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 systolic BP <130 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 coprimary 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: 1.79; 95% confidence interval [CI], 1.45, 2.20), 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.

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.

Chronic Exposure to Drinking Water Arsenic and Gallbladder Cancer Risk: Preliminary Evidence from Endemic Regions of India.

BACKGROUND: Evidence linking arsenic in drinking water to digestive tract cancers is limited. We evaluated the association between arsenic levels in groundwater and gallbladder cancer risk in a case-control study (2019-2021) of long-term residents (≥10years) in two arsenic-impacted and high gallbladder cancer risk states of India-Assam and Bihar. METHODS: We recruited men and women aged 30 to 69 years from hospitals (73.4% women), with newly diagnosed, biopsy-confirmed gallbladder cancer (N = 214) and unrelated controls frequency-matched for 5-year age, sex, and state (N = 166). Long-term residential history, lifestyle factors, family history, socio-demographics, and physical measurements were collected. Average-weighted arsenic concentration (AwAC) was extrapolated from district-level groundwater monitoring data (2017-2018) and residential history. We evaluated gallbladder cancer risk for tertiles of AwAC (µg/L) in multivariable logistic regression models adjusted for important confounders [Range: 0-448.39; median (interquartile range), T1-0.45 (0.0-1.19); T2-3.75 (2.83-7.38); T3-17.6 (12.34-20.54)]. RESULTS: We observed a dose-response increase in gallbladder cancer risk based on AwAC tertiles [OR = 2.00 (95% confidence interval, 1.05-3.79) and 2.43 (1.30-4.54); Ptrend = 0.007]. Participants in the highest AwAC tertile consumed more tubewell water (67.7% vs. 27.9%) and reported more sediments (37.9% vs. 18.7%) with unsatisfactory color, odor, and taste (49.2% vs. 25.0%) than those in the lowest tertile. CONCLUSIONS: These findings suggest chronic arsenic exposure in drinking water at low-moderate levels may be a potential risk factor for gallbladder cancer. IMPACT: Risk factors for gallbladder cancer, a lethal digestive tract cancer, are not fully understood. Data from arsenic-endemic regions of India, with a high incidence of gallbladder cancer, may offer unique insights. Tackling 'arsenic pollution' may help reduce the burden of several health outcomes.

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.

Can ultrasonic biometric indices with optimal cut-offs be a potential screening tool for primary angle closure disease? A case-control study.

BACKGROUND/OBJECTIVES: Despite a significant disease burden and potential to cause blindness, primary angle closure disease (PACD) does not have a population-based screening programme. Biometric indices using ultrasound A-scan is a potential tool for glaucoma case-detection. Given that genetic and environmental factors influence these parameters and paucity of data on their discrimination thresholds in Indian populace, we conducted a matched case-control study to determine the biometric indices and their discrimination thresholds associated with PACD. METHODS: We studied 172 eyes of 86 participants (43 cases; 43 controls). We compared the following biometric parameters of cases (PACD, occludable angle ≥180° ± raised intraocular pressure) with age and gender-matched controls (1:1): Anterior chamber depth (ACD), lens thickness (LT), axial length (AXL), lens position (LP), relative lens position (RLP), lens axial factor (LAF), simple crowding value (Cs), ACD/AXL). We performed conditional logistic regression (to identify factors associated with PACD) and Receiver operating characteristic (ROC) analysis (to determine discrimination thresholds). RESULTS: Reduced ACD (Adj OR 0.01; 95% CI: 0.0003-0.15, p < 0.001) and increased LT (Adj OR 10.3; 95% CI:2.42-43.93, p < 0.001) were associated with PACD. On ROC analysis, ACD, Cs, and ACD/AXL had optimum sensitivity/specificity at ≤3.015, ≥0.056 and ≤0.1303, respectively. ACD (88.4%) and Cs (94.2%) had highest sensitivity and specificity, respectively. CONCLUSION: Ultrasonic biometric parameters differed significantly between PACD and controls. ACD and Cs (at discrimination thresholds of ≤3.015 mm and ≥ 0.056, respectively) using ultrasound A-scan could be a potential tool for PACD case-detection that requires evaluation of its diagnostic yield and cost-effectiveness.

Time intervals and patient-level factors in oral cancer diagnostic pathways: An application of the WHO framework in India.

BACKGROUND: Oral cancer, a leading cancer-site in India, is often detected at advanced stages. We evaluated the time intervals from first symptom to help-seeking and diagnosis among oral cancer patients. METHODOLOGY: In this cross-sectional study, we recruited 226 consecutive oral cancer patients (mean age ( ± SD) 51.9 years ( ± 10.9); 81.9% men; 70.3% advanced stage) registered for diagnosis and treatment, between 2019 and 2021 at a cancer care centre in South India. We used WHO framework and previously standardized tools to record time intervals (appraisal, help-seeking and diagnostic) and baseline characteristics. We utilized multivariable logistic regression models to test the associations between 'prolonged (i.e., over 1 month) time intervals') and patient-level factors to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Over a half of patients presented with prolonged appraisal (60%) and help-seeking intervals (57%), and a third (34%) reported prolonged diagnostic interval. Patients with no formal education, no routine healthcare visits, no self-reported risk factors, and those who did not perceive initial symptoms to be serious were 2-4 times more likely to have prolonged appraisal and help-seeking than the rest. High travel costs and self-decision for visiting healthcare facility prolonged help-seeking. Diagnostic interval was prolonged only among women OR= 2.7 (95% CI: 1.2-6.1)) and in patients whose first doctor's opinion was 'nothing to worry' OR (=7.3 (95% CI: 2.6-20.5)). 'Correct knowledge of cancer' shortened appraisal and help-seeking intervals and 'incorrect knowledge and negative beliefs' prolonged diagnostic interval. CONCLUSION: Our findings highlight that interventions targeting sociocultural and economic determinants, symptom awareness, sensitizing persons at risk (especially women) and primary care providers might reduce overall time to diagnosis. Further, patients without any known risk factors for oral cancer might be at-risk for prolonged appraisal interval. These might help inform 'pull' strategies for cancer control in India and similar settings.

Correction: Cardiovascular Risk Factors and Clinical Outcomes among Patients Hospitalized with COVID-19: Findings from the World Heart Federation COVID-19 Study.

[This corrects the article DOI: 10.5334/gh.1128.].

Correction: Cardiovascular Health in India - a Report Card from Three Urban and Rural Surveys of 22,144 Adults.

[This corrects the article DOI: 10.5334/gh.1137.].

Cardiovascular Health in India - a Report Card from Three Urban and Rural Surveys of 22,144 Adults.

Background: Markers of ideal cardiovascular health (CVH) predict cardiovascular events. We estimated the prevalence of ideal CVH markers in two levels of cities and villages in India. Methods: We did pooled analysis of individual-level data from three cross sectional surveys of adults ≥ 30 years over 2010-14 (CARRS: Centre for cArdiometabolic Risk Reduction in South Asia; UDAY and Solan Surveillance Study) representing metropolitan cities; smaller cities and rural areas in diverse locations of India. We defined ideal CVH using modified American Heart Association recommendations: not smoking, ≥ 5 servings of fruits and vegetables (F&V), high physical activity (PA), body mass index (BMI) <25 Kg/m2, blood pressure (BP) <120/80 mm Hg, fasting plasma glucose (FPG) <100 mg/dl, and total cholesterol (TC) <200 mg/dL. We estimated (1) age-and sex-standardized prevalence of ideal CVH and (2) prevalence of good (≥6 markers), moderate (4-5), and poor CVH (≤3) adjusted for age, sex, education, and stratified by setting and asset tertiles. Results: Of the total 22,144 participants, the prevalence of ideal CVH markers were: not smoking (76.7% [95% CI 76.1, 77.2]), consumed ≥5 F&V (4.2% [3.9, 4.5]), high PA (67.5% [66.8, 68.2]), optimum BMI (59.6% [58.9, 60.3]), ideal BP (34.5% [33.9, 35.2]), FPG (65.8% [65.1, 66.5]) and TC (65.4% [64.7, 66.1]). The mean number of ideal CVH metrics was 3.7(95% CI: 3.7, 3.8). Adjusted prevalence of good, moderate, and poor CVH, varied across settings: metropolitan (3.9%, 41.0%, and 55.1%), smaller cities (7.8%, 49.2%, and 43%), and rural (10.4%, 60.9%, and 28.7%) and across asset tertiles: Low (11.0%, 55.9%, 33.1%), Middle (6.3%, 52.2%, 41.5%), and High (5.0%, 46.4%, 48.7%), respectively. Conclusion: Achievement of ideal CVH varied, with higher prevalence in rural and lower asset tertiles. Multi-sectoral and targeted policy and program actions are needed to improve CVH in diverse contexts in India.

Cardiovascular Risk Factors and Clinical Outcomes among Patients Hospitalized with COVID-19: Findings from the World Heart Federation COVID-19 Study.

Background and aims: Limited data exist on the cardiovascular manifestations and risk factors in people hospitalized with COVID-19 from low- and middle-income countries. This study aims to describe cardiovascular risk factors, clinical manifestations, and outcomes among patients hospitalized with COVID-19 in low, lower-middle, upper-middle- and high-income countries (LIC, LMIC, UMIC, HIC). Methods: Through a prospective cohort study, data on demographics and pre-existing conditions at hospital admission, clinical outcomes at hospital discharge (death, major adverse cardiovascular events (MACE), renal failure, neurological events, and pulmonary outcomes), 30-day vital status, and re-hospitalization were collected. Descriptive analyses and multivariable log-binomial regression models, adjusted for age, sex, ethnicity/income groups, and clinical characteristics, were performed. Results: Forty hospitals from 23 countries recruited 5,313 patients with COVID-19 (LIC = 7.1%, LMIC = 47.5%, UMIC = 19.6%, HIC = 25.7%). Mean age was 57.0 (±16.1) years, male 59.4%, pre-existing conditions included: hypertension 47.3%, diabetes 32.0%, coronary heart disease 10.9%, and heart failure 5.5%. The most frequently reported cardiovascular discharge diagnoses were cardiac arrest (5.5%), acute heart failure (3.8%), and myocardial infarction (1.6%). The rate of in-hospital deaths was 12.9% (N = 683), and post-discharge 30 days deaths was 2.6% (N = 118) (overall death rate 15.1%). The most common causes of death were respiratory failure (39.3%) and sudden cardiac death (20.0%). The predictors of overall mortality included older age (≥60 years), male sex, pre-existing coronary heart disease, renal disease, diabetes, ICU admission, oxygen therapy, and higher respiratory rates (p < 0.001 for each). Compared to Caucasians, Asians, Blacks, and Hispanics had almost 2-4 times higher risk of death. Further, patients from LIC, LMIC, UMIC versus. HIC had 2-3 times increased risk of death. Conclusions: The LIC, LMIC, and UMIC's have sparse data on COVID-19. We provide robust evidence on COVID-19 outcomes in these countries. This study can help guide future health care planning for the pandemic globally.