Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Experimental and theoretical investigation of ligand effects on the synthesis of ZnO nanoparticles

ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence

Beyond knowing nature: Contact, emotion, compassion, meaning, and beauty are pathways to nature connection

Feeling connected to nature has been shown to be beneficial to wellbeing and pro-environmental behaviour. General nature contact and knowledge based activities are often used in an attempt to engage people with nature. However the specific routes to nature connectedness have not been examined systematically. Two online surveys (total n = 321) of engagement with, and value of, nature activities structured around the nine values of the Biophila Hypothesis were conducted. Contact, emotion, meaning, and compassion, with the latter mediated by engagement with natural beauty, were predictors of connection with nature, yet knowledge based activities were not. In a third study (n = 72), a walking intervention with activities operationalising the identified predictors, was found to significantly increase connection to nature when compared to walking in nature alone or walking in and engaging with the built environment. The findings indicate that contact, emotion, meaning, compassion, and beauty are pathways for improving nature connectedness. The pathways also provide alternative values and frames to the traditional knowledge and identification routes often used by organisations when engaging the public with nature.N/

Cause-of-death ascertainment for deaths that occur outside hospitals in Thailand: application of verbal autopsy methods

Background: Ascertainment of cause for deaths that occur in the absence of medical attention is a significant problem in many countries, including Thailand, where more than 50% of such deaths are registered with ill-defined causes. Routine implementation of standardized, rigorous verbal autopsy methods is a potential solution. This paper reports findings from field research conducted to develop, test, and validate the use of verbal autopsy (VA) methods in Thailand.Methods: International verbal autopsy methods were first adapted to the Thai context and then implemented to ascertain causes of death for a nationally representative sample of 11,984 deaths that occurred in Thailand in 2005. Causes of death were derived from completed VA questionnaires by physicians trained in ICD-based cause-of-death certification. VA diagnoses were validated in the sample of hospital deaths for which reference diagnoses were available from medical record review. Validated study findings were used to adjust VA-based causes of death derived for deaths in the study sample that had occurred outside hospitals. Results were used to estimate cause-specific mortality patterns for deaths outside hospitals in Thailand in 2005.Results: VA-based causes of death were derived for 6,328 out of 7,340 deaths in the study sample that had occurred outside hospitals, constituting the verification arm of the study. The use of VA resulted in large-scale reassignment of deaths from ill-defined categories to specific causes of death. The validation study identified that VA tends to overdiagnose important causes such as diabetes, liver cancer, and tuberculosis, while undercounting deaths from HIV/AIDS, liver diseases, genitourinary (essential renal), and digestive system disorders.Conclusions: The use of standard VA methods adapted to Thailand enabled a plausible assessment of cause-specific mortality patterns and a substantial reduction of ill-defined diagnoses. Validation studies enhance the utility of findings from the application of verbal autopsy. Regular implementation of VA in Thailand could accelerate development of the quality and utility of vital registration data for deaths outside hospitals

Factors Associated with Physician Agreement on Verbal Autopsy of over 11500 Injury Deaths in India

Worldwide, injuries account for 9.8% of all deaths. The majority of these deaths occur in low- and middle-income countries where vital registration systems are often inadequate. Verbal autopsy (VA) is a tool used to ascertain cause of death in such settings. Validation studies for VA using hospital diagnosed causes of death as comparisons have shown that injury deaths can be reliably diagnosed by VA. However, no study has assessed the factors that may affect physicians' abilities to code specific causes of injury death using VA.This study used data from over 11 500 verbal autopsies of injury deaths from the Million Death Study (MDS) in which 6.3 million people in India were monitored from 2001–2003 for vital events. Deaths that occurred in the MDS were coded by two independent physicians. This study focused on whether physician agreement on the classification of injury deaths was affected by characteristics of the deceased and respondent. Agreement was analyzed using three primary methods: 1) kappa statistic; 2) sensitivity and specificity analysis using the final VA diagnosed category of injury death as gold standard; and 3) multivariate logistic regression using a conceptual hierarchical model. The overall agreement for all injury deaths was 77.9% with a kappa of 0.74 (99% CI 0.74–0.75). Deaths in the injury categories of “transport”, “falls”, “drowning” and “other unintentional injury” occurring outside the home were associated with greater physician agreement than those occurring at home. In contrast, self-inflicted injury deaths that occurred outside the home were associated with lower physician agreement.With few exceptions, most characteristics of the deceased and the respondent did not influence physician agreement on the classification of injury deaths. Physician training and continued adaptation of the VA tool should focus on the reasons these factors influenced physician agreement

Validity of Verbal Autopsy Procedures for Determining Malaria Deaths in Different Epidemiological Settings in Uganda

BACKGROUND: Verbal autopsy (VA) procedures can be used to estimate cause of death in settings with inadequate vital registries. However, the sensitivity of VA for determining malaria-specific mortality may be low, and may vary with transmission intensity. We assessed the diagnostic accuracy of VA procedures as compared to hospital medical records for determining cause of death in children under five in three different malaria transmission settings in Uganda, including Tororo (high), Kampala (medium), and Kisoro (low). METHODS AND FINDINGS: Caretakers of children who died in participating hospitals were interviewed using a standardized World Health Organization questionnaire. Medical records from the child's hospitalization were also reviewed. Causes of death based on the VA questionnaires and the medical records were assigned independently by physician reviewers and then compared. A total of 719 cases were included in the final analysis, 67 in Tororo, 600 in Kampala, and 52 in Kisoro. Malaria was classified as the underlying or contributory cause of death by review of medical records in 33 deaths in Tororo, 60 in Kampala, and 0 in Kisoro. The sensitivity of VA procedures for determining malaria deaths in Tororo was 61% (95% CI 44-78%) and 50% in Kampala (95% CI 37-63%). Specificity for determining malaria deaths in Tororo and Kampala was high (>88%), but positive predictive value varied widely, from 83% in Tororo to 34% in Kampala (difference 49%, 95% CI 31-67, p<0.001). The difference between the cause-specific mortality fraction for malaria as determined by VA procedures and medical records was -11% in Tororo, +5% in Kampala, and +14% in Kisoro. CONCLUSIONS: Our results suggest that these VA methods have an acceptable level of diagnostic accuracy for determining malaria deaths at the population level in high and medium transmission areas, but not in low transmission areas

A New Era in the Quest for Dark Matter

There is a growing sense of `crisis' in the dark matter community, due to the absence of evidence for the most popular candidates such as weakly interacting massive particles, axions, and sterile neutrinos, despite the enormous effort that has gone into searching for these particles. Here, we discuss what we have learned about the nature of dark matter from past experiments, and the implications for planned dark matter searches in the next decade. We argue that diversifying the experimental effort, incorporating astronomical surveys and gravitational wave observations, is our best hope to make progress on the dark matter problem.Comment: Published in Nature, online on 04 Oct 2018. 13 pages, 1 figur

Risk factors for type 2 diabetes in groups stratified according to metabolic syndrome: a 10-year follow-up of The Tromsø Study

Many incident cases of type 2 diabetes do not fulfil the metabolic syndrome, which accordingly has been questioned both as a research and clinical tool. The aim of this study was to determine differences in risk factors for type 2 diabetes between groups with high or low metabolic score. The study population were 26,093 men and women attending the Tromsø Study in 1994, followed through 2005, and who did not have diabetes when entering the study. A total of 492 incident cases of type 2 diabetes were registered. A metabolic score was defined according to a modified version of the National Cholesterol Education Program Adult Treatment Panel III. For those fulfilling ≥ 3 metabolic score criteria, increasing age, body mass index (BMI), triglycerides and a family history of diabetes were independent predictors. Age, BMI, and triglycerides predicted type 2 diabetes more strongly in subjects with low metabolic score, whereas high HDL cholesterol was not protective in this low risk group. The risk associated with a positive family history was unaffected by level of metabolic score. In addition smoking, low education and in men also physical inactivity were independent risk factors only in those with low metabolic score. Adding these non-metabolic risk factors increased correct classification from an ROC area of 77.2 to 87.1% (P value < 0.0001). One half of the incident cases of type 2 diabetes were missed by using high metabolic score for risk prediction

Performance of InterVA for assigning causes of death to verbal autopsies: multisite validation study using clinical diagnostic gold standards

Background: InterVA is a widely disseminated tool for cause of death attribution using information from verbal autopsies. Several studies have attempted to validate the concordance and accuracy of the tool, but the main limitation of these studies is that they compare cause of death as ascertained through hospital record review or hospital discharge diagnosis with the results of InterVA. This study provides a unique opportunity to assess the performance of InterVA compared to physician-certified verbal autopsies (PCVA) and alternative automated methods for analysis.Methods: Using clinical diagnostic gold standards to select 12,542 verbal autopsy cases, we assessed the performance of InterVA on both an individual and population level and compared the results to PCVA, conducting analyses separately for adults, children, and neonates. Following the recommendation of Murray et al., we randomly varied the cause composition over 500 test datasets to understand the performance of the tool in different settings. We also contrasted InterVA with an alternative Bayesian method, Simplified Symptom Pattern (SSP), to understand the strengths and weaknesses of the tool.Results: Across all age groups, InterVA performs worse than PCVA, both on an individual and population level. On an individual level, InterVA achieved a chance-corrected concordance of 24.2% for adults, 24.9% for children, and 6.3% for neonates (excluding free text, considering one cause selection). On a population level, InterVA achieved a cause-specific mortality fraction accuracy of 0.546 for adults, 0.504 for children, and 0.404 for neonates. The comparison to SSP revealed four specific characteristics that lead to superior performance of SSP. Increases in chance-corrected concordance are attained by developing cause-by-cause models (2%), using all items as opposed to only the ones that mapped to InterVA items (7%), assigning probabilities to clusters of symptoms (6%), and using empirical as opposed to expert probabilities (up to 8%).Conclusions: Given the widespread use of verbal autopsy for understanding the burden of disease and for setting health intervention priorities in areas that lack reliable vital registrations systems, accurate analysis of verbal autopsies is essential. While InterVA is an affordable and available mechanism for assigning causes of death using verbal autopsies, users should be aware of its suboptimal performance relative to other methods