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

Background: Few national-level studies have evaluated the impact of ‘hybrid’ immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000–9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels. Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11–14%) before omicron to 78% (76–80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity. Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform. Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael’s Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.

Background: The extent to which the Omicron variant of SARS-CoV-2 raised death rates in China during its viral wave of December 2022–January 2023 remains largely undocumented. Methods: We worked with an established national survey organization to survey 8,004 adults in all 31 administrative areas of China to ask about deaths in families since January 2020. We examined age-specific death rates, focusing on deaths above age 60 years, and at 15–59 years. We compared these to the United Nations (UN) estimates of age-specific mortality in 2019. Findings: The survey participants were broadly similar to the 2020 census and other national surveys in age, sex, region, and smoking status, but had lower SARS-CoV-2 vaccination rates and higher education levels. There were no differences in reporting of deaths during the Omicron period (after November 2021) versus earlier. The survey captured 456 deaths, of which 329 occurred at ages 60+ years and 212 were of women. At ages 60+ years, death rates approximately doubled during December 2022-January 2023. Deaths at ages 15–59 years did not rise appreciably. The UN estimates approximately 675,000 deaths per month at ages 60+ years in 2019. If rates doubled nationally as in our survey, China had approximately 1.35 million excess deaths from December 2022-January 2023. Interpretation: China experienced a sharp but short increase in excess deaths among its elderly during the Omicron wave. If death registry data corroborate our estimates of substantial excess deaths in China, the worldwide estimates of excess deaths due to SARS-CoV-2 in 2022–2023 may need upward adjustment.

Summary: Background: Ethiopia, with about 10% of Africa's population, has little direct information on causes of death, particularly in rural areas where 80% of Ethiopians live. In 2019–2020, we conducted electronic verbal autopsies (e-VA) to examine causes of death and quantify cause-specific mortality rates in rural Ethiopia. Methods: We examined deaths under 70 years in the three years prior to the survey dates (November 25, 2019–February 29, 2020) among 2% of East Gojjam Zone (Amhara Region) using registered deaths and adding random sampling in this cross-sectional study. Trained surveyors interviewed relatives of the deceased with central dual-physician assignment of causes as the main outcome. We documented details on age, sex and location of death, and derived overall rural death rates using 2007 Census data and the United Nations national estimates for 2019. To these, we applied our sample-weighted causes to derive cause-specific mortality rates. We calculated death risks for the leading causes for major age groups. Findings: We studied 3516 deaths: 55% male, 97% rural, and 68% occurring at home. At ages 5 and older, injuries were notable, accounting for over a third of deaths at 5–14 years, half of the deaths at ages 15–29 years, and a quarter of deaths at ages 30–69 years. Neonatal mortality was high, mostly from prematurity/low birthweight and infections. Among children under 5 (excluding neonates), infections caused nearly two-thirds of deaths. Most maternal deaths (84%) arose from direct causes. After injuries, especially suicide, assaults, and road traffic accidents, vascular disease (15%) and cancer (13%) were the leading causes among adults at 30–69 years. HIV/AIDS and tuberculosis deaths were also important causes among adults. Interpretation: Rural Ethiopia has a high burden of avoidable mortality, particularly injury, including suicide, assaults, and road traffic accidents. Funding: International Development Research Centre, and the Canadian Institutes of Health Research.

Abstract After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.

Objective: To look at the associations between labour market outcomes and major risk factors for non-communicable diseases (NCDs) (smoking, heavy alcohol consumption), key metabolic changes resultant of the risk factors (overweight and obesity, hypertension, type 2 diabetes), and major depressive disorder, and examine any gender differences. Design: Systematic review of cohort and longitudinal studies, to establish causality between exposures and outcomes. Methods: A systematic literature search was conducted in MEDLINE (Ovid), Embase (Ovid), EconLit (EBSCO), EconPapers, and Cochrane Database of Systematic Reviews, from inception to July 2022 for all peer-reviewed literature published, guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) framework. Results: 109 studies were eligible for this review. All studies were published in English. 96% of the studies were conducted in high-income countries with 63% from Europe and Central Asia. High BMI was the most frequently reported exposure (reported by 46% of the studies), while income was the most studied outcome (reported by 33% of studies). Though not all estimates presented in the literature can be interpreted as causal impacts, 77% of the studies reported significant (p

Introduction Causes of deaths often go unrecorded in lower income countries, yet this information is critical. Verbal autopsy is a questionnaire interview with a family member or caregiver to elicit the symptoms and circumstances preceding a death and assign a probable cause. The social and cultural aspects of verbal autopsy have gotten less attention than the technical aspects and have not been widely explored in South and Southeast Asia settings.Methods Between October 2021 and March 2023, prior to implementing a verbal autopsy study at rural sites in Bangladesh, Cambodia, Laos, Myanmar and Thailand, focus group discussions were conducted with village heads, religious leaders and community members from varied demographic backgrounds. Thematic analysis elucidated customs and traditional views surrounding death to understand local ethnocultural sensitivities.Results We found that death rituals varied greatly among religions, ethnicities and by socioeconomic status. Mourning periods were reported to last 3–100 days and related to the cause of death, age and how close the deceased person was to the family. Participants advised that interviews should happen after mourning periods to avoid emotional distress, but not long after so as to avoid recall bias. Interviewers should be introduced to respondents by a trusted local person. To provide reassurance and confidentiality, a family’s residence is the preferred interview location. Interview questions require careful local language translation, and community sensitisation is important before data collection.Conclusion Verbal autopsy is acceptable across a wide range of cultural settings in Southeast Asia, provided that local norms are preidentified and followed.

Objetivo. Estimar los beneficios económicos y en salud, por sexo y por quintil de ingreso, del incremento de los precios de los cigarros mediante impuestos en México. Métodos. Con un modelo de costo-efectividad extendido (ECEA, por su sigla en inglés) se estimaron los beneficios distributivos en mujeres y hombres con un escenario de incremento del precio de los cigarros de 44% (de 56,4 pesos mexicanos [MX$] a MX$81,2 por cajetilla), como resultado de triplicar el impuesto específico actual (de MX$0,49/cigarro a MX$1,49/cigarro). El modelo se calibró con fuentes oficiales de información nacional Resultados. Con el incremento del impuesto de un peso por cigarro, cerca de 1,5 millones de fumadores abandonarían el consumo (351 300 mujeres y 1,1 millón de hombres). Así, se evitarían aproximadamente 630 000 muertes prematuras atribuibles al tabaco. La reducción de la carga de enfermedad permitiría ahorros para el sector salud cercanos a MX$42 800 millones y evitaría que más de 250 000 personas (entre ellas, 50 200 mujeres fumadoras) cayeran en situación de pobreza. Además, se recaudarían MX$16 200 millones adicionales por año, de los cuales el quintil más bajo aportaría menos de 3% (1% en el caso de las mujeres de menores ingresos). Conclusiones. La epidemia de tabaquismo tiene patrones claramente diferenciados entre mujeres y hombres y reflejan un componente de género. Si bien los beneficios del impuesto al tabaco en México tendrían magnitudes relativas al estado actual de la epidemia en cada caso, estos podrían contribuir a un objetivo más amplio de justicia social mediante la reducción de las inequidades de género.

It is uncertain whether malaria is an important cause of death among adults in endemic areas. We performed a chart review of adults admitted to Bo Government Hospital during 2019. Of 893 admissions, 149 (59% female, mean age 58.5 years) had a laboratory diagnosis of malaria and 22 (14.8%) died. Mortality was significantly higher among patients with severe malaria compared with those who had non-severe malaria (6/20 [30%] versus 16/129 [12.4%], p=0.031). Our results suggest that malaria is a common cause of death in hospitalized Sierra Leonian adults.

Neutralisation assays are key to understanding immune responses to SARS-CoV-2 infection or vaccination. Here, the authors report a surrogate virus neutralization assay called Neu-SATiN, which measures neutralization directly from sera, and allows easy adaptation to variant-specific testing.

Abstract Background Modern health surveillance and planning requires an understanding of how preventable risk factors impact population health, and how these effects vary between populations. In this study, we compare how smoking, alcohol consumption, diet and physical activity are associated with all-cause mortality in Canada and the United States using comparable individual-level, linked population health survey data and identical model specifications. Methods The Canadian Community Health Survey (CCHS) (2003–2007) and the United States National Health Interview Survey (NHIS) (2000, 2005) linked to individual-level mortality outcomes with follow up to December 31, 2011 were used. Consistent variable definitions were used to estimate country-specific mortality hazard ratios with sex-specific Cox proportional hazard models, including smoking, alcohol, diet and physical activity, sociodemographic indicators and proximal factors including disease history. Results A total of 296,407 respondents and 1,813,884 million person-years of follow-up from the CCHS and 58,232 respondents and 497,909 person-years from the NHIS were included. Absolute mortality risk among those with a ‘healthy profile’ was higher in the United States compared to Canada, especially among women. Adjusted mortality hazard ratios associated with health behaviours were generally of similar magnitude and direction but often stronger in Canada. Conclusion Even when methodological and population differences are minimal, the association of health behaviours and mortality can vary across populations. It is therefore important to be cautious of between-study variation when aggregating relative effect estimates from differing populations, and when using external effect estimates for population health research and policy development.

Abstract Background India has a substantial burden of malaria, concentrated in specific areas and population groups. Spatio-temporal modelling of deaths due to malaria in India is a critical tool for identifying high-risk groups for effective resource allocation and disease control policy-making, and subsequently for the country’s progress towards United Nations 2030 Sustainable Development Goals. Methods In this study, a spatio-temporal model with the objective of understanding the spatial distribution of malaria mortality rates and the rate of temporal decline, across the country, has been constructed. A spatio-temporal “random slope” model was used, with malaria risk depending on a spatial relative risk surface and a linear time effect with a spatially-varying coefficient. The models were adjusted for urban/rural status (residence of the deceased) and Normalized Difference Vegetation Index (NDVI), using 2004–13 data from the Million Death Study (MDS) (the most recent data available), with nationwide geographic coverage. Previous studies based on MDS had focused only on aggregated analyses. Results The rural population had twice the risk of death due to malaria compared to the urban population. Malaria mortality in some of the highest-risk regions, namely the states of Odisha and Jharkhand, are declining faster than other areas; however, the rate of decline was not uniformly correlated with the level of risk. The overall decline was faster after 2010. Conclusion The results suggest a need for increased attention in high-risk rural populations, which already face challenges like inadequate infrastructure, inaccessibility to health care facilities, awareness, and education around malaria mortality and prevalence. It also points to the urgent need to restart the MDS to document changes since 2013, to develop appropriate malaria control measures.

Abstract Background Several studies have shown the beneficial effects of tobacco fiscal policy, but distributional effects have been less examined, especially at the subnational level. The objective of this study is to analyse the distributional effects of a one-peso tobacco tax increase (roughly equivalent to tripling the current excise tax) on health, poverty, and financial outcomes at the subnational level in Mexico. Methods We employ an extended cost-effectiveness analysis that estimates life-years gained, smoking attributable deaths averted, treatment costs averted, number of persons avoiding poverty and catastrophic health expenditures, and additional tax revenues by income group across five regions. Results With the one-peso tax increase (or 44% price increase), about 1.5 million smokers would quit smoking across the five regions, resulting in nearly 630 thousand premature deaths averted and 12.6 million life years gained. The bottom income quintile would gain three times more life years gains than the top quintile (ratio 3:1), and the largest gain for the most deprived would occur in the South (ratio 19:1), the region with the highest poverty incidence. Costs averted and additional tax revenues would reach 44.6 and 16.2 billion pesos, respectively. Moreover, 251 thousand individuals would avoid falling into poverty, including 53.2 in the lowest income quintile, and 563.9 thousand would avoid catastrophic health expenditures. Overall, the bottom income group would obtain 26% of the life years gained and 24% of the cost averted, while only paying 3% of the additional tax revenue. Conclusions The most significant gains from a substantial cigarette price increase would be for the poorest 20%, especially in the South, the most impoverished region of Mexico. Therefore, tobacco taxes are an opportunity for governments to advance in equity and towards the achievement of sustainable development goals on non-communicable diseases.

Abstract Background Machine learning (ML) algorithms have been successfully employed for prediction of outcomes in clinical research. In this study, we have explored the application of ML-based algorithms to predict cause of death (CoD) from verbal autopsy records available through the Million Death Study (MDS). Methods From MDS, 18826 unique childhood deaths at ages 1–59 months during the time period 2004–13 were selected for generating the prediction models of which over 70% of deaths were caused by six infectious diseases (pneumonia, diarrhoeal diseases, malaria, fever of unknown origin, meningitis/encephalitis, and measles). Six popular ML-based algorithms such as support vector machine, gradient boosting modeling, C5.0, artificial neural network, k-nearest neighbor, classification and regression tree were used for building the CoD prediction models. Results SVM algorithm was the best performer with a prediction accuracy of over 0.8. The highest accuracy was found for diarrhoeal diseases (accuracy = 0.97) and the lowest was for meningitis/encephalitis (accuracy = 0.80). The top signs/symptoms for classification of these CoDs were also extracted for each of the diseases. A combination of signs/symptoms presented by the deceased individual can effectively lead to the CoD diagnosis. Conclusions Overall, this study affirms that verbal autopsy tools are efficient in CoD diagnosis and that automated classification parameters captured through ML could be added to verbal autopsies to improve classification of causes of death.

Background: With the enactment of the Drug Act in 1978, through the establishment of different bodies under the act, drug-related activities have been regulated and controlled in Nepal so as to provide safe and efficacious drugs of standard quality to the general public. However, with the overgrowing use of drugs, cosmetics, biotechnological products, nutraceuticals, and veterinary products in the present market and the present act failing to include these aspects, this paper tries to critically analyze the Drug Act 1978 of Nepal which will comprise strengths, weaknesses, opportunities, and threats faced in current scenario regarding the act. The regulation of drugs in Nepal was started with the enactment of the Drugs Act in 1978 AD, which is being carried out by the Department of Drug Administration as provisioned in the section 5 of the act. To facilitate the proper implementation of the act, various rules, regulations and guidelines are framed. The objective of this study was to explore the areas to improve in the Drugs Act and help foster the use of safe, efficacious and quality drugs. Method: The Drugs Act 1978 was critically analyzed focusing on the strengths, weaknesses, opportunities, and threats of the act as of current scenario. Result: After critically analyzing the drugs act 1978 we found out that there is lack in regulations of use of cosmetics, newer biotechnology products, nutraceuticals, veterinary product, innovative pharmaceutical products as well as the online pharmacy services. Conclusion: A major amendment and periodic revision is required with the consequence of meeting timely needs and promoting the idea of safety and efficacy in drug related activities.

Individuals recently diagnosed with a cardiovascular disease are at higher risk of developing a mental illness, with mortality increasing when both conditions are present.

SARS-CoV-2 polymerase chain reaction (PCR) tests generally report only binary (positive or negative) outcomes. Quantitative PCR tests can provide epidemiological information on viral transmission patterns in populations. SARS-CoV-2 transmission patterns during India’s SARS-CoV-2 viral waves remain largely undocumented. We analyzed 2.7 million real-time PCR testing records collected in Mumbai, a bellwether for other Indian cities. We used the inverse of cycle threshold (Ct) values to determine the community-level viral load. We quantified wave-specific differences by age, sex, and slum population density. Overall, PCR positivity was 3.4% during non-outbreak periods, rising to 23.2% and 42.8% during the original (June–November 2020) and Omicron waves (January 2022), respectively, but was a surprisingly low 9.9% during the Delta wave (March–June 2021; which had the largest increase in COVID deaths). The community-level median Ct values fell and rose ~7–14 days prior to PCR positivity rates. Viral loads were four-fold higher during the Delta and Omicron waves than during non-outbreak months. The Delta wave had high viral loads at older ages, in women, and in areas of higher slum density. During the Omicron wave, differences in viral load by sex and slum density had disappeared, but older adults continued to show a higher viral load. Mumbai’s viral waves had markedly high viral loads representing an early signal of the pandemic trajectory. Ct values are practicable monitoring tools.

Preference for sons and smaller families and, in the case of China, a one-child policy, have contributed to missing girl births in India and China over the last few decades due to sex-selective abortions. Selective abortion occurs also among Indian and Chinese diaspora, but their variability and trends over time are unknown. We examined conditional sex ratio (CSR) of girl births per 1000 boy births among second or third births following earlier daughters or sons in India, China, and their diaspora in Australia, Canada, United Kingdom (UK), and United States (US) drawing upon 18.4 million birth records from census and nationally representative surveys from 1999 to 2019. Among Indian women, the CSR in 2016 for second births following a first daughter favoured boys in India (866), similar to those in diaspora in Australia (888) and Canada (882). For third births following two earlier daughters in 2016, CSRs favoured sons in Canada (520) and Australia (653) even more than in India (769). Among women in China outside the one-child restriction, CSRs in 2015 for second order births somewhat favoured more girls after a first son (1154) but more heavily favoured boys after a first daughter (561). Third-birth CSRs generally fell over time among diaspora, except among Chinese diaspora in the UK and US. In the UK, third-birth CSRs fell among Indian but not among other South Asian diasporas. Selective abortion of girls is notable among Indian diaspora, particularly at higher-order births.

Introduction: Neuronavigation guided biopsy (Frameless and Framebased stereotactic) is a simplified procedure which helps the neurosurgeons to precisely obtain the biopsy of intracranial lesions to establish the complex histopathological diagnosis.These procedures are commonly performed at our centre. The small tissue sample acquired when viewed against the vast heterogenicity of lesions and the rapidly progressive nature of few tumours make the adequacy of sample, an important parameter in determining the effectiveness of the procedure, which also has profound financial and disease related impact on the patients’ life. The objective of this study was to determine the rate of adequate sample for histopathological examination from intracranial lesions. Methods: A prospective observational study was done in 49 patients who underwent frameless and framebased biopsies at National Neurological Referral Centre,Bir Hospital in one year. Results: A total of 36 (73.5%) patients underwent frameless biopsy and 13(23.5%) patients underwent frame based stereotactic biopsy of intracranial lesions.Overall diagnostic yield was 89.8% with Frameless procedure giving histopathological diagnostic yield of 91.66% and framebased procedure had diagnostic yield of 84.61%.Hematoma occurred in 2 patients and seizure occurred in one patient. Majority of histopathological diagnosis was Glioblastoma(44.9%). Conclusion: Neuronavigation guided biopsy sample of intracranial lesions obtained for histopathological diagnosis is adequate in establishing the final histopathological diagnosis which helps in enhancing patient management and outcome.

Giant aneurysms are lesions with diameter greater than or equal to 25 mm. They are uncommon lesions presenting with features of mass effect and rarely rupture. Diagnosis confirmed on angiography. This case describes a young female with giant paraclinoid internal carotid artery aneurysm. The patient was managed with superficial temporal artery to middle cerebral artery bypass with aneurysm trapping. Keywords Giant aneurysm, STA-MCA bypass, aneurysm trapping

Background Stereotactic surgery or stereotaxy is a minimally invasive form of surgical intervention which makes use of a three-dimensional coordinate system to locate small targets inside the body and to perform on them some action such as ablation, biopsy, lesion, injection, stimulation, implantation, radiosurgery (SRS), etc. Though it was developed a long time ago as a useful adjunct to brain lesions evaluation, use in Nepal is quite recent. Materials and Methods The study included eight patients who underwent frame based stereotactic biopsy and pathological evaluation of specimen at National Academy of Medical Sciences (NAMS). Results Out of eight patients the results were positive in seven patient and negative in one patient. Conclusions The basic advantages of stereotaxy were realized in our cases with minimal morbidity and no mortality. Craniotomy for biopsy could be avoided.

The focus of this paper is on strategic approaches for establishing population-based prospective cohorts that collect and store biological samples from very large numbers of participants to help identify the determinants of common health outcomes. In particular, it aims to address key issues related to investigation of genetic, as well as social, environmental, and ancestral, diversity; generation of detailed genetic and other types of assay data; collection of detailed lifestyle and environmental exposure information; follow-up and characterization of incident health outcomes; and overcoming obstacles to data sharing and access (including capacity building). It concludes that there is a need for strategic planning at an international level (rather than the current ad hoc approach) toward the development of a carefully selected set of deeply characterized large-scale prospective cohorts that are readily accessible by researchers around the world.

Objective We sought to quantify the impact of vaping introduction on cigarette smoking across settings with varied regulatory approaches to vaping.Design Interrupted time series analysis, adjusted for cigarette tax levels.Setting Four Canadian provinces, UK and Australia.Participants Entire population of smokers in each country.Interventions The year that vaping was widely introduced in each country.Primary and secondary outcome measures The primary outcome is cigarette consumption per adult, and the secondary outcome is smoking prevalence among young adults.Results Based on allowable nicotine levels, restrictions on e-cigarette advertising, sales and access, and taxation, the least to most restrictive jurisdictions were, in order, Alberta, Ontario, Quebec and British Columbia (all in Canada), UK and Australia. In most, but not all, settings where higher nicotine content was permitted in vaping products (66 mg/mL), vaping introduction led to a reduction in cigarette consumption per capita (Ontario: p=0.037, Quebec: p=0.007) or in smoking prevalence among young adults (Alberta men, p=0.027; Quebec men, p=0.008; Quebec women, p=0.008). In the UK, where the maximum permitted nicotine content in vaping products was 20 mg/mL, vaping introduction slowed the declining trend in cigarette smoking among men aged 16–24 years (p=0.031) and 25–34 years (p=0.002) but not in cigarette consumption per adult. In Australia, where nicotine was not permitted in e-cigarettes, e-cigarette introduction slowed the declining trend in cigarette consumption per capita and in smoking prevalence among men aged 18–24 years (cigarette consumption: p=0.015, prevalence: p=0.044).Conclusion In environments that enable substitution of cigarettes with e-cigarettes, e-cigarette introduction reduces overall cigarette consumption. Thus, to reduce cigarette smoking, policies that encourage adults to substitute cigarette smoking with vaping should be considered.

The authors report a case of Moyamoya disease in a middle aged Nepali female. Though the disease is common in other parts of Asia only one case has been reported previously from Nepal. It should be suspected as a rare cause for spontaneous intracerebral hemorrhage in adults.

Craniopharyngiomas usually involve the sellar and suprasellar space. Very few cases of craniopharyngiomas arising in the posterior fossa without extension to the sellar and suprasellar space have been reported in literature. This case describes a patient with craniopharyngioma confined only to the ventricular system.

Abstract Background Validated algorithms to classify type 1 and 2 diabetes (T1D, T2D) are mostly limited to white pediatric populations. We conducted a large study in Hong Kong among children and adults with diabetes to develop and validate algorithms using electronic health records (EHRs) to classify diabetes type against clinical assessment as the reference standard, and to evaluate performance by age at diagnosis. Methods We included all people with diabetes (age at diagnosis 1.5–100 years during 2002–15) in the Hong Kong Diabetes Register and randomized them to derivation and validation cohorts. We developed candidate algorithms to identify diabetes types using encounter codes, prescriptions, and combinations of these criteria (“combination algorithms”). We identified 3 algorithms with the highest sensitivity, positive predictive value (PPV), and kappa coefficient, and evaluated performance by age at diagnosis in the validation cohort. Results There were 10,196 (T1D n = 60, T2D n = 10,136) and 5101 (T1D n = 43, T2D n = 5058) people in the derivation and validation cohorts (mean age at diagnosis 22.7, 55.9 years; 53.3, 43.9% female; for T1D and T2D respectively). Algorithms using codes or prescriptions classified T1D well for age at diagnosis

Objective: Tobacco taxes are a well-established cost-effective policy to prevent Noncommunicable Diseases. This paper evaluates the expected effects of a tobacco tax increase on the Sustainable Development Goals in Colombia.Methods: We use microsimulation to build an artificial society that mimics the observed characteristics of Colombia’s population, and from there we simulate the behavioral response to a tax increase of COP$4,750 (an increase that has been discussed by policy makers and legislators) and the subsequent effects in all SDGs.Results: The tobacco tax hike reduces the number of smokers (from 4.51 to 3.45 MM smokers) and smoking intensity, resulting in a drop in the number of cigarettes smoked in Colombia (from 332.3 to 215.5 MM of 20-stick packs). Such reduction is expected to decrease premature mortality, healthcare costs, poverty and people facing catastrophic expenditure on healthcare, to increase health, income and gender equity, and to strengthen domestic resource mobilization even in the presence of illicit cigarettes.Conclusion: Tobacco taxes are an effective intervention for public health and a powerful instrument to advance on the 2030 Sustainable Development Agenda.Relevance: A comprehensive analysis of the impact of tobacco taxes on all areas of Sustainable Development is missing in the empirical literature. Such perspective is needed to break the barriers for further tobacco tax increases by gathering wider societal support, especially from stakeholders and key decision makers from development areas other than health.SDG Nr: SDG3 (health), SDG 1 (no poverty), SDG 4 (education), SDG 5 (gender equality), SDG6 (water), SDG10 (inequality), SDG12 (responsible production and consumption), SDG17 (partnerships).

Summary: Background: Sierra Leone's child and maternal mortality rates are among the highest in the world. However, little is known about the causes of premature mortality in the country. To rectify this, the Ministry of Health and Sanitation of Sierra Leone launched the Sierra Leone Sample Registration System (SL-SRS) of births and deaths. Here, we report cause-specific mortality from the first SL-SRS round, representing deaths from 2018 to 2020. Methods: The Countrywide Mortality Surveillance for Action platform established the SL-SRS, which involved conducting electronic verbal autopsies in 678 randomly selected villages and urban blocks throughout the country. 61 surveyors, in teams of four or five, enrolled people and ascertained deaths of individuals younger than 70 years in 2019–20, capturing verbal autopsies on deaths from 2018 to 2020. Centrally, two trained physicians independently assigned causes of death according to the International Classification of Diseases (tenth edition). SL-SRS death proportions were applied to 5-year mortality averages from the UN World Population Prospects (2019) to derive cause-specific death totals and risks of death nationally and in four Sierra Leone regions, with comparisons made with the Western region where Freetown, the capital, is located. We compared SL-SRS results with the cause-specific mortality estimates for Sierra Leone in the 2019 WHO Global Health Estimates. Findings: Between Sept 1, 2019, and Dec 15, 2020, we enrolled 343 000 people and ascertained 8374 deaths of individuals younger than 70 years. Malaria was the leading cause of death in children and adults, nationally and in each region, representing 22% of deaths under age 70 years in 2020. Other infectious diseases accounted for an additional 16% of deaths. Overall maternal mortality ratio was 510 deaths per 100 000 livebirths (95% CI 483–538), and neonatal mortality rate was 31·1 deaths per 1000 livebirths (95% CI 30·4–31·8), both among the highest rates in the world. Haemorrhage was the major cause of maternal mortality and birth asphyxia or trauma was the major cause of neonatal mortality. Excess deaths were not detected in the months of 2020 corresponding to the peak of the COVID-19 pandemic. Half of the deaths occurred in rural areas and at home. If the Northern, Eastern, and Southern regions of Sierra Leone had the lower death rates observed in the Western region, about 20 000 deaths (just over a quarter of national total deaths in people younger than 70 years) would have been avoided. WHO model-based data vastly underestimated malaria deaths and some specific causes of injury deaths, and substantially overestimated maternal mortality. Interpretation: Over 60% of individuals in Sierra Leone die prematurely, before age 70 years, most from preventable or treatable causes. Nationally representative mortality surveys such as the SL-SRS are of high value in providing reliable cause-of-death information to set public health priorities and target interventions in low-income countries. Funding: Bill & Melinda Gates Foundation, Canadian Institutes of Health Research, Queen Elizabeth Scholarship Program.

Background: Understanding vaccination intention during early vaccination rollout in Canada can help the government's efforts in vaccination education and outreach. Method: Panel members age 18 and over from the nationally representative Angus Reid Forum were invited to complete an online survey about their experience with COVID-19, including their intention to get vaccinated. Respondents were asked “When a vaccine against the coronavirus becomes available to you, will you get vaccinated or not?” Having no intention to vaccinate was defined as choosing “No – I will not get a coronavirus vaccination” as a response. Odds ratios and predicted probabilities are reported for no vaccine intentionality in demographic groups. Findings: 14,621 panel members completed the survey. Having no intention to vaccinate against COVID-19 is relatively low overall (9%) with substantial variation among demographic groups. Being a resident of Alberta (predicted probability = 15%; OR 0.58 [95%CI 0.14-2.24]), aged 40-59 (predicted probability = 12%; OR 0.87 [0.78-0.97]), identifying as a visible minority (predicted probability = 15%; OR 0.56 [0.37-0.84]), having some college level education or lower (predicted probability = 14%) and living in households of at least five members (predicted probability = 13%; OR 0.82 [0.76-0.88]) are related to lower vaccination intention. Interpretation: The study identifies population groups with greater and lesser intention to vaccinate in Canada. As the Canadian COVID-19 vaccination effort continues, policymakers may use this information to focus outreach, education, and other efforts on the latter groups, which also have had higher risks for contracting and dying from COVID-19. Funding: Pfizer Global Medical, Unity Health Foundation, Canadian COVID-19 Immunity Task Force.

Background: The cardiovascular outcomes of hypertension and diabetes in India have never been studied at the national level. Objectives: We conducted a nationally-representative proportional mortality study to measure the associations of hypertension and diabetes with premature mortality due to ischemic heart disease (IHD) and stroke among Indian adults. Methods: We determined causes of death by verbal autopsy from 2001–14 among 2.4 million households. We defined cases as those who died of the study outcomes and controls as those who died of injuries, respiratory causes, or cancer. We used multivariable logistic regression models to compute adjusted odds ratios (OR) measuring the association of hypertension and diabetes with IHD or stroke mortality, population-attributable fractions (PAF), and time trends. Results: The mean age at death was 55.6 (standard deviation 9.9) years for IHD, 58.2 (9.0) years for stroke, and 46.8 (injury) to 59.8 (respiratory) years for controls. There were more men among both the cases (IHD: 70.1%; stroke: 59.0%) and controls (injury: 76.6%; cancer: 55.4%; respiratory: 59.8%). Hypertension was associated with six- to eight-fold increases in the odds of IHD (OR 5.9, 99% CI 5.6–6.2) and stroke mortality (7.9, 7.4–8.5). Diabetes was associated with double the odds (1.9, 1.7–2.0) of IHD mortality and increased odds of stroke mortality (1.6, 1.4–1.7). Hypertension accounted for an increasing PAF of IHD mortality and decreasing PAF of stroke mortality. Diabetes was associated with relatively lower PAFs and variable time trends. Conclusions: Hypertension is associated with an unexpectedly high burden of cardiovascular mortality, and contributes to an increasing proportion of IHD deaths and a decreasing proportion of stroke deaths. Better management of hypertension and diabetes is urgently required to reduce premature cardiovascular mortality.

Abstract Background A verbal autopsy (VA) is a post-hoc written interview report of the symptoms preceding a person’s death in cases where no official cause of death (CoD) was determined by a physician. Current leading automated VA coding methods primarily use structured data from VAs to assign a CoD category. We present a method to automatically determine CoD categories from VA free-text narratives alone. Methods After preprocessing and spelling correction, our method extracts word frequency counts from the narratives and uses them as input to four different machine learning classifiers: naïve Bayes, random forest, support vector machines, and a neural network. Results For individual CoD classification, our best classifier achieves a sensitivity of.770 for adult deaths for 15 CoD categories (as compared to the current best reported sensitivity of.57), and.662 with 48 WHO categories. When predicting the CoD distribution at the population level, our best classifier achieves.962 cause-specific mortality fraction accuracy for 15 categories and.908 for 48 categories, which is on par with leading CoD distribution estimation methods. Conclusions Our narrative-based machine learning classifier performs as well as classifiers based on structured data at the individual level. Moreover, our method demonstrates that VA narratives provide important information that can be used by a machine learning system for automated CoD classification. Unlike the structured questionnaire-based methods, this method can be applied to any verbal autopsy dataset, regardless of the collection process or country of origin.

Abstract Background Verbal 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. Methods We 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. Results The 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. Conclusions While 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 registration ClinicalTrials.gov, NCT02810366. Submitted on 11 April 2016.

The Disease Control Priorities (DCP) project has substantially influenced national and global health priorities since 1993. DCP’s basic framework involves identification of disease burdens based on premature deaths and disability and application of the most cost-effective interventions to the largest burdens, taking into account local feasibility. The future impact of DCP will need to take into account growing national wealth and needs for endogenous capacity to design and implement evidence-based interventions, the rapid emergence of non-communicable disease (NCD), and the universal health coverage (UHC) agenda. This in turn requires three improvements to the DCP framework: greater local capacity, supported by a global effort to cost health interventions, stronger national and international technical capacity and networks, and the use of direct, versus modelled, mortality data to assign priorities and to assess progress. Properly done, DCP could be as important over the next 25 years as it has been in the past 25 years.

Summary: Background: Half of the world's missing female births occur in India, due to sex-selective abortion. It is unknown whether selective abortion of female fetuses has changed in recent years across different birth orders. We sought to document the trends in missing female births, particularly among second and third children, at national and state levels. Methods: We examined birth histories from five nationally representative household surveys (National Family Health Surveys 1–4 and District Level Household Survey 2) to compute the conditional sex ratio (defined as the number of girls born per 1000 boys depending on previous birth sex) in India during 1981–2016. We estimated decadal variation in conditional sex ratio for 1987–96, 1997–2006, and 2007–16, and quantified trends in the numbers of missing female births for the states constituting >95% of India's population, as well as in 5-year intervals for each survey round. We used multivariate logistic regression to calculate the odds ratio of a second (or third) girl depending on the sex of the earlier child (or children), adjusting for education, wealth, religion, caste, and place of residence. Findings: We assessed 2·1 million birth histories across the five surveys. Applying the conditional sex ratios from the surveys to national births, we found that 13·5 million female births were missing during the three decades of observation (1987–2016), on the basis of a natural sex ratio of 950 girls per 1000 boys. Missing female births increased from 3·5 million in 1987–96 to 5·5 million in 2007–16. Contrasting the conditional sex ratio from the first decade of observation (1987–96) to the last (2007–16) showed worsening for the whole of India and almost all states, among both birth orders. Punjab, Haryana, Gujarat, and Rajasthan had the most skewed sex ratios, comprising nearly a third of the national totals of missing second-born and third-born females at birth. From about 1986, the conditional sex ratio for second-order or third-order births after an earlier daughter or daughters diverged notably from that after an earlier son or sons. From 1981 to 2016, the sex ratio for second-born children after an earlier daughter decreased from 930 (99% CI 869–990) to 885 (859–912), and that for third-born children after two earlier daughters decreased from 968 (866–1069) to 788 (746–830). The probability of missing girls was mostly determined by earlier daughters, even after considering wealth quintile and education levels. The conditional sex ratio among the richest and most educated mothers was most distorted compared with lower wealth and education groups, and generally decreased with time, until a modest improvement in 2007–16. Interpretation: In contrast to the substantial improvements in female child mortality in India, missing female births, driven by selective abortion of female fetuses, continues to increase across the states. Inclusion of a question on sex composition of births in the forthcoming census would provide local information on sex-selective abortion in each village and urban area of the country. Funding: None. Translation: For the Hindi translation of the abstract see Supplementary Materials section.

Introduction The Healthy Life Trajectories Initiative is an international consortium comprising four harmonised but independently powered trials to evaluate whether an integrated intervention starting preconceptionally will reduce non-communicable disease risk in their children. This paper describes the protocol of the India study.Methods and analysis The study set in rural Mysore will recruit ~6000 married women over the age of 18 years. The village-based cluster randomised design has three arms (preconception, pregnancy and control; 35 villages per arm). The longitudinal multifaceted intervention package will be delivered by community health workers and comprise: (1) measures to optimise nutrition; (2) a group parenting programme integrated with cognitive–behavioral therapy; (3) a lifestyle behaviour change intervention to support women to achieve a diverse diet, exclusive breast feeding for the first 6 months, timely introduction of diverse and nutritious infant weaning foods, and adopt appropriate hygiene measures; and (4) the reduction of environmental pollution focusing on indoor air pollution and toxin avoidance.The primary outcome is adiposity in children at age 5 years, measured by fat mass index. We will report on a host of intermediate and process outcomes. We will collect a range of biospecimens including blood, urine, stool and saliva from the mothers, as well as umbilical cord blood, placenta and specimens from the offspring.An intention-to-treat analysis will be adopted to assess the effect of interventions on outcomes. We will also undertake process and economic evaluations to determine scalability and public health translation.Ethics and dissemination The study has been approved by the institutional ethics committee of the lead institute. Findings will be published in peer-reviewed journals. We will interact with policy makers at local, national and international agencies to enable translation. We will also share the findings with the participants and local community through community meetings, newsletters and local radio.Trial registration number ISRCTN20161479, CTRI/2020/12/030134; Pre-results.

Background. Acute pancreatitis (AP) is associated with extensive fluid sequestration. The aim of this study was to determine association of fluid sequestration at 48 hours after hospital admission (FS48) in AP patients with demographics, clinical parameters, and outcomes of AP. Methods. A prospective observational study was carried out on all adult patients with AP admitted to Tribhuvan University Teaching Hospital, Nepal, from January to September 2017. FS48 was calculated as the difference between fluid input and output in the first 48 hours of admission. The Kruskal-Wallis test with post hoc Dunn’s test examined the difference in FS48 between mild AP, moderately severe AP, and severe AP. Linear regression analysis was used to evaluate association between FS48 with patients’ characteristics and outcomes of AP. Outcomes of AP assessed included pancreatic necrosis, persistent organ failure, length of stay, and in-hospital mortality. Results. Eighty patients (median age 44 years; 57% male) with a median FS48 of 1610 mL were evaluated. The median FS48 for mild AP, moderately severe AP, and severe AP were 1,180 mL, 2,380 mL, and 3,500 mL, respectively. There was a significant difference in pairwise comparisons between mild AP and moderately severe AP, along with mild AP and severe AP. Younger age, other etiology, and higher creatinine were independently associated with increased FS48. Increased FS48 was significantly associated with pancreatic necrosis, persistent organ failure, and in-hospital mortality. Conclusions. In our study population, younger age and higher creatinine were predictors of increased FS48. Increased FS48 was associated with poorer outcomes of AP.

The World Health Organization call to halve global snakebite deaths by 2030 will require substantial progress in India. We analyzed 2833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001 to 2014, and conducted a systematic literature review from 2000 to 2019 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. Nearly half occurred at ages 30–69 years and over a quarter in children < 15 years. Most occurred at home in the rural areas. About 70% occurred in eight higher burden states and half during the rainy season and at low altitude. The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. More crudely, we estimate 1.11–1.77 million bites in 2015, of which 70% showed symptoms of envenomation. Prevention and treatment strategies might substantially reduce snakebite mortality in India.

Background: In India, about one million deaths occur every year due to smoking. Tobacco taxation is the most effective intervention in reducing smoking. In this paper, we examine the impact of a one-time large cigarette price increase, through an increase in excise tax, on health and financing outcomes in four Indian states. Methods: We used extended cost-effectiveness analysis to estimate, across income quintiles, the life-years gained, treatment cost averted, number of men avoiding catastrophic health expenditures and extreme poverty, additional tax revenue collected, and savings to the Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB-PMJAY) with a cigarette price increase to Indian Rupees (INR) 10 plus 10% ad valorem in four Indian states. Results: With the price increase, about 1.5 million men would quit smoking across the four states, with the bottom income group having 7.4 times as many quitters as the top income group (485,725 vs 65,762). As a result of quitting, about 665,000 deaths would be averted. This would yield about 11.9 million life-years, with the bottom income group gaining 7.3 times more than the top income group. Of the INR 1,729 crore in treatment cost averted, the bottom income group would avert 7.4 times more than the top income group. About 454,000 men would avoid catastrophic health expenditures and 75,000 men would avoid falling into extreme poverty. The treatment cost and impoverishment averted would save about INR 672 crore in AB-PMJAY. The tax increase would in turn, generate an additional tax revenue of about INR 4,385 crore. In contrast to the distribution of health benefits, the extra revenue generated from the top income group would be about 3.1 times that from the bottom income group. Conclusions: Cigarette tax increase can provide significant health and economic gains and is a pro-poor policy for India.

In high-income countries, the biggest cause of premature death, defined as death before 70 years, is smoking of manufactured cigarettes. Smoking-related disease was responsible for about 41 million deaths in the United States, United Kingdom and Canada, cumulatively, from 1960 to 2020. Every million cigarettes smoked leads to one death in the US and Canada, but slightly more than one death in the UK. The 21st century hazards reveal that smokers who start smoking early in adult life and do not quit lose a decade of life expectancy versus non-smokers. Cessation, particularly before age 40 years, yields large reductions in mortality risk. Up to two-thirds of deaths among smokers are avoidable at non-smoking death rates, and former smokers have about only a quarter of the excess risk of death compared to current smokers. The gap between scientific and popular understanding of smoking hazards is surprisingly large.

Random population-based surveys to estimate prevalence of SARS-CoV2 infection causing coronavirus disease (COVID-19) are useful to understand distributions and predictors of the infection. In April 2020, the first-ever nationally representative survey in Canada polled 4,240 adults age 18 years and older about self-reported COVID experience in March, early in the epidemic. We examined the levels and predictors of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than in older adults, and among visible minorities. Overall, only 3% of respondents and/or household members reported testing for SARS-CoV-2. Being tested was associated with having COVID symptoms, Indigenous identity, and living in Quebec. Periodic nationally representative surveys of symptoms, as well as SARS-CoV-2 antibodies, are required in many countries to understand the pandemic and prepare for the future.

Abstract Background Bronchobiliary fistula and hepatic artery pseudoaneurysm are rare complications of hepatic trauma. There are isolated case reports for both pseudoaneurysm and bronchobiliary fistula following hepatic trauma but there aren’t reports of both conditions developing in a single patient. Case presentation This case describes an 18 year old hindu male who developed right hepatic artery pseudoaneurysm and bronchobiliary fistula following blunt abdominal trauma. Patient was managed with exploratory laparotomy followed by coil embolization and Endoscopic retrograde cholangiopancreatography stenting respectively. Conclusion Rare complications of liver trauma include pseudoaneurysm and bronchobiliary fistula. These complications can rarely co- exist in a single patient.

Abstract Background Decreasing trends in measles mortality have been reported in recent years. However, such estimates of measles mortality have depended heavily on assumed regional measles case fatality risks (CFRs) and made little use of mortality data from low- and middle-income countries in general and India, the country with the highest measles burden globally, in particular. Methods We constructed a dynamic model of measles transmission in India with parameters that were empirically inferred using spectral analysis from a time series of measles mortality extracted from the Million Death Study, an ongoing longitudinal study recording deaths across 2.4 million Indian households and attributing causes of death using verbal autopsy. The model was then used to estimate the measles CFR, the number of measles deaths, and the impact of vaccination in 2000–2015 among under-five children in India and in the states of Bihar and Uttar Pradesh (UP), two states with large populations and the highest numbers of measles deaths in India. Results We obtained the following estimated CFRs among under-five children for the year 2005: 0.63% (95% confidence interval (CI): 0.40–1.00%) for India as a whole, 0.62% (0.38–1.00%) for Bihar, and 1.19% (0.80–1.75%) for UP. During 2000–2015, we estimated that 607,000 (95% CI: 383,000–958,000) under-five deaths attributed to measles occurred in India as a whole. If no routine vaccination or supplemental immunization activities had occurred from 2000 to 2015, an additional 1.6 (1.0–2.6) million deaths for under-five children would have occurred across India. Conclusions We developed a data- and model-driven estimation of the historical measles dynamics, CFR, and vaccination impact in India, extracting the periodicity of epidemics using spectral and coherence analysis, which allowed us to infer key parameters driving measles transmission dynamics and mortality.

Summary: Background: Many countries, including India, seek locally constructed disease burden estimates comprising mortality and loss of health to aid priority setting for the prevention and treatment of diseases. We created the National Burden Estimates (NBE) to provide transparent and understandable disease burdens at the national and subnational levels, and to identify gaps in knowledge. Methods: To calculate the NBE for India, we combined 2017 UN death totals with national and subnational mortality rates for 2010–17 and causes of death from 211 166 verbal autopsy interviews in the Indian Million Death Study for 2010–14. We calculated years of life lost (YLLs) and years lived with disability (YLDs) for 2017 using published YLD–YLL ratios from WHO Global Health Estimates. We grouped causes of death into 45 groups, including ill-defined deaths, and summed YLLs and YLDs to calculate disability-adjusted life-years (DALYs) for these causes in eight age groups covering rural and urban areas and 21 major states of India. Findings: In 2017, there were about 9·7 million deaths and 486 million DALYs in India. About three quarters of deaths and DALYs occurred in rural areas. More than a third of national DALYs arose from communicable, maternal, perinatal, and nutritional disorders. DALY rates in rural areas were at least twice those of urban areas for perinatal and nutritional conditions, chronic respiratory diseases, diarrhoea, and fever of unknown origin. DALY rates for ischaemic heart disease were greater in urban areas. Injuries caused 11·4% of DALYs nationally. The top 15 conditions that accounted for the most DALYs were mostly those causing mortality (ischaemic heart disease, perinatal conditions, chronic respiratory diseases, diarrhoea, respiratory infections, cancer, stroke, road traffic accidents, tuberculosis, and liver and alcohol-related conditions), with disability mostly due to a few conditions (nutritional deficiencies, neuropsychiatric conditions, vision and other sensory loss, musculoskeletal disorders, and genitourinary diseases). Every condition that was common in one part of India was uncommon elsewhere, suggesting state-specific priorities for disease control. Interpretation: The NBE method quantifies disease burden using transparent, intuitive, and reproducible methods. It provides a simple, locally operable tool to aid policy makers in priority setting in India and other low-income and middle-income countries. The NBE underlines the need for many more countries to collect nationally representative cause of death data, paired with focused surveys of disability. Funding: Ministry of Health and Family Welfare, Government of India.

Background: Limited infrastructure is available to collect, store and transport venous blood in field epidemiological studies. Dried blood spot (DBS) is a robust potential alternative sample source for epidemiological studies & bio banking. A stable source of genomic DNA (gDNA) is required for long term storage in bio bank for its downstream applications. Our objective is to optimize the methods of gDNA extraction from stored DBS and with the aim of revealing its utility in large scale epidemiological studies. Methods: The purpose of this study was to extract the maximum amount of gDNA from DBS on Whatman 903 protein saver card. gDNA was extracted through column (Qiagen) & magnetic bead based (Invitrogen) methods. Quantification of extracted gDNA was performed with a spectrophotometer, fluorometer, and integrity analyzed by agarose gel electrophoresis. Result: Large variation was observed in quantity & purity (260/280 ratio, 1.8-2.9) of the extracted gDNA. The intact gDNA bands on the electrophoresis gel reflect the robustness of DBS for gDNA even after prolonged storage time. The extracted gDNA amount 2.16 – 24 ng/µl is sufficient for its PCR based downstream application, but unfortunately it can’t be used for whole genome sequencing or genotyping from extracted gDNA. Sequencing or genotyping can be achieved by after increasing template copy number through whole genome amplification of extracted gDNA. The obtained results create a base for future research to develop high-throughput research and extraction methods from blood samples. Conclusion: The above results reveal, DBS can be utilized as a potential and robust sample source for bio banking in field epidemiological studies.

Control of pneumonia and diarrhea mortality in India requires understanding of their etiologies. We combined time series analysis of seasonality, climate region, and clinical syndromes from 243,000 verbal autopsies in the nationally representative Million Death Study. Pneumonia mortality at 1 month-14 years was greatest in January (Rate ratio (RR) 1.66, 99% CI 1.51–1.82; versus the April minimum). Higher RRs at 1–11 months suggested respiratory syncytial virus (RSV) etiology. India’s humid subtropical region experienced a unique summer pneumonia mortality. Diarrhea mortality peaked in July (RR 1.66, 1.48–1.85) and January (RR 1.37, 1.23–1.48), while deaths with fever and bloody diarrhea (indicating enteroinvasive bacterial etiology) showed little seasonality. Combining mortality at ages 1–59 months with prevalence surveys, we estimate 40,600 pneumonia deaths from Streptococcus pneumoniae, 20,700 from RSV, 12,600 from influenza, and 7200 from Haemophilus influenzae type b and 24,700 diarrheal deaths from rotavirus occurred in 2015. Careful mortality studies can elucidate etiologies and inform vaccine introduction.

Summary: Background: Firearm mortality is a leading, and largely avoidable, cause of death in the USA, Mexico, Brazil, and Colombia. We aimed to assess the changes over time and demographic determinants of firearm deaths in these four countries between 1990 and 2015. Methods: In this comparative analysis of firearm mortality, we examined national vital statistics data from 1990–2015 from four publicly available data repositories in the USA, Mexico, Brazil, and Colombia. We extracted medically-certified deaths and underlying population denominators to calculate the age-specific and sex-specific firearm deaths and the risk of firearm mortality at the national and subnational level, by education for all four countries, and by race or ethnicity for the USA and Brazil. Analyses were stratified by intent (homicide, suicide, unintentional, or undetermined). We quantified avoidable mortality for each country using the lowest number of subnational age-specific and period-specific death rates. Findings: Between 1990 and 2015, 106·3 million medically-certified deaths were recorded, including 2 472 000 firearm deaths, of which 851 000 occurred in the USA, 272 000 in Mexico, 855 000 in Brazil, and 494 000 in Colombia. Homicides accounted for most of the firearm deaths in Mexico (225 000 [82·7%]), Colombia (463 000 [93·8%]), and Brazil (766 000 [89·5%]). Suicide accounted for more than half of all firearm deaths in the USA (479 000 [56·3%]). In each country, firearm mortality was highest among men aged 15–34 years, accounting for up to half of the total risk of death in that age group. During the study period, firearm mortality risks increased in Mexico and Brazil but decreased in the USA and Colombia, with marked national and subnational geographical variation. Young men with low educational attainment were at increased risk of firearm homicide in all four countries, and in the USA and Brazil, black and brown men, respectively, were at the highest risk. The risk of firearm homicide was 14 times higher in black men in the USA aged 25–34 years with low educational attainment than comparably-educated white men (1·52% [99% CI 1·50–1·54] vs 0·11% [0·10–0·12]), and up to four times higher than in comparably-educated men in Brazil, Colombia, and Mexico. In the USA, the risk of firearm homicide was more than 30 times higher in black men with post-secondary education than comparably educated white men. If countries could achieve the same firearm mortality rates nationally as in their lowest-burden states, 1 777 800 firearm deaths at all ages and in both sexes could be avoided, including 1 028 000 deaths in men aged 15–34 years. Interpretation: Firearm mortality in the USA, Mexico, Brazil, and Colombia is highest among young adult men, and is strongly associated with race and ethnicity, and low education levels. Reductions in firearm deaths would improve life expectancy, particularly for black men in the USA, and would reduce racial and educational disparities in mortality. Funding: Canadian Institutes of Health Research and the University of Toronto Connaught Global Challenge.

Summary: Background: India had the largest number of under-5 deaths of all countries in 2015, with substantial subnational disparities. We estimated national and subnational all-cause and cause-specific mortality among children younger than 5 years annually in 2000–15 in India to understand progress made and to consider implications for achieving the Sustainable Development Goal (SDG) child survival targets. Methods: We used a multicause model to estimate cause-specific mortality proportions in neonates and children aged 1–59 months at the state level, with causes of death grouped into pneumonia, diarrhoea, meningitis, injury, measles, congenital abnormalities, preterm birth complications, intrapartum-related events, and other causes. AIDS and malaria were estimated separately. The model was based on verbal autopsy studies representing more than 100 000 neonatal deaths globally and 16 962 deaths among children aged 1–59 months at the subnational level in India. By applying these proportions to all-cause deaths by state, we estimated cause-specific numbers of deaths and mortality rates at the state, regional, and national levels. Findings: In 2015, there were 25·121 million livebirths in India and 1·201 million under-5 deaths (under-5 mortality rate 47·81 per 1000 livebirths). 0·696 million (57·9%) of these deaths occurred in neonates. There were disparities in child mortality across states (from 9·7 deaths [Goa] to 73·1 deaths [Assam] per 1000 livebirths) and regions (from 29·7 deaths [the south] to 63·8 deaths [the northeast] per 1000 livebirths). Overall, the leading causes of under-5 deaths were preterm birth complications (0·330 million [95% uncertainty range 0·279–0·367]; 27·5% of under-5 deaths), pneumonia (0·191 million [0·168–0·219]; 15·9%), and intrapartum-related events (0·139 million [0·116–0·165]; 11·6%), with cause-of-death distributions varying across states and regions. In states with very high under-5 mortality, infectious-disease-related causes (pneumonia and diarrhoea) were among the three leading causes, whereas the three leading causes were all non-communicable in states with very low mortality. Most states had a slower decline in neonatal mortality than in mortality among children aged 1–59 months. Ten major states must accelerate progress to achieve the SDG under-5 mortality target, while 17 are not on track to meet the neonatal mortality target. Interpretation: Efforts to reduce vaccine-preventable deaths and to reduce geographical disparities should continue to maintain progress achieved in 2000–15. Enhanced policies and programmes are needed to accelerate mortality reduction in high-burden states and among neonates to achieve the SDG child survival targets in India by 2030. Funding: Bill & Melinda Gates Foundation.

India comprises much of the persisting global childhood measles mortality. India implemented a mass second-dose measles immunization campaign in 2010. We used interrupted time series and multilevel regression to quantify the campaign’s impact on measles mortality using the nationally representative Million Death Study (including 27,000 child deaths in 1.3 million households surveyed from 2005 to 2013). 1–59 month measles mortality rates fell more in the campaign states following launch (27%) versus non-campaign states (11%). Declines were steeper in girls than boys and were specific to measles deaths. Measles mortality risk was lower for children living in a campaign district (OR 0.6, 99% CI 0.4–0.8) or born in 2009 or later (OR 0.8, 99% CI 0.7–0.9). The campaign averted up to 41,000–56,000 deaths during 2010–13, or 39–57% of the expected deaths nationally. Elimination of measles deaths in India is feasible.