). Young patients had higher SMRs than older patients. Maori had worse all-cause mortality (HR: 1.72; 95% CI: 1.10-2.67) and SLE specific mortality (HR: 2.60; 95% CI: 1.29-5.24) than others. CONCLUSIONS: The outcomes of SLE in New Zealand were still very poor compared with the general population. Maori with SLE had worse survival than others. Further research is needed to identify the reasons to this disparity.

Quality of death certification based on the documented underlying cause of death: A retrospective study.

BACKGROUND: The underlying cause of death (UCOD) documented in the death certificate is a cornerstone in the mortality data that has significant impact on national policies, health system, and socioeconomics. However, a wide range of inaccuracies have been reported worldwide and were linked to multiple factors, including sociodemographic development and lack of physician training. Hence, this study aimed to assess the quality of death certification by reviewing the reported UCOD in the death certificate and study the potential factors that might be associated with inaccuracies. METHODS: All in-patient deaths that occurred in the Sultan Qaboos University Hospital from January 2020 to 31 December 2020 were included in this retrospective study. The study investigators reviewed all death certifications that were recorded during the study period for the accuracy of the documented UCOD using a systemic framework recommended by the World Health Organization. RESULTS: The study included 384 mortality cases. The mean age at the time of death was 55.7 ± 27.1 years, and 209 (54.3%) cases were men. Approximately 80% (95% confidence interval: 84-76%) of the deceased patients had inaccurate data on the UCOD. Old age (58.1 ± 25.8 vs 46.5 ± 30.1, p < 0.001), death certification by doctor in training (70.8% vs 51.9%, p = 0.001), and admission under the Department of Medicine (68.5% vs 54.4%, p = 0.019) were more common in mortality cases with inaccurate data on the UCOD. Regression analysis confirmed that old age, male sex, and certification by doctor in training were independent predictors of inaccurate data on the UCOD. CONCLUSION: Inaccurate data on the UCOD is a prevalent issue in many healthcare settings, especially in the developing countries. Introduction of death certification training in the medical curriculum for medical doctors, implementation of periodic auditing, and provision of feedback are among the evidence-based approaches that are likely to improve the overall accuracy of mortality data.

Impact of Cardiovascular Disease on the Death Certificate Diagnosis of Heart Failure, Ischemic Heart Disease, and Cerebrovascular Disease　- The Japan Public Health Center-Based Prospective Study.

BACKGROUND: There is considerable interest in the trending discrepancy between ischemic heart disease (IHD) and heart failure (HF) in vital statistics. Clinically, acute myocardial infarction (AMI) and stroke are closely associated with HF, but their contribution to HF as the underlying cause of death (UCD) is unclear.Methods and Results: In 1990 and 1992-1993, we enrolled a total of 140,420 residents of Japanese nationality (aged 40-69 years) from 11 public health center areas. We prospectively examined the occurrence of cardiovascular disease (CVD), including AMI, sudden cardiac death within 1 h (SCD), and stroke, and analyzed the 14,375 participants without a history of CVD at baseline who died during the 20-year follow-up. A time-dependent Cox proportional hazards model was used to estimate hazard ratios and the population attributable fraction (PAF) of AMI, AMI+SCD, stroke, and CVD for deaths due to HF, IHD, and cerebrovascular disease as the UCD, adjusted for individuals' lifestyles and comorbid conditions. The PAF of AMI for HF deaths was 2.4% (95% confidence interval [CI] 1.7-2.9%), which increased to 12.0% (95% CI 11.6-12.2%) for AMI+SCD. The PAF of CVD-attributed HF deaths was estimated to be 17.6% (95% CI 15.9-18.9%). CONCLUSIONS: HF as the UCD was partly explained by CVD. The data imply that most HF deaths reported in vital statistics may be associated with underlying causes other than CVD.

Assessment of the underlying causes of adult deaths using a short version of verbal autopsy in Xaiyabouli Province, Lao People's Democratic Republic.

BACKGROUND: In developing countries, it is difficult to collect the data of the underlying cause of death (UCOD), especially when a death does not occur in a health facility. This study aimed to develop a short version of verbal autopsy (VA) and identify the UCOD of adults in Lao People's Democratic Republic (Lao PDR). METHODS: A short version of VA for deaths outside health facilities was developed. This study included all deaths of people aged 15 years old or older in Xaiyabouli Province in 2020. Socio-demographic factors, place of death, and UCOD of the deceased were collected from health facilities or from family members using a questionnaire including the short VA form. UCOD was compared between home deaths and hospital deaths, between the age group of 15-59 years old and the age group ≥ 60 years old, and between males and females. RESULTS: Of all the 1,235 deaths included in this study, 1,012 deaths (81.9%) occured at home and 223 deaths (18.1%) at hospitals. The most common UCOD was senility (13.3%), followed by heart/renal failure (10.5%), pneumonia (9.6%) and traffic accident (7.1%). Compared to hospital deaths, home deaths had more people who were females, 75 years old or older, and Lao-Tai. Home deaths had more deaths than hospital deaths due to accident/injury (16.0% vs. 8.1%), tumor (4.7% vs. 1.8%), and senility (16.2% vs. 0%); fewer deaths due to heart/renal disease (15.1% vs. 32.3%), respiratory disease (12.2% vs. 18.8%), liver/gastro-intestine disease (5.3% vs. 9.0%), and infection (3.1% vs. 14.3%). The age group of 15-59 years had more deaths in the categories of accident/injury (28.1% vs. 4.4%), liver/gastro-intestine disease (8.1% vs. 4.4%), infection (7.2% vs. 3.5%), and tumor (6.0% vs. 2.8%). Males had more deaths due to tumor (5.2% vs. 3.0%) and fewer natural deaths (11.2% vs. 15.9%) than females. CONCLUSIONS: The major UCOD category was heart/renal disease in the adult generation in Xaiyabouli Province. Cost-effective interventions based on the multisectoral noncommunicable disease prevention plan should be appropriately implemented. Mortality surveillance using the short VA tool should be conducted for all home deaths in Lao PDR.

Long-term secular trends in dermatomyositis and polymyositis mortality in the USA from 1981 to 2020 according to underlying and multiple cause of death mortality data.

BACKGROUND: People with dermatomyositis (DM) or polymyositis (PM) often die from cancer, pulmonary, cardiac complications, or infections. In such cases, DM or PM might not be designated as the underlying cause of death (UCD) for mortality tabulation. In this study, we investigated DM/PM mortality trends in the USA from 1981 to 2020 with respect to UCD and multiple causes of death (MCD) data. METHODS: We used the MCD data to identify all deaths with DM or PM mentioned anywhere on the death certificate and as the UCD in the USA from 1981-1982 to 2019-2020. We calculated age-adjusted mortality rates (AAMRs) and annual percentage changes (APCs) based on joinpoint regression analysis. RESULTS: We identified 12,249 (3985 with DM and 7097 with PM) and 23,608 (8264 with DM and 15,344 with PM) people who died between 1981 and 2020 according to the UCD and MCD data, respectively. For DM, the APC was - 6.7% (from 1981-1982 to 1985-1986), - 0.1% (from 1985-1986 to 2003-2004), and - 1.9% (from 2003-2004 to 2019-2020) according UCD and was - 1.2% (from 1981-1982 to 2003-2004), - 2.5% (from 2003-2004 to 2015-2016), and 2.8% (from 2015-2016 to 2019-2020) according MCD. For PM, the APC was 1.9% (from 1981-1982 to 1989-1990), - 2.3% (from 1989-1990 to 2005-2006), and - 5.2% (from 2005-2006 to 2019-2020) according UCD and was 1.3% (from 1981-1982 to 1991-1992) and - 4.1% (from 1991-1992 to 2019-2020) according MCD. CONCLUSION: We identified two times as many DM/PM deaths using the MCD as those identified using the UCD. Similar downward DM/PM mortality trends were noted according to UCD and MCD. However, the year of significant decline in PM mortality was about 10 years earlier according to MCD than those according to UCD.

Survival of infants and children born with severe microcephaly, Texas, 1999-2015.

BACKGROUND: Severe microcephaly is a brain reduction defect where the delivery head circumference is <3rd percentile for gestational age and sex with subsequent lifelong morbidities. Our objective was to evaluate survival among 2,704 Texas infants with severe microcephaly delivered 1999-2015. METHODS: Infants with severe microcephaly from the Texas Birth Defects Registry were linked to death certificates and the national death index. Survival estimates, hazard ratios (HR) and confidence intervals (CI) were calculated using the Kaplan-Meier method and Cox proportional hazards models stratified by presence versus absence of co-occurring defects. RESULTS: We identified 496 deaths by age 4 years; most (42.9%) occurred in the neonatal period, and another 39.9% died by 1 year of age. Overall infant survival was 84.8%. Lowest infant survival subgroups included those with chromosomal/syndromic conditions (66.1%), very preterm deliveries (63.9%), or co-occurring critical congenital heart defects (44.0%). Among infants with severe microcephaly and a chromosomal/syndromic co-occurring defect, the risk of death was nearly three-fold higher among those with: proportionate microcephaly (i.e., small baby overall), relative to non-proportionate (HR = 2.84, 95% CI = 2.17-3.71); low-birthweight relative to normal (HR = 2.72, 95% CI = 1.92-3.85); critical congenital heart defects (CCHD) relative to no CCHD (HR = 2.90, 95% CI = 2.20-3.80). Trisomies were a leading underlying cause of death (27.5%). CONCLUSIONS: Overall, infants with severe microcephaly had high 4-year survival rates which varied by the presence of co-occurring defects. Infants with co-occurring chromosomal/syndromic anomalies have a higher risk of death by age one than those without any co-occurring birth defects.

Real-Time Classification of Causes of Death Using AI: Sensitivity Analysis.

BACKGROUND: In 2021, the European Union reported >270,000 excess deaths, including >16,000 in Portugal. The Portuguese Directorate-General of Health developed a deep neural network, AUTOCOD, which determines the primary causes of death by analyzing the free text of physicians' death certificates (DCs). Although AUTOCOD's performance has been established, it remains unclear whether its performance remains consistent over time, particularly during periods of excess mortality. OBJECTIVE: This study aims to assess the sensitivity and other performance metrics of AUTOCOD in classifying underlying causes of death compared with manual coding to identify specific causes of death during periods of excess mortality. METHODS: We included all DCs between 2016 and 2019. AUTOCOD's performance was evaluated by calculating various performance metrics, such as sensitivity, specificity, positive predictive value (PPV), and F1-score, using a confusion matrix. This compared International Statistical Classification of Diseases and Health-Related Problems, 10th Revision (ICD-10), classifications of DCs by AUTOCOD with those by human coders at the Directorate-General of Health (gold standard). Subsequently, we compared periods without excess mortality with periods of excess, severe, and extreme excess mortality. We defined excess mortality as 2 consecutive days with a Z score above the 95% baseline limit, severe excess mortality as 2 consecutive days with a Z score >4 SDs, and extreme excess mortality as 2 consecutive days with a Z score >6 SDs. Finally, we repeated the analyses for the 3 most common ICD-10 chapters focusing on block-level classification. RESULTS: We analyzed a large data set comprising 330,098 DCs classified by both human coders and AUTOCOD. AUTOCOD demonstrated high sensitivity (≥0.75) for 10 ICD-10 chapters examined, with values surpassing 0.90 for the more prevalent chapters (chapter II-"Neoplasms," chapter IX-"Diseases of the circulatory system," and chapter X-"Diseases of the respiratory system"), accounting for 67.69% (223,459/330,098) of all human-coded causes of death. No substantial differences were observed in these high-sensitivity values when comparing periods without excess mortality with periods of excess, severe, and extreme excess mortality. The same holds for specificity, which exceeded 0.96 for all chapters examined, and for PPV, which surpassed 0.75 in 9 chapters, including the more prevalent ones. When considering block classification within the 3 most common ICD-10 chapters, AUTOCOD maintained a high performance, demonstrating high sensitivity (≥0.75) for 13 ICD-10 blocks, high PPV for 9 blocks, and specificity of >0.98 in all blocks, with no significant differences between periods without excess mortality and those with excess mortality. CONCLUSIONS: Our findings indicate that, during periods of excess and extreme excess mortality, AUTOCOD's performance remains unaffected by potential text quality degradation because of pressure on health services. Consequently, AUTOCOD can be dependably used for real-time cause-specific mortality surveillance even in extreme excess mortality situations.

Heart failure describing the underlying cause of death: a misconception, lack of information on the true underlying causes, or both?

AIM: The underlying cause of death represents the most important information on death certificates. Often, conditions that cannot represent a true underlying cause of death are listed as such. This phenomenon affects the quality of vital statistics and results of studies using cause-specific mortality as endpoints. We aimed at exploring the magnitude and factors associated with the use of heart failure to describe the underlying cause of death. METHODS: In this cross-sectional, register based study we linked data from the Norwegian Cause of Death Registry and the Norwegian Patient Registry. We used logistic regression models to analyse the association between external factors and heart failure listed as the underlying cause of death. RESULTS: Heart failure was listed as the underlying cause of death in 3.6% of all deaths. The odds of heart failure increased: (a) by 35% for 5-year increment in age; (b) by 78% for deaths occurring at nursing homes (compared with in-hospital deaths); and (c) by 602% for deaths not followed by an autopsy (compared with those followed by an autopsy). Deceased with a previous hospitalisation with heart failure as the discharge diagnosis had 514% higher odds of having heart failure listed as their underlying cause of death. Of the deceased with heart failure listed as the underlying cause of death, 9.4% did not have any, and 69.2% had only irrelevant additional information for assessing the true underlying cause of death in their death certificates. CONCLUSIONS: Heart failure listed as the underlying cause of death was associated with age, place of death, autopsy and previous hospitalisations - all factors that should not influence coding procedures. Better completion of death certificates in accordance with the World Health Organization rules will help reduce the use of heart failure to describe the underlying cause of death.

Secular Trends in Systemic Sclerosis Mortality in the United States from 1981 to 2020.

BACKGROUND: Systemic sclerosis (SSc) has the highest mortality rate among autoimmune disorders. Individuals with SSc frequently die from complications or infections related to SSc. Nonetheless, the sex-age-period interaction of SSc is complex and remains unclear. The study aims to analyze the secular trend of SSc mortality based on data regarding underlying cause of death (UCD) and multiple causes of death (MCD) and clarify the sex-age interaction with time. METHODS: The multiple-cause mortality statistics provided by the National Center for Health Statistics were used to identify all deaths in the United States from 1981 to 2020 in which SSc was indicated anywhere on the death certificates. The age-standardized mortality rate (ASMR) was determined for both sexes, as well as the variations in these rates. Joinpoint regression analysis was utilized to determine the annual percentage change (APC) of ASMR. RESULTS: A total of 44,672 and 66,259 individuals who died between 1981 and 2020 were identified based on the UCD and MCD data, respectively. According to the UCD data, SSc-related AMSR (SSc-ASMR) of the male and female decedents, respectively, declined from 5.01 and 1.94 in 1981-1990 to 4.77 and 1.32 in 2011-2020, respectively (mortality rate ratio 0.95, 95% confidence interval 0.92-0.98). From 1986 to 1999, the APC of SSc-ASMR in female decedents decreased except for those aged 45-64 years (APC 2.1%, p = 0.002). For MCD analysis, in trend 1, only APC of SSc-ASMR in male decedents aged 45-64 years decreased. The SSc-ASMR of both male and female decedents fell on trend 2 arm. In 2011-2020, the ratio of UCD to MCD increased across all age groups for both sexes compared to 1981-1990. Overall, compared to the male decedents, the SSc-ASMR in female decedents increased significantly before 1999, peaked in 1999, followed by continuous decrease until 2020 according to UCD and MCD statistics. CONCLUSIONS: Over the past four decades, the SSc deaths based on the MCD data were 1.48 times more than the UCD data, and the proportion of UCD over MCD increased over time. The SSc-ASMRs in all the sex-age groups significantly decreased over the past two decades. Notably, the mortality rate ratio of women to men with SSc increased in the past four decades.

Longitudinal analysis of ovarian cancer death patterns during a rapid transition period (2005-2020) in Shanghai, China: A population-based study.

Objectives: It is important to assess the burden of ovarian cancer related premature death so as to develop appropriate evidence-based care and improve women's health. This study aimed to characterize the long-term trends in mortality, survival and disease burden of ovarian cancer in Shanghai, China. Materials and Methods: Co-morbidities, crude mortality rate (CMR), age-standardised mortality rate by Segi's world standard population (ASMRW), years of life lost (YLL), and survival rates were analysed. Temporal trends for the mortality rates and disease burden were analyzed using the Joinpoint Regression Program. Mortality rate increases by demographic and non-demographic factors were estimated by the decomposition method. Results: A total of 1088 ovarian cancer as underlying cause of deaths were recorded. CMR and ASMRW were 4.82/105 and 2.32/105 person-years, respectively. The YLL was 16372.96 years, and the YLL rate was 72.46/105 person-years. The YLL rate increased only in the age group of 70-79 years (P = 0.017). The survival rates of ovarian cancer patients did not improve during the ten year period (2005-2015). The top co-morbidities were diseases of the respiratory system, digestive system, and circulatory system. The rates of ovarian cancer deaths caused by non-demographic and demographic factors increased by 21.29% (95%CI: 4.01% to 41.44%, P = 0.018) and 25.23% (95%CI: 14.64% to 36.81%, P < 0.001), respectively. Conclusions: Population ageing and all cause of death may affect ovarian cancer related deaths in Pudong, Shanghai. The high mortality and the stagnant survival rates suggest the need for more efforts in targeted prevention and treatment of this disease.

Underlying cause of death at medical facilities in Xaiyabouli Province, Lao People's Democratic Republic.

In Lao PDR, Ministry of Health introduced District Health Information Software 2 (DHIS2) in 2013. Although DHIS2 includes cause of death, Lao government did not request to report cause of death through DHIS2, resulting in no information on frequency of underlying cause of death even for the deaths at medical facility. This study aimed to collect the information on the underlying cause of death at all medical facilities in Xaiyabouli province, a rural area in Lao PDR. As well as the point estimate of the proportion, a 95% confidence interval (CI) based on a binomial distribution was calculated for each cause of death. According to the local government request, 226 deaths (128 males and 98 females) in 2019 were reported from all medical facilities in the province. Among them, infectious diseases were the most frequent (33.6%, 95% CI 27.5-40.2%); sepsis (16.8%, 95% CI 12.2-22.3%), pneumonia (8.8%, 95% CI 5.5-13.3%), and meningitis (4.9%, 95% CI 2.5-8.5%). Heart diseases were 15.9% (95% CI 11.4-21.4%) including heart failure and myocardial infarction. Injury was 10.2% (95% CI 6.2-14.4%) including brain injury. Neonatal death was 10.6% (95% CI 6.9-15.4%). Among those, preterm death was common (8.8%, 95% CI 5.3-13.3%). Renal failure was 8.0% (95% CI 4.8-12.3%). According to civil registration covering all deaths both at facilities and outside facilities, deaths at facilities were 16.8% of the whole deaths (1,372 deaths) in Xaiyabouli province. Although deaths outside facilities were not included, this is the first report demonstrating cause of death in one province in Lao PDR.

Validation of physician certified verbal autopsy using conventional autopsy: a large study of adult non-external causes of death in a metropolitan area in Brazil.

BACKGROUND: Reliable mortality data are essential for the development of public health policies. In Brazil, although there is a well-consolidated universal system for mortality data, the quality of information on causes of death (CoD) is not even among Brazilian regions, with a high proportion of ill-defined CoD. Verbal autopsy (VA) is an alternative to improve mortality data. This study aimed to evaluate the performance of an adapted and reduced version of VA in identifying the underlying causes of non-forensic deaths, in São Paulo, Brazil. This is the first time that a version of the questionnaire has been validated considering the autopsy as the gold standard. METHODS: The performance of a physician-certified verbal autopsy (PCVA) was evaluated considering conventional autopsy (macroscopy plus microscopy) as gold standard, based on a sample of 2060 decedents that were sent to the Post-Mortem Verification Service (SVOC-USP). All CoD, from the underlying to the immediate, were listed by both parties, and ICD-10 attributed by a senior coder. For each cause, sensitivity and chance corrected concordance (CCC) were computed considering first the underlying causes attributed by the pathologist and PCVA, and then any CoD listed in the death certificate given by PCVA. Cause specific mortality fraction accuracy (CSMF-accuracy) and chance corrected CSMF-accuracy were computed to evaluate the PCVA performance at the populational level. RESULTS: There was substantial variability of the sensitivities and CCC across the causes. Well-known chronic diseases with accurate diagnoses that had been informed by physicians to family members, such as various cancers, had sensitivities above 40% or 50%. However, PCVA was not effective in attributing Pneumonia, Cardiomyopathy and Leukemia/Lymphoma as underlying CoD. At populational level, the PCVA estimated cause specific mortality fractions (CSMF) may be considered close to the fractions pointed by the gold standard. The CSMF-accuracy was 0.81 and the chance corrected CSMF-accuracy was 0.49. CONCLUSIONS: The PCVA was efficient in attributing some causes individually and proved effective in estimating the CSMF, which indicates that the method is useful to establish public health priorities.

Time series of diabetes attributable mortality from 2008 to 2017.

PURPOSE: Diabetes is a growing health problem. The aim of this study was to capture time trends in mortality associated with diabetes. METHODS: The mortality database of the Veneto region (Italy) includes both the underlying causes of death, and all the diseases mentioned in the death certificate. The annual percent change (APC) in age-standardized rates from 2008 to 2017 was computed by the Joinpoint Regression Program. RESULTS: Overall 453,972 deaths (56,074 with mention of diabetes) were observed among subjects aged ≥ 40 years. Mortality rates declined for diabetes as the underlying cause of death and from diabetes-related circulatory diseases. The latter declined especially in females - 4.4 (CI 95% - 5.3/- 3.4), while in males the APC was - 2.8 (CI 95% - 4.0/- 1.6). CONCLUSION: We observed a significant reduction in mortality during the period 2008-2017 in diabetes either as underlying cause of death or when all mentions of diabetes in the death certificate were considered.

Heart failure quantified by underlying cause and multiple cause of death in Brazil between 2006 and 2016.

BACKGROUND: The Global Burden of Disease (GBD) does not produce estimates of heart failure (HF) since this condition is considered the common end to several diseases (i.e., garbage code). This study aims to analyze the interactions between underlying and multiple causes of death related to HF in Brazil and its geographic regions, by sex, from 2006 to 2016. METHODS: Descriptive study of a historical series of death certificates (DCs) related to deaths that occurred in Brazil between 2006 and 2016, including both sexes and all age groups. To identify HF as the underlying cause of death or as a multiple cause of death, we considered the International Classification of Diseases (ICD) code I50 followed by any digit. We evaluated the deaths and constructed graphs by geographic region to compare with national data. RESULTS: We included 1,074,038 DCs issued between 2006 and 2016 that included code I50 in Parts I or II of the certificate. The frequency of HF as the multiple cause of death in both sexes was nearly three times higher than the frequency of HF as an underlying cause of death; this observation remained consistent over the years. The Southeast region had the highest number of deaths in all years (about 40,000 records) and approximately double the number in the Northeast region and more than four times the number in the North region. Codes of diseases clinically unrelated to HF, such as diabetes mellitus, chronic obstructive pulmonary disease, and stroke, were mentioned in 3.11, 2.62, and 1.49% of the DCs, respectively. CONCLUSIONS: When we consider HF as the underlying cause of death, we observed an important underestimation of its impact on mortality, since when analyzed as a multiple cause of death, HF is present in almost three times more deaths recorded in Brazil from 2006 to 2016. The mentioning of conditions with little association with HF at the time of the death highlights the importance of HF as a complex syndrome with multiple components that must be considered in the analysis of mortality trends for implementation of public health management programs.

Population-Based Study on the All-Cause and Cause-Specific Risks of Mortality among Long-Term Opioid Analgesics Users without Cancer in Taiwan.

(1) Background: The prevalence of opioid use in Taiwan increased by 41% between 2002 and 2014. However, little is known regarding the risk of mortality among long-term opioid analgesics users who do not have cancer. This study investigated this mortality risk with an emphasis on the calendar year and patients' age and sex. (2) Methods: This retrospective cohort study included 12,990 adult individuals without cancer who were long-term users of opioid analgesics and were randomly selected from the data set of Taiwan's National Health Insurance program from 2000 to 2012. They were then followed up through 2013. Information on the underlying causes of death was retrieved from the Taiwan Death Registry. Age, sex, and calendar year-standardized mortality ratios (SMRs) of all-cause and cause-specific mortality were calculated with reference to those of the general population. (3) Results: With up to 14 years of follow-up, 558 individuals had all-cause mortality in 48,020 person-years (cumulative mortality: 4.3%, mortality rate: 11.62 per 1000 person-years). Compared with the general population, the all-cause SMR of 4.30 (95% confidence interval (95% CI): 3.95-4.66) was significantly higher: it was higher in men than in women, declined with calendar year and age, and was significantly higher for both natural (4.15, 95% CI: 3.78-4.53) and unnatural (5.04, 95% CI: 3.88-6.45) causes. (4) Conclusions: Long-term opioid analgesics use among individuals without cancer in Taiwan was associated with a significantly increased risk of mortality. The notably increased mortality in younger adults warrants attention. Strategies to reduce long-term opioid analgesics use, especially their overuse or misuse, are in an urgent need.

Mortality Associated with Idiopathic Pulmonary Fibrosis in Northeastern Italy, 2008-2020: A Multiple Cause of Death Analysis.

Mortality from idiopathic pulmonary fibrosis (IPF) is increasing in most European countries, but there are no data for Italy. We analysed the registry data from a region in northeastern Italy to assess the trends in IPF-related mortality during 2008-2019, to compare results of underlying vs. multiple cause of death analyses, and to describe the impact of the COVID-19 epidemic in 2020. We identified IPF (ICD-10 code J84.1) among the causes of death registered in 557,932 certificates in the Veneto region. We assessed time trends in annual age-standardized mortality rates by gender and age (40-74, 75-84, and ≥85 years). IPF was the underlying cause of 1310 deaths in the 2251 certificates mentioning IPF. For all age groups combined, the age-standardized mortality rate from IPF identified as the underlying cause of death was close to the European median (males and females: 3.1 and 1.3 per 100,000/year, respectively). During 2008-2019, mortality rates increased in men aged ≥85 years (annual percent change of 6.5%, 95% CI: 2.0, 11.2%), but not among women or for the younger age groups. A 72% excess of IPF-related deaths was registered in March-April 2020 (mortality ratio 1.72, 95% CI: 1.29, 2.24). IPF mortality was increasing among older men in northeastern Italy. The burden of IPF was heavier than assessed by routine statistics, since less than two out of three IPF-related deaths were directly attributed to this condition. COVID-19 was accompanied by a remarkable increase in IPF-related mortality.