Estimating causes of out-of-hospital deaths in China: application of SmartVA methods.

BACKGROUND: Most deaths in China occur at home, making it difficult to collect reliable cause of death (CoD) information. Verbal autopsy (VA) was applied using the SmartVA tool to a sample of home deaths in China to explore its feasibility as a means of improving the quality of CoD data. METHODS: The study was carried out in 22 districts in 9 provinces, located in north-east, central, and western areas of China during 2017 and 2018. Trained interviewers selected suitable respondents in each household to collect information using the Population Health Metrics Research Consortium (PHMRC) shortened and validated electronic VA questionnaire on tablets. The CoD was diagnosed from the interview data using the SmartVA-Analyze 2.0 software (Tariff 2.0). RESULTS: Non-communicable diseases (NCDs) dominated the leading causes of death in all age groups and for both sexes. After redistribution of undetermined causes, stroke (24%), ischemic heart diseases (IHD) (21%), chronic respiratory diseases (11%), and lung cancer (6%) were the leading causes of death. The cause fractions for level-one cause categories and ranking of specific causes were similar between SmartVA and results from the Global Burden of Disease (GBD) study. CONCLUSION: Evidence from this large pilot study suggests that SmartVA is a feasible and plausible tool and could be a valuable tool to improve the quality and standardization of CoD information across China.

Improving medical certification of cause of death: effective strategies and approaches based on experiences from the Data for Health Initiative.

BACKGROUND: Accurate and timely cause of death (COD) data are essential for informed public health policymaking. Medical certification of COD generally provides the majority of COD data in a population and is an essential component of civil registration and vital statistics (CRVS) systems. Accurate completion of the medical certificate of cause of death (MCCOD) should be a relatively straightforward procedure for physicians, but mistakes are common. Here, we present three training strategies implemented in five countries supported by the Bloomberg Philanthropies Data for Health (D4H) Initiative at the University of Melbourne (UoM) and evaluate the impact on the quality of certification. METHODS: The three training strategies evaluated were (1) training of trainers (TOT) in the Philippines, Myanmar, and Sri Lanka; (2) direct training of physicians by the UoM D4H in Papua New Guinea (PNG); and (3) the implementation of an online and basic training strategy in Peru. The evaluation involved an assessment of MCCODs before and after training using an assessment tool developed by the University of Melbourne. RESULTS: The TOT strategy led to reductions in incorrectly completed certificates of between 28% in Sri Lanka and 40% in the Philippines. Following direct training of physicians in PNG, the reduction in incorrectly completed certificates was 30%. In Peru, the reduction in incorrect certificates was 30% after implementation and training on an online system only and 43% after training on both the online system and basic medical certification principles. CONCLUSIONS: The results of this study indicate that a variety of training strategies can produce benefits in the quality of certification, but further improvements are possible. The experiences of D4H suggest several aspects of the strategies that should be further developed to improve outcomes, particularly key stakeholder engagement from early in the intervention and local committees to oversee activities and support an improved culture in hospitals to support better diagnostic skills and practices.

Automated verbal autopsy: from research to routine use in civil registration and vital statistics systems.

BACKGROUND: The majority of low- and middle-income countries (LMICs) do not have adequate civil registration and vital statistics (CRVS) systems to properly support health policy formulation. Verbal autopsy (VA), long used in research, can provide useful information on the cause of death (COD) in populations where physicians are not available to complete medical certificates of COD. Here, we report on the application of the SmartVA tool for the collection and analysis of data in several countries as part of routine CRVS activities. METHODS: Data from VA interviews conducted in 4 of 12 countries supported by the Bloomberg Philanthropies Data for Health (D4H) Initiative, and at different stages of health statistical development, were analysed and assessed for plausibility: Myanmar, Papua New Guinea (PNG), Bangladesh and the Philippines. Analyses by age- and cause-specific mortality fractions were compared to the Global Burden of Disease (GBD) study data by country. VA interviews were analysed using SmartVA-Analyze-automated software that was designed for use in CRVS systems. The method in the Philippines differed from the other sites in that the VA output was used as a decision support tool for health officers. RESULTS: Country strategies for VA implementation are described in detail. Comparisons between VA data and country GBD estimates by age and cause revealed generally similar patterns and distributions. The main discrepancy was higher infectious disease mortality and lower non-communicable disease mortality at the PNG VA sites, compared to the GBD country models, which critical appraisal suggests may highlight real differences rather than implausible VA results. CONCLUSION: Automated VA is the only feasible method for generating COD data for many populations. The results of implementation in four countries, reported here under the D4H Initiative, confirm that these methods are acceptable for wide-scale implementation and can produce reliable COD information on community deaths for which little was previously known.

Anti-Ascaris immunoglobulin E associated with bronchial hyper-reactivity in 9-year-old rural Bangladeshi children.

BACKGROUND: Studies have addressed the immunomodulatory effects of helminths and their protective effects upon asthma. However, anti-Ascaris IgE has been reported to be associated with an increased risk of asthma symptoms. We examined the association between serum levels of anti-Ascaris IgE and bronchial hyper-responsiveness (BHR) in children living in rural Bangladesh. METHODS: Serum anti-Ascaris IgE level was measured and the BHR test done in 158 children aged 9 years selected randomly from a general population of 1705 in the Matlab Health and Demographic Surveillance Area of the International Centre for Diarrhoeal Disease Research, Bangladesh. We investigated wheezing symptoms using a questionnaire from the International Study of Asthma and Allergies in Childhood. BHR tests were successfully done on 152 children (108 'current wheezers'; 44 'never-wheezers'). We examined the association between anti-Ascaris IgE level and wheezing and BHR using multiple logistic regression analyses. RESULTS: Of 108 current-wheezers, 59 were BHR-positive; of 44 never-wheezers, 32 were BHR-negative. Mean anti-Ascaris IgE levels were significantly higher (12.51 UA/ml; 95% confidence interval (CI), 9.21-17.00) in children with current wheezing with BHR-positive than in those of never-wheezers with BHR-negative (3.89; 2.65-5.70; t test, p < 0.001). A BHR-positive test was independently associated with anti-Ascaris IgE levels with an odds ratio (OR) = 7.30 [95% CI, 2.28-23.33], p = 0.001 when adjusted for total IgE, anti-Dermatophagoides pteronyssinus IgE, pneumonia history, parental asthma, Trichuris infection, forced expiratory volume in one second, eosinophilic leukocyte count, and sex. CONCLUSIONS: Anti-Ascaris IgE level is associated with an increased risk of BHR among 9-year-old rural Bangladeshi children.

A shortened verbal autopsy instrument for use in routine mortality surveillance systems.

BACKGROUND: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach. METHODS: We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates. RESULTS: The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively. CONCLUSIONS: We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand-held electronic tablets and analyzed using Tariff 2.0. The length of a VA questionnaire was shortened by almost 50% without a significant drop in performance. The shortened VAI developed reduces the burden of time and resources required for data collection and analysis of cause of death data in civil registration systems.

Improving performance of the Tariff Method for assigning causes of death to verbal autopsies.

BACKGROUND: Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method. METHODS: This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database. RESULTS: For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in analyses without HCE. CONCLUSIONS: Tariff 2.0 addresses the main shortcomings of the application of the Tariff Method to analyze data from VAs in community settings. It provides an estimation of COD from VAs with better performance at the individual and population level than the previous version of this method, and it is publicly available for use.

Care seeking for fatal illness episodes in neonates: a population-based study in rural Bangladesh.

BACKGROUND: Poor neonatal health is a major contributor to under-five mortality in developing countries. A major constraint to effective neonatal survival programme has been the lack of population level data in developing countries. This study investigated the consultation patterns of caregivers during neonatal fatal illness episodes in the rural Matlab sub-district of eastern Bangladesh. METHODS: Neonatal deaths were identified through a population-based demographic surveillance system in Matlab ICDDR,B maternal and child health (MCH) project area and an adjoining government service area. Trained project staff administered a structured questionnaire on care seeking to mothers at home who had experienced a neonatal death. Univariate, bivariate and binary multivariate logistic regressions were performed to describe care seeking during the fatal illness episode. RESULTS: Of the 365 deaths recorded during 2003 and 2004, 84% died in the early (0-7 days) neonatal period, with the remaining deaths occurring over the subsequent 8 to 28 days. The first resort of care by parents was a qualified doctor or paramedic in 37% of cases, followed by traditional and unqualified health care providers in 25%, while 38% sought no care. Thus, almost two thirds (63%) of neonates who died received only traditional and unqualified care or no care at all during their final illness episode. About 22% sought care from more than one provider, including 6% from 3 or more providers. Such plurality in care seeking was more likely among male infants, in the late neonatal period, and in the MCH project area. CONCLUSIONS: The high proportion of neonatal deaths that had received traditional care or no medical care in a rural area of Bangladesh highlights the need to develop community awareness about prompt medical care seeking for neonatal illnesses and to improve access to effective health care. Integration of traditional care providers into mainstream health programs should also be considered.

A comparison of physicians and medical assistants in interpreting verbal autopsy interviews for allocating cause of neonatal death in Matlab, Bangladesh: can medical assistants be considered an alternative to physicians?

OBJECTIVE: This study assessed the agreement between medical physicians in their interpretation of verbal autopsy (VA) interview data for identifying causes of neonatal deaths in rural Bangladesh. METHODS: The study was carried out in Matlab, a rural sub-district in eastern Bangladesh. Trained persons conducted the VA interview with the mother or another family member at the home of the deceased. Three physicians and a medical assistant independently reviewed the VA interviews to assign causes of death using the International Classification of Diseases - Tenth Revision (ICD-10) codes. A physician assigned cause was decided when at least two physicians agreed on a cause of death. Cause-specific mortality fraction (CSMF), kappa (k) statistic, sensitivity, specificity, and positive predictive values were applied to compare agreement between the reviewers. RESULTS: Of the 365 neonatal deaths reviewed, agreement on a direct cause of death was reached by at least two physicians in 339 (93%) of cases. Physician and medical assistant reviews of causes of death demonstrated the following levels of diagnostic agreement for the main causes of deaths: for birth asphyxia the sensitivity was 84%, specificity 93%, and kappa 0.77. For prematurity/low birth weight, the sensitivity, specificity, and kappa statistics were, respectively, 53%, 96%, and 0.55, for sepsis/meningitis they were 48%, 98%, and 0.53, and for pneumonia they were 75%, 94%, and 0.51. CONCLUSION: This study revealed a moderate to strong agreement between physician- assigned and medical assistant- assigned major causes of neonatal death. A well-trained medical assistant could be considered an alternative for assigning major causes of neonatal deaths in rural Bangladesh and in similar settings where physicians are scarce and their time costs more. A validation study with medically confirmed diagnosis will improve the performance of VA for assigning cause of neonatal death.

Single-dose ciprofloxacin versus 12-dose erythromycin for childhood cholera: a randomised controlled trial.

BACKGROUND: Single-dose ciprofloxacin is effective for the treatment of severe cholera in adults. We assessed whether single-dose ciprofloxacin would be as effective as 3-day, 12-dose erythromycin in achieving clinical cure in children with severe cholera. METHODS: We did a randomised, open label, controlled trial in children age 2-15 years with V cholerae O1 or O139 present in stool on dark-field microscopy. Children received either a single 20 mg/kg dose of ciprofloxacin (n=90) or 12.5 mg/kg of erythromycin (n=90) every 6 h for 3 days, and remained in hospital for 5 days. The primary outcome was clinical success of treatment, defined as cessation of watery stools within 48 h of start of drug treatment. Analysis was per protocol. This study is registered with the ClinicalTrials.gov Protocol Registration System at http://www.clinicaltrials.gov (registration number NCT 00142272) [corrected] FINDINGS: Of 180 children randomised 162 completed the study. Treatment was clinically successful in 60% (47/78) of children treated with ciprofloxacin and in 55% (46/84) of those treated with erythromycin (difference 5% [95% CI -10 to 21]). Children receiving ciprofloxacin vomited less often (58%vs 74%; difference 16% [2 to 30]), had fewer stools (15 vs 21; 6 [0 to 9]), and less stool volume (152 vs 196 mL/kg; 43 mL/kg [13 to 87]) than those receiving erythromycin. Bacteriological failure was more common in ciprofloxacin-treated patients (58%vs 30%; 28% [13 to 43]) than erythromycin-treated patients. INTERPRETATION: Single-dose ciprofloxacin achieves clinical outcomes similar to, or better than, those achieved with 12-dose erythromycin treatment in childhood cholera, but is less effective in eradicating V cholerae from stool.

Distribution of cause of death in rural Bangladesh during 2003-2010: evidence from two rural areas within Matlab Health and Demographic Surveillance site.

OBJECTIVE: This study used the InterVA-4 computerised model to assign probable cause of death (CoD) to verbal autopsies (VAs) generated from two rural areas, with a difference in health service provision, within the Matlab Health and Demographic Surveillance site (HDSS). This study aimed to compare CoD by gender, as well as discussing possible factors which could influence differences in the distribution of CoD between the two areas. DESIGN: Data for this study came from the Matlab the HDSS maintained by the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) since 1966. In late 1977, icddr,b divided HDSS and implemented a high-quality maternal, newborn and child health and family planning (MNCH-FP) services project in one half, called the icddr,b service area (SA), in addition to the usual public and private MNCH-FP services that serve the other half, called the government SA. HDSS field workers registered 12,144 deaths during 2003-2010, and trained interviewers obtained VA for 98.9% of them. The probabilistic model InterVA-4 probabilistic model (version 4.02) was used to derive probable CoD from VA symptoms. Cause-specific mortality rates and fractions were compared across gender and areas. Appropriate statistical tests were applied for significance testing. RESULTS: Mortality rates due to neonatal causes and communicable diseases (CDs) were lower in the icddr,b SA than in the government SA, where mortality rates due to non-communicable diseases (NCDs) were lower. Cause-specific mortality fractions (CSMFs) due to CDs (23.2% versus 18.8%) and neonatal causes (7.4% versus 6%) were higher in the government SA, whereas CSMFs due to NCDs were higher (58.2% versus 50.7%) in the icddr,b SA. The rank-order of CSMFs by age group showed marked variations, the largest category being acute respiratory infection/pneumonia in infancy, injury in 1-4 and 5-14 years, neoplasms in 15-49 and 50-64 years, and stroke in 65+ years. CONCLUSIONS: Automated InterVA-4 coding of VA to determine probable CoD revealed the difference in the structure of CoD between areas with prominence of NCDs in both areas. Such information can help local planning of health services for prevention and management of disease burden.

Causes of death in two rural demographic surveillance sites in Bangladesh, 2004-2010: automated coding of verbal autopsies using InterVA-4.

OBJECTIVE: Population-based information on causes of death (CoD) by age, sex, and area is critical for countries with limited resources to identify and address key public health issues. This study analysed the demographic surveillance and verbal autopsy (VA) data to estimate age- and sex-specific mortality rates and cause-specific mortality fractions in two well-defined rural populations within the demographic surveillance system in Abhoynagar and Mirsarai subdistricts, located in different climatic zones. DESIGN: During 2004-2010, the sample demographic surveillance system registered 1,384 deaths in Abhoynagar and 1,847 deaths in Mirsarai. Trained interviewers interviewed the main caretaker of the deceased with standard VA questionnaires to record signs and symptoms of diseases or conditions that led to death and health care experiences before death. The computer-automated InterVA-4 method was used to analyse VAs to determine probable CoD. RESULTS: Age- and sex-specific death rates revealed a higher neonatal mortality rate in Abhoynagar than Mirsarai, and death rates and sex ratios of male to female death rates were higher in the ages after infancy. Communicable diseases (CDs) accounted for 16.7% of all deaths in Abhoynagar and 21.2% in Mirsarai--the difference was due mostly to more deaths from acute respiratory infections, pneumonia, and tuberculosis in Mirsarai. Non-communicable diseases (NCDs) accounted for 56.2 and 55.3% of deaths in each subdistrict, respectively, with leading causes being stroke (16.5-19.3%), neoplasms (13.2% each), cardiac diseases (8.9-11.6%), chronic obstructive pulmonary diseases (5.1-6.3%), diseases of the digestive system (3.1-4.1%), and diabetes (2.8-3.5%), together accounting for 49.2-51.2% points of the NCD deaths in the two subdistricts. Injury and other external causes accounted for another 7.5-7.7% deaths, with self-harm being higher among females in Abhoynagar. CONCLUSIONS: The computer-automated coding of VA to determine CoD reconfirmed that NCDs were the leading CoD with some differences between the sites. Incorporating VA into the national sample vital registration system can help policy makers to identify the leading CoDs for public health planning.

Asthma in rural Bangladeshi children.

OBJECTIVE: Although bronchial asthma causes a great deal of morbidity among children in Bangladesh, few epidemiological studies addressed this problem. The study aims to determine the prevalence of wheezing and its association with environmental and host factors. METHODS: A total of 1587 children aged 60-71 mth living in 50 villages in rural Bangladesh at Matlab was studied. Trained field workers interviewed caretakers of these children to diagnose wheezing using an adopted questionnaire of the International Studies of Asthma and Allergies in Childhood (ISAAC). History of pneumonia among wheezing and non-wheezing children during their childhood was obtained from the surveillance records. RESULTS: The prevalence of wheezing in the last 12 mth prior to survey was 16.1% (95% CI: 14.3%, 18.0%), significantly higher among children who had attacks of pneumonia during their infancy compared to children who did not (23.0% vs 14.6%, p< 0.0001). Risk factors associated with wheezing were pneumonia at ages 0-12 m (OR= 1.50, 95% CI 1.08, 2.10) and 13-24 m (OR= 2.12, 1.46, 3.08), maternal asthma (OR=3.01, 95% CI 2.02, 4.47), paternal asthma (OR= 3.12, 95% CI 1.85, 5.26), maternal eczema (OR=1.81, 95% CI 1.14, 2.87) and family income 100 pounds US$ (OR for US$ 51-99= 1.63, 95% CI 1.05, 2.53; OR for US$ 50 pounds = 2.12, 95% CI 1.31, 3.44). CONCLUSION: Our results suggest that wheezing is a significant cause of morbidity among children in rural Bangladesh. Greater efforts are needed to prevent pneumonia among children during their infancy to reduce the chances of subsequent development of wheezing.