Assigning Cause Of Death Research Articles

Are multiple coders needed for cause of death assignment: results from telephonic verbal autopsy interviews conducted in 2021 in South Africa.

Verbal autopsy (VA) methods have emerged to estimate causes of death in populations lacking robust civil registration and vital statistics (CRVS) systems. Despite World Health Organization endorsement of routine VA use, cost and efficiency concerns persist. Telephonic verbal autopsies (teleVAs) can reduce cost. Physician coding offers a valuable approach, but the expertise required makes it resource-intensive, often involving multiple coders for consensus. To assess inter-coder agreement for cause of death (CoD) in South African teleVAs using Kappa statistics, evaluating if agreement surpasses a 0.8 cut-off (very high) potentially allowing single coders. A cross-sectional study employed telephonic VA interviews on non-facility deaths in Cape Town (December 2020-September 2021). Trained fieldworkers administered a standard VA questionnaire. Each case's VA responses were reviewed independently by two physicians, medically certifying the CoD. A panel was used to solve disagreements. Cohen's kappa-statistic (k-statistic) tested agreement levels. Decedents were aged between 18 and 98 years. In total, 228 teleVAs (16.6% response rate) were conducted. Physician coding agreement was good overall (k-statistic: 0.63). Diabetes mellitus (47%) and other non-communicable disease (42%) had initial agreement between physician coders in less than 50% of cases in comparison to consensus totals. COVID-19 (89%) and acute cardiac disease (83%) showed initial agreement in more than 80% of cases compared to consensus totals. A chi-square test revealed a significant difference in the number of causes listed on death notification forms for cases with and without agreement in Part 1 (χ2 = 14.71, p < 0.01), but not in Part 2 (χ2 = 4.97, p = 0.17). CoD agreement might not be high enough to infer that single coders can be used instead of multiple coders. Challenges with co-morbidities and specific CoDs with multiple sequelae highlight the need for further research and refinement of VA methodologies for reliable CoD determination in routine practice.

Agreement between cause of death assignment by computer-coded verbal autopsy methods and physician coding of verbal autopsy interviews in South Africa

ABSTRACT Background The South African national cause of death validation (NCODV 2017/18) project collected a national sample of verbal autopsies (VA) with cause of death (COD) assignment by physician-coded VA (PCVA) and computer-coded VA (CCVA). Objective The performance of three CCVA algorithms (InterVA-5, InSilicoVA and Tariff 2.0) in assigning a COD was compared with PCVA (reference standard). Methods Seven performance metrics assessed individual and population level agreement of COD assignment by age, sex and place of death subgroups. Positive predictive value (PPV), sensitivity, overall agreement, kappa, and chance corrected concordance (CCC) assessed individual level agreement. Cause-specific mortality fraction (CSMF) accuracy and Spearman’s rank correlation assessed population level agreement. Results A total of 5386 VA records were analysed. PCVA and CCVAs all identified HIV/AIDS as the leading COD. CCVA PPV and sensitivity, based on confidence intervals, were comparable except for HIV/AIDS, TB, maternal, diabetes mellitus, other cancers, and some injuries. CCVAs performed well for identifying perinatal deaths, road traffic accidents, suicide and homicide but poorly for pneumonia, other infectious diseases and renal failure. Overall agreement between CCVAs and PCVA for the top single cause (48.2–51.6) indicated comparable weak agreement between methods. Overall agreement, for the top three causes showed moderate agreement for InterVA (70.9) and InSilicoVA (73.8). Agreement based on kappa (−0.05–0.49)and CCC (0.06–0.43) was weak to none for all algorithms and groups. CCVAs had moderate to strong agreement for CSMF accuracy, with InterVA-5 highest for neonates (0.90), Tariff 2.0 highest for adults (0.89) and males (0.84), and InSilicoVA highest for females (0.88), elders (0.83) and out-of-facility deaths (0.85). Rank correlation indicated moderate agreement for adults (0.75–0.79). Conclusions Whilst CCVAs identified HIV/AIDS as the leading COD, consistent with PCVA, there is scope for improving the algorithms for use in South Africa.

Bayesian hierarchical factor regression models to infer cause of death from verbal autopsy data.

In low-resource settings where vital registration of death is not routine it is often of critical interest to determine and study the cause of death (COD) for individuals and the cause-specific mortality fraction (CSMF) for populations. Post-mortem autopsies, considered the gold standard for COD assignment, are often difficult or impossible to implement due to deaths occurring outside the hospital, expense, and/or cultural norms. For this reason, Verbal Autopsies (VAs) are commonly conducted, consisting of a questionnaire administered to next of kin recording demographic information, known medical conditions, symptoms, and other factors for the decedent. This article proposes a novel class of hierarchical factor regression models that avoid restrictive assumptions of standard methods, allow both the mean and covariance to vary with COD category, and can include covariate information on the decedent, region, or events surrounding death. Taking a Bayesian approach to inference, this work develops an MCMC algorithm and validates the FActor Regression for Verbal Autopsy (FARVA) model in simulation experiments. An application of FARVA to real VA data shows improved goodness-of-fit and better predictive performance in inferring COD and CSMF over competing methods. Code and a user manual are made available at https://github.com/kelrenmor/farva.

Burden, timing and causes of maternal and neonatal deaths and stillbirths in sub-Saharan Africa and South Asia: protocol for a prospective cohort study.

ObjectivesThe AMANHI mortality study aims to use harmonized methods, across eleven sites in eight countries in South Asia and sub–Saharan Africa, to estimate the burden, timing and causes of maternal, fetal and neonatal deaths. It will generate data to help advance the science of cause of death (COD) assignment in developing country settings.MethodsThis population–based, cohort study is being conducted in the eleven sites where approximately 2 million women of reproductive age are under surveillance to identify and follow–up pregnancies through to six weeks postpartum. All sites are implementing uniform protocols. Verbal autopsies (VAs) are conducted for deaths of pregnant women, newborns or stillbirths to confirm deaths, ascertain timing and collect data on the circumstances around the death to help assign causes. Physicians from the sites are selected and trained to use International Classification of Diseases (ICD) principles to assign CODs from a limited list of programmatically–relevant causes. Where the cause cannot be determined from the VA, physicians assign that option. Every physician who is trained to assign causes of deaths from any of the study countries is tested and accredited before they start COD assignment in AMANHI.Importance of the AMANHI mortality studyIt is one of the first to generate improved estimates of burden, timing and causes of maternal, fetal and neonatal deaths from empirical data systematically collected in a large prospective cohort of women of reproductive age. AMANHI makes a substantial contribution to global knowledge to inform policies, interventions and investment decisions to reduce these deaths.

Automated versus physician assignment of cause of death for verbal autopsies: randomized trial of 9374 deaths in 117 villages in India

BackgroundVerbal autopsies with physician assignment of cause of death (COD) are commonly used in settings where medical certification of deaths is uncommon. It remains unanswered if automated algorithms can replace physician assignment.MethodsWe randomized verbal autopsy interviews for deaths in 117 villages in rural India to either physician or automated COD assignment. Twenty-four trained lay (non-medical) surveyors applied the allocated method using a laptop-based electronic system. Two of 25 physicians were allocated randomly to independently code the deaths in the physician assignment arm. Six algorithms (Naïve Bayes Classifier (NBC), King-Lu, InSilicoVA, InSilicoVA-NT, InterVA-4, and SmartVA) coded each death in the automated arm. The primary outcome was concordance with the COD distribution in the standard physician-assigned arm. Four thousand six hundred fifty-one (4651) deaths were allocated to physician (standard), and 4723 to automated arms.ResultsThe two arms were nearly identical in demographics and key symptom patterns. The average concordances of automated algorithms with the standard were 62%, 56%, and 59% for adult, child, and neonatal deaths, respectively. Automated algorithms showed inconsistent results, even for causes that are relatively easy to identify such as road traffic injuries. Automated algorithms underestimated the number of cancer and suicide deaths in adults and overestimated other injuries in adults and children. Across all ages, average weighted concordance with the standard was 62% (range 79–45%) with the best to worst ranking automated algorithms being InterVA-4, InSilicoVA-NT, InSilicoVA, SmartVA, NBC, and King-Lu. Individual-level sensitivity for causes of adult deaths in the automated arm was low between the algorithms but high between two independent physicians in the physician arm.ConclusionsWhile desirable, automated algorithms require further development and rigorous evaluation. Lay reporting of deaths paired with physician COD assignment of verbal autopsies, despite some limitations, remains a practicable method to document the patterns of mortality reliably for unattended deaths.Trial registrationClinicalTrials.gov, NCT02810366. Submitted on 11 April 2016.

Findings in Stillbirths Associated with Placental Disease.

Placental disease is a leading cause of stillbirth. Our purpose was to characterize stillbirths associated with placental disease. The Stillbirth Collaborative Research Network conducted a prospective, case-control study of stillbirths and live births from 2006 to 2008. This analysis includes 512 stillbirths with cause of death assignment and a comparison group of live births. We compared exposures between women with stillbirth due to placental disease and those due to other causes as well as between women with term (≥ 37 weeks) stillbirth due to placental disease and term live births. A total of 121 (23.6%) out of 512 stillbirths had a probable or possible cause of death due to placental disease by Initial Causes of Fetal Death. Characteristics were similar between stillbirths due to placental disease and other stillbirths. When comparing term live births to stillbirths due to placental disease, women with non-Hispanic black race, Hispanic ethnicity, lack of insurance, or who were born outside of the United States had higher odds of stillbirth due to placental disease. Nulliparity and antenatal bleeding also increased risk of stillbirth due to placental disease. Multiple discrete exposures were associated with stillbirth caused by placental disease. The relationship between these factors and utility of surveillance warrants further study.

Population-based rates, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa: a multi-country prospective cohort study.

SummaryBackgroundModelled mortality estimates have been useful for health programmes in low-income and middle-income countries. However, these estimates are often based on sparse and low-quality data. We aimed to generate high quality data about the burden, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa.MethodsIn this prospective cohort study done in 11 community-based research sites in south Asia and sub-Saharan Africa, between July, 2012, and February, 2016, we conducted population-based surveillance of women of reproductive age (15–49 years) to identify pregnancies, which were followed up to birth and 42 days post partum. We used standard operating procedures, data collection instruments, training, and standardisation to harmonise study implementation across sites. Verbal autopsies were done for deaths of all women of reproductive age, neonatal deaths, and stillbirths. Physicians used standardised methods for cause of death assignment. Site-specific rates and proportions were pooled at the regional level using a meta-analysis approach.FindingsWe identified 278 186 pregnancies and 263 563 births across the study sites, with outcomes ascertained for 269 630 (96·9%) pregnancies, including 8761 (3·2%) that ended in miscarriage or abortion. Maternal mortality ratios in sub-Saharan Africa (351 per 100 000 livebirths, 95% CI 168–732) were similar to those in south Asia (336 per 100 000 livebirths, 247–458), with far greater variability within sites in sub-Saharan Africa. Stillbirth and neonatal mortality rates were approximately two times higher in sites in south Asia than in sub-Saharan Africa (stillbirths: 35·1 per 1000 births, 95% CI 28·5–43·1 vs 17·1 per 1000 births, 12·5–25·8; neonatal mortality: 43·0 per 1000 livebirths, 39·0–47·3 vs 20·1 per 1000 livebirths, 14·6–27·6). 40–45% of pregnancy-related deaths, stillbirths, and neonatal deaths occurred during labour, delivery, and the 24 h postpartum period in both regions. Obstetric haemorrhage, non-obstetric complications, hypertensive disorders of pregnancy, and pregnancy-related infections accounted for more than three-quarters of maternal deaths and stillbirths. The most common causes of neonatal deaths were perinatal asphyxia (40%, 95% CI 39–42, in south Asia; 34%, 32–36, in sub-Saharan Africa) and severe neonatal infections (35%, 34–36, in south Asia; 37%, 34–39 in sub-Saharan Africa), followed by complications of preterm birth (19%, 18–20, in south Asia; 24%, 22–26 in sub-Saharan Africa).InterpretationThese results will contribute to improved global estimates of rates, timing, and causes of maternal and newborn deaths and stillbirths. Our findings imply that programmes in sub-Saharan Africa and south Asia need to further intensify their efforts to reduce mortality rates, which continue to be high. The focus on improving the quality of maternal intrapartum care and immediate newborn care must be further enhanced. Efforts to address perinatal asphyxia and newborn infections, as well as preterm birth, are critical to achieving survival goals in the Sustainable Development Goals era.FundingBill & Melinda Gates Foundation.

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

BackgroundDeaths 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.MethodsThis 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.ResultsOf 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%).ConclusionThe 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.

High Norwegian prostate cancer mortality: evidence of over-reporting

Objective: This study aimed to determine the level of misattribution of prostate cancer deaths in Norway based on the county of Vestfold in the years 2009–2014.Materials and methods: The study included 328 patients registered as dead from prostate cancer (PCD; part I of death certificate), 126 patients with prostate cancer as other significant condition at death (OCD; part II of death certificate) and 310 patients who died with a diagnosis of prostate cancer not registered on the death certificate (PC-DCneg) in Vestfold County in 2009–2014. The complete cohort with patients’ names and dates of birth was provided by the Norwegian Institute of Public Health and the Norwegian Cancer Registry. The true cause of death of all patients was evaluated based on patient journals.Results: Over-reporting of prostate cancer deaths in the PCD group was 33% while under-reporting in the OCD and PC-DCneg groups was 19% and 5%, respectively. The correlation between registered and observed causes of death was 0.81 (95% confidence interval 0.78–0.83). Misattribution of prostate cancer deaths increased significantly with patient age and decreasing Gleason score.Conclusions: Prostate cancer mortality statistics in Norway are relatively accurate for patients aged <75 years at death. However, overall accuracy of cause of death assignment is significantly reduced by misattribution among older patients (> 75 years), who represent the large majority of prostate cancer deaths. Over-reporting of prostate cancer deaths among elderly people may not be an exclusively Norwegian phenomenon and may affect prostate cancer mortality statistics in other countries.

Evaluation of data sources and approaches for estimation of influenza-associated mortality in India.

BackgroundNo estimates of influenza‐associated mortality exist for India.ObjectiveTo evaluate national mortality and viral surveillance data from India for assessing their appropriateness in estimating influenza‐associated mortality using varied analytic approaches.MethodsWe reviewed influenza virus surveillance data from a national influenza surveillance network. We also reviewed national mortality data from Civil Registration System (CRS), Medical Certification of Cause of Death (MCCD) and the Sample Registration System (SRS). We compared and scored the different sources of mortality data using specific criteria, including the process of cause of death assignment, sample size, proportion of ill‐defined deaths, representativeness and availability of time series data. Each of these 5 parameters was scored on a scale from 1 to 5. To evaluate how to generate an influenza‐associated mortality estimate for India, we also reviewed 4 methodologic approaches to assess the appropriateness of their assumptions and requirements for these data sets.ResultsThe influenza virus surveillance data included year‐round sample testing for influenza virus and was found to be suitable for influenza mortality estimation modelling. Based on scoring for the 5 mortality data criteria, the SRS data had the highest score with 20 of 25 possible score, whereas MCCD and CRS scored 16 and 12, respectively. The SRS which used verbal autopsy survey methods was determined to be nationally representative and thus adequate for estimating influenza‐associated mortality. Evaluation of the modelling methods demonstrated that Poisson regression, risk difference and mortality multiplier methods could be applied to the Indian setting.ConclusionDespite significant challenges, it is possible to estimate influenza‐associated mortality in India.

PD55-04 THE ERSPC VERSUS THE PROTECT STUDY: OUTCOMES AFTER ACTIVE SURVEILLANCE COMPARED TO SURGERY AND RADIOTHERAPY FOR LOCALIZED PROSTATE CANCER.

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance III1 Apr 2017PD55-04 THE ERSPC VERSUS THE PROTECT STUDY: OUTCOMES AFTER ACTIVE SURVEILLANCE COMPARED TO SURGERY AND RADIOTHERAPY FOR LOCALIZED PROSTATE CANCER. Frank-Jan Drost, Arnout Alberts, Chris Bangma, Monique Roobol, and for the ERSPC Rotterdam group Frank-Jan DrostFrank-Jan Drost More articles by this author , Arnout AlbertsArnout Alberts More articles by this author , Chris BangmaChris Bangma More articles by this author , Monique RoobolMonique Roobol More articles by this author , and for the ERSPC Rotterdam groupfor the ERSPC Rotterdam group More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2427AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The safety of active surveillance (AS) remains topic of debate, but must be evaluated in light of results from the ′golden standard′ therapies, e.g. radiotherapy (RT) and radical prostatectomy (RP). The ProtecT study published 10-yr outcomes after randomization to active monitoring (AM), RT or RP; with higher risk patients and a less strict follow-up protocol than contemporary AS. In the European Randomized study of Screening for Prostate Cancer (ERSPC) Rotterdam, a subgroup of patients also received AM/AS, although more often according to a strict protocol (e.g. PRIAS). METHODS We evaluated death rates among men with low to intermediate risk prostate cancer (PC) treated with AS, RT or RP in the ERSPC and compared these to ProtecT. Men with low risk (Gleason score (GS) 6, cT1C/cT2A) and intermediate risk (GS ≤3+4, cT1c/cT2) PC, diagnosed in the 1st and 2nd screening round (1993-2003) were included. Controlling for age, PSA, clinical stage, GS and comorbidities, we performed cox proportional hazard analyses. RESULTS Of the 2280 PC patients, 905 and 1275 had low and intermediate risk PC, resp. Median age and PSA were 66.4 yrs and 4.3 ng/mL; 66,6 yrs and 4.5 ng/mL, resp. Median follow-up was 13 yrs. In the low risk group, the hazard ratio (HR) for PC specific death for RT/RP (n=370/312) vs AS (n=223) was 0.61 (95%CI 0.18-2, p=0.41). The HR for overall death was 1.29 (95% CI 0.97-1.72).In the intermediate risk group, the HR for PC specific death for RT/RP (n=501/526) vs AS (n=248) was 0.65 (95%CI 0.25-1.64, p=0.36). The HR for overall death was 1.23 (95% CI 0.95-1.59). See Figure 1.In the ProtecT study, the HR for PC specific death for RT vs. AM was 0.51 (95% CI 0.15-1.69) and for RP vs. AM 0.63 (95% CI 0.21-1.93), p=0.48. The HR for overall death was not specified (p=0.87 across treatment groups). CONCLUSIONS The HR for PC specific death for AS vs immediate active therapy, between the ERSPC Rotterdam and ProtecT, seem comparable. Although the ERSPC was not randomized, but includes 13 yr complete follow-up and consensus based cause of death assignment, these data confirm that AS as an initial treatment, as compared to immediate active therapy, results in similar low PC specific death rates. In the end, quality of life and hence the personal treatment preference of the patient should be decisive. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1052 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Frank-Jan Drost More articles by this author Arnout Alberts More articles by this author Chris Bangma More articles by this author Monique Roobol More articles by this author for the ERSPC Rotterdam group More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The paradox of verbal autopsy in cause of death assignment: symptom question unreliability but predictive accuracy.

BackgroundWe 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.MethodsThe 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.ResultsA 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.ConclusionsFamilies 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12963-016-0104-2) contains supplementary material, which is available to authorized users.

Use of Smartphone for Verbal Autopsy.

Traditionally, verbal autopsies (VA) are collected on paper-based questionnaires and reviewed by physicians for cause of death assignment, it is resource intensive and time consuming. The Population Health Metrics Research Consortium VA questionnaires was made available on an Android-based application and cause of death was derived using the Tariff method. Over one year, all adult deaths occurring in 48 villages in 4 counties were identified and a VA interview was conducted using the smartphone VA application. A total of 507 adult deaths were recorded and VA interviews were conducted. Cardiovascular disease was the leading cause of death (35.3%) followed by injury (14.6%) and neoplasms (13.5%). The total cost of the pilot study was USD28 835 (USD0.42 per capita). The interviewers found use of smartphones to conduct interviews to be easier. The study showed that using a smartphone application for VA interviews was feasible for implementation in rural China.

Gallstones and the Risk of Gallbladder Cancer Mortality: A Cohort Study.

Despite epidemiologic data, definitive evidence for the role of gallstones as a cause for gallbladder cancer is lacking. The goal of this study was to evaluate the association between gallstones, determined by ultrasound, and the risk of gallbladder cancer mortality in a large study of Korean men and women. In addition, the association between gallstones and cholecystectomy, and risk of hepatobiliary cancer mortality was investigated. A cohort study was performed for 396,720 South Korean men and women who underwent a health checkup from 2002 to 2012. Hazard ratios for mortality outcomes were estimated using Cox-proportional hazards regression analysis. Vital status and cause of death assignment were based on linkage to the National Death Index of death certificate records. From a total of 2,158,906.2 person-years of follow-up (median follow-up of 5.4 years), we identified 224 deaths from hepatobiliary cancer, comprising 174 cases of liver/intrahepatic bile ducts cancer, 20 cases of gallbladder cancer, and 30 cases of biliary tract cancer. Gallstones were significantly associated with increased risk of hepatobiliary cancer mortality, especially liver/intrahepatic biliary cancer, and gallbladder cancer mortality. The multivariable-adjusted hazard ratios (95% confidence intervals) for hepatobiliary cancer, liver/intrahepatic biliary cancer, and gallbladder cancer mortality comparing subjects having gallstones with those without gallstone disease were 2.74 (1.83-4.10), 2.34 (1.45-3.77), and 7.35 (2.60-20.8), respectively. Cholecystectomy was not significantly associated with hepatobiliary cancer mortality. In this large cohort study, gallstones were associated with increased risk of hepatobiliary cancer mortality, especially liver/intrahepatic cancer, and gallbladder cancer mortality independent of potential confounders. Future studies with longer follow-up periods that include data on incident cancer cases should provide a more comprehensive view of the role of gallstones in cancer development.

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee.

Background:Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes.Methods:We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002–2015).Results:Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis.Conclusions:UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials.

Diverse Empirical Evidence on Epidemiological Transition in Low- and Middle-Income Countries: Population-Based Findings from INDEPTH Network Data.

BackgroundLow- and middle-income countries are often described as being at intermediate stages of epidemiological transition, but there is little population-based data with reliable cause of death assignment to examine the situation in more detail. Non-communicable diseases are widely seen as a coming threat to population health, alongside receding burdens of infection. The INDEPTH Network has collected empirical population data in a number of health and demographic surveillance sites in low- and middle-income countries which permit more detailed examination of mortality trends over time.ObjectiveTo examine cause-specific mortality trends across all ages at INDEPTH Network sites in Africa and Asia during the period 1992–2012. Emphasis is given to the 15–64 year age group, which is the main focus of concern around the impact of the HIV pandemic and emerging non-communicable disease threats.MethodsINDEPTH Network public domain data from 12 sites that each reported at least five years of cause-specific mortality data were used. Causes of death were attributed using standardised WHO verbal autopsy methods, and mortality rates were standardised for comparison using the INDEPTH standard population. Annual changes in mortality rates were calculated for each site.ResultsA total of 96,255 deaths were observed during 9,487,418 person years at the 12 sites. Verbal autopsies were completed for 86,039 deaths (89.4%). There were substantial variations in mortality rates between sites and over time. HIV-related mortality played a major part at sites in eastern and southern Africa. Deaths in the age group 15–64 years accounted for 43% of overall mortality. Trends in mortality were generally downwards, in some cases quite rapidly so. The Bangladeshi sites reflected populations at later stages of transition than in Africa, and were largely free of the effects of HIV/AIDS.ConclusionsTo some extent the patterns of epidemiological transition observed followed theoretical expectations, despite the impact of the HIV pandemic having a major effect in some locations. Trends towards lower overall mortality, driven by decreasing infections, were the general pattern. Low- and middle-income country populations appear to be in an era of rapid transition.

Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer).

BackgroundIn cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. To minimise bias, the UCD should be independently verified by expert reviewers, blinded to death certificate data and trial arm. We investigated whether standardising the information submitted for UCD assignment in a population-based randomised controlled trial of prostate-specific antigen (PSA) testing for prostate cancer reduced the reviewers’ ability to correctly guess the trial arm.MethodsOver 550 General Practitioner (GP) practices (>415,000 men aged 50–69 years) were cluster-randomised to PSA testing (intervention arm) or the National Health Service (NHS) prostate cancer risk management programme (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews of researcher-written clinical vignettes that masked trial arm and death certificate information. A period of time after the process began (the initial phase), we analysed whether the reviewers could correctly identify trial arm from the vignettes, and the reasons for their choice. This feedback led to further standardisation of information (second phase), after which we re-assessed the extent of correct identification of trial arm.Results1099 assessments of 509 vignettes were completed by January 2014. In the initial phase (n = 510 assessments), reviewers were unsure of trial arm in 33% of intervention and 30% of control arm assessments and were influenced by symptoms at diagnosis, PSA test result and study-specific criteria. In the second phase (n = 589), the respective proportions of uncertainty were 45% and 48%. The percentage of cases whereby reviewers were unable to determine the trial arm was greater following the standardisation of information provided in the vignettes. The chances of a correct guess and an incorrect guess were equalised in each arm, following further standardisation.ConclusionsIt is possible to mask trial arm from cause of death reviewers, by using their feedback to standardise the information submitted to them.Trial registrationISRCTN92187251Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2288-15-6) contains supplementary material, which is available to authorized users.

Correction: Robust metrics for assessing the performance of different verbal autopsy cause assignment methods in validation studies.

Verbal autopsy (VA) is an important method for obtaining cause of death information in settings without vital registration and medical certification of causes of death. An array of methods, including physician review and computer-automated methods, have been proposed and used. Choosing the best method for VA requires the appropriate metrics for assessing performance. Currently used metrics such as sensitivity, specificity, and cause-specific mortality fraction (CSMF) errors do not provide a robust basis for comparison. We use simple simulations of populations with three causes of death to demonstrate that most metrics used in VA validation studies are extremely sensitive to the CSMF composition of the test dataset. Simulations also demonstrate that an inferior method can appear to have better performance than an alternative due strictly to the CSMF composition of the test set. VA methods need to be evaluated across a set of test datasets with widely varying CSMF compositions. We propose two metrics for assessing the performance of a proposed VA method. For assessing how well a method does at individual cause of death assignment, we recommend the average chance-corrected concordance across causes. This metric is insensitive to the CSMF composition of the test sets and corrects for the degree to which a method will get the cause correct due strictly to chance. For the evaluation of CSMF estimation, we propose CSMF accuracy. CSMF accuracy is defined as one minus the sum of all absolute CSMF errors across causes divided by the maximum total error. It is scaled from zero to one and can generalize a method's CSMF estimation capability regardless of the number of causes. Performance of a VA method for CSMF estimation by cause can be assessed by examining the relationship across test datasets between the estimated CSMF and the true CSMF. With an increasing range of VA methods available, it will be critical to objectively assess their performance in assigning cause of death. Chance-corrected concordance and CSMF accuracy assessed across a large number of test datasets with widely varying CSMF composition provide a robust strategy for this assessment.

Performance of four computer-coded verbal autopsy methods for cause of death assignment compared with physician coding on 24,000 deaths in low- and middle-income countries

BackgroundPhysician-coded verbal autopsy (PCVA) is the most widely used method to determine causes of death (CODs) in countries where medical certification of death is uncommon. Computer-coded verbal autopsy (CCVA) methods have been proposed as a faster and cheaper alternative to PCVA, though they have not been widely compared to PCVA or to each other.MethodsWe compared the performance of open-source random forest, open-source tariff method, InterVA-4, and the King-Lu method to PCVA on five datasets comprising over 24,000 verbal autopsies from low- and middle-income countries. Metrics to assess performance were positive predictive value and partial chance-corrected concordance at the individual level, and cause-specific mortality fraction accuracy and cause-specific mortality fraction error at the population level.ResultsThe positive predictive value for the most probable COD predicted by the four CCVA methods averaged about 43% to 44% across the datasets. The average positive predictive value improved for the top three most probable CODs, with greater improvements for open-source random forest (69%) and open-source tariff method (68%) than for InterVA-4 (62%). The average partial chance-corrected concordance for the most probable COD predicted by the open-source random forest, open-source tariff method and InterVA-4 were 41%, 40% and 41%, respectively, with better results for the top three most probable CODs. Performance generally improved with larger datasets. At the population level, the King-Lu method had the highest average cause-specific mortality fraction accuracy across all five datasets (91%), followed by InterVA-4 (72% across three datasets), open-source random forest (71%) and open-source tariff method (54%).ConclusionsOn an individual level, no single method was able to replicate the physician assignment of COD more than about half the time. At the population level, the King-Lu method was the best method to estimate cause-specific mortality fractions, though it does not assign individual CODs. Future testing should focus on combining different computer-coded verbal autopsy tools, paired with PCVA strengths. This includes using open-source tools applied to larger and varied datasets (especially those including a random sample of deaths drawn from the population), so as to establish the performance for age- and sex-specific CODs.

A commentary on changing infant death rates and a plea to use sudden infant death syndrome as a cause of death

In his editorial entitled Changing Infant Death Rates— Diagnostic Shift, Success Story, Or Both, Byard concludes that changes in rates away from sudden infant death syndrome (SIDS) towards another cause of death (COD) are appropriate [1]. Improved death scene investigations and autopsies leading to increased awareness of potential dangers imposed by infant sleep sites have been instrumental to the diagnostic shift occurring in cases of sudden unexpected infant death. Given abundant supportive data accumulating over the past few years, we certainly agree. But where do we go from here in order to bring about greater consensus and accuracy in establishing CODs in these cases? Over the past four decades, the original definition of SIDS [2] has undergone several refinements focusing principally on mandating death scene investigations, circumstances of death, association with sleep, and certainty of the COD [3–5]. Yet, each subsequent iteration has remained exclusionary with respect to the COD and is encumbered with its own diagnostic dilemmas given the lack of a pathognomonic postmortem marker, incomplete death scene investigations, and limited postmortem examinations and ancillary testing as well as philosophical differences with and objections to the concept of SIDS itself among death certifiers [6]. As a result, other labels including sudden unexpected death in infancy (SUDI), sudden unexpected infant death (SUID), unclassified sudden infant death (USID), Undetermined, and Unascertained, have gained wider currency in an ever increasing proportion of these challenging cases. The choice between SIDS and these latter COD certifications now often centers on death scene findings that suggest an asphyxial risk to the sleeping infant. However, present investigative methods neither precisely quantify nor determine the certainty of its lethality in the absence of reliable postmortem evidence of its significance; hence the slippery slope of COD assignment. The present uncertainty in analyzing the circumstances of death in these cases is demonstrated in our recent study wherein five pathologists blinded to one another and using a classification scheme focused on the estimated risk of asphyxia at the death scene as described in the investigative reports assigned a COD to 117 sudden infant death cases including 83 cases with SIDS as the original COD [7]. The reviewers concluded that the death scene contributed to or actually caused death in 32–50 % of the entire case study group and in 40–59 % of the 83 SIDS cases. Among the 83 original SIDS cases, SIDS as the COD decreased by 55–69 % and another COD was considered plausible in 2–12 % of the cases. Although SIDS remains an exclusionary COD, its underlying elements and the mechanism of death as hypothesized in the triple risk hypothesis are being unraveled [8]. According to this hypothesis, ‘‘SIDS, or an important subset of SIDS, is due to abnormal brainstem mechanisms in the control of respiration, chemosensitivity, autonomic regulation, and/or arousal which impairs the infant’s response to life-threatening, but often occurring, stressors during sleep (e.g., hypoxia, hypercarbia, asphyxia, hyperthermia) and leads to sudden death in a vulnerable developmental period’’ [9]. Thus, according to this hypothesis, SIDS infants who are intrinsically vulnerable as a result of underlying pathology must be exposed simultaneously to risk factors, such as prone sleep position, during their physiologically unstable stage of development during sleep, before they will succumb. This period of H. F. Krous (&) Department of Pathology, Rady Children’s Hospital, 3020 Children’s Way, M5007, San Diego, CA 92123, USA e-mail: hkrous@rchsd.org