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Background: There are scant data on the causes of adult deaths in sub-Saharan Africa. We estimated the level and trends in adult mortality, overall and by different causes, in rural Rakai, Uganda, by age, sex, and HIV status., Objectives: To estimate and analyse adult cause-specific mortality trends in Rakai, Uganda., Methodology: Mortality information by cause, age, sex, and HIV status was recorded in the Rakai Community Cohort study using verbal autopsy interviews, HIV serosurveys, and residency data. We estimated the average number of years lived in adulthood. Using demographic decomposition methods, we estimated the contribution of each cause of death to adult mortality based on the average number of years lived in adulthood., Results: Between 1999 and 2019, 63082 adults (15-60 years) were censused, with 1670 deaths registered. Of these, 1656 (99.2%) had completed cause of death data from verbal autopsy. The crude adult death rate was 5.60 (95% confidence interval (CI): 5.33-5.87) per 1000 person-years of observation (pyo). The crude death rate decreased from 11.41 (95% CI: 10.61-12.28) to 3.27 (95% CI: 2.89-3.68) per 1000 pyo between 1999-2004 and 2015-2019. The average number of years lived in adulthood increased in people living with HIV and decreased in HIV-negative individuals between 2000 and 2019. Communicable diseases, primarily HIV and Malaria, had the biggest decreases, which improved the average number of years lived by approximately extra 12 years of life in females and 6 years in males. There were increases in deaths due to non-communicable diseases and external causes, which reduced the average number of years lived in adulthood by 2.0 years and 1.5 years in females and males, respectively., Conclusion: There has been a significant decline in overall mortality from 1999 to 2019, with the greatest decline seen in people living with HIV since the availability of antiretroviral therapy in 2004. By 2020, the predominant causes of death among females were non-communicable diseases, with external causes of death dominating in males.

The American College of Medical Toxicology and the National Association of Medical Examiners convened an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance. The panel finds the following: 1. A complete autopsy is necessary for optimal interpretation of toxicology results, which must also be considered in the context of the circumstances surrounding death, medical history, and scene findings. 2. A complete scene investigation extends to reconciliation of prescription information and pill counts. 3. Blood, urine, and vitreous humor, when available, should be retained in all cases. Blood from the femoral vein is preferable to blood from other sites. 4. A toxicological panel should be comprehensive and include opioid and benzodiazepine analytes, as well as other potent depressant, stimulant, and anti-depressant medications. 5. Interpretation of postmortem opioid concentrations requires correlation with medical history, scene investigation, and autopsy findings. 6. If death is attributed to any drug or combination of drugs (whether as cause or contributing factor), the certifier should list all the responsible substances by generic name in the autopsy report and on the death certificate. 7. The best classification for manner of death in deaths due to the misuse or abuse of opioids without any apparent intent of self-harm is "accident." Reserve "undetermined" as the manner for the rare cases in which evidence exists to support more than one possible determination.

Cause specific mortality was analysed among 883 white male workers from a paper company in Berlin, New Hampshire. Subjects were assigned to different exposure groups on the basis of their having worked in the pulp mill, the paper mill, or elsewhere in the paper company. A standardised mortality ratio (SMR) analysis was used to compare death rates for each of the exposure groups with United States national rates. For all the subjects, deaths due to all causes, all malignant neoplasms, and lung cancer were close to the number expected and excesses were noted for cancers of the digestive system and leukaemia. Among pulp mill workers, the number of cancers of the digestive system was raised and the SMR for pancreatic cancer was especially high (SMR = 305, 95% CI = 98-712). Among paper mill workers, more deaths were due to leukaemia and cancers of the digestive system than expected. These results are consistent with the findings from other studies that employment in pulp and paper mills is associated with excess mortality due to digestive and lymphopoietic cancers.

Context.—: Autopsies performed on COVID-19 patients have provided critical information about SARS-CoV-2's tropism, mechanisms of tissue injury, and spectrum of disease., Objective.—: To provide an updated database of postmortem disease in COVID-19 patients, assess relationships among clinical and pathologic variables, evaluate the accuracy of death certification, and correlate disease variables to causes of death., Design.—: The 272 postmortem examinations reported in this paper were submitted by 14 pathologists from 9 medical or forensic institutions across the United States. The study spans the eras of the 3 principal COVID-19 strains and incorporates surveyed demographic, clinical, and postmortem data from decedents infected with SARS-CoV-2, including primary and contributing causes of death. It is the largest database of its kind to date., Results.—: Demographics of the decedents reported here correspond well to national statistics. Primary causes of death as determined by autopsy and official death certificates were significantly correlated. When specifically cited disease conditions found at autopsy were correlated with COVID-19 versus non-COVID-19 deaths, only lung findings characteristic of SARS-CoV-2 infection or the absence of lung findings were significantly associated., Conclusions.—: Changes in hospitalization and disease likely stem from longer lifespans after COVID-19 diagnosis and alteration in treatment approaches. Although Omicron variants preferentially replicate in the upper airways, autopsied patients who died of COVID-19 in that time period showed the same lung damage as earlier decedents. Most importantly, findings suggest that there are still unelucidated risk factors for death from COVID-19 including possibly genetic susceptibility., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

The Manhiça Health Research Centre (Manhiça HDSS) was established in 1996 in Manhiça, a rural district at Maputo Province in the southern part of Mozambique with approximately 49,000 inhabited households, a total population of 209.000 individuals, and an annual estimated birth cohort of about 5000 babies. Since 2016, Manhiça HDSS is implementing the Child Health and Mortality Prevention Surveillance (CHAMPS) program aiming to investigate causes of death (CoD) in stillbirths and children under the age of 5 years using an innovative post-mortem technique known as Minimally Invasive Tissue sampling (MITS), comprehensive pathogen screening using molecular methods, clinical record abstraction and verbal autopsy. Both in-hospital and community pediatric deaths are investigated using MITS. For this, community-wide socio-demographic approaches (notification of community deaths by key informants, formative research involving several segments of the community, availability of free phone lines for notification of medical emergencies and deaths, etc.) are conducted alongside to foster community awareness, involvement and adherence as well as to compute mortality estimates and collect relevant information of health and mortality determinants. The main objective of this paper is to describe the Manhiça Health and Demographic Surveillance System (HDSS) site and the CHAMPS research environment in place including the local capacities among its reference hospital, laboratories, data center and other relevant areas involved in this ambitious surveillance and research project, whose ultimate aim is to improve child survival through public health actions derived from credible estimates and understanding of the major causes of childhood mortality in Mozambique., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Sacoor C et al.)

Background: In human health, vitamins play a vital role in various metabolic and regulatory processes and in the proper functioning of cells. Currently, the effect of Vitamin E (VE) intake on multiple causes of death in Chronic obstructive pulmonary disease (COPD) patients is unclear. Therefore, this paper aims to investigate the relationship between VE and multiple causes of death in COPD patients, to guide the rationalization of dietary structure and reduce the risk of COPD death., Methods: This study screened patients with COPD aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) database 2008-2018. Weighted COX regression was used to analyze the association between VE intake and multiple causes of death in COPD. The restricted cubic spline(RCS) is drawn to show their relationship. Finally, we conducted a subgroup analysis for further verification., Results: A total of 1261 participants were included in this study. After adjustment for multiple covariates, VE intake was associated with all-cause death in COPD patients, and chronic lower respiratory disease (CLRD) deaths were linearly associated with cardiovascular disease (CVD) deaths there was no such correlation. Subgroup analyses showed no interaction between subgroups, further validating the robustness of the relationship., Conclusion: In COPD patients, VE intake was negatively associated with all-cause mortality and CLRD death. Higher VE intake reduces the risk of all-cause mortality and CLRD death in COPD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Tian et al.)

Objective: For ICD-10 coding causes of death in France in 2018 and 2019, predictions by deep neural networks (DNNs) are employed in addition to fully automatic batch coding by a rule-based expert system and to interactive coding by the coding team focused on certificates with a special public health interest and those for which DNNs have a low confidence index., Methods: Supervised seq-to-seq DNNs are trained on previously coded data to ICD-10 code multiple causes and underlying causes of death. The DNNs are then used to target death certificates to be sent to the coding team and to predict multiple causes and underlying causes of death for part of the certificates. Hence, the coding campaign for 2018 and 2019 combines three modes of coding and a loop of interaction between the three., Findings: In this campaign, 62% of the certificates are automatically batch coded by the expert system, 3% by the coding team, and the remainder by DNNs. Compared to a traditional campaign that would have relied on automatic batch coding and manual coding, the present campaign reaches an accuracy of 93.4% for ICD-10 coding of the underlying cause (95.6% at the European shortlist level). Some limitations (risks of under- or overestimation) appear for certain ICD categories, with the advantage of being quantifiable., Conclusion: The combination of the three coding methods illustrates how artificial intelligence, automated and human codings are mutually enriching. Quantified limitations on some chapters of ICD codes encourage an increase in the volume of certificates sent for manual coding from 2021 onward., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA., Methods: A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990-March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted., Results: Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%., Conclusions: The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible., (© 2024. The Author(s).)

Background: Vitamin D insufficiency is a prevalent issue in patients suffering from CKD. The purpose of this study was to determine whether serum 25(OH)D levels are associated with all-cause and cardiovascular mortality in patients with CKD., Methods: To examine the associations between 25(OH)D levels and cardiovascular mortality, this retrospective cohort study used the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI) 2007‒2018 database. A total of 2,668 eligible subjects were included in this study, with follow-up conducted until December 31, 2019. The associations were assessed using Cox proportional hazards regression, restricted cubic splines, Kaplan-Meier survival curves, and competing risks survival analysis. Furthermore, subgroup and sensitivity analyses were performed., Results: During a median follow-up of 72 months in a weighted population of 11,715,452 eligible participants, there were 665 deaths from any cause, including 196 cardiovascular-related deaths. After adjusting for covariates, lower levels of 25(OH)D were significantly associated with increased risks for both all-cause mortality (HR= 0.85, 95 % CI 0.77∼0.94) and cardiovascular mortality (SHR= 0.80, 95 % CI 0.67∼0.94). Consistent results were also observed when analyzing 25(OH)D as a categorical variable (quartile). Compared to group Q1, both group Q3 (HR = 0.71, 95 % CI 0.54‒0.93) and group Q4 (HR = 0.72, 95 % CI 0.55‒0.94) exhibited a significantly reduced mortality risk. Weighted restricted cubic splines revealed an inverse J-shaped linear association between levels of 25(OH) D and all-cause mortality ((PNonliner > 0.05). Subgroup analysis and sensitivity analysis yielded similar findings., Conclusions: All-cause mortality and cardiovascular disease-related mortality were significantly increased by lower 25(OH)D levels, both as continuous and categorical variables. 25(OH)D has an inverse J-shaped linear association with all-cause and cardiovascular mortality., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to conduct a systematic analysis of studies to report estimates of the causes of deaths from diarrhoea in children younger than 5 years at global and regional levels during 2000-21., Methods: For this systematic review and Bayesian multinomial analysis, we included 12 pathogens with the highest attributable incidence in the Global Enteric Multicenter Study. We searched PubMed, Scopus, Embase, Web of Science, Global Health Index Medicus, Global Health OVID, IndMed, Health Information Platform for the Americas (PLISA), Africa-Wide Information, and Cochrane Collaboration for articles published between Jan 1, 2000, and Dec 31, 2020, using the search terms "child", "hospital", "diarrhea", "diarrhoea", "dysentery", "rotavirus", "Escherichia coli", "salmonella", "shigella", "campylobacter", "Vibrio cholerae", "cryptosporidium", "norovirus", "astrovirus", "sapovirus", and "adenovirus". To be included, studies had to have a patient population of children younger than 5 years who were hospitalised for diarrhoea (at least 90% of study participants), at least a 12-month duration, reported prevalence in diarrhoeal stools of at least two of the 12 pathogens, all patients with diarrhoea being included at the study site or a systematic sample, at least 100 patients with diarrhoea, laboratory tests done on rectal swabs or stool samples, and standard laboratory methods (ie, quantitative PCR [qPCR] or non-qPCR). Studies published in any language were included. Studies were excluded if they were limited to nosocomial, chronic, antibiotic-associated, or outbreak diarrhoea or to a specific population (eg, only children with HIV or AIDS). Each article was independently reviewed by two researchers; a third arbitrated in case of disagreement. If both reviewers identified an exclusion criterion, the study was excluded. Data sought were summary estimates. Data on causes from published studies were adjusted when necessary to account for the poor sensitivity of non-qPCR methods and for attributable fraction based on quantification of pathogens in children who are ill or non-ill. The causes of deaths from diarrhoea were modelled on the causes of hospitalisations for diarrhoea. We separately modelled studies reporting causes of diarrhoea in children who were hospitalised in low-income and middle-income countries (LMICs) and in high-income countries (HICs)., Findings: Of 74 282 papers identified in the initial database search, we included 138 studies (91 included data from LMICs and 47 included data from HICs) from 73 countries. We modelled estimates for 194 WHO member states (hereafter referred to as countries), including 42 HICs and 152 LMICs. We could attribute a cause to 1 003 448 (83·8%) of the estimated 1 197 044 global deaths from diarrhoea in children younger than 5 years in 2000 and 360 730 (81·3%) of the estimated 443 833 global deaths from diarrhoea in children younger than 5 years in 2021. The cause with the largest estimated global attribution was rotavirus; in LMICs, the proportion of deaths from diarrhoea due to rotavirus in children younger than 5 years appeared lower in 2021 (108 322 [24·4%] of 443 342, 95% uncertainty interval 21·6-29·5) than in 2000 (316 382 [26·5%] of 1 196 134, 25·7-28·5), but the 95% CIs overlapped. In 2000, the second largest estimated attribution was norovirus GII (95 817 [8·0%] of 1 196 134 in LMICs and 225 [24·7%] of 910 in HICs); in 2021, Shigella sp had the second largest estimated attribution in LMICs (36 082 [8·1%] of 443 342), but norovirus remained with the second largest estimated attribution in HICs (84 [17·1%] of 490)., Interpretation: Our results indicate progress in the reduction of deaths from diarrhoea caused by 12 pathogens in children younger than 5 years in the past two decades. There is a need to increase efforts for prevention, including with rotavirus vaccine, and treatment to eliminate further deaths., Funding: Bill & Melinda Gates Foundation via Johns Hopkins University and the University of Virginia., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Research over the past decade has suggested that prenatal and early postnatal nutrition influence the risk of developing chronic degenerative diseases up to 60 years later. We now present evidence that risk of death from infectious diseases in young adulthood is similarly programmed by early life events., Methods: In three rural Gambian villages, affected by a marked annual seasonality in diet and disease, we have kept detailed demographic, anthropometric and health records since 1949. Fate was known with certainty for 3,162 individuals (2,059 alive/1,103 dead, most dying in childhood). For this case-control analysis of antecedent predictors of premature mortality, all adult deaths (n = 61) were paired with two randomly selected controls matched for sex and year of birth., Results: Mean age at death was 25 (SD: 8) years. Adult death was associated with a profound bias in month of birth with 49 cases born in the nutritionally-debilitating hungry season (Jul-Dec) versus 12 in the harvest season (Jan-Jun). Relative to harvest season the hazard ratio for early death in hungry-season births rose from 3.7 (for deaths >14.5 years, P = 0.000013) to 10.3 (for deaths >25 years, P = 0.00002). Anthropometric and haematological status at 18 months of age was identical in cases and controls, indicating an earlier origin to the defect. Most deaths for which cause was known had a definite or possible infectious aetiology; none were from degenerative diseases of affluence., Conclusions: Early life exposures, correlated with season of birth, strongly influence susceptibility to fatal infections in young adulthood. The evidence suggests that nutritionally-mediated intrauterine growth retardation may permanently impair the development of immune function.

Although 25% of US men indicate that they are trying to lose weight, the association between intentional weight loss and longevity in men is unknown. The authors analyzed prospective data from 49,337 overweight (initial body mass index > or =27) white men aged 40-64 years who, in 1959-1960, answered questions on weight change direction, amount, time interval, and intent. Vital status was determined in 1972. Proportional hazards regression estimated mortality rate ratios for men who intentionally lost weight compared with men with no weight change. Analyses were stratified by health status and adjusted for age, initial body mass index, smoking status, alcohol intake, education, physical activity, health history, and physical symptoms. Among men with no reported health conditions (n = 36,280), intentional weight loss was not associated with total, cardiovascular (CVD), or cancer mortality, but diabetes-associated mortality was increased 48% (95% confidence interval (CI) -7% to +133%) among those who lost 20 pounds (9.1 kg) or more; this increase was largely related to non-CVD mortality. Among men with reported health conditions (n = 13,057), intentional weight loss had no association with total or CVD mortality, but cancer mortality increased 25% (95% confidence interval -4% to +63%) among those who lost 20 pounds or more. Diabetes-associated mortality was reduced 32% (95% confidence interval -52% to -5%) among those who lost less than 20 pounds and 36% (95% confidence interval -49% to -20%) among those who lost more than 20 pounds. These results and those from our earlier study in women (Williamson et al., Am J Epidemiol 1995;141:1128-41) suggest that intentional weight loss may reduce the risk of dying from diabetes, but not from CVD. In observational studies, however, it is difficult to separate intentional weight loss from unintentional weight loss due to undiagnosed, underlying disease. Well-designed observational studies, as well as randomized controlled trials, are needed to determine whether intentional weight loss reduces CVD mortality.

Mortality indicators and causes of death in Jordan were assessed by verbal autopsy. A random sample of 100 clusters of ca. 300 households each were monitored for one year by notification assistants selected from the study area itself. Registered deaths were reported to research assistants who visited the family to complete the verbal autopsy form, which was structured and contained about 100 questions. Causes of death were determined by two physicians according to preset algorithms. A total of 965 deaths were reported among 198,989 persons, giving a crude death rate of 5 per 1000 population per year. The three leading causes of death were diseases of the circulatory system, malignancies and accidents. In the absence of a health information system, verbal autopsy as implemented in Jordan can serve as a reliable substitute.

COVID-19 outbreaks have had high mortality in low- and middle-income countries such as Ecuador. Human mobility is an important factor influencing the spread of diseases possibly leading to a high burden of disease at the country level. Drastic control measures, such as complete lockdown, are effective epidemic controls, yet in practice one hopes that a partial shutdown would suffice. It is an open problem to determine how much mobility can be allowed while controlling an outbreak. In this paper, we use statistical models to relate human mobility to the excess death in Ecuador while controlling for demographic factors. The mobility index provided by GRANDATA, based on mobile phone users, represents the change of number of out-of-home events with respect to a benchmark date (March 2nd, 2020). The study confirms the global trend that more men are dying than expected compared to women, and that people under 30 show less deaths than expected, particularly individuals younger than 20 with a death rate reduction between 22 and 27%. The weekly median mobility time series shows a sharp decrease in human mobility immediately after a national lockdown was declared on March 17, 2020 and a progressive increase towards the pre-lockdown level within two months. Relating median mobility to excess deaths shows a lag in its effect: first, a decrease in mobility in the previous two to three weeks decreases excess death and, more novel, we found an increase of mobility variability four weeks prior increases the number of excess deaths., (© 2022. The Author(s).)

Background: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death., Methods and Findings: We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings., Conclusions: Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: QB, a co-author of this paper is also a Guest Editor on this special issue on Global Child Health: From Birth to Adolescence and Beyond. QB was not directly involved in editorial decisions regarding this paper. JAGS reports current funding for other projects to his institution (London School of Hygiene & Tropical Medicine) from the UK Medical Research Council, Wellcome Trust, Gavi, Bill & Melinda Gates Foundation, and the UK National Institute for Health Research.

This paper quantifies the net impact (direct and indirect effects) of the pandemic on the United States population in 2020 using three metrics: excess deaths, life expectancy, and total years of life lost. The findings indicate there were 375,235 excess deaths, with 83% attributable to direct, and 17% attributable to indirect effects of COVID-19. The decrease in life expectancy was 1.67 years, translating to a reversion of 14 years in historical life expectancy gains. Total years of life lost in 2020 was 7,362,555 across the USA (73% directly attributable, 27% indirectly attributable to COVID-19), with considerable heterogeneity at the individual state level., Competing Interests: The authors have declared that no competing interests exist.

Autoimmune diseases are not always recognized as urgent health issues, despite a worldwide prevalence of 4%-5%. Most estimates come from high-income countries, as low- and middle-income countries face more issues of under-reporting. Despite this and the lack of recognition under current reporting practices, the role these diseases play in mortality must be acknowledged. In particular, considering multiple causes of death as opposed to a single cause of death results in a 1.5-4.2-fold increase in deaths classified as relating to autoimmune diseases, evidence of their share in overall mortality burden, a factor important for patient care and healthcare policy decision making. However, formulating such policies and programs for timely, appropriate diagnoses and care is stymied in low- and middle-income countries by the shortage of methodologically sound studies on mortality from systemic autoimmune diseases. This limitation exacerbates inequalities and health gaps among patients in different countries and localities. Multiple cause-of-death methodology has been validated for research on other diseases and demonstrates the mortality burden of these illnesses in countries where traditional methodological approaches, primarily based on prospective cohort studies, are not feasible. Studying mortality from systemic autoimmune diseases by analyzing multiple causes of death with data from national mortality registries is a low-cost alternative to traditional mortality analysis. The objective of this paper is to demonstrate and defend the usefulness of this approach to estimate mortality burden.

Purpose: The associations of high-density lipoprotein cholesterol (HDL-C) with mortality are still unclear. We explored the associations of HDL-C with all-cause and cause-specific mortality in an adult population., Methods: Deaths were classified into all-cause, cardiovascular, and cancer mortality. Survival curve, multivariate Cox regression, and subgroup analyses were conducted, and hazard ratio (HR) and 95% confidence interval (CI) were performed. We fitted Cox regression models for all-cause, cardiovascular, and cancer mortality to evaluate their associations with categories of HDL-C (≤30, 31-40, 41-50, 51-60 [reference], 61-70, >70 mg/dL)., Results: A total of 42,145 (20,415 (48.44%) males, mean age 47.12±19.40 years) subjects were enrolled. At an average follow-up of 97.52±54.03 months, all-cause, cardiovascular, and cancer mortality numbers were 5,061 (12.01), 1,081 (2.56%), and 1,061 (2.52%), respectively. When compared with the reference group (HDL-C: 51-60 mg/dL), a U-shaped association was apparent for all-cause mortality, with elevated risk in participants with the lowest (≤30 mg/dL) (HR=1.33; 95% CI=1.14- 1.56) and highest (>70 mg/dL) (HR=1.14; 95% CI=1.02-1.27) HDL-C concentration. Associations for cardiovascular and cancer mortality were non-linear. An elevated risk for cancer mortality was observed in those with the highest HDL-C concentration (HR=1.06; 95% CI-0.84-1.34) compared with the reference group, although it was not statistically significant. The effect of HDL-C on mortality was adjusted by some traditional risk factors including age, gender, race, or comorbidities., Conclusion: A U-shaped association was observed between HDL-C and all-cause mortality among an adult population., Competing Interests: The authors of this paper reported no financial conflicts of interest., (© 2020 Huang et al.)

We examined family isolation, economic hardship, and long-distance migration as potential patterns of an extreme outcome of a lonely death: bodily remains that remain unclaimed and are left to the state. This paper combines a unique dataset-Los Angeles County's records of unclaimed deaths-with the Vital Statistics' Mortality data and the Annual Social and Economic Survey (ASEC) to examine 1) whose remains are more likely to become unclaimed after death and, 2) whether population-level differences and trends in family isolation, economic hardship, and long-distance migration explain the differences in the rates of unclaimed deaths. We employ multivariate Poisson models to estimate relative rates of unclaimed deaths by social and demographic characteristics. We find that increases in never married, divorced/separated, and living without family were positively associated with rates of unclaimed deaths. Unemployment among men and poverty among women was associated with higher unclaimed deaths. Long-distance migration was not associated with more unclaimed bodies., Competing Interests: The authors have declared that no competing interests exist.

Measurement of alcohol use and associated harms at the city level is often incomplete or non-existent even though such data are often critical to informing local prevention strategies. This paper models how to generate local estimates of the morbidity, mortality, and cost of current alcohol use instead of abstaining. Administrative data sources, including medical examiner records, hospital records, and police records, among others, were used to obtain local estimates of alcohol-attributable outcomes. In 2018, we used alcohol-attributable fractions and scaled national estimates to quantify the burden of current alcohol use in Baltimore, MD, in 2013. Fifty-two percent of Baltimore adults reported past 30-day drinking. There were 276 alcohol-attributable deaths in 2013, and 106 (38.4%) of these were persons other than the drinker. In 2013, current alcohol use cost $582.3 million in Baltimore City. This burden was distributed across drinkers (40.1%), persons other than the drinker (21.3%), and the government (38.6%). It is possible to quantify this burden at the local level, and these data could be used to inform evidence-based alcohol policy strategies at the local level.

Life expectancy at a given age is a summary measure of mortality rates present in a population (estimated as the area under the survival curve), and represents the average number of years an individual at that age is expected to live if current age-specific mortality rates apply now and in the future. A complementary metric is the number of Life Years Lost, which is used to measure the reduction in life expectancy for a specific group of persons, for example those diagnosed with a specific disease or condition (e.g. smoking). However, calculation of life expectancy among those with a specific disease is not straightforward for diseases that are not present at birth, and previous studies have considered a fixed age at onset of the disease, e.g. at age 15 or 20 years. In this paper, we present the R package lillies (freely available through the Comprehensive R Archive Network; CRAN) to guide the reader on how to implement a recently-introduced method to estimate excess Life Years Lost associated with a disease or condition that overcomes these limitations. In addition, we show how to decompose the total number of Life Years Lost into specific causes of death through a competing risks model, and how to calculate confidence intervals for the estimates using non-parametric bootstrap. We provide a description on how to use the method when the researcher has access to individual-level data (e.g. electronic healthcare and mortality records) and when only aggregated-level data are available., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This paper analyses the patterns and trends in the mortality rates of infants and children under the age of 5 in India (1992-2016) and quantifies the variation in performance between different geographical states through three rounds of nationally representative household surveys., Design: Three rounds of cross-sectional survey data., Setting: The study is conducted at the national level: India and its selected good-performing states, namely Haryana, Kerala, Maharashtra, Punjab and Tamil Nadu, and selected poor-performing states, namely Bihar, Chhattisgarh, Madhya Pradesh and Uttar Pradesh., Participants: Adopting a multistage, stratified random sampling, 601 509 households with 699 686 women aged 15-49 years in 2015-2016, 109 041 households with 124 385 women aged 15-49 years in 2005-2006, and 88 562 households with 89 777 ever married women in the age group 13-49 years in 1992-1993 were selected., Results: Through the use of maps, this paper clearly shows that the overall trend in infant and child mortality is on a decline in India. Computation of relative change shows that majority of the states have witnessed over 50% reduction in both infant and under-5 mortality rates from National Family Health Survey (NFHS)-I to NFHS-4. However, the improvements are not evenly distributed, and there is huge variation in performance between states over time. Funnel plots show that the most populous states like Uttar Pradesh Bihar and Madhya Pradesh have underperformed consistently across the survey period from 1992 to 2016. Regression analysis comparing high-performing and low-performing states revealed that female infants and women with shorter birth intervals had greater risk of infant deaths in poor-performing states., Conclusion: Attempts to reduce infant and child mortality rates in India are heading in the right direction. Even so, there is huge variation in performance between states. This paper recommends a mix of strategies that reduce child and infant mortality among the high-impact states where the biggest improvements can be expected, including the need to address neonatal mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The World Health Organization recommends a minimum requirement of 0.8 g/day protein/kg ideal weight. Low protein diets are used against kidney failure progression. Efficacy and safety of these diets are uncertain. This paper reviews epidemiological studies about associations of protein intake with kidney function decline and mortality. Three studies investigated these associations; two reported data on mortality. Protein intake averaged >60 g/day and 1.2 g/day/kg ideal weight. An association of baseline protein intake with long-term kidney function decline was absent in the general population and/or persons with normal kidney function but was significantly positive in persons with below-normal kidney function. Independent of kidney function and other confounders, a J-curve relationship was found between baseline protein intake and mortality due to ≈35% mortality excess for non-cardiovascular disease in the lowest quintile of protein intake, a quintile where protein intake averaged <0.8 g/day/kg ideal weight. Altogether, epidemiological evidence suggests that, in patients with reduced kidney function, protein intakes of ≈0.8 g/d/kg ideal weight could limit kidney function decline without adding non-renal risks. Long-term lower protein intake could increase mortality. In most patients, an intake of ≈0.8 g/day/kg would represent a substantial reduction of habitual intake considering that average intake is largely higher., Competing Interests: The authors declare no conflict of interest.

Half of the world's deaths and their causes pass unrecorded by routine registration systems, particularly in low- and middle-income countries. Verbal autopsy (VA) collects information on medical signs, symptoms and circumstances from witnesses of a death that is used to assign likely medical causes. To further contextualise information on mortality, understanding underlying determinants, such as logistics, barriers to service utilisation and health systems responses, is important for health planning. Adding systematic methods for categorising circumstantial determinants of death to conventional VA tools is therefore important. In this context, the World Health Organization (WHO) leads the development of international standards for VA, and added questions on the social and health systems circumstances of death in 2012. This paper introduces a pragmatic and scalable approach for assigning relevant Circumstances Of Mortality CATegories (COMCATs) within VA tools, and examines their consistency, reproducibility and plausibility for health policy making, as well as assessing additional effort and cost to the routine VA process. This innovative COMCAT model is integrated with InterVA-5 software (which processes WHO-2016 VA data), for assigning numeric likelihoods to six circumstantial categories for each death. VA data from 4,116 deaths in the Agincourt Health and Socio-Demographic Surveillance System in South Africa from 2012 to 2016 were used to demonstrate proof of principle for COMCATs. Lack of resources to access health care, poor recognition of diseases and inadequate health systems responses ranked highest among COMCATs in the demonstration dataset. COMCATs correlated plausibly with age, sex, causes of death and local knowledge of the demonstration population. The COMCAT approach appears to be plausible, feasible and enhances the functionality of routine VA to account for critical limiting circumstances at and around the time of death. It is a promising tool for evaluating progress towards the Sustainable Development Goals and the roll-out of Universal Health Coverage.

The gender gap in life expectancy (GGLE) varies substantially in EU 28 Member States. This paper addresses the question of whether gender inequality affects the GGLE as well as life expectancy (LE) in both genders. We conducted an ecological study and used the gender inequality index (GII) developed by the United Nations as well as the gender difference in LE in 2015. We found a correlation between GGLE and GII (r2=0.180) and between GII and LE of 0.418 (women) and 0.430 (men). Gender equality policies are still necessary and will have an effect on women's as well as men's health.

Significant increases in excess all-cause mortality, particularly in the elderly, were observed during the winter of 2014/15 in England. With influenza A(H3N2) the dominant circulating influenza A subtype, this paper determines the contribution of influenza to this excess controlling for weather. A standardised multivariable Poisson regression model was employed with weekly all-cause deaths the dependent variable for the period 2008-2015. Adjusting for extreme temperature, a total of 26 542 (95% CI 25 301-27 804) deaths in 65+ and 1942 (95% CI 1834-2052) in 15-64-year-olds were associated with influenza from week 40, 2014 to week 20, 2015. This is compatible with the circulation of influenza A(H3N2). It is the largest estimated number of influenza-related deaths in England since prior to 2008/09. The findings highlight the potential health impact of influenza and the important role of the annual influenza vaccination programme that is required to protect the population including the elderly, who are vulnerable to a severe outcome.

Background: Recently, a new algorithm for automatic computer certification of verbal autopsy data named InSilicoVA was published. The authors presented their algorithm as a statistical method and assessed its performance using a single set of model predictors and one age group., Methods: We perform a standard procedure for analyzing the predictive accuracy of verbal autopsy classification methods using the same data and the publicly available implementation of the algorithm released by the authors. We extend the original analysis to include children and neonates, instead of only adults, and test accuracy using different sets of predictors, including the set used in the original paper and a set that matches the released software., Results: The population-level performance (i.e., predictive accuracy) of the algorithm varied from 2.1 to 37.6% when trained on data preprocessed similarly as in the original study. When trained on data that matched the software default format, the performance ranged from -11.5 to 17.5%. When using the default training data provided, the performance ranged from -59.4 to -38.5%. Overall, the InSilicoVA predictive accuracy was found to be 11.6-8.2 percentage points lower than that of an alternative algorithm. Additionally, the sensitivity for InSilicoVA was consistently lower than that for an alternative diagnostic algorithm (Tariff 2.0), although the specificity was comparable., Conclusions: The default format and training data provided by the software lead to results that are at best suboptimal, with poor cause-of-death predictive performance. This method is likely to generate erroneous cause of death predictions and, even if properly configured, is not as accurate as alternative automated diagnostic methods.

Background: Digoxin is widely used in patients with atrial fibrillation (AF)., Objectives: The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration., Methods: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment., Results: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration ≥1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users., Conclusions: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations ≥1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is increasing interest in using verbal autopsy to produce nationally representative population-level estimates of causes of death. However, the burden of processing a large quantity of surveys collected with paper and pencil has been a barrier to scaling up verbal autopsy surveillance. Direct electronic data capture has been used in other large-scale surveys and can be used in verbal autopsy as well, to reduce time and cost of going from collected data to actionable information., Methods: We collected verbal autopsy interviews using paper and pencil and using electronic tablets at two sites, and measured the cost and time required to process the surveys for analysis. From these cost and time data, we extrapolated costs associated with conducting large-scale surveillance with verbal autopsy., Results: We found that the median time between data collection and data entry for surveys collected on paper and pencil was approximately 3 months. For surveys collected on electronic tablets, this was less than 2 days. For small-scale surveys, we found that the upfront costs of purchasing electronic tablets was the primary cost and resulted in a higher total cost. For large-scale surveys, the costs associated with data entry exceeded the cost of the tablets, so electronic data capture provides both a quicker and cheaper method of data collection., Conclusions: As countries increase verbal autopsy surveillance, it is important to consider the best way to design sustainable systems for data collection. Electronic data capture has the potential to greatly reduce the time and costs associated with data collection. For long-term, large-scale surveillance required by national vital statistical systems, electronic data capture reduces costs and allows data to be available sooner.

Introduction: Verbal autopsy (VA) is a method that determines the cause of death by interviewing a relative of the deceased about the events occurring before the death, in regions where medical certification of cause of death is incomplete. This paper aims to review the ethical standards reported in peer-reviewed VA studies., Methods: A systematic review of Medline and Ovid was conducted by two independent researchers. Data were extracted and analysed for articles based on three key areas: Institutional Review Board (IRB) clearance and consenting process; data collection and management procedures, including: time between death and interview; training and education of interviewer, confidentiality of data and data security; and declarations of funding and conflict of interest., Results: The review identified 802 articles, of which 288 were included. The review found that 48% all the studies reported having IRB clearance or obtaining consent of participants. The interviewer training and education levels were reported in 62% and 21% of the articles, respectively. Confidentiality of data was reported for 14% of all studies, 18% did not report the type of respondent interviewed and 51% reported time between death and the interview for the VA. Data security was reported in 8% of all studies. Funding was declared in 63% of all studies and conflict of interest in 42%. Reporting of all these variables increased over time., Conclusions: The results of this systematic review show that although there has been an increase in ethical reporting for VA studies, there still remains a large gap in reporting., (© The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

One of the tasks of the forensic specialist is to attempt to determine the interval between fatal injuries and death, and to assess whether the victim could be physically active before death and, if so, to what extent. There is ongoing research aimed at the application of additional tests (histological, immunohistochemical and others) to answer these questions. Unfortunately, currently used methods have numerous limitations and require further improvements. Moreover, they are not commonly employed in medicolegal practice in Poland. The greatest difficulty in assessing the time of survival and activity occurs when the period is relatively short (seconds-minutes-hours). Therefore, in practice, injury examination is often the only tool to assess the interval between fatal injuries and death, and the possibility of physical activity during that time. The aim of the paper is review the literature on this topic with a focus on biological methods and attempt to find a correlation between the nature of injuries and survival time, and between the nature of injuries and the capability to be physically active. An analysis of available cases has shown that unfortunately, on account of numerous limitations, the approach with the exception of specific situations, allows determining at most an approximate time interval during which the victim could be alive and active.

Background: Suggested strategies in reducing the impact of non-communicable diseases (NCD) are early diagnosing and screening. We have limited proof of benefit of population screening for NCD. Increased mortality in persons with diagnosed NCD has been shown for decades. However, mortality in undetected NCD has barely been studied. This paper explores whether all-cause mortality differed between persons with diagnosed hypothyroidism, type 2 diabetes (T2DM), and hypertension, compared with persons with undetected-, and with persons without the corresponding disease., Methods: A prospective cohort study of the general population in Nord-Trøndelag, Norway. Persons ≥20 years at baseline 1995-97 were followed until death or June 15, 2016. Cox proportional hazards models were used to compute age and multiple adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between disease status and all-cause mortality. The number of participants in the hypothyroidism study was 31,960, in the T2DM study 37,957, and in the hypertension study 63,371., Results: Mortality was increased in persons with diagnosed type 2 diabetes and hypertension, compared to persons without corresponding disease; HR 1.69 (95% CI 1.55-1.84) and HR 1.23 (95% CI 1.09-1.39), respectively. Among persons with undetected T2DM, the HR was 1.21 (95% CI 1.08-1.37), whilst among undetected hypothyroidism and hypertension, mortality was not increased compared with persons without the diseases. Further, the association with mortality was stronger in persons with long duration of T2DM (HR 1.96 (95% CI 1.57-2.44)) and hypertension (HR 1.32 (95% CI 1.17-1.49)), compared with persons with short duration (HR 1.29 (1.09-1.53) and HR 1.16 (1.03-1-30) respectively)., Conclusions: Mortality was increased in persons with diagnosed T2DM and hypertension, and in undetected T2DM, compared with persons without the diseases. The strength of the association with mortality in undetected T2DM was however lower compared with persons with diagnosed T2DM, and mortality was not increased in persons with undetected hypothyroidism and hypertension, compared with persons without the diseases. Thus, future research needs to test more thoroughly if early diagnosing of these diseases, such as general population screening, is beneficial for health.

Biomarkers of all-cause mortality are of tremendous clinical and research interest. Because of the long potential duration of prospective human lifespan studies, such biomarkers can play a key role in quantifying human aging and quickly evaluating any potential therapies. Decades of research into mortality biomarkers have resulted in numerous associations documented across hundreds of publications. Here, we present MortalityPredictors.org , a manually-curated, publicly accessible database, housing published, statistically-significant relationships between biomarkers and all-cause mortality in population-based or generally healthy samples. To gather the information for this database, we searched PubMed for appropriate research papers and then manually curated relevant data from each paper. We manually curated 1,576 biomarker associations, involving 471 distinct biomarkers. Biomarkers ranged in type from hematologic (red blood cell distribution width) to molecular (DNA methylation changes) to physical (grip strength). Via the web interface, the resulting data can be easily browsed, searched, and downloaded for further analysis. MortalityPredictors.org provides comprehensive results on published biomarkers of human all-cause mortality that can be used to compare biomarkers, facilitate meta-analysis, assist with the experimental design of aging studies, and serve as a central resource for analysis. We hope that it will facilitate future research into human mortality and aging.

Background: Cause-specific (CS) and net survival in a relative survival framework (RS) are two of the most common methods for estimating cancer survival. In this paper, we assess the differences in results produced by two permutations of cause-specific and relative survival applied to estimating cancer survival and disparities in cancer survival, using data from First Nations and non-Aboriginal populations in Canada., Methods: Subjects were members of the 1991 Canadian Census Mortality Cohort, a population-based cohort of adult respondents to the 1991 Long Form Census who have been followed up for incident cancers and death through linkage to administrative databases. We compared four methods: relative survival analyses with ethnicity-specific life tables (RS-ELT); relative survival with general population life tables (RS-GLT); cause-specific survival with a broad definition of cancer death (CS-Broad); and cause-specific survival with a narrow definition of cause of death (CS-Narrow) and applied these to the nine most common cancers among First Nations., Results: Apart from breast and prostate cancers, RS-ELT, RS-GLT, and CS-Broad tended to produce similar estimates of age-standardized five-year survival, whereas CS-Narrow yielded higher estimates of survival. CS-Narrow estimates were particularly unlike those based on the other methods for cancers of the digestive and respiratory tracts. Estimates of disparities in survival were generally comparable across the four methods except for breast and prostate cancers., Conclusions: Cancer surveillance efforts in sub-populations defined by race, ethnicity, geography, socioeconomic status, or similar factors are necessary for identifying disparities and monitoring progress toward reducing them. In the absence of routine monitoring of cancer survival and cancer survival disparities in these populations, estimates generated by different methods will inevitably be compared over time and across populations. In this study, we demonstrate that caution should be exercised in making these comparisons, particularly in interpreting cause-specific survival rates with an unknown or narrow definition of cancer death and in estimates of breast and prostate cancer survival and/or disparities in survival generated by different methods.

Objectives: To assess the scope of the published literature on the consequences of maternal morbidity on health-related functioning at the global level and identify key substantive findings as well as research and methodological gaps., Methods: We searched for articles published between 2005 and 2014 using Medline, Embase, Popline, CINAHL Plus and three regional bibliographic databases in January 2015., Design: Systematic scoping review PRIMARY OUTCOME: Health-related functioning RESULTS: After screening 17 706 studies, 136 articles were identified for inclusion. While a substantial number of papers have documented mostly negative effects of morbidity on health-related functioning and well-being, the body of evidence is not spread evenly across conditions, domains or geographical regions. Over 60% of the studies focus on indirect conditions such as depression, diabetes and incontinence. Health-related functioning is often assessed by instruments designed for the general population including the 36-item Short Form or disease-specific tools. The functioning domains most frequently documented are physical and mental; studies that examined physical, mental, social, economic and specifically focused on marital, maternal and sexual functioning are rare. Only 16 studies were conducted in Africa., Conclusions: Many assessments have not been comprehensive and have paid little attention to important functioning domains for pregnant and postpartum women. The development of a comprehensive instrument specific to maternal health would greatly advance our understanding of burden of ill health associated with maternal morbidity and help set priorities. The lack of attention to consequences on functioning associated with the main direct obstetric complications is of particular concern., Review Registration: CRD42015017774., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The Vadinienses were a Cantabrian people who lived between the first and fourth centuries in the north of the Iberian Peninsula, northeast of the present province of León and the corresponding part of the current territory of Asturias. In this paper we study the possible causes of illness and death of the Vadinienses represented in their gravestones. The analysis of Vadinienses epitaphs shows that two-thirds of the deaths occurred in people between the ages of 20-30, a finding that is not interpreted as representative of the usual age of death at that time. The most likely causes of death are infections and violent deaths in sports competitions or work accidents. Analyzing females independently, almost half of the deceased were under the age of 20, being the main possibilities the deaths related to pregnancy and childbirth at very early ages.

Background: Virtually all low- and middle-income countries are undergoing an epidemiological transition whose progression is more varied than experienced in high-income countries. Observed changes in mortality and disease patterns reveal that the transition in most low- and middle-income countries is characterized by reversals, partial changes and the simultaneous occurrence of different types of diseases of varying magnitude. Localized characterization of this shifting burden, frequently lacking, is essential to guide decentralised health and social systems on the effective targeting of limited resources. Based on a rigorous compilation of mortality data over two decades, this paper provides a comprehensive assessment of the epidemiological transition in a rural South African population., Methods: We estimate overall and cause-specific hazards of death as functions of sex, age and time period from mortality data from the Agincourt Health and socio-Demographic Surveillance System and conduct statistical tests of changes and differentials to assess the progression of the epidemiological transition over the period 1993-2013., Results: From the early 1990s until 2007 the population experienced a reversal in its epidemiological transition, driven mostly by increased HIV/AIDS and TB related mortality. In recent years, the transition is following a positive trajectory as a result of declining HIV/AIDS and TB related mortality. However, in most age groups the cause of death distribution is yet to reach the levels it occupied in the early 1990s. The transition is also characterized by persistent gender differences with more rapid positive progression in females than males., Conclusions: This typical rural South African population is experiencing a protracted epidemiological transition. The intersection and interaction of HIV/AIDS and antiretroviral treatment, non-communicable disease risk factors and complex social and behavioral changes will impact on continued progress in reducing preventable mortality and improving health across the life course. Integrated healthcare planning and program delivery is required to improve access and adherence for HIV and non-communicable disease treatment. These findings from a local, rural setting over an extended period contribute to the evidence needed to inform further refinement and advancement of epidemiological transition theory.

Little is known about specific modes of death in patients with heart failure with preserved ejection fraction (HFpEF). Herein, the authors critically appraise the current state of data and offer potential future directions. They conducted a systematic review of 1,608 published HFpEF papers from January 1, 1985, to December 31, 2015, which yielded 8 randomized clinical trials and 24 epidemiological studies with mode-of-death data. Noncardiovascular modes of death represent an important competing risk in HFpEF. Although sudden death accounted for ∼25% to 30% of deaths in trials, its definition is nonspecific; it is unclear what proportion represents arrhythmic deaths. Moving forward, reporting and definitions of modes of death must be standardized and tailored to the HFpEF population. Broad-scale systematic autopsies and long-term rhythm monitoring may clarify the underlying pathology and mechanisms driving mortal events. There is an unmet need for a longitudinal multicenter, global registry of patients with HFpEF to map its natural history., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In Lao People's Democratic Republic (Lao PDR), the cause of death is not registered in death reports. As a result, the government cannot produce official reports that show mortality according to cause of death. This study aimed to report the underlying cause of death in a tertiary general hospital (Mittaphab Hospital) in Vientiane capital. Mittaphab hospital is a governmental teaching hospital with 300 beds for inpatient services specialized in orthopedics, neurology, and hemodialysis. Since a children hospital exists beside Mittaphab Hospital, severe pediatric cases are referred to the child hospital. HIV-positive cases and sputum positive tuberculosis are also transferred to the other specialized hospitals. All of the subjects in this study were patients who died in 2013-2015 at Mittaphab Hospital. Paper-based medical charts were examined by a medical doctor and staff from the medical records division. This chart review revealed that 1,509 patients (1,006 males and 503 females) died in this hospital during the study period. Of those, the number of patients aged <20 years and >80 years was small (6.2% and 7.7%, respectively). The most common underlying causes were injury (29.7%), cerebrovascular diseases (26.8%), renal disease (13.3%), infectious diseases (12.4%), and malignant neoplasm including brain tumor (4.8%). Among those aged 20-59 years, these percentages were 37.9%, 23.7%, 12.3%, 10.2%, and 5.0%, respectively. Although the patients visiting the hospital did not represent the whole population, the distribution of cause of death in the hospital was the only available information reported in Lao PDR.

Background: The European Randomised Study of Prostate Cancer Screening has shown a 21% relative reduction in prostate cancer mortality at 13 years. The causes of death can be misattributed, particularly in elderly men with multiple comorbidities, and therefore accurate assessment of the underlying cause of death is crucial for valid results. To address potential unreliability of end-point assessment, and its possible impact on mortality results, we analysed the study outcome adjudication data in six countries., Methods: Latent class statistical models were formulated to compare the accuracy of individual adjudicators, and to assess whether accuracy differed between the trial arms. We used the model to assess whether correcting for adjudication inaccuracies might modify the study results., Results: There was some heterogeneity in adjudication accuracy of causes of death, but no consistent differential accuracy by trial arm. Correcting the estimated screening effect for misclassification did not alter the estimated mortality effect of screening., Conclusions: Our findings were consistent with earlier reports on the European screening trial. Observer variation, while demonstrably present, is unlikely to have materially biased the main study results. A bias in assigning causes of death that might have explained the mortality reduction by screening can be effectively ruled out., Competing Interests: Dr Sigrid Carlsson's work on this paper was supported in part by a Cancer Center Support Grant from the National Cancer Institute made to Memorial Sloane Kettering Cancer Center (P30 CA008748). Dr Carlsson is also supported by a post-doctoral grant from AFA Insurance. Dr Carlsson has received travel reimbursement from Sanofi-aventis. No other authors have any conflicts of interest.

Background: Reliable and representative cause of death (COD) statistics are essential to inform public health policy, respond to emerging health needs, and document progress towards Sustainable Development Goals. However, less than one-third of deaths worldwide are assigned a cause. Civil registration and vital statistics (CRVS) systems in low- and lower-middle-income countries are failing to provide timely, complete and accurate vital statistics, and it will still be some time before they can provide physician-certified COD for every death. Proposals: Verbal autopsy (VA) is a method to ascertain the probable COD and, although imperfect, it is the best alternative in the absence of medical certification. There is extensive experience with VA in research settings but only a few examples of its use on a large scale. Data collection using electronic questionnaires on mobile devices and computer algorithms to analyse responses and estimate probable COD have increased the potential for VA to be routinely applied in CRVS systems. However, a number of CRVS and health system integration issues should be considered in planning, piloting and implementing a system-wide intervention such as VA. These include addressing the multiplicity of stakeholders and sub-systems involved, integration with existing CRVS work processes and information flows, linking VA results to civil registration records, information technology requirements and data quality assurance., Conclusions: Integrating VA within CRVS systems is not simply a technical undertaking. It will have profound system-wide effects that should be carefully considered when planning for an effective implementation. This paper identifies and discusses the major system-level issues and emerging practices, provides a planning checklist of system-level considerations and proposes an overview for how VA can be integrated into routine CRVS systems.

The Millennium Development Goals (MDGs) triggered increased demand for data on child and maternal mortality for monitoring progress. With the advent of the Sustainable Development Goals (SDGs) and growing evidence of an epidemiological transition towards non-communicable diseases, policy makers need data on mortality and disease trends and distribution to inform effective policies and support monitoring progress. Where there are limited capacities to produce national health estimates (NHEs), global health estimates (GHEs) can fill gaps for global monitoring and comparisons. This paper draws lessons learned from Thailand's burden of disease study (BOD) on capacity development for NHEs, and discusses the contributions and limitation of GHEs in informing policies at country level. Through training and technical support by external partners, capacities are gradually strengthened and institutionalized to enable regular updates of BOD at national and sub-national levels. Initially, the quality of cause of death reporting in the death certificates was inadequate, especially for deaths occurring in the community. Verbal autopsies were conducted, using domestic resources, to determine probable causes of deaths occurring in the community. This helped improve the estimation of years of life lost. Since the achievement of universal health coverage in 2002, the quality of clinical data on morbidities has also considerably improved. There are significant discrepancies between the 2010 Global Burden of Diseases (GBD) estimates for Thailand and the 1999 nationally generated BOD, especially for years of life lost due to HIV/AIDS, and the ranking of priority diseases. National ownership of NHEs and effective interfaces between researchers and decision makers contribute to enhanced country policy responses, while sub-national data are intended to be used by various sub-national-level partners. Though GHEs contribute to benchmarking country achievement compared with global health commitments, they may hamper development of NHE capacities. GHEs should encourage and support countries to improve their data systems and develop a data infrastructure that supports the production of empirical data needed to underpin estimation efforts.

Background: We believe that it is important that governments understand the reliability of the mortality data which they have at their disposable to guide policy debates. In many instances, verbal autopsy (VA) will be the only source of mortality data for populations, yet little is known about how the accuracy of VA diagnoses is affected by the reliability of the symptom responses. We previously described the effect of the duration of time between death and VA administration on VA validity. In this paper, using the same dataset, we assess the relationship between the reliability and completeness of symptom responses and the reliability and accuracy of cause of death (COD) prediction., Methods: The study was based on VAs in the Population Health Metrics Research Consortium (PHMRC) VA Validation Dataset from study sites in Bohol and Manila, Philippines and Andhra Pradesh, India. The initial interview was repeated within 3-52 months of death. Question responses were assessed for reliability and completeness between the two survey rounds. COD was predicted by Tariff Method., Results: A sample of 4226 VAs was collected for 2113 decedents, including 1394 adults, 349 children, and 370 neonates. Mean question reliability was unexpectedly low ( kappa  = 0.447): 42.5 % of responses positive at the first interview were negative at the second, and 47.9 % of responses positive at the second had been negative at the first. Question reliability was greater for the short form of the PHMRC instrument ( kappa  = 0.497) and when analyzed at the level of the individual decedent ( kappa  = 0.610). Reliability at the level of the individual decedent was associated with COD predictive reliability and predictive accuracy., Conclusions: Families give coherent accounts of events leading to death but the details vary from interview to interview for the same case. Accounts are accurate but inconsistent; different subsets of symptoms are identified on each occasion. However, there are sufficient accurate and consistent subsets of symptoms to enable the Tariff Method to assign a COD. Questions which contributed most to COD prediction were also the most reliable and consistent across repeat interviews; these have been included in the short form VA questionnaire. Accuracy and reliability of diagnosis for an individual death depend on the quality of interview. This has considerable implications for the progressive roll out of VAs into civil registration and vital statistics (CRVS) systems.

Context/problem: Comparative analysis of relative and absolute mortality differentials between socioeconomic groups are now available. These show consistently increasing relative increases in mortality differentials but complex trends in absolute mortality differentials., Objective: This paper provides an analysis of relative and absolute trends in mortality by cause of death and socioeconomic group (SEG) from 1984 to 2008 among men and active women aged 30-64 years in Ireland and compares these results with recent European and US studies to give an overview of trends., Methods: This paper uses mortality data from the Irish Central Statistics Office from 1984 to 2008 to calculate standardized death rates by age, sex, socioeconomic status and cause of death showing trends in SEG inequalities in mortality in Ireland. These show which specific causes of death are driving all-cause mortality trends., Results: SEG differentials in all-cause mortality among men and women have been increasing since the 1980s. Some of this increase reflects larger falls in cardiovascular causes among advantaged groups, but the trend is largely accounted for by increasing inequalities in mortality in digestive, neoplasm and external causes of deaths., Conclusions: These findings are in line with international findings that show that socioeconomic differentials in digestive, neoplasm and external cause deaths are driving general socioeconomic differentials in all-cause mortality. External cause deaths may have been influenced by levels of economic activity, particularly in construction, during the economic boom among manual workers. Furthermore, deaths from digestive diseases during the 1990s and 2000s may well be the result of increases in liver disease associated with excessive alcohol consumption., (© The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Understanding the determinants of preventable deaths of children under the age of five is important for accelerated annual declines - even as countries achieve the UN's Millennium Development Goals and the target date of 2015 has been reached. While research has documented the extent and nature of the overall rapid decline in child mortality in Niger, there is less clear evidence to provide insight into the contributors to such deaths. This issue is the central focus of this paper., Methods: We analyzed a nationally representative cross-sectional sample of 620 child deaths from the 2012 Niger Verbal Autopsy/Social Autopsy (VASA) Survey. We conducted a descriptive analysis of the data on preventive and curative care, guided by the coverage of proven indicators along the continuum of well child care and illness recognition and care-seeking for child illnesses encompassed by the BASICS/CDC Pathway to Survival model., Results: Six hundred twenty deaths of children (1-59 months of age) were confirmed from the VASA survey. The majority of these children lived in households with precarious socio-economic conditions. Among the 414 children whose fatal illnesses began at age 0-23 months, just 24.4% were appropriately fed. About 24% of children aged 12-59 months were fully immunized. Of 601 children tracked through the Pathway to Survival, 62.4% could reach the first health care provider after about 67 minutes travel time. Of the 306 children who left the first health care provider alive, 161 (52.6%) were not referred for further care nor received any home care recommendations, and just 19% were referred to a second provider. About 113 of the caregivers reported cost (35%), distance (35%) and lack of transport (30%) as constraints to care-seeking at a health facility., Conclusion: Despite Niger's recent major achievements in reducing child mortality, the following determinants are crucial to continue building on the gains the country has made: improved socio-economic state of the poor in the country, investment in women's education, adoption of the a law to prevent marriage of young girls before 18 years of age, and implementation of health programs that encourage breastfeeding and complementary feeding, immunization, illness recognition, prompt and appropriate care-seeking, and improved referral rates.

In China, sample-based mortality surveillance systems, such as the Chinese Center for Disease Control and Prevention's disease surveillance points system and the Ministry of Health's vital registration system, have been used for decades to provide nationally representative data on health status for health-care decision-making and performance evaluation. However, neither system provided representative mortality and cause-of-death data at the provincial level to inform regional health service needs and policy priorities. Moreover, the systems overlapped to a considerable extent, thereby entailing a duplication of effort. In 2013, the Chinese Government combined these two systems into an integrated national mortality surveillance system to provide a provincially representative picture of total and cause-specific mortality and to accelerate the development of a comprehensive vital registration and mortality surveillance system for the whole country. This new system increased the surveillance population from 6 to 24% of the Chinese population. The number of surveillance points, each of which covered a district or county, increased from 161 to 605. To ensure representativeness at the provincial level, the 605 surveillance points were selected to cover China's 31 provinces using an iterative method involving multistage stratification that took into account the sociodemographic characteristics of the population. This paper describes the development and operation of the new national mortality surveillance system, which is expected to yield representative provincial estimates of mortality in China for the first time.

Purpose: This paper describes SalHUD, a prototype web-based application for visualizing health data from Puerto Rico. Our initial focus was to provide interactive maps displaying years of potential life lost (YPLL)., Methods: The public-use mortality file for year 2008 was downloaded from the Puerto Rico Institute of Statistics website. Data was processed with R, Python and EpiInfo to calculate years of potential life lost for the leading causes of death on each of the 78 municipalities in the island. Death records were classified according to ICD-10 codes. YPLL for each municipality was integrated into AtlasPR, a D3 Javascript map library. Additional Javascript, HTML and CSS programing was required to display maps as a web-based interface., Results: YPLL for all municipalities are displayed on a map of Puerto Rico for each of the ten leading causes of death and for all causes combined, so users may dynamically explore the impact of premature mortality., Discussion: This work is the first step in providing the general public in Puerto Rico with user-friendly, interactive, visual access to public health data that is usually published in numerical, text-based media.