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Abstract Background We examined the trajectory of estimated glomerular filtrate rate (eGFR), associated risk factors, and its relationship with end‐stage kidney disease (ESKD) among a multiethnic patient population with type 2 diabetes in Singapore. Methods A follow‐up study included 62 080 individuals with type 2 diabetes aged ≥18 years in a multi‐institutional SingHealth Diabetes Registry between 2013 and 2019. eGFR trajectories were analyzed using latent class linear mixed models. Factors associated with eGFR trajectories were evaluated using multinomial logistic regression. The association of eGFR trajectories with ESKD was assessed via competing risk models. Results Trajectory of kidney function, determined by eGFR, was nonlinear. The trajectory pattern was classified as stable initially then gradual decline (75%), progressive decline (21.9%), and rapid decline (3.1%). Younger age, female sex, Malay ethnicity, lower‐income housing type, current smoking, higher glycated hemoglobin, lower low‐density lipoprotein, higher triglyceride, uncontrolled blood pressure, albuminuria, cardiovascular disease, hypertension, and higher eGFR levels each were associated with progressive or rapid decline. Compared with the trajectory of stable initially then gradual eGFR decline, progressive decline increased the hazard of ESKD by 6.14‐fold (95% confidence interval [CI]: 4.96–7.61)) and rapid decline by 82.55 folds (95% CI: 55.90–121.89). Conclusions Three nonlinear trajectory classes of kidney function were identified among multiethnic individuals with type 2 diabetes in Singapore. About one in four individuals had a progressive or rapid decline in eGFR. Our results suggest that eGFR trajectories are correlated with multiple social and modifiable risk factors and inform the risk of ESKD.

Abstract Background We aimed to explore the three-way interaction among age, gender, and kidney function on the risk of all-cause mortality and cardiovascular mortality among patients with type 2 diabetes (T2D). Methods In a retrospective cohort study, patients aged > 40 years with T2D with serum creatinine and urine albumin measured from 2013 to 2019 were included from a multi-institutional diabetes registry. The exposure was estimated glomerular filtration rate (eGFR), outcomes were all-cause mortality (primary outcome) and cardiovascular disease (CVD) mortality (secondary outcome). We applied multivariable cox proportional hazards regression analysis to compute the association between eGFR and mortality. Results A total of 36,556 patients were followed for up to 6 years during which 2492 (6.82%) died from all causes, and 690 (1.9%) died from CVD. We observed a significant three-way interaction (p = 0.021) among age (younger,

Background The SingHypertension primary care clinic intervention, which consisted of clinician training in hypertension management, subsidized single‐pill combination medications, nurse‐delivered motivational conversations and telephone follow‐ups, improved blood pressure control and cardiovascular disease (CVD) risk scores relative to usual care among patients with uncontrolled hypertension in Singapore. This study quantified the incremental cost‐effectiveness, in terms of incremental cost per unit reduction disability‐adjusted life years, of SingHypertension relative to usual care for patients with hypertension from the health system perspective. Methods and Results We developed a Markov model to simulate CVD events and associated outcomes for a hypothetical cohort of patients over a 10‐year period. Costs were measured in US dollars, and effectiveness was measured in disability‐adjusted life years averted. We present base‐case results and conducted deterministic and probabilistic sensitivity analyses. Based on a willingness‐to‐pay threshold of US $55 500 per DALY averted, SingHypertension was cost‐effective for patients with hypertension (incremental cost‐effectiveness ratio: US $24 765 per disability‐adjusted life year averted) relative to usual care. This result held even if risk reduction was assumed to decline linearly to 0 over 10 years but not sooner than 7 years. Incremental cost‐effectiveness ratios were most sensitive to the magnitude of the reduction in CVD risk; at least a 0.13% to 0.16% point reduction in 10‐year CVD risk is required for cost‐effectiveness. Probabilistic sensitivity analysis indicates that SingHypertension has a 78% chance of being cost‐effective at the willingness‐to‐pay threshold. Conclusions SingHypertension represents good value for the money for reducing CVD incidence, morbidity, and mortality and should be considered for wide‐scale implementation in Singapore and possibly other countries. Registration Information REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02972619.

Assessing glomerular filtration rate (GFR) is critical for diagnosis, staging, and management of kidney disease. However, accuracy of estimated GFR (eGFR) is limited by large errors (>30% error present in >10-50% of patients), adversely impacting patient care. Errors often result from variation across populations of non-GFR determinants affecting the filtration markers used to estimate GFR. We hypothesized that combining multiple filtration markers with non-overlapping non-GFR determinants into a panel GFR could improve eGFR accuracy, extending current recognition that adding cystatin C to serum creatinine improves accuracy. Non-GFR determinants of markers can affect the accuracy of eGFR in two ways: first, increased variability in the non-GFR determinants of some filtration markers among application populations compared to the development population may result in outlying values for those markers. Second, systematic differences in the non-GFR determinants of some markers between application and development populations can lead to biased estimates in the application populations. Here, we propose and evaluate methods for estimating GFR based on multiple markers in applications with potentially higher rates of outlying predictors than in development data. We apply transfer learning to address systematic differences between application and development populations. We evaluated a panel of 8 markers (5 metabolites and 3 low molecular weight proteins) in 3,554 participants from 9 studies. Results show that contamination in two strongly predictive markers can increase imprecision by more than two-fold, but outlier identification with robust estimation can restore precision nearly fully to uncontaminated data. Furthermore, transfer learning can yield similar results with even modest training set sample size. Combining both approaches addresses both sources of error in GFR estimates. Once the laboratory challenge of developing a validated targeted assay for additional metabolites is overcome, these methods can inform the use of a panel eGFR across diverse clinical settings, ensuring accuracy despite differing non-GFR determinants.

BACKGROUND Elevated blood pressure (BP) is associated with increased risk of cardiovascular mortality. However, there is ongoing debate whether intensive BP lowering may paradoxically increase the risk of cardiovascular disease (CVD), especially in patients with type 2 diabetes (T2D). We investigated the association of BP with risk of CVD mortality in patients with T2D. METHODS AND RESULTS We used data on 83 721 patients with T2D from a multi‐institutional diabetes registry in Singapore from 2013 to 2019. BP was analyzed as categories and restricted cubic splines using Cox multivariable regression analysis stratified by preexisting CVD and age (120 to 129 mm Hg. Diastolic BP levels >90 mm Hg were significantly associated with CVD mortality in those aged ≥65 years. In addition, diastolic BP

Abstract Introduction The burden of chronic kidney disease (CKD) is rising globally including in Singapore. Primary care is the first point of contact for most patients with early stages of CKD. However, several barriers to optimal CKD management exist. Knowing healthcare professionals’ (HCPs) perspectives is important to understand how best to strengthen CKD services in the primary care setting. Integrating a theory-based framework, we explored HCPs’ perspectives on the facilitators of and barriers to CKD management in primary care clinics in Singapore. Methods In-depth interviews were conducted on a purposive sample of 20 HCPs including 13 physicians, 2 nurses and 1 pharmacist from three public primary care polyclinics, and 4 nephrologists from one referral hospital. Interviews were audio recorded, transcribed verbatim and thematically analyzed underpinned by the Theoretical Domains Framework (TDF) version 2. Results Numerous facilitators of and barriers to CKD management identified. HCPs perceived insufficient attention is given to CKD in primary care and highlighted several barriers including knowledge and practice gaps, ineffective CKD diagnosis disclosure, limitations in decision-making for nephrology referrals, consultation time, suboptimal care coordination, and lack of CKD awareness and self-management skills among patients. Nevertheless, intensive CKD training of primary care physicians, structured CKD-care pathways, multidisciplinary team-based care, and prioritizing nephrology referrals with risk-based assessment were key facilitators. Participants underscored the importance of improving awareness and self-management skills among patients. Primary care providers expressed willingness to manage early-stage CKD as a collaborative care model with nephrologists. Our findings provide valuable insights to design targeted interventions to enhance CKD management in primary care in Singapore that may be relevant to other countries. Conclusions The are several roadblocks to improving CKD management in primary care settings warranting urgent attention. Foremost, CKD deserves greater priority from HCPs and health planners. Multipronged approaches should urgently address gaps in care coordination, patient-physician communication, and knowledge. Strategies could focus on intensive CKD-oriented training for primary care physicians and building novel team-based care models integrating structured CKD management, risk-based nephrology referrals coupled with education and motivational counseling for patients. Such concerted efforts are likely to improve outcomes of patients with CKD and reduce the ESKD burden.

Background. Cardiovascular disease is a major cause of morbidity and mortality in kidney transplant recipients. Trial evidence to improve cardiovascular outcomes is limited by inconsistent reporting of outcomes, which may also lack patient-relevance. This study aimed to assess the range and consistency of cardiovascular outcomes reported by contemporary trials in kidney transplant recipients. Methods. A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of the cardiovascular outcome measures reported were analyzed (the measure definition, metric‚ and method of aggregation). Measures assessing a similar aspect of cardiovascular disease were categorized into outcomes. Results. From 93 eligible trials involving 27 609 participants, 490 outcome measures were identified. The outcome measures were grouped into 38 outcomes. A cardiovascular composite was the most common outcome reported (40 trials, 43%) followed by cardiovascular mortality (42%) and acute coronary syndrome (31%). Cardiovascular composite was also the most heterogeneous outcome with 77 measures reported followed by cardiovascular mortality (n = 58) and inflammatory biomarkers (n = 51). The most common cardiovascular composite outcome components reported were major cardiovascular events (18 trials), stroke unspecified (11 trials), and myocardial infarction unspecified (10 trials). Conclusions. There is substantial heterogeneity in cardiovascular outcome reporting in kidney transplant trials.

Background COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multicomponent, community health-worker (CHW)-led hypertension management program, has been shown to be effective in rural communities in South Asia. This paper presents the acceptability of COBRA-BPS multicomponent intervention among the key stakeholders. Methods We conducted post-implementation interviews of 87 stakeholder including 23 community health workers (CHWs), 19 physicians and 45 patients in 15 rural communities randomized to COBRA-BPS multicomponent intervention in in Bangladesh, Pakistan, and Sri Lanka. We used Theoretical Framework for Acceptability framework (TFA) with a focus on affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness and self-efficacy. Results COBRA-BPS multicomponent intervention was acceptable to most stakeholders. Despite some concerns about workload, most CHWs were enthusiastic and felt empowered. Physicians appreciated the training sessions and felt trusted by their patients. Patients were grateful to receive the intervention and valued it. However, patients in Pakistan and Bangladesh expressed the need for supplies of free medicines from the primary health facilities, while those in Sri Lanka were concerned about supplies’ irregularities. All stakeholders favoured scaling-up COBRA-BPS at a national level. Conclusions COBRA-BPS multicomponent intervention is acceptable to the key stakeholders in Bangladesh, Pakistan and Sri Lanka. Community engagement for national scale-up of COBRA-BPS is likely to be successful in all three countries.

BackgroundInconsistent conclusions in past studies on the association between poor glycaemic control and the risk of hospitalization for heart failure (HHF) have been reported largely due to the analysis of non-trajectory-based HbA1c values. Trajectory analysis can incorporate the effects of HbA1c variability across time, which may better elucidate its association with macrovascular complications. Furthermore, studies analysing the relationship between HbA1c trajectories from diabetes diagnosis and the occurrence of HHF are scarce.MethodsThis is a prospective cohort study of the SingHealth Diabetes Registry (SDR). 17,389 patients diagnosed with type 2 diabetes mellitus (T2DM) from 2013 to 2016 with clinical records extending to the end of 2019 were included in the latent class growth analysis to extract longitudinal HbA1c trajectories. Association between HbA1c trajectories and risk of first known HHF is quantified with the Cox Proportional Hazards (PH) model.Results5 distinct HbA1c trajectories were identified as 1. low stable (36.1%), 2. elevated stable (40.4%), 3. high decreasing (3.5%), 4. high with a sharp decline (10.8%), and 5. moderate decreasing (9.2%) over the study period of 7 years. Poorly controlled HbA1c trajectories (Classes 3, 4, and 5) are associated with a higher risk of HHF. Using the diabetes diagnosis time instead of a commonly used pre-defined study start time or time from recruitment has an impact on HbA1c clustering results.ConclusionsFindings suggest that tracking the evolution of HbA1c with time has its importance in assessing the HHF risk of T2DM patients, and T2DM diagnosis time as a baseline is strongly recommended in HbA1c trajectory modelling. To the authors' knowledge, this is the first study to identify an association between HbA1c trajectories and HHF occurrence from diabetes diagnosis time.

Introduction Most of the global non-communicable disease (NCD)-related death burden is borne by low and middle-income countries (LMICs). In LMICs like Pakistan, however, a major gap in responding to NCDs is a lack of high-quality research leading to policy development and implementation of NCDs. To assess institutional opportunities and constraints to NCD research and training we conducted a situational analysis for NCD research and training at Aga Khan University Pakistan.Methods We conducted a descriptive exploratory study using grounded theory as a qualitative approach: semistructured interviews of 16 NCD stakeholders (three excluded) and two focus group discussions with postgraduate and undergraduate trainees were conducted. A simple thematic analysis was done where themes were identified, and then recurring ideas were critically placed in their specific themes and refined based on the consensus of the investigators.Results The major themes derived were priority research areas in NCDs; methods to improve NCD research integration; barriers to NCD research in LMICs like Pakistan; design of NCD research programme and career paths; and NCD prevention at mass level, policy and link to the government. In general, participants opined that while there was an appetite for NCD research and training, but few high-quality research training programmes in NCDs existed, such programmes needed to be established. The ideal NCD research and training programmes would have in-built protected time, career guidance and dedicated mentorship. Most participants identified cardiovascular diseases as a priority thematic area and health information technology and data science as key methodological approaches to be introduced into research training.Conclusion We conclude from this qualitative study on NCD research and training that high-quality research training programmes for NCDs are rare. Such programmes need to be established with in-built protected time, career guidance and mentorship for the trainees to improve their research capacity in Pakistan.

Objective The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) Program is a diabetes prevention trial comparing the diabetes conversion rate at 3 years between the intervention group, which receives the incentivized lifestyle intervention program with stepwise addition of metformin, and the control group, which receives the standard of care. We describe the baseline characteristics and compare Pre-DICTED participants with other diabetes prevention trials cohort.Research design and methods Participants were aged between 21 and 64 years, overweight (body mass index (BMI) ≥23.0 kg/m2), and had pre-diabetes (impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)).Results A total of 751 participants (53.1% women) were randomized. At baseline, mean (SD) age was 52.5 (8.5) years and mean BMI (SD) was 29.0 (4.6) kg/m2. Twenty-three per cent had both IFG and IGT, 63.9% had isolated IGT, and 13.3% had isolated IFG. Ethnic Asian Indian participants were more likely to report a family history of diabetes and had a higher waist circumference, compared with Chinese and Malay participants. Women were less likely than men to meet the physical activity recommendations (≥150 min of moderate-intensity physical activity per week), and dietary intake varied with both sex and ethnicity. Compared with other Asian diabetes prevention studies, the Pre-DICTED cohort had a higher mean age and BMI.Conclusion The Pre-DICTED cohort represents subjects at high risk of diabetes conversion. The study will evaluate the effectiveness of a community-based incentivized lifestyle intervention program in an urban Asian context.

Abstract Background Community-based diabetes prevention programs varied widely in effectiveness, and the intervention strategy consisting of lifestyle interventions, stepwise addition of metformin, and financial incentives has not been studied in real-world clinical practice settings. The Pre-Diabetes Interventions and Continued Tracking to Ease-out Diabetes (Pre-DICTED) trial is a pragmatic trial that aims to compare the effectiveness of a community-based stepwise diabetes prevention program with added financial incentives (intervention) versus the standard of care (control) in reducing the risk of type 2 diabetes over 3 years among overweight or obese individuals with pre-diabetes. Methods This is an open-label, 1:1 randomized controlled trial which aims to recruit 846 adult individuals with isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), or both IFG and IGT from Singapore. Intervention arm participants attend 12 group-based sessions (2 nutrition workshops, 9 exercise sessions, and a goal-setting workshop) delivered at community sites (weeks 1 to 6), receive weekly physical activity and nutrition recommendations delivered by printed worksheets (weeks 7 to 12), and receive monthly health tips delivered by text messages (months 4 to 36). From month 6 onwards, intervention arm participants who remain at the highest risk of conversion to diabetes are prescribed metformin. Intervention arm participants are also eligible for a payment/rewards program with incentives tied to attendance at the group sessions and achievement of the weight loss target (5% of baseline weight). All participants are assessed at baseline, month 3, month 6, and every 6 months subsequently till month 36. The primary endpoint is the proportion of participants with diabetes at 3 years. Secondary endpoints include the mean change from baseline at 3 years in fasting plasma glucose, 2-hour plasma glucose, HbA1c, body weight, body mass index, physical activity, and dietary intake. Discussion The Pre-DICTED trial will provide evidence of the effectiveness and feasibility of a community-based stepwise diabetes prevention program with added financial incentives for individuals with pre-diabetes in Singapore. The study will provide data for a future cost-effectiveness analysis, which will be used to inform policymakers of the value of a nationwide implementation of the diabetes prevention program. Trial registration ClinicalTrials.gov NCT03503942 . Retrospectively registered on April 20, 2018. Protocol version: 5.0 Date: 1 March 2019

Introduction: The creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation was calibrated for the general Pakistan population (eGFRcr-PK) to eliminate bias and improve accuracy. Cystatin C–based CKD-EPI equations (eGFRcys and eGFRcr-cys) have not been assessed in this population, and non-GFR determinants of cystatin C are unknown. Methods: We assessed eGFRcys, eGFRcr-cys, and non-GFR determinants of cystatin C in a cross-sectional study of 557 participants (≥40 years of age) from Pakistan. We compared bias (median difference in measured GFR [mGFR] and eGFR), precision (interquartile range [IQR] of differences), accuracy (percentage of eGFR within 30% of mGFR), root mean square error (RMSE), and classification of mGFR

Background Nepal is a South Asian country with a high burden of non-communicable diseases. Electronic health technologies are a promising strategy to mitigate the rising burden of non-communicable diseases by strengthening primary healthcare center service delivery. However, electronic health implementation in Nepal is limited. Furthermore, electronic health use at the primary healthcare center level is chronically understudied. This qualitative study seeks to understand the perceived awareness, benefits, and determinants of electronic health uptake in Nepal, focusing on primary healthcare center-level non-communicable disease management. Methods We conducted in-depth interviews with 27 participants including policymakers, health experts, facility administrators, providers, and non-communicable diseases patients in 2019. We selected six urban primary healthcare center facilities via cluster convenience sampling for recruiting facility administrators, providers, and patients, and used convenience sampling to recruit policymakers and experts. We conducted thematic data analysis inductively and deductively using the electronic health readiness assessment framework to understand perceived barriers and facilitators of electronic health implementation. Results While there was general awareness and acceptance of electronic health, multiple barriers impede readiness for implementation. These include policy making gaps, language barriers, low user technical literacy, concerns of overreliance on technology, and inadequate training for administrators and providers. Stakeholder suggestions include creating electronic health interfaces that meet the needs of end users (providers and patients), providing training to enable end users to effectively use electronic health technologies, and strong policy support at the national level. Conclusion We identify several determinants for effectively promoting the use of electronic health for non-communicable diseases service delivery at the primary healthcare center level in Nepal.

Abstract Introduction Cardiovascular disease (O'Lone E, Viecelli AK, Craig JC, Tong A, Sautenet B, Herrington WG, et al., Am J Kidney Dis 76(1):109–20, 2020) remains the leading cause of death in Singapore. Uncontrolled hypertension confers the highest attributable risk of CVD and remains a significant public health issue with sub-optimal blood pressure (BP) control rates. The aim of the trial is to evaluate the effectiveness and cost-effectiveness of a multicomponent intervention (MCI) versus usual care on lowering BP among adults with uncontrolled hypertension visiting primary care clinics in Singapore. This article describes the statistical analysis plan for the primary and secondary objectives related to intervention effectiveness. Methods The study is a cluster randomized trial enrolling 1000 participants with uncontrolled hypertension aged ≥ 40 years from eight primary care clinics in Singapore. The unit of randomization is the clinic, with eight clusters (clinics) randomized in a 1:1 ratio to either MCI or usual care. All participants will be assessed at baseline, 12 months, and 24 months with measurements of systolic and diastolic BP, antihypertensive and statin medication use, medication adherence, physical activity level, anthropometric parameters, smoking status, and dietary habits. The primary objective of this study is to assess the effectiveness of MCI versus usual care on mean SBP at the 2-year follow-up. The primary outcome is SBP at 24 months. SBP at baseline, 12, and 24 months will be modeled at the subject level using a likelihood-based, linear mixed-effects model repeated measures (MMRM) analysis with treatment group and follow-up as fixed effects, random cluster (clinic) effects, Gaussian error distribution, and adjustment to degrees of freedom using the Satterthwaite approximation. Secondary outcomes will be analyzed using a similar modeling approach incorporating generalized techniques appropriate for the type of outcome. Discussion The trial will allow us to determine whether the MCI has an impact on BP and cardiovascular risk factors over a 2-year follow-up period and inform recommendations for health planners in scaling up these strategies for the benefit of society at large. A pre-specified and pre-published statistical analysis plan mitigates reporting bias and data driven approaches. Trial registration ClinicalTrials.gov NCT02972619 . Registered on 23 November 2016.

Abstract Background Patients with chronic kidney disease (CKD) are at high risk of end-stage kidney disease (ESKD). The Kidney Failure Risk Equation (KFRE), which predicts ESKD risk among patients with CKD, has not been validated in primary care clinics in Southeast Asia (SEA). Therefore, we aimed to (1) evaluate the performance of existing KFRE equations, (2) recalibrate KFRE for better predictive precision, and (3) identify optimally feasible KFRE thresholds for nephrologist referral and dialysis planning in SEA. Methods All patients with CKD visiting nine primary care clinics from 2010 to 2013 in Singapore were included and applied 4-variable KFRE equations incorporating age, sex, estimated glomerular filtration rate (eGFR), and albumin-to-creatinine ratio (ACR). ESKD onset within two and five years were acquired via linkage to the Singapore Renal Registry. A weighted Brier score (the squared difference between observed vs predicted ESKD risks), bias (the median difference between observed vs predicted ESKD risks) and precision (the interquartile range of the bias) were used to select the best-calibrated KFRE equation. Results The recalibrated KFRE (named Recalibrated Pooled KFRE SEA) performed better than existing and other recalibrated KFRE equations in terms of having a smaller Brier score (square root: 2.8% vs. 4.0–9.3% at 5 years; 2.0% vs. 6.1–9.1% at 2 years), less bias (2.5% vs. 3.3–5.2% at 5 years; 1.8% vs. 3.2–3.6% at 2 years), and improved precision (0.5% vs. 1.7–5.2% at 5 years; 0.5% vs. 3.8–4.2% at 2 years). Area under ROC curve for the Recalibrated Pooled KFRE SEA equations were 0.94 (95% confidence interval [CI]: 0.93 to 0.95) at 5 years and 0.96 (95% CI: 0.95 to 0.97) at 2 years. The optimally feasible KFRE thresholds were > 10–16% for 5-year nephrologist referral and > 45% for 2-year dialysis planning. Using the Recalibrated Pooled KFRE SEA, an estimated 82 and 89% ESKD events were included among 10% of subjects at highest estimated risk of ESKD at 5-year and 2-year, respectively. Conclusions The Recalibrated Pooled KFRE SEA performs better than existing KFREs and warrants implementation in primary care settings in SEA.

Abstract Background Elderly end stage kidney patients face a decision concerning whether or not to initiate dialysis. In Asia, this decision is highly influenced by family caregivers. The objective of this paper was to understand patients’ experience with and preferences for family involvement in treatment decisions, and via a series of hypothetical vignettes, to identify whether there was discordance in treatment preferences between patients and their caregivers, and how any potential conflicts were reconciled. Methods We conducted a survey with 151 elderly (aged ≥65) chronic kidney disease patients and their caregivers at outpatient renal clinics. The survey asked, when making treatment decisions, whom they wish makes the final decisions (i.e., preference) and who usually makes the final decisions (i.e., experience). The survey also presented a series of choice vignettes for managing patient’s condition and asked respondents to choose between two hypothetical treatment profiles in each vignette. Patients and caregivers were first interviewed separately in tandem, and then were brought together to choose a treatment jointly for vignettes where the initial treatment choice differed within the dyad. We used multivariate regressions to investigate the predictors of discordance and reconciliation. Results We found that most (51%) patients preferred and experienced (64%) significant involvement from caregivers. However, 38% of patients preferred to make final decisions alone but only 27% of patients did. In the hypothetical vignettes, caregivers chose the more intensive option (i.e., dialysis) more than patients did (26% vs 19%; p

Introduction The burden of type 2 diabetes mellitus (T2DM) and related vascular complications is particularly high in Asians and ethnic minorities living in the West. However, the association of T2DM with socioeconomic status (SES) and ethnicity has not been widely studied in populations living in Asia. Therefore, we investigated these associations among the multiethnic population with uncontrolled hypertension in Singapore.Research design and methods In a cross-sectional study using baseline data of a 2-year randomized trial in Singapore, we obtained demographic, SES, lifestyle and clinical factors from 915 patients aged ≥40 years with uncontrolled hypertension. T2DM was defined as having either: (i) self-reported ‘physician-diagnosed diabetes confirmed through medical records’ or taking antidiabetes medications, (ii) fasting blood glucose levels ≥7.0 mmol/dL or (iii) hemoglobin A1c ≥6.5%. The SES proxies included education, employment status, housing ownership and housing type, and the ethnicities were Chinese, Malays and Indians. Logistic regression analyses were used to evaluate the association of T2DM with SES and ethnicity.Results Higher proportion of T2DM was observed in Malays (40.0%) and Indians (56.0%) than Chinese (26.8%) (p

Background Asian populations are at high risk of diabetes and related vascular complications. We examined risk factor control, preventive care, and disparities in these trends among adults with diabetes in Singapore. Methods The sample included 209,930 adults with diabetes aged≥18 years from a multi-institutional SingHealth Diabetes Registry between 2013 and 2019 in Singapore. We performed logistic generalized estimating equations (GEEs) regression analysis and used linear mixed effect modeling to evaluate the temporal trends. Results Between 2013 and 2019, the unadjusted control rates of glycated hemoglobin (4.8%, 95%CI (4.4 to 5.1) and low-density lipoprotein cholesterol (LDL-C) (11.5%, 95%CI (11.1 to 11.8)) improved, but blood pressure (BP) control worsened (systolic BP (SBP)/diastolic BP (DBP) Conclusions Trends in risk factor control improved for glycated hemoglobin and LDL-C, but worsened for BP among diabetic adults in Singapore from 2013 to 2019. Control rates for all risk factors remain inadequate.

Objective To outline the facilitators and barriers to patients’ self-management of predialysis chronic kidney disease (CKD).Design Qualitative.Setting Three polyclinics in a public primary care institution in Singapore.Participants 20 patients entered and completed the study. Inclusion criteria were: (1) English speaking, (2) aged 40 years and above, (3) identified by clinical coding as ‘DM (diabetes mellitus) nephropathy-overt’ and ‘DM nephropathy-incipient’, by their physicians in the polyclinic, with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 (based on electronic health records) and (4) aware of their CKD illness. Exclusion criteria were: (1) receiving dialysis or had received a kidney transplant, (2) suffered from any visual, auditory or cognitive impairment which could hinder their ability to participate in the study or (3) pregnant.Results We found that the major barriers to CKD management were a lack of knowledge and awareness of CKD, a passive attitude toward self-management and insufficient patient-physician communication. Major facilitators included patient trust and satisfaction with the physician and family support. Many patients reported that there was an overload of information and too little guidance on how to manage their condition, especially regarding dietary recommendations.Conclusion We identified several barriers and facilitators to the management of predialysis CKD among patients. A multi-pronged approach for raising CKD awareness is required: improving patient-physician communication, implementing CKD workshops and home-visits and disseminating accurate online information about CKD. Strategies should also focus on increasing patient engagement and optimising family support by involving family members in patients’ care. Furthermore, clear dietary recommendations and patient-specific advice are needed to empower patients to manage their own condition.

Background: Chronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. “CKD Patch” is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures. Methods: Utilizing data from 4,143,535 adults from 35 datasets, we developed several “CKD Patches” incorporating eGFR and albuminuria, to enhance prediction of risk of atherosclerotic CVD (ASCVD) by the Pooled Cohort Equation (PCE) and CVD mortality by Systematic COronary Risk Evaluation (SCORE). The risk enhancement by CKD Patch was determined by the deviation between individual CKD measures and the values expected from their traditional CVD risk factors and the hazard ratios for eGFR and albuminuria. We then validated this approach among 4,932,824 adults from 37 independent datasets, comparing the original PCE and SCORE equations (recalibrated in each dataset) to those with addition of CKD Patch. Findings: We confirmed the prediction improvement with the CKD Patch for CVD mortality beyond SCORE and ASCVD beyond PCE in validation datasets (Δc-statistic 0.027 [95% CI 0.018–0.036] and 0.010 [0.007–0.013] and categorical net reclassification improvement 0.080 [0.032–0.127] and 0.056 [0.044–0.067], respectively). The median (IQI) of the ratio of predicted risk for CVD mortality with CKD Patch vs. the original prediction with SCORE was 2.64 (1.89–3.40) in very high-risk CKD (e.g., eGFR 30–44 ml/min/1.73m2 with albuminuria ≥30 mg/g), 1.86 (1.48–2.44) in high-risk CKD (e.g., eGFR 45–59 ml/min/1.73m2 with albuminuria 30–299 mg/g), and 1.37 (1.14–1.69) in moderate risk CKD (e.g., eGFR 60–89 ml/min/1.73m2 with albuminuria 30–299 mg/g), indicating considerable risk underestimation in CKD with SCORE. The corresponding estimates for ASCVD with PCE were 1.55 (1.37–1.81), 1.24 (1.10–1.54), and 1.21 (0.98–1.46). Interpretation: The “CKD Patch” can be used to quantitatively enhance ASCVD and CVD mortality risk prediction equations recommended in major US and European guidelines according to CKD measures, when available. Funding: US National Kidney Foundation and the NIDDK.

Abstract Background In rural south Asia, hypertension remains a significant public health issue with sub-optimal blood pressure (BP) control rates. The goal of the trial is to evaluate the effectiveness and cost-effectiveness of a multicomponent intervention (MCI) compared to usual care on lowering BP among adults with hypertension in rural south-Asian communities. This article describes the statistical analysis plan for the primary and secondary objectives related to intervention effectiveness based on clinical and patient-reported endpoints. Methods/Design The study is a cluster randomized trial which will enroll 2550 participants aged ≥ 40 years with hypertension from rural communities in Bangladesh, Pakistan, and Sri Lanka. The unit of randomization is a cluster defined by 250–300 households. Thirty clusters, 10 from each country, are randomized in a 1:1 ratio to either MCI or usual care, stratified by country and their distance from the clinic. All participants will be assessed every six months over a two-year period after baseline with measurements of systolic and diastolic BP, antihypertensive and statin medication use, medication adherence, physical activity level, anthropometric parameters, smoking status, and dietary habits. The primary objective is to assess the effectiveness of MCI as compared with usual care in terms of mean change in systolic BP from baseline to final follow-up at two years. The primary outcome will be modelled using a generalized linear mixed-model for repeated measures based on a participant-level analysis. The model will include cluster random-effects and will use a non-independence residual correlation matrix to account for repeated measures on the same participant. Sensitivity analyses for the primary endpoint will be based on multiple imputation as well as pattern mixture model tipping point analyses. Secondary outcomes will be analyzed using the same modeling approach as for the primary outcome, with appropriate distributions within the exponential family and corresponding link functions. Discussion The a priori statistical analysis plan will avoid reporting bias and data-driven analysis for the primary and key secondary outcomes. The results of the study will provide evidence of the benefits and risks of the MCI for BP control in rural communities in south Asian countries with low-resourced public health infrastructure. Trial registration Clinicaltrials.gov, NCT02657746. Registered on 14 January 2016.

Abstract Background Hypertension is a serious public health problem in Singapore and is associated with significant morbidity and mortality from cardiovascular disease (CVD) with considerable implications for health-care resources. The goal of the trial is to compare a multicomponent intervention (MCI) to usual care to evaluate the effectiveness and cost-effectiveness of the MCI for lowering blood pressure (BP) among adults with uncontrolled hypertension in Singapore primary-care clinics. Methods/design The study is a cluster randomized trial in eight polyclinics in Singapore: four deliver a structured MCI and four deliver usual care. The components of the MCI are: (1) an algorithm-driven antihypertensive treatment for all hypertensive individuals using single-pill combination (SPC) and lipid-lowering medication for high-risk hypertensive individuals, (2) a motivational conversation for high-risk hypertensive individuals, (3) telephone-based follow-ups of all hypertensive individuals by polyclinic nurses, and (4) discounts on SPC antihypertensive medications. The trial will be conducted with 1000 individuals aged ≥ 40 years with uncontrolled hypertension (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg, based on the mean of the last two of three measurements) in eight polyclinics in Singapore. The primary outcome is change in systolic BP from baseline to follow-up at 24 months post-randomization. The incremental cost of MCI per CVD disability adjusted life years (DALY) averted and quality adjusted life years (QALY) saved will be computed. Discussion The demonstration of an effective and cost-effective hypertension control program that is implementable in busy polyclinics would provide compelling evidence for upscaling the program across all primary-care centers in Singapore, and possibly other regional countries with a similar health-care structure. Trial registration Clinicaltrials.gov, NCT02972619. Registered on 23 November 2016.

Abstract Background High blood pressure (BP) is the leading attributable risk for cardiovascular disease (CVD). In rural South Asia, hypertension continues to be a significant public health issue with sub-optimal BP control rates. The goal of the trial is to compare a multicomponent intervention (MCI) to usual care to evaluate the effectiveness and cost-effectiveness of the MCI for lowering BP among adults with hypertension in rural communities in Bangladesh, Pakistan and Sri Lanka. Methods/design This study is a stratified, cluster randomized controlled trial with a qualitative component for evaluation of processes and stakeholder feedback. The MCI has five components: (1) home health education by government community health workers (CHWs), (2) BP monitoring and stepped-up referral to a trained general practitioner using a checklist, (3) training public and private providers in management of hypertension and using a checklist, (4) designating hypertension triage counter and hypertension care coordinators in government clinics and (5) a financing model to compensate for additional health services and provide subsidies to low income individuals with poorly controlled hypertension. Usual care will comprise existing services in the community without any additional training. The trial will be conducted on 2550 individuals aged ≥40 years with hypertension (with systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, based on the mean of the last two of three measurements from two separate days, or on antihypertensive therapy) in 30 rural communities in Bangladesh, Pakistan and Sri Lanka. The primary outcome is change in systolic BP from baseline to follow-up at 24 months post-randomization. The incremental cost of MCI per CVD disability-adjusted life years averted will be computed. Stakeholders including policy makers, provincial- and district-level coordinators of relevant programmes, physicians, CHWs, key community leaders, hypertensive individuals and family members in the identified clusters will be interviewed. Discussion The study will provide evidence of the effectiveness and cost-effectiveness of MCI strategies for BP control compared to usual care in the rural public health infrastructure in South Asian countries. If shown to be successful, MCI may be a long-term sustainable strategy for tackling the rising rates of CVD in low resourced countries. Trial registration ClinicalTrials.gov, NCT02657746. Registered on 14 January 2016.

For elderly end-stage renal disease (ESRD) patients with multiple comorbidities, dialysis may offer little survival benefit compared to conservative management (CM). Yet, many elderly ESRD patients undergo dialysis, partly due to physicians’ recommendations regarding treatment choice. This study aims to elucidate the factors that influence these recommendations. Methods: We surveyed a convenience sample of physicians who attended the 9th Asian Forum of Chronic Kidney Disease Initiative conference. We used vignettes that vary by age and comorbidity status, and asked physicians to recommend dialysis or CM for a hypothetical patient with that profile and to predict survival with both treatment options. We also compared the physician’s recommendations to patients for what they would recommend for themselves if they were diagnosed with ESRD. Results: On average, physicians believed that dialysis extends life relative to CM. Yet, a large subset believed that CM confers greater survival. Estimates range from 17.3% (for a 65-year-old with diabetes and CHF) to 50% for patients with advanced cancer. Results further reveal high discordance regarding treatment recommendations. For a 65-year-old patient with diabetes, 62% recommended dialysis and 38% did not. For advanced cancer, the split was 25% and 75%. Physicians were far more likely to recommend dialysis for themselves than for their patients. Discussion: This study suggests that physicians would benefit from a greater understanding of survival benefits of dialysis and CM for elderly patients with different comorbidity profiles. This would allow patients to make more informed decisions.

BackgroundThe Coronavirus Disease 2019 (COVID-19) outbreak has escalated the burden of psychological distress. We aimed to evaluate factors associated with psychological distress among the predominantly general population during the COVID-19 pandemic.MethodsWe searched PubMed, EMBASE, Scopus, Cochrane Library, PsycINFO, and World Health Organization COVID-19 databases (Dec 2019-15 July 2020). We included cross-sectional studies that reported factors associated with psychological distress during the COVID-19 pandemic. Primary outcomes were self-reported symptoms of anxiety and depression. Random-effects models were used to pool odds ratios (OR) and 95% confidence intervals (CI). The protocol was registered in PROSPERO (#CRD42020186735).FindingsWe included 68 studies comprising 288,830 participants from 19 countries. The prevalence of anxiety and depression was 33% (95% CI: 28%-39%) and 30% (26%-36%). Women versus men (OR: 1.48 [95% CI: 1.29-1.71; I2 = 90.8%]), younger versus older (< versus ≥35 years) adults (1.20 [1.13-1.26]; I2 = 91.7%), living in rural versus urban areas (1.13 [1.00-1.29]; I2 = 82.9%), lower versus higher socioeconomic status (e.g. lower versus higher income: 1.45 [1.24-1.69; I2 = 82.3%]) were associated with higher anxiety odds. These factors (except for residential area) were also associated with higher depression odds. Furthermore, higher COVID-19 infection risk (suspected/confirmed cases, living in hard-hit areas, having pre-existing physical or mental conditions) and longer media exposure were associated with higher odds of anxiety and depression.InterpretationOne in three adults in the predominantly general population have COVID-19 related psychological distress. Concerted efforts are urgently needed for interventions in high-risk populations to reduce urban-rural, socioeconomic and gender disparities in COVID-19 related psychological distress.

Introduction Uncontrolled hypertension is the leading risk factor for mortality globally, including low-income and middle-income countries (LMICs). However, pathways for seeking hypertension care and patients’ experience with the utilisation of health services for hypertension in LMICs are not well understood.Objectives This study aimed to explore patients’ perspectives on different dimensions of accessibility and availability of healthcare for the management of uncontrolled hypertension in Sri Lanka.Setting Primary care in rural areas in Sri Lanka.Participants 20 patients with hypertension were purposively sampled from an ongoing study of Control of Blood Pressure and Risk Attenuation in rural Bangladesh, Pakistan, Sri Lanka.Method We conducted in-depth interviews with patients. Interviews were audio-recorded and transcribed into local language (Sinhala) and translated to English. Thematic analysis was used and patient pathways on their experiences accessing care from government and private clinics are mapped out.Results Overall, most patients alluded to the fact that their hypertension was diagnosed accidentally in an unrelated visit to a healthcare provider and revealed lack of adherence and consuming alternatives as barriers to control hypertension. Referring to the theme ‘Accessibility and availability of hypertension care’, patients complained of distance to the hospitals, long waiting time and shortage of medicine supplies at government clinics as the main barriers to accessing health services. They often resorted to private physicians and paid out of pocket when they experienced acute symptoms attributable to hypertension. Considering the theme ‘Approachability and ability to perceive’, the majority of patients mentioned increasing public awareness, training healthcare professionals for effective communication as areas of improvement. Under the theme ‘Appropriateness and ability to engage’, few patients were aware of the names or purpose of their medications and reportedly missed doses frequently. Reminders from family members were considered a major facilitator to adherence to antihypertensive medications. Patients welcomed the idea of outreach services for hypertension and health education closer to home in the theme ‘Things the patients reported to improve the system’.Conclusion Patients identified several barriers to accessing hypertension care in Sri Lanka. Measures recommended improving hypertension management in Sri Lanka including public education on hypertension, better communication between healthcare professionals and patients, and efforts to improve access and understanding of antihypertensive medications.Trial registration number NCT02657746.

Objective To determinate the prevalence and correlates of cardiometabolic multimorbidity (CMM), and their cross-country variation among individuals with hypertension residing in rural communities in South Asia.Design A cross-sectional study.Setting Rural communities in Bangladesh, Pakistan and Sri Lanka.Participants A total of 2288 individuals with hypertension aged ≥40 years from the ongoing Control of Blood Pressure and Risk Attenuation- Bangladesh, Pakistan and Sri Lanka clinical trial.Main outcome measures CMM was defined as the presence of ≥2 of the conditions: diabetes, chronic kidney disease, heart disease and stroke. Logistic regression was done to evaluate the correlates of CMM.Results About 25.4% (95% CI 23.6% to 27.2%) of the hypertensive individuals had CMM. Factors positively associated with CMM included residing in Bangladesh (OR 3.42, 95% CI 2.52 to 4.65) or Sri Lankan (3.73, 95% CI 2.48 to 5.61) versus in Pakistan, advancing age (2.33, 95% CI 1.59 to 3.40 for 70 years and over vs 40–49 years), higher waist circumference (2.15, 95% CI 1.42 to 3.25) for Q2–Q3 and 2.14, 95% CI 1.50 to 3.06 for Q3 and above), statin use (2.43, 95% CI 1.84 to 3.22), and higher levels of triglyceride (1.01, 95% CI 1.01 to 1.02 per 5 mg/dL increase). A lower odds of CMM was associated with being physically active (0.75, 95% CI 0.57 to 0.97). A weak inverted J-shaped association between International Wealth Index and CMM was found (p for non-linear=0.058), suggesting higher risk in the middle than higher or lower socioeconomic strata.Conclusions CMM is highly prevalent in rural South Asians affecting one in four individuals with hypertension. There is an urgent need for strategies to concomitantly manage hypertension, cardiometabolic comorbid conditions and associated determinants in South Asia.

An amendment to this paper has been published and can be accessed via the original article.

Hypertension is the leading risk factor for cardiovascular disease and leading cause of premature death globally. In 2008, approximately 40% of adults were diagnosed with hypertension, with more than 1.5 billion people estimated to be affected globally by 2025. Hypertension disproportionally affects low- and middle-income countries, where the prevalence is higher and where the health systems are more fragile. This qualitative study explored patients' experiences on the management and control of hypertension in rural Bangladesh, Sri Lanka and Pakistan. We conducted sixty semi-structured interviews, with 20 participants in each country. Hypertensive individuals were recruited based on age, gender and hypertensive status. Overall, patients' reported symptoms across the three countries were quite similar, although perceptions of hypertension were mixed. The majority of patients reported low knowledge on how to prevent or treat hypertension. The main barriers to accessing health services, as reported by participants, were inadequate services and poor quality of existing facilities, shortage of medicine supplies, busyness of doctors due to high patient load, long travel distance to facilities, and long waiting times once facilities were reached. Patients also mentioned that cost was a barrier to accessing services and adhering to medication. Many patients, when asked for areas of improvement, reported on the importance of the provider-patient relationship and mentioned valuing doctors who spent time with them, provided advice, and could be trusted. However, most patients reported that, especially at primary health care level and in government hospitals, the experience with their doctor did not meet their expectations. Patients in the three countries reported desire for good quality local medical services, the need for access to doctors, medicine and diagnostics and decreased cost for medication and medical services. Patients also described welcoming health care outreach activities near their homes. Areas of improvement could focus on reorienting community health workers' activities; involving family members in comprehensive counseling for medication adherence; providing appropriate training for health care staff to deliver effective information and services for controlling hypertension to patients; enhancing primary health care and specialist services; improving supplies of hypertensive medication in public facilities; taking into account patients' cultural and social background when providing services; and facilitating access and treatment to those who are most vulnerable.

We aimed to explore the cross-country variation in the prevalence of comorbid prediabetes or diabetes and determine the sociodemographic, lifestyle, and clinical factors, especially body mass index (BMI) and waist circumference, associated with comorbid diabetes in individuals with hypertension in rural South Asia. We analyzed cross-sectional data of 2426 hypertensive individuals of ≥40 years from 30 randomly selected rural communities in Bangladesh, Pakistan, and Sri Lanka. Prediabetes was defined as fasting plasma glucose (FPG) between 100 and 125 mg/dL without use of antidiabetic treatment and diabetes as FPG ≥126 mg/dL or use of antidiabetic medication. The prevalence (95% CI) of prediabetes or diabetes (53.5% (51.5%, 55.5%)) and diabetes (27.7% (25.9%, 29.5%)) was high in the overall hypertensive study population in rural communities in 3 countries. Rural communities in Sri Lanka had the highest crude prevalence of prediabetes or diabetes and diabetes (73.1% and 39.3%) with hypertension, followed by those in Bangladesh (47.4% and 23.1%) and Pakistan (39.2% and 20.5%). The factors independently associated with comorbid diabetes and hypertension were residing in rural communities in Sri Lanka, higher education, international wealth index, waist circumference, pulse pressure, triglyceride, and lower high-density lipoprotein. The association of diabetes with waist circumference was stronger than with BMI in hypertensive individuals. Prediabetes or diabetes are alarmingly common among adults with hypertension and vary among countries in rural South Asia. The high prevalence of comorbid diabetes in Sri Lanka among hypertensives is not fully explained by conventional risk factors and needs further etiological research. Urgent public health efforts are needed to integrate diabetes control within hypertension management programs in rural South Asia, including screening waist circumference.