Redesigning telemedicine: preliminary findings from an innovative assisted telemedicine healthcare model.

BACKGROUND: Telemedicine holds immense potential to revolutionise healthcare delivery, particularly in resource-limited settings and for patients with chronic diseases. Despite proven benefits and policy reforms, the use of telemedicine remains low due to several patient, technology, and system-level barriers. Assisted telemedicine employs trained health professionals to connect patients with physicians, which can improve access and scope of telemedicine. The study aims to describe the design, service utilisation and chronic disease outcomes following the implementation of an assisted telemedicine initiative. METHODS: This is an observational implementation study. Barriers and potential solutions to the implementation of telemedicine were identified through interviews with key stakeholders. The assisted telemedicine solution using an interoperable platform integrating electronic health records, point-of-care diagnostics, and electronic clinical decision support systems was designed and piloted at three telemedicine clinics in Tamil Nadu, India. Nurses were trained in platform use and facilitation of tele-consultations. Health records of all patients from March 2021 to June 2023 were included in the analysis. Data were analysed to assess the utilisation of clinic services and improvements in health outcomes in patients with diabetes mellitus and hypertension. RESULTS: Over 2.4 years, 11,388 patients with a mean age of 45 (± 20) years and median age of 48 years, predominantly female (59.3%), accessed the clinics. The team completed 15,437 lab investigations and 26,998 consultations. Among 5542 (48.6%) patients that reported chronic conditions, diabetes mellitus (61%) and hypertension (45%) were the most frequent. In patients with diabetes mellitus and hypertension, 43% and 75.3% were newly diagnosed, respectively. Diabetes mellitus and hypertension patients had significant reductions in fasting blood sugar (-33.0 mg/dL (95% CI (-42.4, -23.7, P < 0.001)), and systolic (-9.6 mmHg (95% CI (-12.1, -7.0), P < 0.0001)) and diastolic blood pressure (-5.5 mmHg (95% CI (-7.0, -4.08), P < 0.0001)) at nine months from first visit, respectively. CONCLUSIONS: The 'Digisahayam' model demonstrated feasibility in enhancing healthcare accessibility and quality by bridging healthcare gaps, diagnosing chronic conditions, and improving patient outcomes. The model presents a scalable and sustainable approach to revolutionising patient care and achieving digital health equity, with the potential for adaptation in similar settings worldwide.

Individual-level determinants of breast and cervical cancer screening and early testing in two regionally representative urban Indian populations.

Introduction: Region-specific data on individual factors associated with uptake of breast and cervical cancer screening or early testing in diverse Indian populations are limited. Aim: To assess the prevalence and individual determinants of uptake of breast and/or cervical cancer screening or testing among women aged 30-69 years in regionally representative populations of two large Indian cities: New Delhi and Chennai. Methods: We conducted an analysis of the cross-sectional data (2016-2017) nested within the Centre for Cardiometabolic Risk Reduction in South Asia cohort, established in 2010-2011 with 12,271 participants (5365 in New Delhi; 6906 in Chennai). Among 3310 women participants, we evaluated the associations of demographic, socioeconomic, lifestyle, medical, psychosocial, and reproductive factors with breast and/or cervical cancer screening or testing using multivariable logistic regression models with results expressed as adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: At any point prior to 2016-2017, 193 women self-reported having undergone evaluations for breast and/or cervical cancer. The reasons for evaluation were 'general examination' or 'physician's advice' (i.e., screening) or 'being symptomatic' (i.e., early testing). The overall prevalence was 5.8% for screening or testing and 2.5% for screening alone. Formal education (OR:1.88; 95% CI:1.12-3.15), high monthly household income (OR:2.27; 95% CI:1.59-3.25) and less 'fear-of-judgement' (OR:1.65; 95% CI:1.05-2.58) were positively associated with screening or testing uptake. When screening uptake was analysed separately, the results were generally similar. Conclusion: Our findings may have important implications for interventions at community-level (e.g., reducing 'fear-of-judgement', increasing awareness to screening programs and early symptoms) and health-system level (e.g., opportunistic screening).

Rate and risk factors of kidney function decline among South Asians with type 2 diabetes: analysis of the CARRS Trial.

INTRODUCTION: People with diabetes are at risk of developing chronic kidney disease. However, limited data are available to quantify their risk of kidney function decline in South Asia. This study evaluates the rate and predictors of kidney function decline among people with type 2 diabetes in South Asia. RESEARCH DESIGN AND METHODS: We analyzed data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) Trial to quantify the rate of decline in estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (n=1146) over 2.5 years of follow-up. The CARRS Trial evaluated a multicomponent intervention of decision-supported electronic health records and non-physician care coordinator to improve diabetes management at 10 diabetes clinics in India and Pakistan. We used linear mixed models to estimate eGFR slope among all participants and tested the association of eGFR slope with demographic, disease-related, and self-care parameters, accounting for randomization and site. RESULTS: The mean age of participants was 54.2 years, with a median duration of diabetes of 7.0 years (IQR: 3.0 - 12.0) and median CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) eGFR of 83.6 (IQR: 67.7 to 97.9) mL/min/1.73 m2. The overall mean eGFR slope was -1.33/mL/min/1.73 m2/year. There were no differences in the eGFR slope by treatment assignment to intervention versus usual care. In the adjusted regression model, pre-existing diabetic retinopathy (slope difference: -2.11; 95% CI: -3.45 to -0.77), previous cardiovascular disease (-1.93; 95% CI: -3.45 to -0.40), and statins use (-0.87; 95% CI: -1.65 to -0.10) were associated with faster eGFR decline. CONCLUSIONS: People with diabetes receiving care at urban diabetes clinics in South Asia experienced annual eGFR decline at two times higher rate than that reported from other contemporary international diabetes cohorts. Risk factors for faster decline were similar to those previously established, and thus care delivery models must put an additional emphasis on kidney protective therapies among subgroups with microvascular and macrovascular diabetes complications. TRIAL REGISTRATION NUMBER: NCT01212328.

Prospective Study on Kidney Dysfunction Markers and Risk for Mortality among South Asians.

Introduction: Associations between markers of impaired kidney function and adverse outcomes among South Asians is understudied and could differ from existing data derived mostly from North American or European cohorts. Methods: We conducted a prospective analysis of 9797 participants from the ongoing cardiometabolic risk reduction study in South Asia, India. We examined the associations between baseline spot urine albumin-to-creatinine (UACR) ratio and creatinine-based estimated glomerular filtration rate (eGFR) estimating equations with all-cause mortality using Cox proportional hazards regression, adjusting for baseline age, sex, diabetes, systolic blood pressure, tobacco, history of cardiovascular disease, and cholesterol. Additionally, we calculated population attributable fraction (PAF) for both markers. Results: Over a median 7-year follow-up, with 66,909 person-years, 791 deaths occurred. At baseline, the weighted prevalence of UACR ≥ 30 mg/g and eGFRCKD-EPI 2009 <60 ml/min per 1.73 m2 was 6.6% and 1.6%, respectively. The risk for mortality was increased with higher UACR (10-30 hazard ratio [HR]: 1.6 [1.2-2.1]), 30-300 HR: 2.4 [1.8-3.1]), and ≥300 (HR: 6.0 [3.8-9.4] relative to UACR <10 mg/g). Risk for mortality was also higher with lower eGFRCKD-EPI 2009 (44-30; HR: 4.5 [2.5-8.3] and <30 HR: 7.0 [3.7-13.0], relative to 90-104 ml/min per 1.73 m2). PAF for mortality because of UACR ≥30 mg/g and eGFRCKD-EPI 2009 <45 ml/min per 1.73 m2 were 24.4% and 13.4%, respectively. Conclusion: Single-time point assessment of UACR ≥30 mg/g or eGFRCKD-EPI 2009 <45 ml/min per 1.73 m2 portends higher mortality risk among urban South Asians. Because albuminuria is common and associated with accelerated decline in GFR, screening and targeted efforts to reduce albuminuria are warranted.

Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: a cross-sectional analysis across 11 prospective studies.

BACKGROUND: The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established. The aim is to describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies. METHODS: We harmonised individual-level data from 11 prospective cohort studies from Western Europe, North America, South Asia and East Asia. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics. RESULTS: 2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China. CONCLUSIONS: Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.

Rationale, Design and Baseline Characteristics of a Randomized Controlled Trial of a Cardiovascular Quality Improvement Strategy in India: The C-QIP Trial.

BACKGROUND: Quality of chronic care for cardiovascular disease (CVD) remains suboptimal worldwide. The Collaborative Quality ImProvement (C-QIP) trial aims to develop and test the feasibility and clinical effect of a multicomponent strategy among patients with prevalent CVD in India. METHODS: The C-QIP is a clinic-based, open randomized trial of a multicomponent intervention vs usual care that was locally developed and adapted for use in Indian settings through rigorous formative research guided by Consolidated Framework for Implementation Research (CFIR). The C-QIP intervention consisted of 5 components: 1) electronic health records and decision support system for clinicians, 2) trained nonphysician health workers (NPHW), 3) text-message based lifestyle reminders, 4) patient education materials, 5) quarterly audit and feedback reports. Patients with CVD (ischemic heart disease, ischemic stroke, or heart failure) attending outpatient CVD clinics were recruited from September 2022 to September 2023 and were randomized to the intervention or usual care arm for at least 12 months follow-up. The co-primary outcomes are implementation feasibility, fidelity (ie, dose delivered and dose received), acceptability, adoption and appropriateness, measured at multiple levels: patient, provider and clinic site-level, The secondary outcomes include prescription of guideline directed medical therapy (GDMT) (provider-level), and adherence to prescribed therapy, change in mean blood pressure (BP) and LDL-cholesterol between the intervention and control groups (patient-level). In addition, a trial-based process and economic evaluations will be performed using standard guidelines. RESULTS: We recruited 410 socio-demographically diverse patients with CVD from 4 hospitals in India. Mean (SD) age was 57.5 (11.7) years, and 73.0% were males. Self-reported history of hypertension (48.5%) and diabetes (41.5%) was common. At baseline, mean (SD) BP was 127.9 (18.2) /76.2 (11.6) mm Hg, mean (SD) LDLc: 80.3 (37.3) mg/dl and mean (SD) HbA1c: 6.8% (1.6%). At baseline, the GDMT varied from 62.4% for patients with ischemic heart disease, 48.6% for ischemic stroke and 36.1% for heart failure. CONCLUSION: This study will establish the feasibility of delivering contextually relevant, and evidence-based C-QIP strategy and assess whether it is acceptable to the target populations. The study results will inform a larger scale confirmatory trial of a comprehensive CVD care model in low-resource settings. TRIAL REGISTRATION: Clinical Trials Registry India: CTRI/2022/04/041847; Clinicaltrials.gov number: NCT05196659.

Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.

BACKGROUND: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. METHODS AND FINDINGS: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. CONCLUSIONS: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01212328.

Establishing Apolipoprotein-B and non-high-density-lipoprotein-C goals in Indian population: A Cross-sectional study.

BACKGROUND: Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines. METHODS: A community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets. RESULTS: Spearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively. CONCLUSION: Based on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.

Natural History of Type 2 Diabetes in Indians: Time to Progression.

OBJECTIVE: To describe the natural history of diabetes in Indians. RESEARCH DESIGN AND METHODS: Data are from participants older than 20 years in the Centre for Cardiometabolic Risk Reduction in South Asia longitudinal study. Glycemic states were defined per American Diabetes Association criteria. Markov models were used to estimate annual transition probabilities and sojourn time through states. RESULTS: Among 2,714 diabetes-free participants, 641 had isolated impaired fasting glucose (iIFG), and 341 had impaired glucose tolerance (IGT). The annual transition to diabetes for those with IGT was 13.9% (95% CI 12.0, 15.9) versus 8.6% (7.3, 9.8) for iIFG. In the normoglycemia ↔ iIFG → diabetes model, mean sojourn time in normoglycemia was 40.3 (34.6, 48.2) years, and sojourn time in iIFG was 9.7 (8.4, 11.4) years. For the normoglycemia ↔ IGT → diabetes model, mean sojourn time in normoglycemia was 34.5 (29.5, 40.8) years, and sojourn time in IGT was 6.1 (5.3, 7.1) years. CONCLUSIONS: Individuals reside in normoglycemia for 35-40 years; however, progression from prediabetes to diabetes is rapid.

Association of pro-inflammatory cytokines, adipokines and hepatokine with incident diabetes in India: a nested case-control study within CARRS cohort.

AIMS: To study the association of pro-inflammatory markers with incident diabetes in India. METHODS: We did a nested case-control study within the CARRS (Centre for Ardiometabolic Risk Reduction in South Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use. RESULTS: Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI: 1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI: 1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI: 0.06, 0.55]). CONCLUSIONS: Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians.

Statistical analysis plan for the phaco TIp position during clear corneal Phacoemulsification Surgery (TIPS) randomized controlled trial.

BACKGROUND: Cornea is the most important refractive media in the eye, and damage to the corneal endothelium is one of the most common causes of poor visual outcome following cataract surgery, particularly in those with predisposing factors. The role of phaco tip position during phacoemulsification on corneal endothelial damage is ambiguous, and there is no consensus regarding the most cornea-friendly phaco tip position (bevel-up or bevel-down). The objective of the trial is to compare the effect of phaco tip position (bevel-up vs. bevel-down) during phacoemulsification using direct chop technique on corneal endothelial cell count. METHODS AND DESIGN: TIPS is a randomised, multicentre, parallel-group, triple-masked (participant, outcome assessor, and statistician) trial with 1:1 allocation ratio. A total of 480 eligible participants, aged > 18 years with immature cataract, will be randomly allocated into bevel-up and bevel-down groups at two centres. Randomisation will be stratified according to the cataract grade. The primary outcome is postoperative endothelial cell count at 1 month. Secondary outcomes are central corneal thickness on postoperative days 1, 15, and 30 and difference in intraoperative complications. CONCLUSION: In this paper, we describe the detailed statistical analysis plan (SAP) for the TIPS trial, which was prepared prior to database lock. The SAP includes details of planned analyses and unpopulated tables, which will be reported in the publications. We plan to lock the database in July 2023 and publish the results later in the same year. SAP Version 0.1 (dated: 28 April 2023) Protocol version:2.0 TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2019/02/017464. Registered on 5 February 2019; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=29764&EncHid=&userName=2019/02/017464.

Evaluating bias with loss to follow-up in a community-based cohort: empirical investigation from the CARRS Study.

BACKGROUND: Retention of participants is a challenge in community-based longitudinal cohort studies. We aim to evaluate the factors associated with loss to follow-up and estimate attrition bias. METHODS: Data are from an ongoing cohort study, Center for cArdiometabolic Risk Reduction in South Asia (CARRS) in India (Delhi and Chennai). Multinomial logistic regression analysis was used to identify sociodemographic factors associated with partial (at least one follow-up) or no follow-up (loss to follow-up). We also examined the impact of participant attrition on the magnitude of observed associations using relative ORs (RORs) of hypertension and diabetes (prevalent cases) with baseline sociodemographic factors. RESULTS: There were 12 270 CARRS cohort members enrolled in Chennai and Delhi at baseline in 2010, and subsequently six follow-ups were conducted between 2011 and 2022. The median follow-up time was 9.5 years (IQR: 9.3-9.8) and 1048 deaths occurred. Approximately 3.1% of participants had no follow-up after the baseline visit. Younger (relative risk ratio (RRR): 1.14; 1.04 to 1.24), unmarried participants (RRR: 1.75; 1.45 to 2.11) and those with low household assets (RRR: 1.63; 1.44 to 1.85) had higher odds of being lost to follow-up. The RORs of sociodemographic factors with diabetes and hypertension did not statistically differ between baseline and sixth follow-up, suggesting minimal potential for bias in inference at follow-up. CONCLUSION: In this representative cohort of urban Indians, we found low attrition and minimal bias due to the loss to follow-up. Our cohort's inconsistent participation bias shows our retention strategies like open communication, providing health profiles, etc have potential benefits.

Household cooking fuel and gallbladder cancer risk: a multi-centre case-control study in India.

PURPOSE: Gallbladder cancers (GBC), unique to certain geographical regions, are lethal digestive tract cancers, disproportionately affecting women, with limited information on risk factors. METHODS: We evaluated the association between household cooking fuel and GBC risk in a hospital-based case-control study conducted in the North-East and East Indian states of Assam and Bihar. We explored the potential mediation by diet, fire-vents, 'daily exposure duration' and parity (among women). We recruited biopsy-confirmed GBC (n = 214) men and women aged 30-69 years between 2019 and 2021, and controls frequency-matched by age, sex and region (n = 166). Information about cooking fuel, lifestyle, personal and family history, female reproductive factors, socio-demographics, and anthropometrics was collected. We tested associations using multivariable logistic regression analyses. RESULTS: All participants (73.4% women) were categorised based on predominant cooking fuel use. Group-1: LPG (Liquefied Petroleum Gas) users in the previous 20 years and above without concurrent biomass use (26.15%); Group-2: LPG users in the previous 20 years and above with concurrent secondary biomass use (15.9%); Group-3: Biomass users for ≥ 20 years (57.95%). Compared to group-1, accounting for confounders, GBC risk was higher in group-2 [OR: 2.02; 95% CI: 1.00-4.07] and group-3 [OR: 2.01; 95% CI: 1.08-3.73] (p-trend:0.020). These associations strengthened among women that attenuated with high daily consumption of fruits-vegetables but not with fire-vents, 'daily exposure duration' or parity. CONCLUSION: Biomass burning was associated with a high-risk for GBC and should be considered as a modifiable risk factor for GBC. Clean cooking fuel can potentially mitigate, and a healthy diet can partially reduce the risk among women.

Docosahexaenoic Acid Supplementation in Lactating Women Increases Breast Milk and Erythrocyte Membrane Docosahexaenoic Acid Concentrations and Alters Infant n-6:n-3 Fatty Acid Ratio.

Background: Low concentrations of docosahexaenoic acid (DHA) or high n-6 (ω-6):n-3 ratio in pregnant women is associated with poor fetal growth velocity and suboptimal neurodevelopment. However, there is a lack of data on levels of important n-6 and n-3 fatty acids (FAs) at different time points during pregnancy and lactation from India. Data on how much DHA is transferred during actual supplementation are also scarce. Objectives: We report the concentrations of n-6 and n-3 FAs in maternal and infant blood and in breast milk following maternal supplementation with DHA or placebo. Methods: A total of 957 pregnant women (≤20 wk) from Belagavi, Karnataka, were randomly assigned to receive either 400 mg/d of algal DHA or placebo through 6 mo postpartum. Blood samples were collected from the mother at recruitment/baseline, delivery, and 6 mo postpartum and from the infant at birth (cord) and 12 mo (venous). Breast milk samples were collected from a subsample at delivery, 1 mo and 6 mo postpartum. The FA profile was analyzed using gas chromatography. Results: The concentration of DHA appeared to be higher in erythrocyte and breast milk samples of the DHA-supplemented group at all subsequent time points. The n-6:n-3 ratio was lower among women in the DHA group at delivery [DHA: 4.08 (1.79); placebo: 5.84 (3.57); P < 0.001] and at 6 mo postpartum [DHA: 5.34 (2.64); placebo: 7.69 (2.9); P < 0.001]. Infants of DHA-supplemented mothers also had a lower n-6:n-3 ratio at delivery and 12 mo. The n-6:n-3 ratio of breast milk increased from delivery through 1 to 6 mo but remained lower in the DHA-supplemented group than in the placebo. Conclusions: Maternal DHA supplementation with 400 mg/d from early pregnancy through 6 mo postpartum significantly increased circulating DHA in breast milk and infant erythrocyte, whereas decreased erythrocyte and breast milk n-6:n-3 ratio. However, maternal supplementation did not get the ratio to the recommended levels.

PM2.5 exposure, glycemic markers and incidence of type 2 diabetes in two large Indian cities.

INTRODUCTION: Exposure to fine particulate matter has been associated with several cardiovascular and cardiometabolic diseases. However, such evidence mostly originates from low-pollution settings or cross-sectional studies, thus necessitating evidence from regions with high air pollution levels, such as India, where the burden of non-communicable diseases is high. RESEARCH DESIGN AND METHODS: We studied the associations between ambient PM2.5 levels and fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and incident type 2 diabetes mellitus (T2DM) among 12 064 participants in an adult cohort from urban Chennai and Delhi, India. A meta-analytic approach was used to combine estimates, obtained from mixed-effects models and proportional hazards models, from the two cities. RESULTS: We observed that 10 µg/m3 differences in monthly average exposure to PM2.5 was associated with a 0.40 mg/dL increase in FPG (95% CI 0.22 to 0.58) and 0.021 unit increase in HbA1c (95% CI 0.009 to 0.032). Further, 10 µg/m3 differences in annual average PM2.5 was associated with 1.22 (95% CI 1.09 to 1.36) times increased risk of incident T2DM, with non-linear exposure response. CONCLUSIONS: We observed evidence of temporal association between PM2.5 exposure, and higher FPG and incident T2DM in two urban environments in India, thus highlighting the potential for population-based mitigation policies to reduce the growing burden of diabetes.

ABDA Score: A Non-invasive Model to Identify Subjects with Fibrotic Non-alcoholic Steatohepatitis in the Community.

Background: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are prevalent in the community, especially among those with metabolic syndrome. Patients with fibrotic NASH are at increased risk of liver-related-events. Currently available non-invasive tests have not been utilized for screening for fibrotic NASH among the community. We aimed to develop a screening tool for fibrotic NASH among community members. Methods: We included two large cohorts aimed at assessing cardiovascular disease among community members. Fibrotic NASH was defined using the FibroScan-aspartate aminotransferase score of ≥0.67 that identifies ≥F2 fibrosis and a non-alcoholic fatty liver disease activity score ≥4 with a specificity of 90%. Metabolic parameters, biochemical tests and anthropometry were used to develop a multivariate model. Results: The derivation cohort (n = 1660) included a population with a median age 45 years, 42.5% males, metabolic syndrome in 66% and 2.7% (n = 45) with fibrotic NASH. Multivariate analysis identified the four significant variables (Age, body mass index , Diabetes and alanine aminotransferas levels) used to derive an ABDA score. The score had high diagnostic accuracy (the area under receiver-operating characteristic curve, 0.952) with adequate internal validity. An ABDA score ≥-3.52 identified fibrotic NASH in the derivation cohort with a sensitivity and specificity of 88.9% and 88.3%. The score was validated in a second cohort (n = 357) that included 21 patients (5.9%) with fibrotic NASH, where it demonstrated a high area under receiver-operating characteristic curve (0.948), sensitivity (81%) and specificity (89.3%). Conclusions: ABDA score utilizes four easily available parameters to identify fibrotic NASH with high accuracy in the community.

Epidemiological pattern of COVID-19 and its association with periodontal health in an urban Indian cohort.

Background: Studies have highlighted a possible influence of gingival and periodontal disease (PD) on COVID-19 risk and severity. However, the evidence is based on hospital-based studies and community-level data are sparse. Objectives: We described the epidemiological pattern of SARS-CoV-2 infection in Delhi and evaluated the associations of gingival and PD with incident COVID-19 disease in a regionally representative urban Indian population. Methods: In a prospective study nested within the Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) study, participants with clinical gingival and periodontal status available at baseline (2014-16) (n = 1,727) were approached between October 2021 to March 2022. Information on COVID-19 incidence, testing, management, severity was collected as per the WHO case criteria along with COVID-19 vaccination status. Absolute incidence of COVID-19 disease was computed by age, sex, and oral health. Differences in rates were tested using log-rank test. Poisson regression models were used to evaluate independent associations between gingival and PD and incidence of COVID-19, adjusted for socio-demographic and behavioral factors, presence of comorbidity, and medication use. Results: Among 1,727 participants, the mean age was 44.0 years, 45.7% were men, 84.5% participants had baseline gingival or PD and 89.4% participants had received at least one dose of COVID-19 vaccine. Overall, 35% (n = 606) participants were tested for COVID-19 and 24% (n = 146/606) tested positive. As per the WHO criteria total number of cases was 210, constituting 12% of the total population. The age and sex-specific rates of COVID-19 were higher among men and older participants, but women aged >60 years had higher rates than men of same age. The incidence rate did not differ significantly between those having gingival or PD and healthy periodontium (19.1 vs. 16.5/1,000 person-years) and there was no difference in risk of COVID-19 by baseline oral disease status. Conclusion: Gingival and PD were not associated with increased risk of COVID-19.

Linking population-based cohorts with cancer registries in LMIC: a case study and lessons learnt in India.

OBJECTIVES: In resource-constrained settings, cancer epidemiology research typically relies on self-reported diagnoses. To test a more systematic alternative approach, we assessed the feasibility of linking a cohort with a cancer registry. SETTING: Data linkage was performed between a population-based cohort in Chennai, India, with a local population-based cancer registry. PARTICIPANTS: Data set of Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) cohort participants (N=11 772) from Chennai was linked with the cancer registry data set for the period 1982-2015 (N=140 986). METHODS AND OUTCOME MEASURES: Match*Pro, a probabilistic record linkage software, was used for computerised linkages followed by manual review of high scoring records. The variables used for linkage included participant name, gender, age, address, Postal Index Number and father's and spouse's name. Registry records between 2010 and 2015 and between 1982 and 2015, respectively, represented incident and all (both incident and prevalent) cases. The extent of agreement between self-reports and registry-based ascertainment was expressed as the proportion of cases found in both data sets among cases identified independently in each source. RESULTS: There were 52 self-reported cancer cases among 11 772 cohort participants, but 5 cases were misreported. Of the remaining 47 eligible self-reported cases (incident and prevalent), 37 (79%) were confirmed by registry linkage. Among 29 self-reported incident cancers, 25 (86%) were found in the registry. Registry linkage also identified 24 previously not reported cancers; 12 of those were incident cases. The likelihood of linkage was higher in more recent years (2014-2015). CONCLUSIONS: Although linkage variables in this study had limited discriminatory power in the absence of a unique identifier, an appreciable proportion of self-reported cases were confirmed in the registry via linkages. More importantly, the linkages also identified many previously unreported cases. These findings offer new insights that can inform future cancer surveillance and research in low-income and middle-income countries.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

OBJECTIVES: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. DESIGN: Economic evaluation from healthcare system and societal perspectives. SETTING: Ten diverse urban clinics in India and Pakistan. PARTICIPANTS: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. INTERVENTION: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). RESULTS: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. CONCLUSIONS: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.

A cluster randomized controlled trial of an electronic decision-support system to enhance antenatal care services in pregnancy at primary healthcare level in Telangana, India: trial protocol.

BACKGROUND: India contributes 15% of the total global maternal mortality burden. An increasing proportion of these deaths are due to Pregnancy Induced Hypertension (PIH), Gestational Diabetes Mellitus (GDM), and anaemia. This study aims to evaluate the effectiveness of a tablet-based electronic decision-support system (EDSS) to enhance routine antenatal care (ANC) and improve the screening and management of PIH, GDM, and anaemia in pregnancy in primary healthcare facilities of Telangana, India. The EDSS will work at two levels of primary health facilities and is customized for three cadres of healthcare providers - Auxiliary Nurse Midwifes (ANMs), staff nurses, and physicians (Medical Officers). METHODS: This will be a cluster randomized controlled trial involving 66 clusters with a total of 1320 women in both the intervention and control arms. Each cluster will include three health facilities-one Primary Health Centre (PHC) and two linked sub-centers (SC). In the facilities under the intervention arm, ANMs, staff nurses, and Medical Officers will use the EDSS while providing ANC for all pregnant women. Facilities in the control arm will continue to provide ANC services using the existing standard of care in Telangana. The primary outcome is ANC quality, measured as provision of a composite of four selected ANC components (measurement of blood pressure, blood glucose, hemoglobin levels, and conducting a urinary dipstick test) by the healthcare providers per visit, observed over two visits. Trained field research staff will collect outcome data via an observation checklist. DISCUSSION: To our knowledge, this is the first trial in India to evaluate an EDSS, targeted to enhance the quality of ANC and improve the screening and management of PIH, GDM, and anaemia, for multiple levels of health facilities and several cadres of healthcare providers. If effective, insights from the trial on the feasibility and cost of implementing the EDSS can inform potential national scale-up. Lessons learned from this trial will also inform recommendations for designing and upscaling similar mHealth interventions in other low and middle-income countries. CLINICALTRIALS: gov, NCT03700034, registered 9 Oct 2018, https://www. CLINICALTRIALS: gov/ct2/show/NCT03700034 CTRI, CTRI/2019/01/016857, registered on 3 Mar 2019, http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=28627&EncHid=&modid=&compid=%27,%2728627det%27.