Cardiovascular disease mortality based on verbal autopsy in low- and middle-income countries: a systematic review.

Objective: To conduct a systematic review of verbal autopsy studies in low- and middle-income countries to estimate the fraction of deaths due to cardiovascular disease. Method: We searched MEDLINE®, Embase® and Scopus databases for verbal autopsy studies in low- and middle-income countries that reported deaths from cardiovascular disease. Two reviewers screened the studies, extracted data and assessed study quality. We calculated cause-specific mortality fractions for cardiovascular disease for each study, both overall and according to age, sex, geographical location and type of cardiovascular disease. Findings: We identified 42 studies for inclusion in the review. Overall, the cardiovascular disease cause-specific mortality fractions for people aged 15 years and above was 22.9%. This fraction was generally higher for males (24.7%) than females (20.9%), but the pattern varied across World Health Organization regions. The highest cardiovascular disease mortality fraction was reported in the Western Pacific Region (26.3%), followed by the South-East Asia Region (24.1%) and the African Region (12.7%). The cardiovascular disease mortality fraction was higher in urban than rural populations in all regions, except the South-East Asia Region. The mortality fraction for ischaemic heart disease (12.3%) was higher than that for stroke (8.7%). Overall, 69.4% of cardiovascular disease deaths were reported in people aged 65 years and above. Conclusion: The burden of cardiovascular disease deaths outside health-care settings in low- and middle-income countries is substantial. Increasing coverage of verbal autopsies in these countries could help fill gaps in cardiovascular disease mortality data and improve monitoring of national, regional and global health goals.

Validation studies of verbal autopsy methods: a systematic review.

BACKGROUND: Verbal autopsy (VA) has emerged as an increasingly popular technique to assign cause of death in parts of the world where the majority of deaths occur without proper medical certification. The purpose of this study was to examine the key characteristics of studies that have attempted to validate VA cause of death against an established cause of death. METHODS: A systematic review was conducted by searching the MEDLINE, EMBASE, Cochrane-library, and Scopus electronic databases. Included studies contained 1) a VA component, 2) a validation component, and 3) original analysis or re-analysis. Characteristics of VA studies were extracted. A total of 527 studies were assessed, and 481 studies screened to give 66 studies selected for data extraction. RESULTS: Sixty-six studies were included from multiple countries. Ten studies used an existing database. Sixteen studies used the World Health Organization VA questionnaire and 5 studies used the Population Health Metrics Research Consortium VA questionnaire. Physician certification was used in 36 studies and computer coded methods were used in 14 studies. Thirty-seven studies used high level comparator data with detailed laboratory investigations. CONCLUSION: Most studies found VA to be an effective cause of death assignment method and compared VA cause of death to a high-quality established cause of death. Nonetheless, there were inconsistencies in the methodologies of the validation studies, and many used poor quality comparison cause of death data. Future VA validation studies should adhere to consistent methodological criteria so that policymakers can easily interpret the findings to select the most appropriate VA method. PROSPERO REGISTRATION: CRD42020186886.

Monitoring progress in reducing maternal mortality using verbal autopsy methods in vital registration systems: what can we conclude about specific causes of maternal death?

Reducing maternal mortality is a key focus of development strategies and one of the indicators used to measure progress towards achieving the Sustainable Development Goals. In the absence of medical certification of the cause of deaths that occur in the community, verbal autopsy (VA) methods are the only available means to assess levels and trends of maternal deaths that occur outside health facilities. The 2016 World Health Organization VA Instrument facilitates the identification of eight specific causes of maternal death, yet maternal deaths are often unsupervised, leading to sparse and generally poor symptom reporting to inform a reliable diagnosis using VAs. There is little research evidence to support the reliable identification of specific causes of maternal death in the context of routine VAs. We recommend that routine VAs are only used to capture the event of a maternal death and that more detailed follow-up interviews are used to identify the specific causes.

Improving coverage of civil registration and vital statistics, Bangladesh.

PROBLEM: Bangladesh has no national system for registering deaths and determining their causes. As a result, policy-makers lack reliable and complete data to inform public health decisions. APPROACH: In 2016, the government of Bangladesh introduced a pilot project to strengthen the civil registration and vital statistics system and generate cause of death data in Kaliganj Upazila. Community-based health workers were trained to notify births and deaths to the civil registrar, and to conduct verbal autopsy interviews with family members of a deceased person. International experts in cause-of-death certification and coding trained master trainers on how to complete the international medical certificate of cause of death. These trainers then trained physicians and coders. LOCAL SETTING: Kaliganj Upazila has an estimated population of 304 600, and 5600 births and 1550 deaths annually. Health assistants and family welfare assistants make regular visits to households to track certain health outcomes. RELEVANT CHANGES: Following the start of the project in 2016, the number of births registered within 45 days rose from 873 to 4630 in 2018. The number of deaths registered within 45 days increased from 458 to 1404. During this period, health assistants conducted 7837 verbal autopsy interviews. Between January 2017 and December 2018, 105 master trainers and more than 7000 physicians were trained to complete the international medical certificate of cause of death and they completed more than 12 000 certificates. LESSONS LEARNT: Training community-based health workers, physicians and coders were successful approaches to improve death registration completeness and availability of cause-of-death data.

Robustness of the Tariff method for diagnosing verbal autopsies: impact of additional site data on the relationship between symptom and cause.

BACKGROUND: Verbal autopsy (VA) is increasingly being considered as a cost-effective method to improve cause of death information in countries with low quality vital registration. VA algorithms that use empirical data have an advantage over expert derived algorithms in that they use responses to the VA instrument as a reference instead of physician opinion. It is unclear how stable these data driven algorithms, such as the Tariff 2.0 method, are to cultural and epidemiological variations in populations where they might be employed. METHODS: VAs were conducted in three sites as part of the Improving Methods to Measure Comparable Mortality by Cause (IMMCMC) study: Bohol, Philippines; Chandpur and Comila Districts, Bangladesh; and Central and Eastern Highlands Provinces, Papua New Guinea. Similar diagnostic criteria and cause lists as the Population Health Metrics Research Consortium (PHMRC) study were used to identify gold standard (GS) deaths. We assessed changes in Tariffs by examining the proportion of Tariffs that changed significantly after the addition of the IMMCMC dataset to the PHMRC dataset. RESULTS: The IMMCMC study added 3512 deaths to the GS VA database (2491 adults, 320 children, and 701 neonates). Chance-corrected cause specific mortality fractions for Tariff improved with the addition of the IMMCMC dataset for adults (+ 5.0%), children (+ 5.8%), and neonates (+ 1.5%). 97.2% of Tariffs did not change significantly after the addition of the IMMCMC dataset. CONCLUSIONS: Tariffs generally remained consistent after adding the IMMCMC dataset. Population level performance of the Tariff method for diagnosing VAs improved marginally for all age groups in the combined dataset. These findings suggest that cause-symptom relationships of Tariff 2.0 might well be robust across different population settings in developing countries. Increasing the total number of GS deaths improves the validity of Tariff and provides a foundation for the validation of other empirical algorithms.

Comparing tariff and medical assistant assigned causes of death from verbal autopsy interviews in Matlab, Bangladesh: implications for a health and demographic surveillance system.

BACKGROUND: Deaths in developing countries often occur outside health facilities, making it extremely difficult to gather reliable cause of death (COD) information. Automated COD assignment using a verbal autopsy instrument (VAI) has been proposed as a reliable and cost-effective alternative to traditional physician-certified verbal autopsy, but its performance is still being evaluated. The purpose of this study was to compare the similarity of diagnosis by Medical Assistants (MA) in the Matlab Health and Demographic Surveillance System (HDSS) with the SmartVA Analyze 1.2 (Tariff 2.0) diagnosis. METHODS: This study took place between January 2011 and April 2014 in Matlab, Bangladesh. MA with 3 years of medical training assigned COD to Matlab residents by reviewing the information collected using the Population Health Metrics Research Consortium (PHMRC) long-form VAI. Smart VA Analyze 1.2 automatically assigned COD using the same questionnaire. COD agreement and cause-specific mortality fractions (CSMFs) were compared for MA and Tariff. RESULTS: Of the 4969 verbal autopsy cases reviewed, 4328 were adults, 296 were children, and 345 were neonates. Cohen's kappa was 0.38 (0.36, 0.40) for adults, 0.43 (0.38, 0.49) for children, and 0.27 (0.22, 0.33) for neonates. For adults, the top two COD for MA were stroke (29.6%) and ischemic heart diseases (IHD) (14.2%) and for Tariff these were stroke (32.0%) and IHD (14.0%). For children, the top two COD for MA were drowning (33.5%) and pneumonia (13.2%) and for Tariff these were also drowning (36.8%) and pneumonia (12.4%). For neonates, the top two COD for MA were birth asphyxia (41.2%) and meningitis/sepsis (22.3%) and for Tariff these were birth asphyxia (37.0%) and preterm delivery (30.9%). CONCLUSION: The CSMFs for Tariff and MA showed very close agreement across all age categories but some differences were observed for neonate preterm delivery and meningitis/sepsis. Given the known advantages of automated methods over physician certified verbal autopsy, the SmartVA software, incorporating the shortened VAI questionnaire and Tariff 2.0, could serve as a cost-effective alternative to Matlab MA to routinely collect and analyze verbal autopsy data in a HDSS to generate essential population level COD data for planning.

The quality of medical death certification of cause of death in hospitals in rural Bangladesh: impact of introducing the International Form of Medical Certificate of Cause of Death.

BACKGROUND: Accurate and timely data on cause of death are critically important for guiding health programs and policies. Deaths certified by doctors are implicitly considered to be reliable and accurate, yet the quality of information provided in the international Medical Certificate of Cause of Death (MCCD) usually varies according to the personnel involved in certification, the diagnostic capacity of the hospital, and the category of hospitals. There are no published studies that have analysed how certifying doctors in Bangladesh adhere to international rules when completing the MCCD or have assessed the quality of clinical record keeping. METHODS: The study took place between January 2011 and April 2014 in the Chandpur and Comilla districts of Bangladesh. We introduced the international MCCD to all study hospitals. Trained project physicians assigned an underlying cause of death, assessed the quality of the death certificate, and reported the degree of certainty of the medical records provided for a given cause. We examined the frequency of common errors in completing the MCCD, the leading causes of in-hospital deaths, and the degree of certainty in the cause of death data. RESULTS: The study included 4914 death certificates. 72.9% of medical records were of too poor quality to assign a cause of death, with little difference by age, hospital, and cause of death. 95.6% of death certificates did not indicate the time interval between onset and death, 31.6% required a change in sequence, 13.9% required to include a new diagnosis, 50.7% used abbreviations, 41.5% used multiple causes per line, and 33.2% used an ill-defined condition as the underlying cause of death. 99.1% of death certificates had at least one error. The leading cause of death among adults was stroke (15.8%), among children was pneumonia (31.7%), and among neonates was birth asphyxia (52.8%). CONCLUSION: Physicians in Bangladeshi hospitals had difficulties in completing the MCCD correctly. Physicians routinely made errors in death certification practices and medical record quality was poor. There is an urgent need to improve death certification practices and the quality of hospital data in Bangladesh if these data are to be useful for policy.

Improving methods to measure comparable mortality cause (IMMCMC) gold standard verbal autopsy dataset.

OBJECTIVES: Gold standard cause of death data is critically important to improve verbal autopsy (VA) methods in diagnosing cause of death where civil and vital registration systems are inadequate or poor. As part of a three-country research study-Improving Methods to Measure Comparable Mortality by Cause (IMMCMC) study-data were collected on clinicopathological criteria-based gold standard cause of death from hospital record reviews with matched VAs. The purpose of this data note is to make accessible a de-identified format of these gold standard VAs for interested researchers to improve the diagnostic accuracy of VA methods. DATA DESCRIPTION: The study was conducted between 2011 and 2014 in the Philippines, Bangladesh, and Papua New Guinea. Gold standard diagnoses of underlying causes of death for deaths occurring in hospital were matched to VAs conducted using a standardized VA questionnaire developed by the Population Health Metrics Consortium. 3512 deaths were collected in total, comprised of 2491 adults (12 years and older), 320 children (28 days to 12 years), and 702 neonates (0-27 days).

Diversity of epidemiological transition in the Pacific: Findings from the application of verbal autopsy in Papua New Guinea and the Solomon Islands.

BACKGROUND: Cause of death data are essential for rational health planning yet are not routinely available in Papua New Guinea (PNG) and Solomon Islands. Indirect estimation of cause of death patterns suggests these populations are epidemiologically similar, but such assessments are not based on direct evidence. METHODS: Verbal autopsy (VA) interviews were conducted at three sites in PNG and nationwide in Solomon Islands. Training courses were also facilitated to improve data from medical certificates of cause of death (MCCODs) in both countries. Data were categorised into broad groups of endemic and emerging conditions to aid assessment of the epidemiological transition. FINDINGS: Between 2017 and 2020, VAs were collected for 1,814 adult deaths in PNG and 819 adult deaths in Solomon Islands. MCCODs were analysed for 662 deaths in PNG and 1,408 deaths in Solomon Islands. The VA data suggest lower NCD mortality (48.8% versus 70.3%); higher infectious mortality (27.0% versus 18.3%) and higher injury mortality (24.5% versus 11.4%) in PNG compared to Solomon Islands. Higher infectious mortality in PNG was evident for both endemic and emerging infections. Higher NCD mortality in Solomon Islands reflected much higher emerging NCDs (43.6% vs 21.4% in PNG). A similar pattern was evident from the MCCOD data. INTERPRETATION: The cause of death patterns suggested by VA and MCCOD indicate that PNG is earlier in its epidemiological transition than Solomon Islands, with relatively higher infectious mortality and lower NCD mortality. Injury mortality was also particularly high in PNG.This study was funded by Bloomberg Philanthropies.

Causes of neonatal deaths in a rural subdistrict of Bangladesh: implications for intervention.

The study assessed the timing and causes of neonatal deaths in a rural area of Bangladesh. A population-based demographic surveillance system, run by the International Centre for Diarrhoeal Disease Research, Bangladesh, recorded livebirths and neonatal deaths during 2003-2004 among a population of 224,000 living in Matlab, a rural subdistrict of eastern Bangladesh. Deaths were investigated using the INDEPTH/ World Health Organization verbal autopsy. Three physicians independently reviewed data from verbal autopsy interview to assign the cause of death. There were 11,291 livebirths and 365 neonatal deaths during the two-year period. The neonatal mortality rate was 32.3 per 1,000 livebirths. Thirty-seven percent of the neonatal deaths occurred within 24 hours, 76% within 0-3 days, 84% within 0-7 days, and the remaining 16% within 8-28 days. Birth asphyxia (45%), prematurity/low birthweight (15%), sepsis/meningitis (12%), respiratory distress syndrome (7%), and pneumonia (6%) were the major direct causes of death. Birth asphyxia (52.8%) was the single largest category of cause of death in the early neonatal period while meningitis/sepsis (48.3%) was the single largest category in the late neonatal period. The high proportion of deaths during the early neonatal period and the far-higher proportion of neonatal deaths caused by birth asphyxia compared to the global average (45% vs 23-29%) indicate the lack of skilled birth attendance and newborn care for the large majority of births that occur in the home in rural Bangladesh. Resuscitation of newborns and management of low-birthweight/premature babies need to be at the core of neonatal interventional packages in rural Bangladesh.

Causes of death of adults and elderly and healthcare-seeking before death in rural Bangladesh.

The health system of a country needs to be adjusted to patterns of morbidity and mortality to mitigate the income-erosion consequences of prolonged ill-health and premature death of adults. Population-based data on mortality by cause are a key to modifying the health system. However, these data are scarce, particularly for rural populations in developing countries. The objectives of this study were to determine the burdens of health due to major causes of death obtained from verbal autopsy of adults and the elderly and their healthcare-seeking patterns before death in a well-defined rural population. There were 2,397 deaths--613 were among adults aged 15-59 years and 1,784 among the elderly aged 60+ years--during 2003-2004 in the health and demographic surveillance area in Matlab, a rural area of Bangladesh. Trained interviewers interviewed close relatives of the deceased using a structured verbal-autopsy questionnaire to record signs and symptoms of diseases/conditions that led to death and medical consultations before death. Two physicians independently assigned the underlying causes of deaths with disagreements resolved by a third physician. The physicians were able to assign a specific cause in 91% of the cases. Rates and proportions were used for estimating the burden of diseases by cause. Of all deaths of adults and the elderly, communicable diseases accounted for 18% and non-communicable diseases for 66%, with the proportion of non-communicable diseases increasing with age. Leading non-communicable diseases were diseases of the circulatory system (35%), neoplasms (11%), diseases of the respiratory system (10%), diseases of the digestive system (6%), and endocrine and metabolic disorders (6%), all of which accounted for 68% of deaths. Injury and other external causes accounted for another 5% of the deaths. During terminal illness, 31% of the adults and 25% of the elderly sought treatment from medical doctors, and 14% of the adults and 4% of the elderly died in healthcare facilities. The findings suggest that the health managers and policy-makers of Bangladesh should recognize the importance of prevention and management of chronic diseases and place it on the health agenda for rural people.

A population-based study of hospital admission incidence rate and bacterial aetiology of acute lower respiratory infections in children aged less than five years in Bangladesh.

The research was carried out to study the rate of population-based hospital admissions due to acute lower respiratory infections (ALRIs) and bacterial aetiology of ALRIs in children aged less than five years in Bangladesh. A cohort of children aged less than five years in a rural surveillance population in Matlab, Bangladesh, was studied for two years. Cases were children admitted to the Matlab Hospital of ICDDR,B with a diagnosis of severe ALRIs. Bacterial aetiology was determined by blood culture. Antimicrobial resistance patterns of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Spn) isolates were determined using the disc-diffusion method. In total, 18,983 children aged less than five years contributed to 24,902 child-years of observation (CYO). The incidence of ALRI-related hospital admissions was 50.2 per 1,000 CYO. The incidences of ALRI were 67% higher in males than in females and were higher in children aged less than two years than in older children. About 34% of the cases received antibiotics prior to hospitalization. Of 840 blood samples cultured, 39.4% grew a bacterial isolate; 11.3% were potential respiratory pathogens, and the rest were considered contaminants. The predominant isolates were Staphylococcus aureus (4.5%). Hib (0.4%) and Spn (0.8%) were rarely isolated; however, resistance of both these pathogens to trimethoprim-sulphamethoxazole was common. The rate of ALRI-related hospitalizations was high. The high rate of contamination, coupled with high background antibiotic use, might have contributed to an underestimation of the burden of Hib and Spn. Future studies should use more sensitive methods and more systematically look for resistance patterns of other pathogens in addition to Hib and Spn.

Weekly iron supplementation does not block increases in serum zinc due to weekly zinc supplementation in Bangladeshi infants.

Because infants and young children in many developing countries are deficient in both iron and zinc, and zinc can affect iron metabolism, evaluation of optimum strategies to simultaneously supplement iron and zinc is an important public health priority. This study evaluated the efficacy of weekly supplementation of iron or zinc or both on iron, zinc, and copper status in Bangladeshi infants. In a double-blind, randomized, controlled community trial, 6-mo-old infants were assigned to receive weekly supplements of 1 mg riboflavin (control, n = 82) or 1 mg riboflavin + 20 mg iron (n = 83), 20 mg zinc (n = 83), or both (n = 85) for 6 mo. Hemoglobin, serum ferritin, transferrin receptor, zinc, and copper concentrations were measured at baseline and at the end of intervention. Serum Zn increased in both groups receiving zinc; the increase was greatest among children with low baseline serum zinc concentration. Iron status indicators did not differ among the groups before or after 6 mo of supplementation. Supplementation with either zinc or iron decreased serum copper after 6 mo. Joint supplementation did not alter the individual effects of iron or zinc supplementation in these Bangladeshi children. However, the dosing regimen may not have been adequate to achieve the desired biochemical effects.