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.

Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact.

The Global Diabetes Compact is a WHO-driven initiative uniting stakeholders around goals of reducing diabetes risk and ensuring that people with diabetes have equitable access to comprehensive, affordable care and prevention. In this report we describe the development and scientific basis for key health metrics, coverage, and treatment targets accompanying the Compact. We considered metrics across four domains: factors at a structural, system, or policy level; processes of care; behaviours and biomarkers such as glycated haemoglobin (HbA1c); and health events and outcomes; and three risk tiers (diagnosed diabetes, high risk, or whole population), and reviewed and prioritised them according to their health importance, modifiability, data availability, and global inequality. We reviewed the global distribution of each metric to set targets for future attainment. This process led to five core national metrics and target levels for UN member states: (1) of all people with diabetes, at least 80% have been clinically diagnosed; and, for people with diagnosed diabetes, (2) 80% have HbA1c concentrations below 8·0% (63·9 mmol/mol); (3) 80% have blood pressure lower than 140/90 mm Hg; (4) at least 60% of people 40 years or older are receiving therapy with statins; and (5) each person with type 1 diabetes has continuous access to insulin, blood glucose meters, and test strips. We also propose several complementary metrics that currently have limited global coverage, but warrant scale-up in population-based surveillance systems. These include estimation of cause-specific mortality, and incidence of end-stage kidney disease, lower-extremity amputations, and incidence of diabetes. Primary prevention of diabetes and integrated care to prevent long-term complications remain important areas for the development of new metrics and targets. These metrics and targets are intended to drive multisectoral action applied to individuals, health systems, policies, and national health-care access to achieve the goals of the Global Diabetes Compact. Although ambitious, their achievement can result in broad health benefits for people with diabetes.

Body mass index changes and their association with SARS-CoV-2 infection: a real-world analysis.

OBJECTIVE: To study body mass index (BMI) changes among individuals aged 18-99 years with and without SARS-CoV-2 infection. SUBJECTS/METHODS: Using real-world data from the OneFlorida+ Clinical Research Network of the National Patient-Centered Clinical Research Network, we compared changes over time in BMI in an Exposed cohort (positive SARS-CoV-2 test between March 2020-January 2022), to a contemporary Unexposed cohort (negative SARS-CoV-2 tests), and an age/sex-matched Historical control cohort (March 2018-January 2020). BMI (kg/m2) was retrieved from objective measures of height and weight in electronic health records. We used target trial approaches to estimate BMI at start of follow-up and change per 100 days of follow-up for Unexposed and Historical cohorts relative to the Exposed cohort by categories of sex, race & ethnicity, age, and hospitalization status. RESULTS: The study sample consisted of 249,743 participants (19.2% Exposed, 61.5% Unexposed, 19.3% Historical cohort) of whom 62% were women, 21.5% Non-Hispanic Black, 21.4% Hispanic and 5.6% Non-Hispanic other and had an average age of 51.9 years (SD: 18.9). At start of follow-up, relative to the Unexposed cohort (mean BMI: 29.3 kg/m2 [95% CI: 29.1, 29.4]), the Exposed (0.07 kg/m2 [95% CI; 0.01, 0.12]) had higher mean BMI and Historical controls (-0.20 kg/m2 [95% CI; -0.25, -0.15]) had lower mean BMI. Over 100 days, BMI did not change (0 kg/m2 [95% CI: -0.03, 0.03]) for the Exposed cohort, decreased (-0.04 kg/m2 [95% CI; -0.05, -0.02]) for the Unexposed cohort and increased (0.03 kg/m2 [95% CI; 0.01, 0.04]) for the Historical cohort. Observed differences in BMI at start of follow-up and over 100 days were consistent between Unexposed and Exposed cohorts for most subgroups, except at start of follow-up period among Males and those 65 years or older who had lower BMI among Exposed. CONCLUSIONS: In a diverse real-world cohort of adults, mean BMI of those with and without SARS-CoV2 infection varied in their trajectories. The mechanisms and implications of weight retention following SARS-CoV-2 infection remain unclear.

Is Electronic Information Exchange Associated With Lower 30-Day Readmission Charges Among Medicare Beneficiaries?

OBJECTIVE: Fragmented readmissions, when admission and readmission occur at different hospitals, are associated with increased charges compared with nonfragmented readmissions. We assessed if hospital participation in health information exchange (HIE) was associated with differences in total charges in fragmented readmissions. DATA SOURCE: Medicare Fee-for-Service Data, 2018. STUDY DESIGN: We used generalized linear models with hospital referral region and readmission month fixed effects to assess relationships between information sharing (same HIE, different HIEs, and no HIE available) and total charges of 30-day readmissions among fragmented readmissions; analyses were adjusted for patient-level clinical/demographic characteristics and hospital-level characteristics. DATA EXTRACTION METHODS: We included beneficiaries with a hospitalization for acute myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease, syncope, urinary tract infection, dehydration, or behavioral issues with a 30-day readmission for any reason. PRINCIPAL FINDINGS: In all, 279,729 admission-readmission pairs were included, 27% of which were fragmented (n=75,438); average charges of fragmented readmissions were $64,897-$71,606. Compared with fragmented readmissions where no HIE was available, the average marginal effects of same-HIE and different-HIE admission-readmission pairs were -$2329.55 (95% CI: -7333.73, 2674.62) and -$3905.20 (95% CI: -7592.85, -307.54), respectively. While the average marginal effects of different-HIE pairs were lower than those for no-HIE fragmented readmissions, the average marginal effects of same-HIE and different-HIE pairs were not significantly different from each other. CONCLUSIONS: There were no statistical differences in charges between fragmented readmissions to hospitals that share an HIE or that do not share an HIE compared with hospitals with no HIE available.

Risk of New-Onset Diabetes Before and During the COVID-19 Pandemic: A Real-World Cohort Study.

BACKGROUND: Studies of new-onset diabetes as a post-acute sequela of SARS-CoV-2 infection are difficult to generalize to all socio-demographic subgroups. OBJECTIVE: To study the risk of new-onset diabetes after SARS-CoV-2 infection in a socio-demographically diverse sample. DESIGN: Retrospective cohort study of electronic health record (EHR) data available from the OneFlorida + clinical research network within the National Patient-Centered Clinical Research Network (PCORnet). SUBJECTS: Persons aged 18 or older were included as part of an Exposed cohort (positive SARS-CoV-2 test or COVID-19 diagnosis between 1 March 2020 and 29 January 2022; n = 43,906), a contemporary unexposed cohort (negative SARS-CoV-2 test; n = 162,683), or an age-sex matched historical control cohort (index visits between 2 Mar 2018 and 30 Jan 2020; n = 40,957). MAIN MEASURES: The primary outcome was new-onset type 2 diabetes ≥ 30 days after index visit. Hazard ratios and cases per 1000 person-years of new-onset diabetes were studied using target trial approaches for observational data. Associations were reported by sex, race/ethnicity, age, and hospitalization status subgroups. KEY RESULTS: The sample was 62% female, 21.4% non-Hispanic Black, and 21.4% Hispanic; mean age was 51.8 (SD, 18.9) years. Relative to historical controls (cases, 28.2 [26.0-30.5]), the unexposed (HR, 1.28 [95% CI, 1.18-1.39]; excess cases, [5.1-10.3]), and exposed cohorts (HR, 1.64 [95% CI, 1.50-1.80]; excess cases, 17.3 [13.7-20.8]) had higher risk of new-onset T2DM. Relative to the unexposed cohort, the exposed cohort had a higher risk (HR, 1.28 [1.19-1.37]); excess cases, 9.5 [6.4-12.7]). Findings were similar across subgroups. CONCLUSION: The pandemic period was associated with increased T2DM cases across all socio-demographic subgroups; the greatest risk was observed among individuals exposed to SARS-CoV-2.

Factors influencing diabetes treatment satisfaction in the INtegrating DEPrEssioN and Diabetes treatmENT randomized clinical trial: A multilevel model analysis.

AIMS: Patient satisfaction is associated with positive diabetes outcomes. However, there are no identified studies that evaluate both patient- and clinic-level predictors influencing diabetes care satisfaction longitudinally. METHODS: Data from the INtegrating DEPrEssioN and Diabetes treatmENT trial was used to perform the analysis. We used fixed and random effects models to assess whether and how changes in patient-level predictors (treatment assignment, depression symptom severity, systolic blood pressure, body mass index, LDL cholesterol, and haemoglobin A1C) from 0 to 24 months and clinic-level predictors (visit frequency, visit cost, number of specialists, wait time, time spent with healthcare provider, and receiving verbal reminders) measured at 24 months influence diabetes care satisfaction from 0 to 24 months. RESULTS: Model 1 (patient-level predictors) accounted for 7% of the change in diabetes satisfaction and there was a significant negative relationship between change in depressive symptoms and care satisfaction (ß = -0.23, SE = 0.12, p < 0.05). Within Model 1, 2% of the variance was explained by clinic-level predictors. Model 2 included both patient- and clinic-level predictors and accounted for 18% of the change in diabetes care satisfaction. Within Model 2, 9% of the variance was attributed to clinic-level predictors. There was also a cross-level interaction where the change in depression had less of an impact on the change in satisfaction for those who received a verbal reminder (ß = -0.11, SE = 0.21, p = 0.34) compared with those who did not receive a reminder (ß = -0.62, SE = 0.08, p < 0.01). CONCLUSIONS: Increased burden of depressive symptoms influences diabetes care satisfaction. Clinic-level predictors also significantly influence diabetes care satisfaction and can reduce dissatisfaction in primary care, specifically, reminder calls from clinic staff.

5-Year simulation of diabetes-related complications in people treated with tirzepatide or semaglutide versus insulin glargine.

AIM: This study compared the 5-year incidence rate of macrovascular and microvascular complications for tirzepatide, semaglutide and insulin glargine in individuals with type 2 diabetes, using the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes simulation model. RESEARCH DESIGN AND METHODS: This study was a 5-year SURPASS-2 trial extrapolation, with an insulin glargine arm added as an additional comparator. The 1-year treatment effects of tirzepatide (5, 10 or 15 mg), semaglutide (1 mg) and insulin glargine on glycated haemoglobin, systolic blood pressure, low-density lipoprotein and body weights were obtained from the SUSTAIN-4 and SURPASS-2 trials. We used the BRAVO model to predict 5-year complications for each study arm under two scenarios: the 1-year treatment effects persisted (optimistic) or diminished to none in 5 years (conservative). RESULTS: When compared with insulin glargine, we projected a 5-year risk reduction in cardiovascular adverse events [rate ratio (RR) 0.64, 95% confidence interval (CI) 0.61-0.67] and microvascular composite (RR 0.67, 95% CI 0.64-0.70) with 15 mg tirzepatide, and 5-year risk reduction in cardiovascular adverse events (RR 0.75, 95% CI 0.72-0.79) and microvascular composite (RR 0.79, 95% CI 0.76-0.82) with semaglutide (1 mg) under an optimistic scenario. Lower doses of tirzepatide also had similar, albeit smaller benefits. Treatment effects for tirzepatide and semaglutide were smaller but still significantly higher than insulin glargine under a conservative scenario. The 5-year risk reduction in diabetes-related complication events and mortality for the 15 mg tirzepatide compared with insulin glargine ranged from 49% to 10% under an optimistic scenario, which was reduced by 17%-33% when a conservative scenario was assumed. CONCLUSION: With the use of the BRAVO diabetes model, tirzepatide and semaglutide exhibited potential to reduce the risk of macrovascular and microvascular complications among individuals with type 2 diabetes, compared with insulin glargine in a 5-year window. Based on the current modelling assumptions, tirzepatide (15 mg) may potentially outperform semaglutide (1 mg). While the BRAVO model offered insights, the long-term cardiovascular benefit of tirzepatide should be further validated in a prospective clinical trial.

Renal function as an effect modifier of intensive glucose control in delaying cognitive function decline among individuals with type 2 diabetes: A revisit to the ACCORD MIND trial.

AIM: Dysglycaemia accelerates cognitive decline. Intensive glucose control may help delay or prevent cognitive function decline (CFD). We aimed to determine how patient characteristics influence the effect of intensive glucose control [glycated haemoglobin (HbA1c) <6.0%] on delaying CFD in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this post-hoc analysis of 2977 type 2 diabetes participants from the ACCORD MIND trial, we applied the causal forest and causal tree algorithms to identify the effect modifier of intensive glucose control in delaying CFD from 68 variables (demographics, disease history, medications, vitals and baseline biomarkers). The exposure was intensive versus standard glucose control (HbA1c <6.0% vs. 7.0%-7.9%). The main outcome was cognitive function changes from baseline to the 40th month follow-up, which were evaluated using the digit symbol substitution test, Rey auditory verbal learning test, mini-mental state examination and Stroop test. We used Cohen's d, a measure of standardized difference, to quantify the effect size of intensive glucose control on delaying CFD. RESULTS: Among all the baseline characteristics, renal function was the most significant effect modifier. Participants with urinary albumin levels <0.4 mg/dl [absolute function change (AFC): 0.51 in mini-mental state examination, 95% confidence interval (CI): 0.04, 0.98, Cohen's d: 0.25] had slower CFD with intensive glucose control. Patients with preserved renal function (estimated glomerular filtration rate between 60 and 90 ml/min/1.73 m2) were associated with small benefits (AFC: 1.28 in Stroop, 95% CI: 0.28, 2.27, Cohen's d: 0.12) when undergoing intensive glucose control. Conversely, participants with an estimated glomerular filtration rate <60 ml/min/1.73 m2 (AFC: -0.57 in the Rey auditory verbal learning test, 95% CI: -1.09, -0.05, Cohen's d: -0.30) exhibited faster CFD when undergoing intensive glucose control. Participants who were <60 years old showed a significant benefit from intensive glucose control in delaying CFD (AFC: 1.08 in the digit symbol substitution test, 95% CI: 0.06, 2.10, Cohen's d: 0.13). All p < .05. CONCLUSIONS: Our findings linked renal function with the benefits of intensive glucose control in delaying CFD, informing personalized HbA1c goals for those with diabetes and at risk of CFD.

Association between low cognitive performance and diabetes-related health indicators across racial and ethnic groups in adults with diabetes.

AIM: To examine the associations between low cognitive performance (LCP) and diabetes-related health indicators (including body mass index [BMI], HbA1c, systolic blood pressure [SBP], low-density lipoprotein [LDL] and self-reported poor physical health) and whether these associations vary across racial/ethnic subgroups. METHODS: We identified adults aged 60 years or older with self-reported diabetes from the 2011-2014 National Health and Nutrition Examination Survey. Individuals with cognitive test scores in the lowest quartile were defined as having LCP. We used regression models to measure the associations of LCP with diabetes-related biometrics (BMI, HbA1c, SBP and LDL); and self-reported poor physical health. Moreover, we explored potential variations in these associations across racial/ethnic subgroups. RESULTS: Of 873 (261 with LCP) adults with diabetes, LCP was associated with higher HbA1c, SBP and LDL (adjusted difference: 0.41%, 5.01 mmHg and 5.08 mg/dL, respectively; P < .05), and greater odds of reporting poor physical health (adjusted odds ratio: 1.59, P < .05). The association between LCP and HbA1c was consistent across racial/ethnic groups, and notably pronounced in Hispanic and Other. BMI worsened with LCP, except for non-Hispanic Black. Excluding the Other group, elevated SBP was observed in people with LCP, with Hispanic showing the most significant association. LDL levels were elevated with LCP for Hispanic and Other. Physical health worsened with LCP for both non-Hispanic Black and Hispanic. CONCLUSIONS: We quantified the association between LCP and diabetes-related health indicators. These associations were more pronounced in Hispanic and Other racial/ethnic groups.

Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study.

SUMMARY: Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

Concordance of weight status between mothers and children: a secondary analysis of the Pakistan Demographic and health survey VII.

BACKGROUND: Familial concordance of weight status is an emerging field of study that may guide the development of interventions that operate beyond the individual and within the family context. There is a dearth of published data for concordance of weight status within Pakistani households. METHODS: We assessed the associations between weight status of mothers and their children in a nationally representative sample of households in Pakistan using Demographic and Health Survey data from 2017-18. Our analysis included 3465 mother-child dyads, restricting to children under-five years of age with body mass index (BMI) information on their mothers. We used linear regression models to assess the associations between maternal BMI category (underweight, normal weight, overweight, obese) and child's weight-for-height z-score (WHZ), accounting for socio-demographic characteristics of mothers and children. We assessed these relationships in all children under-five and also stratified by age of children (younger than 2 years and 2 to 5 years). RESULTS: In all children under-five and in children 2 to 5 years, maternal BMI was positively associated with child's WHZ. For all children under-five, children of normal weight, overweight, and obese women had WHZ scores that were 0.21 [95% CI (confidence interval): 0.04, 0.37], 0.43 [95% CI: 0.25, 0.62], and 0.51 [95% CI: 0.30, 0.71] units higher than children of underweight women, respectively. For children ages 2 to 5, children of normal weight, overweight, and obese women had WHZ scores that were 0.26 [95% CI: 0.08, 0.44), 0.50 [95% CI: 0.30, 0.71), and 0.61 [95% CI: 0.37, 0.84] units higher than children of underweight women, respectively. There was no association between maternal BMI and child WHZ for children under-two. CONCLUSIONS: The findings indicate that the weight status of mother's is positively associated with that of their children, particularly after age 2. These associations further strengthen the call for research regarding interventions and policies aimed at healthy weight promotion among mothers and their children collectively, rather than focusing on individuals in isolation.

Effectiveness of WhatsApp based debunking reminders on follow-up visit attendance for individuals with hypertension: a randomized controlled trial in India.

BACKGROUND: Individuals with high blood pressure in India often miss essential follow-up visits. Missed visits contribute to gaps across the hypertension care continuum and preventable cardiovascular disease. Widespread misconceptions around hypertension care and treatment may contribute to low follow-up attendance rates, but to date, there is limited evidence of the effect of interventions to debunk such misconceptions on health-seeking behavior. We conducted a randomized controlled trial to measure whether combining information debunking commonly-held misconceptions with a standard reminder reduces missed follow-up visits among individuals with high blood pressure and investigated whether any observed effect was moderated through belief change. METHODS: We recruited 388 patients with uncontrolled blood pressure from the outpatient wards of two public sub-district hospitals in Punjab, India. Participants randomly assigned to the intervention arm received two WhatsApp messages, sent 3 and 1 days before their physician-requested follow-up visit. The WhatsApp message began with a standard reminder, reminding participants of their upcoming follow-up visit and its purpose. Following the standard reminder, we included brief debunking statements aimed at acknowledging and correcting common misconceptions and misbeliefs about hypertension care seeking and treatment. Participants in the control group received usual care and did not receive any messages. RESULTS: We did not find evidence that the enhanced WhatsApp reminders improved follow-up visit attendance (Main effect: 2.2 percentage points, p-value = 0.603), which remained low across both treatment (21.8%, 95% CI: 15.7%, 27.9%) and control groups (19.6%, 95% CI: 14.2%, 25.0%). Participants had widespread misconceptions about hypertension care but our debunking messages did not successfully correct these beliefs (p-value = 0.187). CONCLUSIONS: This study re-affirms the challenge of continuity of care for chronic diseases in India and suggests that simple phone-based health communication methods may not suffice for changing prevalent misconceptions and improving health-seeking behavior. TRIAL REGISTRATION: The trial began on July 18th. We registered the trial on July 18th (before recruitment began), including the main outcomes, on the German Clinical Trial Register [Identifier: DRKS00029712] and published a pre-analysis plan in the Open Science Framework [osf.io/67g35].

Community Control of Hypertension and Diabetes (CoCo-HD) program in the Indian states of Kerala and Tamil Nadu: a study protocol for a type 3 hybrid trial.

INTRODUCTION: India grapples with a formidable health challenge, with an estimated 315 million adults afflicted with hypertension and 100 million living with diabetes mellitus. Alarming statistics reveal rates for poor treatment and control of hypertension and diabetes. In response to these pressing needs, the Community Control of Hypertension and Diabetes (CoCo-HD) program aims to implement structured lifestyle interventions at scale in the southern Indian states of Kerala and Tamil Nadu. AIMS: This research is designed to evaluate the implementation outcomes of peer support programs and community mobilisation strategies in overcoming barriers and maximising enablers for effective diabetes and hypertension prevention and control. Furthermore, it will identify contextual factors that influence intervention scalability and it will also evaluate the program's value and return on investment through economic evaluation. METHODS: The CoCo-HD program is underpinned by a longstanding collaborative effort, engaging stakeholders to co-design comprehensive solutions that will be scalable in the two states. This entails equipping community health workers with tailored training and fostering community engagement, with a primary focus on leveraging peer supportat scale in these communities. The evaluation will undertake a hybrid type III trial in, Kerala and Tamil Nadu states, guided by the Institute for Health Improvement framework. The evaluation framework is underpinned by the application of three frameworks, RE-AIM, Normalisation Process Theory, and the Consolidated Framework for Implementation Research. Evaluation metrics include clinical outcomes: diabetes and hypertension control rates, as well as behavioural, physical, and biochemical measurements and treatment adherence. DISCUSSION: The anticipated outcomes of this study hold immense promise, offering important learnings into effective scaling up of lifestyle interventions for hypertension and diabetes control in low- and middle-income countries (LMICs). By identifying effective implementation strategies and contextual determinants, this research has the potential to lead to important changes in healthcare delivery systems. CONCLUSIONS: The project will provide valuable evidence for the scaling-up of structured lifestyle interventions within the healthcare systems of Kerala and Tamil Nadu, thus facilitating their future adaptation to diverse settings in India and other LMICs.

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.

Care fragmentation and readmission mortality and length of stay before and during the COVID-19 pandemic: data from the National Readmissions Database, 2018-2020.

IMPORTANCE: A quarter of all 30-day readmissions involve fragmented care, where patients return to a different hospital than their original admission; these readmissions are associated with increased in-hospital mortality and longer lengths-of-stay (LOS). The stress on healthcare systems at the beginning of the COVID-19 pandemic could worsen care fragmentation and related outcomes. OBJECTIVE: To compare fragmented readmissions in 2020 versus 2018-2019 and assess whether mortality and LOS in fragmented readmissions differed in the two time periods. DESIGN: Observational study SETTING: National Readmissions Database (NRD), 2018-2020 PARTICIPANTS: All adults (> 18 y/o) with 30-day readmissions MAIN OUTCOMES AND MEASURES: We examined the percentage of fragmented readmissions over 2018-2020. Using unadjusted and adjusted logistic and linear regressions, we estimated the associations between fragmented readmissions and in-hospital mortality and LOS. RESULTS: 24.0-25.7% of readmissions in 2018-2020 and 27.3%-31.0% of readmissions for COVID-19 were fragmented. 2018-2019 fragmented readmissions were associated with 18-20% higher odds of in-hospital mortality compared to nonfragmented readmissions. Fragmented readmissions for COVID-19 were associated with an 18% increase in in-hospital mortality (AOR 1.18, 95% CI 1.12, 1.24). The LOS of fragmented readmissions in March-November 2018-2019 were on average 0.81 days longer, while fragmented readmissions between March-November of 2020 were associated with a 0.88-1.03 day longer LOS. CONCLUSIONS AND RELEVANCE: A key limitation is that the NRD does not contain information on several patient/hospital-level factors that may be associated with the outcomes of interest. We observed increased fragmentation during COVID-19, but its impact on in-hospital mortality and LOS remained consistent with previous years.

From Evidence to Effectiveness: Implications of the Randomized Trial to Prevent Vascular Events in HIV Study for People With Human Immunodeficiency Virus in Low- and Middle-Income Settings.

The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) study found a 35% reduction in major adverse cardiovascular events for people with human immunodeficiency virus who received daily pitavastatin. However, how this evidence will change practice is far from certain. Here, we outline evidence gaps and political and healthcare delivery challenges that will need to be addressed for REPRIEVE to offer public health benefits in low- and middle-income countries.

Trends and Race/Ethnic Disparities in Diabetes-Related Hospital Use in Medicaid Enrollees: Analyses of Serial Cross-sectional State Data, 2008-2017.

BACKGROUND: Race/ethnic disparities in preventable diabetes-specific hospital care may exist among adults with diabetes who have Medicaid coverage. OBJECTIVE: To examine race/ethnic disparities in utilization of preventable hospital care by adult Medicaid enrollees with diabetes across nine states over time. DESIGN: Using serial cross-sectional state discharge records for emergency department (ED) visits and inpatient (IP) hospitalizations from the Healthcare Cost and Utilization Project, we quantified race/ethnicity-specific, state-year preventable diabetes-specific hospital utilization. PARTICIPANTS: Non-Hispanic Black, non-Hispanic White, and Hispanic adult Medicaid enrollees aged 18-64 with a diabetes diagnosis (excluding gestational or secondary diabetes) who were discharged from hospital care in Arizona, Iowa, Kentucky, Florida, Maryland, New Jersey, New York, North Carolina, and Utah for the years 2008, 2011, 2014, and 2017. MAIN MEASURES: Non-Hispanic Black-over-White and Hispanic-over-White rate ratios constructed using age- standardized state-year, race/ethnicity-specific ED, and IP diabetes-specific utilization rates. KEY RESULTS: The ratio of Black-over-White ED utilization rates for preventable diabetes-specific hospital care increased across the 9 states in our sample from 1.4 (CI 95, 1.31-1.50) in 2008 to 1.73 (CI 95, 1.68-1.78) in 2017. The cross-year-state average non-Hispanic Black-over-White IP rate ratio was 1.46 (CI 95, 1.42-1.50), reflecting increases in some states and decreases in others. The across-state-year average Hispanic-over-White rate ratio for ED utilization was 0.67 (CI 95, 0.63-0.71). The across-state-year average Hispanic-over-White IP hospitalization rate ratio was 0.72 (CI 95, 0.69-0.75). CONCLUSIONS: Hospital utilization by non-Hispanic Black Medicaid enrollees with diabetes was consistently greater and often increased relative to utilization by White enrollees within state programs between 2008 and 2017. Hispanic enrollee hospital utilization was either lower or indistinguishable relative to White enrollee hospital utilization in most states, but Hispanic utilization increased faster than White utilization in some states. Among broader patterns, there is heterogeneity in the magnitude of race/ethnic disparities in hospital utilization trends across states.

Cardiometabolic Risk in Asian Americans by Social Determinants of Health: Serial Cross-sectional Analyses of the NHIS, 1999-2003 to 2014-2018.

BACKGROUND: Diabetes and hypertension are common in Asian Americans and vary by subgroup. There may be further variation by social determinants of health (SDOHs), but few studies have examined this previously. OBJECTIVE: To examine the associations of SDOHs and diabetes and hypertension within and across Asian subgroups in the USA DESIGN: Series cross-sectional analyses SETTING: National Health Interview Surveys (NHIS) from 1999 to 2018 PARTICIPANTS: Asian-American adults (Chinese, Filipino, Asian Indian, and Other Asian [Korean, Vietnamese, Japanese, and other]) MEASUREMENTS: Self-reported diabetes and hypertension prevalence in pooled 5-year increments over 1999-2018 and multivariable regression models to assess the adjusted prevalence of diabetes or hypertension by poverty, marital status, education, and years in the USA, adjusting for age, sex, BMI, and health insurance status RESULTS: From 1999-2003 to 2014-2018, the age- and sex-adjusted prevalence of diabetes increased for Other Asians (absolute change: 4.6%) but not for other subgroups; age- and sex-adjusted hypertension prevalence significantly increased for Asian Indians and Other Asians (absolute change: 5-7.5%). For Filipinos, high school education or less was associated with an increase in diabetes prevalence over time (difference from 1999-2003 to 2014-2018: +6.0 (95% CI: 2.0-10.0)), while for Asian Indians, college education or higher was associated with an increase in diabetes prevalence for the same period (difference: +2.7 (95% CI: 0.01-5.4). Differences over the 2 time periods (1999-2003 and 2014-2018) show that Filipino and Other Asians, who lived in the USA for ≥10 years, increased in diabetes prevalence. Similar variations in associations of SDOHs by Asian subgroup were seen for hypertension. LIMITATIONS: Self-reported primary outcomes and multi-year data were pooled due to small sample sizes. CONCLUSIONS: The influence of SDOHs on cardiometabolic risk is not uniform among Asian Americans, implying tailored strategies may be needed for different population subgroups. PRIMARY FUNDING SOURCE: NIH.

Long-term Effects of a Collaborative Care Model on Metabolic Outcomes and Depressive Symptoms: 36-Month Outcomes from the INDEPENDENT Intervention.

BACKGROUND: Collaborative care (CC) is a multicomponent team-based approach to providing mental health care with systematic integration into outpatient medical settings. The 12-month INDEPENDENT CC intervention improved joint disease control measures in patients with both depression and diabetes at 12 and 24 months following randomization. OBJECTIVE: This study investigated the durability of intervention effects on patient outcomes at 36 months following randomization. PARTICIPANTS: Adult patients with poorly controlled T2D and depression in India randomized to CC or usual care. DESIGN: Post hoc analyses of between-group differences in patient outcomes at 36 months post-randomization (N = 331) and maintenance of outcomes from 12 to 36 months (N = 314). MAIN MEASURES: We evaluated combined risk factor improvement since baseline, defined as ≥ 50.0% reduction in Symptom Checklist Depression Scale (SCL-20) scores along with reduction of at least 0.5 percentage point hemoglobin A1C, 5 mmHg systolic blood pressure, or 10 mg/dL low-density lipoprotein cholesterol. Improvements in single risk factors were also examined. KEY RESULTS: There were no between-group differences in improvements since baseline in multiple or single risk factors at 36 months. Patients in the CC group with improved outcomes at 12 months were more likely to maintain a ≥ 50.0% reduction since baseline in SCL-20 scores (CC [54.9%] vs. UC [40.9%]; RR: 1.27 [95% CI: 1.04, 1.56]) and 0.5 percentage point reduction since baseline in hemoglobin A1C (CC [31.9%] vs. UC [19.5%]; RR: 1.64 [95% CI: 1.11, 2.41]) at 36 months. CONCLUSIONS: While improvements since baseline in patient outcomes did not differ between the collaborative care and usual care groups at 36 months, patients who received CC were more likely to maintain improvements in depressive symptoms and glucose levels at 36 months if they had achieved these improvements at the end of active intervention. TRIAL REGISTRATION NUMBER: NCT02022111.

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.