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Abstract The risk factors for breast cancer have been defined in several studies but there is deficient data for specific subtypes. We report here the pathological characteristics of a breast cancer cohort and risk factors for patients with triple-negative disease. In this case–control study, a prospective breast cancer cohort was evaluated for demographic, reproductive, obesity-related and other risk factors using a validated questionnaire. Tumors were characterized for routine pathological characteristics and immunohistochemical markers of basal-like breast cancer. Patients with triple-negative breast cancer (TNBC) constituted cases and those with non-TNBC were controls. Odds ratios (OR) were calculated for each risk factor and independent associations were tested in an unconditional logistic regression analysis. Between 2011 and 2014, 1146 patients were recruited, of whom 912 [TNBC 266 (29.1%), non-TNBC 646 (70.9%)] with sufficient pathology material were analysed. Reproductive factors of parity, breastfeeding, age-at-menarche, age at first full-term pregnancy and oral contraceptive use were not significantly associated with TNBC. Higher body mass index (BMI > 24.9 vs ≤ 24.9, OR 0.89, 95%CI 0.63–1.24, p = 0.49) was not significantly associated while lesser waist circumference (> 80 cm vs ≤ 80 cm, OR 0.64, 95%CI 0.45–0.9, p = 0.012) and lower waist-to-hip ratio were significantly associated (> 0.85 vs ≤ 0.85, OR 0.72, 95%CI 0.51–1.0, p = 0.056), with TNBC. History of tobacco use was not significantly associated while lower socio-economic status was borderline associated with TNBC (socio-economic category > 5 versus ≤ 5, OR 0.73, 95%CI 0.50–1.06, p = 0.106). No factor was significant after adjustment for covariates. Central obesity seems to be preferentially associated with non-TNBC, and lower socio-economic status with TNBC in India, while most other conventional risk factors of breast cancer show no significant association with TNBC versus non-TNBC.

Screening along with treatment is the foremost tool for cervical cancer elimination in addition to vaccination strategies. At present, India lacks a comprehensive screening programme. There are huge issues in terms of feasibility, acceptability and implementation of the existing cervical screening programme in the country. Less than 2% (Urban-2.2% and Rural-1.7%) of women in India have been screened. The current strategy recommended by Ministry of Health and Family Welfare is Visual Inspection with Acetic Acid (VIA) every 5 years for women aged between 30 and 65 years. A significant improvement in terms of decreasing incidence and mortality of cervical cancer has been seen in two randomized controlled trials conducted in India. However, VIA lacks sensitivity, requires extensive training to be given to the medical staff for accurate diagnosis, has substantial operator variability and has less acceptability among women when compared to the newer methods of cervical cancer screening such as human papillomavirus (HPV) self-sampling. HPV self-sampling is a more sensitive, accurate and more acceptable method of cervical cancer screening for women in India and abroad. It can help the existing VIA-based strategy of cervical screening by increasing participation resulting in more population being screened in the various geographical regions and populations in India. However, VIA-based screening should also be continued because of its affordability and cost-effectiveness in India where there is a significant population belonging to low socio-economic background. There are numerous evidences such as systematic reviews, meta-analyses, randomised controlled trials of India and abroad that have been used as sources in this review article to come to the conclusion that HPV self-sampling is an acceptable, accurate and sensitive method that can be used as a primary screening tool in cervical cancer screening programmes globally and in India. It can also be used as an effective triage test for prioritising high-risk populations who require urgent and effective treatment for cervical pre-cancer and cancer. To conclude, HPV self-sampling should be integrated and implemented by the government and private sector in addition to VIA-based screening strategies for achieving the goal of cervical cancer elimination in India.

Background: In India, cervical cancer is the second-leading cause of cancer incidence among women. Socioeconomic factors play a vital role in cervical cancer survival. Objectives: This study assessed the role of education and income on disparities in time-to-treatment initiation (TTI) and its impact on cervical cancer survival. Materials and Methods: This was a retrospective facility-based record study conducted among newly treated cervical cancer patients registered in a tertiary medical care center in Mumbai between 2014 and 2016. Adjusted hazard ratio with a 95% confidence interval was reported. Results: In total, 1947 cervical cancer patients with a mean age of 52.89 (±10.55) years were included. The average number of days for TTI among highly educated patients was 27 versus 35 days for patients with no formal education. An increasing trend in survival was observed as education levels shift from no formal to higher education category (75.54%, 77.30%, and 85.10%, P = 0.01). All cause mortality was lower in cervical cancer patients with secondary education and above than illiterates (hazard ratio [HR] = 0.63, P < 0.01), among those with higher income (HR = 0.78, P = 0.04) than lower income and among who started on treatment within 30 days (HR = 0.90, P = 0.29) than patients who started treated after 30 days. Conclusions: Inferior survival is found for cervical cancer patients with lower education and income and who initiated treatment after 30 days. Hence, it is important to improve awareness and screening activities, especially among the lower socioeconomic groups, for early diagnosis and better treatment outcomes.

Introduction: The aim was to determine the prevalence and predictors of depression among less symptomatic COVID-19 patients. Methods: A questionnaire-based assessment was conducted among asymptomatic or mildly symptomatic COVID-19 patients when admitted in a COVID-19 facility (T1) and after 6 months (T2). Interviews were conducted using the Patient Health Questionnaire-9 instrument. Socio-demographic details and length of facility stay were recorded. Changes in scores between the two-time points T1 and T2 were compared. Factors predicting depression were determined using Chi-square and Mann–Whitney U test during facility stay, and those predicting worsening over time were obtained using multivariate regression models. Results: Among the 91.4% (n = 450) participants, prevalence of depression was 38.4% (95% confidence interval [CI] = 34.0–43.0) with a significant increase of 7.8-fold (95% CI = 4.8–12.8) in depression as the duration of stay increased beyond a median of 5 days. A significant association was observed between higher income and lower depression (odds ratios = 0.6, P = 0.03). 84% (n = 378) responded at the second timepoint assessment after a median of 6.62 months (T2). There was a significant difference observed between the 2.6% (n = 6) that worsened into depression at T2 and the 73.8% (n = 107) that improved out of depression at T2 (P ≤ 0.001). Age >45 years (P = 0.007), males (P = 0.011) and reinfection (P = 0.039) significantly led to worsening of depression. Conclusion: There is a need for actively detecting and managing depression in institutionally quarantined survivors, considering limiting such quarantine to no more than a week, and providing routine screening and care for depression beyond this period.

PURPOSEAlthough cancer is an important and growing public health issue in Nepal, the country lacked any population-based cancer registry (PBCR) until 2018. In this study, we describe the establishment of the PBCR for the first time in Nepal and use the registry data to understand incidence, mortality, and patterns of cancer in the Kathmandu Valley (consisting of Kathmandu, Lalitpur, and Bhaktapur districts), which comprises 10.5% of the estimated 29 million population of Nepal in 2018.MATERIALS AND METHODSThe PBCR collects information from facilities and communities through the active process. The facilities include cancer or general hospitals, pathology laboratories, hospice, and Ayurvedic centers. In the communities, the field enumerators or female community health volunteers collected the data from the households. In addition, the Social Security and Nursing Division under the Department of Health Services, which provides subsidy for cancer treatment of underprivileged patients, was another major source of data. The collected data were verified for residence, accuracy, and completeness and then entered and analyzed using CanReg5 software.RESULTSIn the Kathmandu Valley, the PBCR registered 2,156 new cancer cases with overall age-adjusted incidence rate for all cancers of 95.7 per 100,000 population (95.3 for males and 98.1 for females). The age-adjusted mortality rate for males was 36.3 (n = 365) and for females 27.0 (n = 305) per 100,000 population. We found that the commonest cancers in males were lung and stomach, whereas in females, they were breast and lung cancer. Gallbladder cancer was among the top five common cancers in both sex.CONCLUSIONThese findings provide a milestone to understand the cancer burden in the country for the first time using the PBCR and will be helpful to develop and prioritize cancer control strategies.

Background: Early thyroid cancers have excellent long-term outcomes, yet the word “cancer” draws unnecessary apprehension. This study aimed to define when the recommendations for observation and surveillance may be extended to early thyroid cancers at the population level. Methods: Non-metastasized thyroid cancers ≤40 mm diameter were identified from the 1975–2016 Surveillance, Epidemiology and End Results (SEER) database. Causes of death were compared across demographic data. Disease-specific outcomes were compared to the age-adjusted healthy United States (US) population. Survival estimates were computed using Kaplan–Meier and compared using the Cox proportional hazard model. Dynamic benchmarks impacting disease-specific overall survival were determined by decision tree modeling and tested by the Cox model. Results: Of the 28,728 thyroid cancers included in this study, 98.4% underwent some form of thyroid-specific treatment and were followed for a maximum of 10.9 years. This group had a 4.3% mortality rate at the end of follow-up (10.9 years maximum), with 13 times more deaths attributed to competing risks rather than thyroid cancer (stage T1a versus stage T1b, P=1.000; T1 versus T2, P26 mm impacted outcomes. Conclusion: Based on the current data, T1a and T1b nodules have similar survival outcomes and are not significantly impacted even when left untreated. Multi-institutional prospective studies are needed to confirm these findings so that current observation and surveillance recommendations can be extended to certain T1 thyroid nodules.

Background: In Punjab, esophageal carcinoma has been reported as leading cancer in rural population. Reason for this high incidence of esophageal carcinoma in this region is unknown. The life style of people in Punjab is different from those of other areas in India. Therefore, the risk factors contributing to esophageal carcinoma in Punjab may also be different than the other parts of India. There are no previous studies on risk factors for high incidence of esophageal carcinoma in this region. Use of pesticides is much higher in Punjab state. Also there is no evidence available for association of use of pesticides/fumigants in occurrence of esophageal carcinoma. Hence this study is planned to identify the risk factors, especially the role of chemical toxicity (Pesticides/fumigants/heavy metals) associated with development of esophageal carcinoma among inhibitants of Punjab. Methods: A case-control design will be used to identify potential risk factors associated with development of carcinoma esophagus in Punjab. Cases will be recruited from PGIMER, Chandigarh, Population based cancer registry Mansa, Sangrur, SAS Nagar and Punjab Cancer control cell. For each esophageal cancer case 2 controls will be selected after matching for gender, age and area of residence. A pre designed questionnaire, including demographic characteristics, family cancer history, personal medical history, height, weight, life-style (habits such as smoking, tobacco chewing, alcohol drinking, etc.), dietary habits, fumigants and pesticide usage and practices etc, will be used. Urine samples will be taken for the analysis of pesticide metabolites. Heavy metals analysis will be done in water samples. Oral health will be examined for mucosal changes as well as for oral hygiene. Discussion: This study will results in identification of risk factors for high occurrence of esophagus carcinoma in Punjab, so that measures for early detection, prevention and control of esophagus carcinoma could be initiated.

Background: Alcohol increases risk of cancer of oral cavity and pharynx, esophagus, colorectal, liver, larynx, and female breast. Objectives: The objective of this study was to determine the relationship of alcohol and cancer in India by meta-analysis. Methods: Systematic Medline searches were performed to identify all the published literature associating alcohol and cancer in India. Initially, we retrieved 1509 studies, but after applying inclusion and exclusion criteria, only 29 studies were found eligible for our meta-analysis. Results: Our meta-analysis shows that alcohol consumption increases the risk of cancer with the odds ratio (OR) of 2.32 (95% confidence interval [CI]: 1.50–3.47) in case–control studies and relative risk of 1.52 (95% CI: 0.97–2.51) in cohort studies. It also shows that risk of oral cavity cancer increases by two times (OR: 1.92, 95% CI: 1.54–3.96) in the population consuming alcohol. Publication analysis showed that studies included in the meta-analysis had wide variation, suggesting good representation all over the country. Conclusion: The result from our meta-analysis supports our hypothesis that alcohol consumption increases the risk of cancer, implying immediate cessation of the habit for cancer risk reduction.

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.

Objective To understand the outcome of hospitalised patients from Mumbai City, which had the highest number of COVID-19 cases in India.Design Observational study with follow-up.Setting Data extraction from medical records of patients with COVID-19 admitted to Nair Hospital & TN Medical College, Mumbai, India.Participants 689 patients with COVID-19 were admitted in the hospital from 26 March 2020 to 11 May 2020.Primary and secondary outcome measures In-hospital mortality; joint effect of comorbidity and age on the risk of dying.Results A total of 689 patients (median age 44 years) admitted with RT-PCR-confirmed COVID-19 were included in the study. Of these, 77.36% of patients were discharged alive while 22.64% died. 11.61% required some kind of oxygen support while 2.8% of patients required intensive care unit admissions. Older age (HR 2.88, 95% CI 2.09 to 3.98), presence of comorbidities (HR 2.56, 95% CI 1.84 to 3.55), history of hypertension (HR 3.19, 95% CI 1.67 to 6.08), and presence of symptoms at the time of admission (HR 3.21, 95% CI 1.41 to 7.26) were associated with increased risk of in-hospital mortality. Treatment with a combination of azithromycin with hydroxychloroquine, antiviral or steroid compared with no treatment did not alter the disease course and in-hospital mortality. The combined effect of old age and presence of comorbid conditions was more pronounced in women than men.Conclusions In-hospital patients were younger, less symptomatic with lesser need of ventilators and oxygen support as compared with many western countries.Trial registration Not applicable (observational study, not a clinical trial).

Tobacco consumption accounts for approximately 80% of total death in low and middle income countries. According to the Global Adult Tobacco Survey (2015) the prevalence of smokeless tobacco (SLT) consumption is being highest in India for about 33% in men and 18% in female. Countries like Bangladesh, Indonesia have highest prevalence of women SLT consumers than males. Quitting of tobacco products is although a difficult process. Evidence suggests two methods that enable a person to quit smokeless tobacco are pharmacotherapy and counselling or advice. The telephonic quit line services is very popular in the US and Europe, however they have predominantly handled smoking cessation. In this study we have done the systematic review on effect of telephone quit line services over smokeless tobacco cessation. We have taken articles from well-known library Pub-Med and Google Scholar with proper inclusion and exclusion criteria. In the systematic review it was noted that use of telephone quit line has reported the quit rate of SLT in the range of 25 to 30% over the population of 1000 despite of many limitations. The smokeless tobacco cessation through telephone quit line is useful and convenient way for tobacco control. The government of India has looked forward into this issue and has recently launched the national telephone quit line services for the tobacco control. This review recommends a policy which has to be made by the Low and Middle income countries to establish the quit line services for the SLT cessation by telephone counselling, which will play important role in tobacco control.

Background: The hazard function is defined as time-dependent. However, it is an overlooked area of research about the estimation of hazard function within the frame of time. The possible explanation could be carried by estimating function through the changes of time points. It is expected that it will provide us the overall idea of survival trend. This work is dedicated to propose a method to work with piecewise hazard rate. It is a data-driven method and provides us the estimates of hazard function with different time points. Methods: The proposed method is explored with prostate cancer patients, registered in the Surveillance, Epidemiology, and End Results Program and having aged at diagnosis with range 40–80 years and above. A total of 610,814 patients are included in this study. The piecewise hazard rate is formulated to serve the objective. The measurement of piecewise hazard rate is compared with Wald-type test statistics, and corresponding R function is provided. The duration of follow-ups is split into different intervals to obtain the piecewise hazard rate estimates. Results: The maximum duration of follow-up observed in this study is 40 years. The piecewise hazard rate changes at different intervals of follow-ups are observed almost same except few later intervals in the follow-up. The likelihood of hazard in earlier aged patients observed lower in comparison to older patients. The hazard rates in different grades of prostate cancer also observed separately. Conclusion: The application of piecewise hazard helps to generate statistical inference in a deeper manner. This analysis will provide us the better understanding of a requirement of effective treatment toward prolonged survival benefit for different aged patients.

Background: The Punjab state health administration has approached to Tata Memorial Centre (TMC), Mumbai, to tackle the cancer problem of the state and requested to provide the support in strengthening the cancer care services. To understand the magnitude of the cancer, population-based cancer registry at Sangrur was established in 2013. Objective: The objective of the study is to show that the population-based rural cancer registration is the way to develop the infrastructure for cancer treatment a model from Sangrur district, Punjab State, India. Methods: Population-based cancer registry staff has visited several hospitals and pathology laboratories, and also, they have interaction with the village leaders for cancer case registration. The cancer treatment facility was not available in the district. The registry has reported that for the cancer treatment, a patient from these areas travels to Patiala, Bhatinda, Faridkot, Ludhiana, Chandigarh, and New Delhi and to the neighboring state Rajasthan. It was felt that there is dire need of cancer treatment facility in the district. Based on the information provided by the rural cancer registry, the Government of Punjab and TMC have established Homi Bhabha Cancer Hospital (HBCH), Sangrur. The hospital has started functioning since January 2015. Results: In the 2-year period (2013–2014), the cancer registry has registered 1735 cancer incidence cases (808 males and 927 females). The age-adjusted incidence rate for males was 46.7/100,000, and for females, it was 57.6/100,000. The rates of the rural area of Sangrur are in comparison with other rural registries. The cancer registry data were utilized in planning the cancer care services in the Sangrur district. Conclusion: Population-based cancer registry with cancer treatment facility and HBCH with mentoring at Sangrur district in Punjab state could be an ideal potential model for the establishing and augmenting of cancer care services in the rural population in 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.

Summary: Introduction: India accounts for about a fifth of cardiovascular deaths globally, but nationally representative data on mortality trends are not yet available. In this nationwide mortality study, we aimed to assess the trends in ischaemic heart disease and stroke mortality over 15 years using the Million Death Study. Methods: We determined national and subnational cardiovascular mortality rates and trends by sex and birth cohort using cause of death ascertained by verbal autopsy from 2001 to 2013 among 2·4 million households. We derived mortality rates for ischaemic heart disease and stroke by applying mortality proportions to UN mortality estimates for India and projected the rates from 2000 to 2015. Findings: Cardiovascular disease caused more than 2·1 million deaths in India in 2015 at all ages, or more than a quarter of all deaths. At ages 30–69 years, of 1·3 million cardiovascular deaths, 0·9 million (68·4%) were caused by ischaemic heart disease and 0·4 million (28·0%) by stroke. At these ages, the probability of dying from ischaemic heart disease increased during 2000–15, from 10·4% to 13·1% in men and 4·8% to 6·6% in women. Ischaemic heart disease mortality rates in rural areas increased rapidly and surpassed those in urban areas. By contrast, the probability of dying from stroke decreased from 5·7% to 5·0% in men and 5·0% to 3·9% in women. A third of premature stroke deaths occurred in the northeastern states, inhabited by a sixth of India's population, where rates increased significantly and were three times higher than the national average. The increased mortality rates of ischaemic heart disease nationally and stroke in the northeastern states were higher in the cohorts of adults born in the 1970s onwards, than in earlier decades. A large and growing proportion of the ischaemic heart disease nationally and stroke deaths in high-burden states reported earlier diagnosis of cardiovascular disease, but low medication use. Interpretation: The unexpectedly diverse patterns of cardiovascular mortality require investigation to identify the role of established and new cardiovascular risk factors. Secondary prevention with effective and inexpensive long-term treatment and adult smoking cessation could prevent substantial numbers of premature deaths. Without progress against the control of cardiovascular disease in India, global goals to reduce non-communicable diseases by 2030 will be difficult to achieve. Funding: Fogarty International Center of the US National Institutes of Health, Dalla Lana School of Public Health, University of Toronto, Indian Council of Medical Research, and the Disease Control Priorities.

Two vaccines that protect against infection by some of the oncogenic human papillomavirus (HPV) subtypes have recently been licensed for use in population-based vaccination strategies in many countries. However, these products are being promoted as ′cervical cancer vaccines′ based on inadequate data. Specifically, there remain several concerns about the duration of immunogenicity, length of follow-up of trial subjects, endpoints chosen in vaccine trials, applicability of trial results to real populations, the safety of these products, and their cost-effectiveness as public health interventions. Furthermore, it is unlikely that vaccination will obviate the need for setting up robust and cost-effective screening programs in countries like India. This article will discuss various aspects of HPV vaccination from a public health perspective, especially from the point of view of its relevance to India and other South Asian countries.

Background: As child mortality decreases rapidly worldwide, premature adult mortality is becoming an increasingly important contributor to global mortality. Any possible worldwide reduction of premature adult mortality before the age of 70 years will depend on progress in India. Indian districts increasingly have responsibility for implementing public health programmes. We aimed to assess age-specific and sex-specific adult mortality risks in India at the district level. Methods: We analysed data from five national surveys of 0·27 million adult deaths at an age of 15–69 years together with 2014 demographic data to estimate age-specific and sex-specific adult mortality risks for 597 districts. Cause of death data were drawn from the verbal autopsies in the Registrar General of India's ongoing Million Death Study. Findings: In 2014, about two-fifths of India's men aged 15–69 years lived in the 253 districts where the conditional probability of a man dying at these ages exceeded 50%, and more than a third of India's women aged 15–69 years lived in the 222 districts where the conditional probability of a woman dying exceeded 40%. The probabilities of a man or woman dying by the age of 70 years in high-mortality districts was 62% and 54%, respectively, whereas the probability of a man or woman dying by the age of 70 years in low-mortality districts was 40% and 30%, respectively. The roughly 10-year survival gap between high-mortality and low-mortality districts was nearly as extreme as the survival gap between the entire Indian population and people living in high-income countries. Adult mortality risks at ages 15–69 years was highest in east India and lowest in west India, by contrast with the north–south divide for child mortality. Vascular disease, tuberculosis, malaria and other infections, and respiratory diseases accounted for about 60% of the absolute gap in adult mortality risk at ages 15–69 years between high-mortality and low-mortality districts. Most of the variation in adult mortality could not be explained by known determinants or risk factors for premature mortality. Interpretation: India's large variation in adult mortality by district, notably the higher death rates in eastern India, requires further aetiological research, particularly to explore whether high levels of adult mortality risks from infections and non-communicable diseases are a result of historical childhood malnutrition and infection. Such research can be complemented by an expanded coverage of known effective interventions to reduce adult mortality, especially in high-mortality districts. Funding: National Institutes of Health, Canadian Institutes of Health Research, University of Toronto.

Tobacco smoking and binge alcohol drinking are two of the leading risk factors for premature mortality worldwide. In India, studies have examined the geographic distributions of tobacco smoking and alcohol drinking only at the state-level; sub-state variations and the spatial association between the two consumptions are poorly understood.We used data from the Special Fertility and Mortality Survey conducted in 1998 to examine the geographic distributions of tobacco smoking and alcohol drinking at the district and postal code levels. We used kriging interpolation to generate smoking and drinking distributions at the postal code level. We also examined spatial autocorrelations and identified spatial clusters of high and low prevalence of smoking and drinking. Finally, we used bivariate analyses to examine the spatial correlations between smoking and drinking, and between cigarette and bidi smoking.There was a high prevalence of any smoking in the central and northeastern states, and a high prevalence of any drinking in Himachal Pradesh, Arunachal Pradesh, and eastern Madhya Pradesh. Spatial clusters of early smoking (started smoking before age 20) were identified in the central states. Cigarette and bidi smoking showed distinctly different geographic patterns, with high levels of cigarette smoking in the northeastern states and high levels of bidi smoking in the central states. The geographic pattern of bidi smoking was similar to early smoking. Cigarette smoking was spatially associated with any drinking. Smoking prevalences in 1998 were correlated with prevalences in 2004 at the district level and 2010 at the state level.These results along with earlier evidence on the complementarities between tobacco smoking and alcohol drinking suggest that local public health action on smoking might also help to reduce alcohol consumption, and vice versa. Surveys that properly represent tobacco and alcohol consumptions at the district level are recommended.