Risk factors for recognized and unrecognized SARS-CoV-2 infection: a seroepidemiologic analysis of the Prospective Urban Rural Epidemiology (PURE) study.

There are limited data on individual risk factors for SARS-CoV-2 infection (including unrecognized infection). In this seroepidemiologic substudy of an ongoing prospective cohort study of community-dwelling adults, participants were thoroughly characterized pre-pandemic. The SARS-CoV-2 infection was ascertained by serology. Among 8,719 participants from 11 high-, middle-, and low-income countries, 3,009 (35%) were seropositive for SARS-CoV-2. Characteristics independently associated with seropositivity were younger age (odds ratio, OR; 95% confidence interval, CI, per five-year increase: 0.95; 0.91-0.98) and body mass index >25 kg/m2 (OR, 95% CI: 1.16, 1.01-1.34). Smoking (as compared with never smoking, OR, 95% CI: 0.83, 0.70-0.97) and COVID-19 vaccination (OR, 95% CI: 0.70, 0.60-0.82) were associated with a reduced risk of seropositivity. Among seropositive participants, 83% were unaware of having been infected with SARS-CoV-2. Seropositivity and a lack of awareness of infection were more common in lower-income countries. The COVID-19 vaccination reduces the risk of SARS-CoV-2 infection (including recognized and unrecognized infections). Overweight or obesity is an independent risk factor for SARS-CoV-2 infection. Infection and lack of infection awareness are more common in lower-income countries.IMPORTANCEIn this large, international study, evidence of SARS-CoV-2 infection was obtained by testing blood specimens from 8,719 community-dwelling adults from 11 countries. The key findings are that (i) the large majority (83%) of community-dwelling adults from several high-, middle-, and low-income countries with blood test evidence of SARS-CoV-2 infection were unaware of this infection-especially in lower-income countries; and (ii) overweight/obesity predisposes to SARS-CoV-2 infection, while COVID-19 vaccination is associated with a reduced risk of SARS-CoV-2 infection. These observations are not attributable to other individual characteristics, highlighting the importance of the COVID-19 vaccination to prevent not only severe infection but possibly any infection. Further research is needed to understand the mechanisms by which overweight/obesity might increase the risk of SARS-CoV-2 infection.

Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome.

BACKGROUND: Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES: We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS: The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS: The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.

Determinants of Kangaroo Mother Care Uptake for Small Babies Along the Health Facility to Community Continuum in Karnataka, India.

INTRODUCTION: Kangaroo mother care (KMC) scale-up is a proposed strategy to accelerate reduction in neonatal mortality rates. We aimed to identify determinants of KMC uptake for small babies (less than 2,000 g birth weight) along the health facility to community continuum in Karnataka, India. METHODS: From June 2017 to March 2020, data on characteristics of health facilities and health care workers (HCWs) from 8 purposively selected health facilities were assessed. Knowledge, attitude, and support the mothers received for KMC uptake were assessed once between 4 weeks and 8 weeks unadjusted age of the cohort of babies. Secondary data on KMC were obtained from the district-wide implementation research project database. Bivariate analysis was used to assess the association of characteristics of health facilities, HCWs, mothers, and small babies with the day of KMC initiation and its duration. Log-binomial regression analysis was then computed to identify determinants of KMC. RESULTS: We recruited 227 (91.5%) of 248 babies eligible to participate with a mean unadjusted age of 35.6 days (±7.5) and 1,693.9 g (±263.1 g) birth weight. KMC was initiated for 95.2% of 227 babies at the health facility; initiated at 3 days or earlier of life for 59.6% of 226 babies; and babies continued to receive KMC for more than 4 weeks (30.2 days [±8.4]) at home. Determinants of KMC initiation were HCWs' attitudes, initiation support at the health facility, and place of hospitalization. Determinants of KMC maintenance at the health facility were HCWs' skills and support the mother received at the facility after initiating KMC. Place of hospitalization and HCWs' knowledge determined KMC duration at home 1 week after discharge. CONCLUSION: These findings emphasize the importance of competent HCWs and support for mothers at the health facility for initiation and maintenance of KMC within the health facility and 1 week after discharge.

Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development. METHODS: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries. FINDINGS: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality. INTERPRETATION: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Prevalence & correlates of COVID-19 vaccine hesitancy in a rural community of Bengaluru district, southern India: A preliminary cross-sectional study.

Background & objectives: Studying vaccine hesitancy is important for helping improve vaccine coverage against COVID-19. The objective of this study was to assess the prevalence and correlates of COVID-19 vaccine hesitancy in a rural community in India. Methods: A cross-sectional study of all adults aged over 18 yr was undertaken during July-August 2021, in a village outside Bengaluru city in southern India. Results: In our study, 68.7 per cent of the eligible 297 adult population accepted vaccination immediately, another 9.4 per cent hesitated but accepted vaccination without delay, a further 10.4 per cent delayed their vaccination and the remaining 11.5 per cent refused vaccination. The prevalence (95% confidence interval) of vaccine hesitancy was 21.9±4.8 per cent. Full vaccination was higher among males (76%) compared to females (58%, P <0.001). Those who hesitated and delayed vaccination (converts) were more likely to be from a nuclear family, whereas those who refused the vaccine were from a joint/three-generation family. Those who refused vaccination were adversely influenced by social media predominantly as also their religious/cultural beliefs and distrust on the pharmaceutical industry. Those who delayed but accepted vaccination were positively influenced by healthcare professionals and others who had accepted the vaccine recently. Geographic factors, cost of vaccine, and mode of administration were not the major concerns. Interpretation & conclusions: Vaccine uptake is a continuum. Our study helped identify the characteristics of those who delayed vaccination versus those who refused vaccination. This will help policymakers, programme managers and healthcare professionals to focus priority action on population subgroups for improving individual- and population-level protection.

Collaborative care compared to enhanced standard treatment of depression with co-morbid medical conditions among patients from rural South India: a cluster randomized controlled trial (HOPE Study).

BACKGROUND: Depression is common among primary care patients in LMIC but treatments are largely ineffective. In this cluster-randomized controlled trial, we tested whether depression outcomes are different among recipients of a collaborative care model compared to enhanced standard treatment in patients with co-morbid chronic medical conditions. METHODS: We conducted a cluster randomized controlled trial among participants 30 years or older seeking care at 49 primary health centers (PHCs) in rural Karnataka, diagnosed with major depressive disorder, dysthymia, generalized anxiety disorder, or panic disorder on the MINI-International Neuropsychiatric Interview plus either hypertension, diabetes, or ischemic heart disease. From a list of all PHCs in the district, 24 PHCs were randomized a priori to deliver collaborative care and 25 PHCs enhanced standard treatment. The collaborative care model consisted of a clinic-based and a community-based component. Study assessment staff was blinded to treatment arm allocation. The primary outcome was the individual-level PHQ-9 score over time. RESULTS: Between May 2015 and Nov 2018, 2486 participants were enrolled, 1264 in the control arm, and 1222 in the intervention arm. They were assessed at baseline, 3, 6 and 12 months. The mean PHQ-9 depression score was around 8.5 at baseline. At each follow-up PHQ-9 scores were significantly lower in the intervention (5.24, 4.81 and 4.22 at respective follow-ups) than in the control group (6.69, 6.13, 5.23, respectively). A significant time-by-treatment interaction (p < 0.001) in a multi-level model over all waves, nested within individuals who were nested within PHCs, confirmed that the decrease in depression score from baseline was larger for collaborative care than enhanced standard care throughout follow-up. CONCLUSIONS: The collaborative care intervention resulted in significantly lower depression scores compared to enhanced standard care among participants with co-morbid physical conditions. The findings have potential implications for integrating mental health and chronic disease treatment in resource constrained settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02310932 , registered on December 8, 2014, and Clinical Trials Registry India CTRI/2018/04/013001 , registered on April 4, 2018. Retrospectively registered.

Association of Sitting Time With Mortality and Cardiovascular Events in High-Income, Middle-Income, and Low-Income Countries.

Importance: High amounts of sitting time are associated with increased risks of cardiovascular disease (CVD) and mortality in high-income countries, but it is unknown whether risks also increase in low- and middle-income countries. Objective: To investigate the association of sitting time with mortality and major CVD in countries at different economic levels using data from the Prospective Urban Rural Epidemiology study. Design, Setting, and Participants: This population-based cohort study included participants aged 35 to 70 years recruited from January 1, 2003, and followed up until August 31, 2021, in 21 high-income, middle-income, and low-income countries with a median follow-up of 11.1 years. Exposures: Daily sitting time measured using the International Physical Activity Questionnaire. Main Outcomes and Measures: The composite of all-cause mortality and major CVD (defined as cardiovascular death, myocardial infarction, stroke, or heart failure). Results: Of 105 677 participants, 61 925 (58.6%) were women, and the mean (SD) age was 50.4 (9.6) years. During a median follow-up of 11.1 (IQR, 8.6-12.2) years, 6233 deaths and 5696 major cardiovascular events (2349 myocardial infarctions, 2966 strokes, 671 heart failure, and 1792 cardiovascular deaths) were documented. Compared with the reference group (<4 hours per day of sitting), higher sitting time (≥8 hours per day) was associated with an increased risk of the composite outcome (hazard ratio [HR], 1.19; 95% CI, 1.11-1.28; Pfor trend < .001), all-cause mortality (HR, 1.20; 95% CI, 1.10-1.31; Pfor trend < .001), and major CVD (HR, 1.21; 95% CI, 1.10-1.34; Pfor trend < .001). When stratified by country income levels, the association of sitting time with the composite outcome was stronger in low-income and lower-middle-income countries (≥8 hours per day: HR, 1.29; 95% CI, 1.16-1.44) compared with high-income and upper-middle-income countries (HR, 1.08; 95% CI, 0.98-1.19; P for interaction = .02). Compared with those who reported sitting time less than 4 hours per day and high physical activity level, participants who sat for 8 or more hours per day experienced a 17% to 50% higher associated risk of the composite outcome across physical activity levels; and the risk was attenuated along with increased physical activity levels. Conclusions and Relevance: High amounts of sitting time were associated with increased risk of all-cause mortality and CVD in economically diverse settings, especially in low-income and lower-middle-income countries. Reducing sedentary time along with increasing physical activity might be an important strategy for easing the global burden of premature deaths and CVD.

Personal and household PM2.5 and black carbon exposure measures and respiratory symptoms in 8 low- and middle-income countries.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has been associated with adverse respiratory effects, but most studies use surveys of fuel use to define HAP exposure, rather than on actual air pollution exposure measurements. OBJECTIVE: To examine associations between household and personal fine particulate matter (PM2.5) and black carbon (BC) measures and respiratory symptoms. METHODS: As part of the Prospective Urban and Rural Epidemiology Air Pollution study, we analyzed 48-h household and personal PM2.5 and BC measurements for 870 individuals using different cooking fuels from 62 communities in 8 countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Self-reported respiratory symptoms were collected after monitoring. Associations between PM2.5 and BC exposures and respiratory symptoms were examined using logistic regression models, controlling for individual, household, and community covariates. RESULTS: The median (interquartile range) of household and personal PM2.5 was 73.5 (119.1) and 65.3 (91.5) µg/m3, and for household and personal BC was 3.4 (8.3) and 2.5 (4.9) x10-5 m-1, respectively. We observed associations between household PM2.5 and wheeze (OR: 1.25; 95%CI: 1.07, 1.46), cough (OR: 1.22; 95%CI: 1.06, 1.39), and sputum (OR: 1.26; 95%CI: 1.10, 1.44), as well as exposure to household BC and wheeze (OR: 1.20; 95%CI: 1.03, 1.39) and sputum (OR: 1.20; 95%CI: 1.05, 1.36), per IQR increase. We observed associations between personal PM2.5 and wheeze (OR: 1.23; 95%CI: 1.00, 1.50) and sputum (OR: 1.19; 95%CI: 1.00, 1.41). For household PM2.5 and BC, associations were generally stronger for females compared to males. Models using an indicator variable of solid versus clean fuels resulted in larger OR estimates with less precision. CONCLUSIONS: We used measurements of household and personal air pollution for individuals using different cooking fuels and documented strong associations with respiratory symptoms.

Variations in the financial impact of the COVID-19 pandemic across 5 continents: A cross-sectional, individual level analysis.

BACKGROUND: COVID-19 has caused profound socio-economic changes worldwide. However, internationally comparative data regarding the financial impact on individuals is sparse. Therefore, we conducted a survey of the financial impact of the pandemic on individuals, using an international cohort that has been well-characterized prior to the pandemic. METHODS: Between August 2020 and September 2021, we surveyed 24,506 community-dwelling participants from the Prospective Urban-Rural Epidemiology (PURE) study across high (HIC), upper middle (UMIC)-and lower middle (LMIC)-income countries. We collected information regarding the impact of the pandemic on their self-reported personal finances and sources of income. FINDINGS: Overall, 32.4% of participants had suffered an adverse financial impact, defined as job loss, inability to meet financial obligations or essential needs, or using savings to meet financial obligations. 8.4% of participants had lost a job (temporarily or permanently); 14.6% of participants were unable to meet financial obligations or essential needs at the time of the survey and 16.3% were using their savings to meet financial obligations. Participants with a post-secondary education were least likely to be adversely impacted (19.6%), compared with 33.4% of those with secondary education and 33.5% of those with pre-secondary education. Similarly, those in the highest wealth tertile were least likely to be financially impacted (26.7%), compared with 32.5% in the middle tertile and 30.4% in the bottom tertile participants. Compared with HICs, financial impact was greater in UMIC [odds ratio of 2.09 (1.88-2.33)] and greatest in LMIC [odds ratio of 16.88 (14.69-19.39)]. HIC participants with the lowest educational attainment suffered less financial impact (15.1% of participants affected) than those with the highest education in UMIC (22.0% of participants affected). Similarly, participants with the lowest education in UMIC experienced less financial impact (28.3%) than those with the highest education in LMIC (45.9%). A similar gradient was seen across country income categories when compared by pre-pandemic wealth status. INTERPRETATION: The financial impact of the pandemic differs more between HIC, UMIC, and LMIC than between socio-economic categories within a country income level. The most disadvantaged socio-economic subgroups in HIC had a lower financial impact from the pandemic than the most advantaged subgroup in UMIC, with a similar disparity seen between UMIC and LMIC. Continued high levels of infection will exacerbate financial inequity between countries and hinder progress towards the sustainable development goals, emphasising the importance of effective measures to control COVID-19 and, especially, ensuring high vaccine coverage in all countries. FUNDING: Funding for this study was provided by the Canadian Institutes of Health Research and the International Development Research Centre.

Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179 000 participants from 63 countries.

BACKGROUND: Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. METHODS: We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. FINDINGS: In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65-2·12) than in MICs (1·41, 1·34-1·49) and LICs (1·35, 1·25-1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 µM) than in MICs (31·1 µM) and LICs (25·2 µM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 µM) and MICs (11·3 µM) than in HICs (5·0 µM; ANCOVA p=0·0001). INTERPRETATION: The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Measuring and predicting personal and household Black Carbon levels from 88 communities in eight countries.

Black Carbon (BC) is an important component of household air pollution (HAP) in low- and middle- income countries (LMICs), but levels and drivers of exposure are poorly understood. As part of the Prospective Urban and Rural Epidemiological (PURE) study, we analyzed 48-hour BC measurements for 1187 individual and 2242 household samples from 88 communities in 8 LMICs (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Light absorbance (10-5 m-1) of collected PM2.5 filters, a proxy for BC concentrations, was calculated via an image-based reflectance method. Surveys of household/personal characteristics and behaviors were collected after monitoring. The geometric mean (GM) of personal and household BC measures was 2.4 (3.3) and 3.5 (3.9)·10-5 m-1, respectively. The correlation between BC and PM2.5 was r = 0.76 for personal and r = 0.82 for household measures. A gradient of increasing BC concentrations was observed for cooking fuels: BC increased 53% (95%CI: 30, 79) for coal, 142% (95%CI: 117, 169) for wood, and 190% (95%CI: 149, 238) for other biomass, compared to gas. Each hour of cooking was associated with an increase in household (5%, 95%CI: 3, 7) and personal (5%, 95%CI: 2, 8) BC; having a window in the kitchen was associated with a decrease in household (-38%, 95%CI: -45, -30) and personal (-31%, 95%CI: -44, -15) BC; and cooking on a mud stove, compared to a clean stove, was associated with an increase in household (125%, 95%CI: 96, 160) and personal (117%, 95%CI: 71, 117) BC. Male participants only had slightly lower personal BC (-0.6%, 95%CI: -1, 0.0) compared to females. In multivariate models, we were able to explain 46-60% of household BC variation and 33-54% of personal BC variation. These data and models provide new information on exposure to BC in LMICs, which can be incorporated into future exposure assessments, health research, and policy surrounding HAP and BC.

Multinational prediction of household and personal exposure to fine particulate matter (PM2.5) in the PURE cohort study.

INTRODUCTION: Use of polluting cooking fuels generates household air pollution (HAP) containing health-damaging levels of fine particulate matter (PM2.5). Many global epidemiological studies rely on categorical HAP exposure indicators, which are poor surrogates of measured PM2.5 levels. To quantitatively characterize HAP levels on a large scale, a multinational measurement campaign was leveraged to develop household and personal PM2.5 exposure models. METHODS: The Prospective Urban and Rural Epidemiology (PURE)-AIR study included 48-hour monitoring of PM2.5 kitchen concentrations (n = 2,365) and male and/or female PM2.5 exposure monitoring (n = 910) in a subset of households in Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania and Zimbabwe. PURE-AIR measurements were combined with survey data on cooking environment characteristics in hierarchical Bayesian log-linear regression models. Model performance was evaluated using leave-one-out cross validation. Predictive models were applied to survey data from the larger PURE cohort (22,480 households; 33,554 individuals) to quantitatively estimate PM2.5 exposures. RESULTS: The final models explained half (R2 = 54%) of the variation in kitchen PM2.5 measurements (root mean square error (RMSE) (log scale):2.22) and personal measurements (R2 = 48%; RMSE (log scale):2.08). Primary cooking fuel type, heating fuel type, country and season were highly predictive of PM2.5 kitchen concentrations. Average national PM2.5 kitchen concentrations varied nearly 3-fold among households primarily cooking with gas (20 µg/m3 (Chile); 55 µg/m3 (China)) and 12-fold among households primarily cooking with wood (36 µg/m3 (Chile)); 427 µg/m3 (Pakistan)). Average PM2.5 kitchen concentration, heating fuel type, season and secondhand smoke exposure were significant predictors of personal exposures. Modeled average PM2.5 female exposures were lower than male exposures in upper-middle/high-income countries (India, China, Colombia, Chile). CONCLUSION: Using survey data to estimate PM2.5 exposures on a multinational scale can cost-effectively scale up quantitative HAP measurements for disease burden assessments. The modeled PM2.5 exposures can be used in future epidemiological studies and inform policies targeting HAP reduction.

Scaling up Kangaroo Mother Care in Ethiopia and India: a multi-site implementation research study.

OBJECTIVES: Kangaroo Mother Care (KMC), prolonged skin-to-skin care of the low birth weight baby with the mother plus exclusive breastfeeding reduces neonatal mortality. Global KMC coverage is low. This study was conducted to develop and evaluate context-adapted implementation models to achieve improved coverage. DESIGN: This study used mixed-methods applying implementation science to develop an adaptable strategy to improve implementation. Formative research informed the initial model which was refined in three iterative cycles. The models included three components: (1) maximising access to KMC-implementing facilities, (2) ensuring KMC initiation and maintenance in facilities and (3) supporting continuation at home postdischarge. PARTICIPANTS: 3804 infants of birth weight under 2000 g who survived the first 3 days, were available in the study area and whose mother resided in the study area. MAIN OUTCOME MEASURES: The primary outcomes were coverage of KMC during the 24 hours prior to discharge and at 7 days postdischarge. RESULTS: Key barriers and solutions were identified for scaling up KMC. The resulting implementation model achieved high population-based coverage. KMC initiation reached 68%-86% of infants in Ethiopian sites and 87% in Indian sites. At discharge, KMC was provided to 68% of infants in Ethiopia and 55% in India. At 7 days postdischarge, KMC was provided to 53%-65% of infants in all sites, except Oromia (38%) and Karnataka (36%). CONCLUSIONS: This study shows how high coverage of KMC can be achieved using context-adapted models based on implementation science. They were supported by government leadership, health workers' conviction that KMC is the standard of care, women's and families' acceptance of KMC, and changes in infrastructure, policy, skills and practice. TRIAL REGISTRATION NUMBERS: ISRCTN12286667; CTRI/2017/07/008988; NCT03098069; NCT03419416; NCT03506698.

Risk factors for severity of depression in participants with chronic medical conditions in rural primary health care settings in India.

BACKGROUND: Depression and chronic medical disorders are strongly linked. There are limited studies addressing the correlates of the severity of depression in patients with co-morbid disorders in primary care settings. This study aimed to identify the socio-demographic and disease-specific risk factors associated with the severity of depression at baseline among patients participating in a randomized controlled trial (HOPE study). METHODS: Participants were part of a randomized controlled trial in 49 primary care health centers in rural India. We included adults (≥ 30 years) with at least mild Depression or Anxiety Disorder and at least one Cardiovascular disorder or Type 2 Diabetes mellitus. They were assessed for the severity of depression using the PHQ-9, severity of anxiety, social support, number of co-morbid chronic medical illnesses, anthropometric measurements, HbA1c, and lipid profile. RESULTS: Proportionately there were more women in the moderate category of depression than men. Ordinal logistic regression showed co-morbid anxiety and a lower level of education significantly increased the odds of more severe depression, while more social support was significantly negatively associated with depression severity in women. In men, anxiety was positively associated with greater depression severity; while reporting more social support was negatively associated with depression. LIMITATIONS: This is a cross-sectional study and thus, no causal conclusions are possible. CONCLUSIONS: Anxiety and poor social support in both genders and lower educational levels in women were associated with increased severity of depression. Early identification of risk factors and appropriate treatment at a primary care setting may help in reducing the morbidity and mortality associated with depression.

Availability and affordability of medicines and cardiovascular outcomes in 21 high-income, middle-income and low-income countries.

OBJECTIVES: We aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study. METHODS: We defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1-all three drug types were available and affordable, group 2-all three drugs were available but not affordable and group 3-all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors. RESULTS: Of 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50). CONCLUSION: Lower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.

Contrasting Associations Between Diabetes and Cardiovascular Mortality Rates in Low-, Middle-, and High-Income Countries: Cohort Study Data From 143,567 Individuals in 21 Countries in the PURE Study.

OBJECTIVE: We aimed to compare cardiovascular (CV) events, all-cause mortality, and CV mortality rates among adults with and without diabetes in countries with differing levels of income. RESEARCH DESIGN AND METHODS: The Prospective Urban Rural Epidemiology (PURE) study enrolled 143,567 adults aged 35-70 years from 4 high-income countries (HIC), 12 middle-income countries (MIC), and 5 low-income countries (LIC). The mean follow-up was 9.0 ± 3.0 years. RESULTS: Among those with diabetes, CVD rates (LIC 10.3, MIC 9.2, HIC 8.3 per 1,000 person-years, P < 0.001), all-cause mortality (LIC 13.8, MIC 7.2, HIC 4.2 per 1,000 person-years, P < 0.001), and CV mortality (LIC 5.7, MIC 2.2, HIC 1.0 per 1,000 person-years, P < 0.001) were considerably higher in LIC compared with MIC and HIC. Within LIC, mortality was higher in those in the lowest tertile of wealth index (low 14.7%, middle 10.8%, and high 6.5%). In contrast to HIC and MIC, the increased CV mortality in those with diabetes in LIC remained unchanged even after adjustment for behavioral risk factors and treatments (hazard ratio [95% CI] 1.89 [1.58-2.27] to 1.78 [1.36-2.34]). CONCLUSIONS: CVD rates, all-cause mortality, and CV mortality were markedly higher among those with diabetes in LIC compared with MIC and HIC with mortality risk remaining unchanged even after adjustment for risk factors and treatments. There is an urgent need to improve access to care to those with diabetes in LIC to reduce the excess mortality rates, particularly among those in the poorer strata of society.

Household and personal air pollution exposure measurements from 120 communities in eight countries: results from the PURE-AIR study.

BACKGROUND: Approximately 2·8 billion people are exposed to household air pollution from cooking with polluting fuels. Few monitoring studies have systematically measured health-damaging air pollutant (ie, fine particulate matter [PM2·5] and black carbon) concentrations from a wide range of cooking fuels across diverse populations. This multinational study aimed to assess the magnitude of kitchen concentrations and personal exposures to PM2·5 and black carbon in rural communities with a wide range of cooking environments. METHODS: As part of the Prospective Urban and Rural Epidemiological (PURE) cohort, the PURE-AIR study was done in 120 rural communities in eight countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Data were collected from 2541 households and from 998 individuals (442 men and 556 women). Gravimetric (or filter-based) 48 h kitchen and personal PM2·5 measurements were collected. Light absorbance (10-5m-1) of the PM2·5 filters, a proxy for black carbon concentrations, was calculated via an image-based reflectance method. Surveys of household characteristics and cooking patterns were collected before and after the 48 h monitoring period. FINDINGS: Monitoring of household air pollution for the PURE-AIR study was done from June, 2017, to September, 2019. A mean PM2·5 kitchen concentration gradient emerged across primary cooking fuels: gas (45 µg/m3 [95% CI 43-48]), electricity (53 µg/m3 [47-60]), coal (68 µg/m3 [61-77]), charcoal (92 µg/m3 [58-146]), agricultural or crop waste (106 µg/m3 [91-125]), wood (109 µg/m3 [102-118]), animal dung (224 µg/m3 [197-254]), and shrubs or grass (276 µg/m3 [223-342]). Among households cooking primarily with wood, average PM2·5 concentrations varied ten-fold (range: 40-380 µg/m3). Fuel stacking was prevalent (981 [39%] of 2541 households); using wood as a primary cooking fuel with clean secondary cooking fuels (eg, gas) was associated with 50% lower PM2·5 and black carbon concentrations than using only wood as a primary cooking fuel. Similar average PM2·5 personal exposures between women (67 µg/m3 [95% CI 62-72]) and men (62 [58-67]) were observed. Nearly equivalent average personal exposure to kitchen exposure ratios were observed for PM2·5 (0·79 [95% 0·71-0·88] for men and 0·82 [0·74-0·91] for women) and black carbon (0·64 [0·45-0·92] for men and 0·68 [0·46-1·02] for women). INTERPRETATION: Using clean primary fuels substantially lowers kitchen PM2·5 concentrations. Importantly, average kitchen and personal PM2·5 measurements for all primary fuel types exceeded WHO's Interim Target-1 (35 µg/m3 annual average), highlighting the need for comprehensive pollution mitigation strategies. FUNDING: Canadian Institutes for Health Research, National Institutes of Health.

Adverse health impacts of cooking with kerosene: A multi-country analysis within the Prospective Urban and Rural Epidemiology Study.

BACKGROUND: Kerosene, which was until recently considered a relatively clean household fuel, is still widely used in low- and middle-income countries for cooking and lighting. However, there is little data on its health effects. We examined cardiorespiratory effects and mortality in households using kerosene as their primary cooking fuel within the Prospective Urban Rural Epidemiology (PURE) study. METHODS: We analyzed baseline and follow-up data on 31,490 individuals from 154 communities in China, India, South Africa, and Tanzania where there was at least 10% kerosene use for cooking at baseline. Baseline comorbidities and health outcomes during follow-up (median 9.4 years) were compared between households with kerosene versus clean (gas or electricity) or solid fuel (biomass and coal) use for cooking. Multi-level marginal regression models adjusted for individual, household, and community level covariates. RESULTS: Higher rates of prevalent respiratory symptoms (e.g. 34% [95% CI:15-57%] more dyspnea with usual activity, 44% [95% CI: 21-72%] more chronic cough or sputum) and lower lung function (differences in FEV1: -46.3 ml (95% CI: -80.5; -12.1) and FVC: -54.7 ml (95% CI: -93.6; -15.8)) were observed at baseline for kerosene compared to clean fuel users. The odds of hypertension was slightly elevated but no associations were observed for blood pressure. Prospectively, kerosene was associated with elevated risks of all-cause (HR: 1.32 (95% CI: 1.14-1.53)) and cardiovascular (HR: 1.34 (95% CI: 1.00-1.80)) mortality, as well as major fatal and incident non-fatal cardiovascular (HR: 1.34 (95% CI: 1.08-1.66)) and respiratory (HR: 1.55 (95% CI: 0.98-2.43)) diseases, compared to clean fuel use. Further, compared to solid fuel users, those using kerosene had 20-47% higher risks for the above outcomes. CONCLUSIONS: Kerosene use for cooking was associated with higher rates of baseline respiratory morbidity and increased risk of mortality and cardiorespiratory outcomes during follow-up when compared to either clean or solid fuels. Replacing kerosene with cleaner-burning fuels for cooking is recommended.

The household economic burden of non-communicable diseases in 18 countries.

Background: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. Methods: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. Results: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. Conclusions: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs.

Kangaroo Mother Care implementation research to develop models for accelerating scale-up in India and Ethiopia: study protocol for an adequacy evaluation.

INTRODUCTION: Kangaroo Mother Care (KMC) is the practice of early, continuous and prolonged skin-to-skin contact between the mother and the baby with exclusive breastfeeding. Despite clear evidence of impact in improving survival and health outcomes among low birth weight infants, KMC coverage has remained low and implementation has been limited. Consequently, only a small fraction of newborns that could benefit from KMC receive it. METHODS AND ANALYSIS: This implementation research project aims to develop and evaluate district-level models for scaling up KMC in India and Ethiopia that can achieve high population coverage. The project includes formative research to identify barriers and contextual factors that affect implementation and utilisation of KMC and design scalable models to deliver KMC across the facility-community continuum. This will be followed by implementation and evaluation of these models in routine care settings, in an iterative fashion, with the aim of reaching a successful model for wider district, state and national-level scale-up. Implementation actions would happen at three levels: 'pre-KMC facility'-to maximise the number of newborns getting to a facility that provides KMC; 'KMC facility'-for initiation and maintenance of KMC; and 'post-KMC facility'-for continuation of KMC at home. Stable infants with birth weight<2000 g and born in the catchment population of the study KMC facilities would form the eligible population. The primary outcome will be coverage of KMC in the preceding 24 hours and will be measured at discharge from the KMC facility and 7 days after hospital discharge. ETHICS AND DISSEMINATION: Ethics approval was obtained in all the project sites, and centrally by the Research Ethics Review Committee at the WHO. Results of the project will be submitted to a peer-reviewed journal for publication, in addition to national and global level dissemination. STUDY STATUS: WHO approved protocol: V.4-12 May 2016-Protocol ID: ERC 2716. Study implementation beginning: April 2017. Study end: expected March 2019. TRIAL REGISTRATION NUMBER: Community Empowerment Laboratory, Uttar Pradesh, India (ISRCTN12286667); St John's National Academy of Health Sciences, Bangalore, India and Karnataka Health Promotion Trust, Bangalore, India (CTRI/2017/07/008988); Society for Applied Studies, Delhi (NCT03098069); Oromia, Ethiopia (NCT03419416); Amhara, SNNPR and Tigray, Ethiopia (NCT03506698).