Regional variation in chronic kidney disease and associated factors in hypertensive individuals in rural South Asia: Findings from control of blood pressure and risk attenuation-Bangladesh, Pakistan and Sri Lanka

Background: We aimed to determine the prevalence of chronic kidney disease (CKD) and its cross-country variation among hypertensive individuals in rural Bangladesh, Pakistan and Sri Lanka. We also explored the factors associated with CKD in these populations.Method: We studied baseline data from the Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan and Sri Lanka (COBRA-BPS) trial, an ongoing cluster randomized controlled trial on 2643 hypertensive adults ≥40 years of age from 30 randomly selected rural clusters, 10 in each of the three countries. CKD was defined as an estimated glomerular filtration rate (eGFR) /min/1.73 m2 or a urine albumin:creatinine ratio (UACR) ≥30 mg/g. Determinants for CKD were assessed using logistic regression analysis.Results: The overall prevalence of CKD was 38.1% (95% confidence interval 36.2-40.1%): 21.5% with eGFR \u3c60 mL/min/1.73 m2 and 24.4% with UACR ≥30 mg/g. CKD prevalence varied across the three countries (58.3% in Sri Lanka, 36.4% Bangladesh and 16.9% Pakistan; P \u3c0.001). The factors independently associated with higher odds of CKD were older age, being unmarried, higher 24-h urinary sodium excretion, presence of diabetes, elevated systolic blood pressure, diuretic use and living in Bangladesh or Sri Lanka (versus Pakistan).Conclusions: The prevalence of CKD is alarmingly high in community-dwelling hypertensive adults, with significant cross-country variation in South Asia. Our findings underscore the urgency for further research into the etiology of CKD and address associated factors in targeted public health strategies with hypertension care outreach services in rural South Asia

Effect of a multicomponent intervention on antihypertensive medication intensification in rural South Asia: post-hoc analysis of a cluster RCT

BACKGROUND: Inadequate treatment of hypertension is a widespread problem, especially in South Asian countries where cardiovascular disease mortality rates are high. We aimed to explore the effect of a multicomponent intervention (MCI) on antihypertensive medication intensification among rural South Asians with hypertension. METHODS: A post-hoc analysis of a two-year cluster-randomized controlled trial including 2645 hypertensives aged≥ 40 years from 30 rural communities, 10 each, in Bangladesh, Pakistan, and Sri Lanka. Independent assessors collected information on participants' self-reports and physical inspection of medications. The main outcomes were the changes from baseline to 24 months in the following: 1) the therapeutic intensity score (TIS) for all (and class specific) antihypertensive medications; 2) the number of antihypertensive medications in all trial participants. RESULTS: At 24 months, the mean increase in the TIS score of all antihypertensive medications was 0.11 in the MCI group and 0.03 in the control group, with a between-group difference in the increase of 0.08 (95% CI (0.03, 0.12); P=0.002). In MCI compared to controls, a greater increase in the TIS of renin angiotensin-aldosterone system blockers (0.05; 95% CI (0.02, 0.07); P<0.001) and calcium channel blockers (0.03; 95% CI (0.00, 0.05);p=0.031) , and in the number of antihypertensive medications (0.11, 95% CI (0.02, 0.19);P=0.016) was observed. CONCLUSIONS: In rural communities in Bangladesh, Pakistan, and Sri Lanka, MCI led to a greater increase in antihypertensive medication intensification compared to the usual care among adults with hypertension. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02657746

Determinants of uncontrolled hypertension in rural communities in south Asia-Bangladesh, Pakistan, and Sri Lanka

Background: Uncontrolled blood pressure (BP) is a leading risk factor for death and disability in South Asia. We aimed to determine the cross-country variation, and the factors associated with uncontrolled BP among adults treated for hypertension in rural South Asia.Methods: We enrolled 1718 individuals aged ≥40 years treated for hypertension in a cross-sectional study from rural communities in Bangladesh, Pakistan, and Sri Lanka. Multivariable logistic regression model was used to determine the factors associated with uncontrolledBP (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg).Results: Among hypertensive individuals, 58.0% (95% confidence interval 55.7, 60.4) had uncontrolled BP: 52.8% (49.0, 56.6) in Bangladesh, 70.6% (65.7, 75.1) in Pakistan, and 56.5% (52.7, 60.1) in Sri Lanka. The odds (odds ratio (95% confidence interval)) of uncontrolled BP were significantly higher in individuals with lower wealth index (1.17 (1.02, 1.35)); single vs married (1.46 (1.10, 1.93)); higher log urine albumin-to-creatinine ratio (1.41 (1.24, 1.60)); lower estimated glomerular filtration rate (1.23 (1.01, 1.49)); low vs high adherence to antihypertensive medication (1.50 (1.16, 1.94)); and Pakistan (2.91 (1.60, 5.28)) vs Sri Lanka. However, the odds were lower in those with vs without self-reported kidney disease (0.51 (0.28, 0.91)); and receiving vs not receiving statins (0.62 (0.44, 0.87)).Conclusions: The majority of individuals with treated hypertension have uncontrolled BP in rural Bangladesh, Pakistan, and Sri Lanka with significant disparities among and within countries. Urgent public health efforts are needed to improve access and adherence to antihypertensive medications in disadvantaged populations in rural South Asia

Regional variation in comorbid prediabetes and diabetes and associated factors among hypertensive individuals in rural Bangladesh, Pakistan, and Sri Lanka

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

Extended Fermion Representation of Multi-Charge 1/2-BPS Operators in AdS/CFT -- Towards Field Theory of D-Branes --

We extend the fermion representation of single-charge 1/2-BPS operators in the four-dimensional N=4 super Yang-Mills theory to general (multi-charge) 1/2-BPS operators such that all six directions of scalar fields play roles on an equal footing. This enables us to construct a field-theorectic representation for a second-quantized system of spherical D3-branes in the 1/2-BPS sector. The Fock space of D3-branes is characterized by a novel exclusion principle (called `Dexclusion' principle), and also by a nonlocality which is consistent with the spacetime uncertainty relation. The Dexclusion principle is realized by composites of two operators, obeying the usual canonical anticommutation relation and the Cuntz algebra, respectively. The nonlocality appears as a consequence of a superselction rule associated with a symmetry which is related to the scale invariance of the super Yang-Mills theory. The entropy of the so-called superstars, with multiple charges, which have been proposed to be geometries corresponding to the condensation of giant gravitons is discussed from our viewpoint and is argued to be consistent with the Dexclusion principle. Our construction may be regarded as a first step towards a possible new framework of general D-brane field theory.Comment: 43 pages, 4 figures; version 2, corrected typos and added reference

Budget impact and cost-effectiveness analyses of the COBRA-BPS multicomponent hypertension management programme in rural communities in Bangladesh, Pakistan, and Sri Lanka.

BACKGROUND: COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multi-component hypertension management programme that is led by community health workers, has been shown to be efficacious at reducing systolic blood pressure in rural communities in Bangladesh, Pakistan, and Sri Lanka. In this study, we aimed to assess the budget required to scale up the programme and the incremental cost-effectiveness ratios. METHODS: In a cluster-randomised trial of COBRA-BPS, individuals aged 40 years or older with hypertension who lived in 30 rural communities in Bangladesh, Pakistan, and Sri Lanka were deemed eligible for inclusion. Costs were quantified prospectively at baseline and during 2 years of the trial. All costs, including labour, rental, materials and supplies, and contracted services were recorded, stratified by programme activity. Incremental costs of scaling up COBRA-BPS to all eligible adults in areas covered by community health workers were estimated from the health ministry (public payer) perspective. FINDINGS: Between April 1, 2016, and Feb 28, 2017, 11 510 individuals were screened and 2645 were enrolled and included in the study. Participants were examined between May 8, 2016, and March 31, 2019. The first-year per-participant costs for COBRA-BPS were US$10·65 for Bangladesh,$10·25 for Pakistan, and $6·42 for Sri Lanka. Per-capita costs were$0·63 for Bangladesh, $0·29 for Pakistan, and$1·03 for Sri Lanka. Incremental cost-effectiveness ratios were $3430 for Bangladesh,$2270 for Pakistan, and $4080 for Sri Lanka, per cardiovascular disability-adjusted life year averted, which showed COBRA-BPS to be cost-effective in all three countries relative to the WHO-CHOICE threshold of three times gross domestic product per capita in each country. Using this threshold, the cost-effectiveness acceptability curves predicted that the probability of COBRA-BPS being cost-effective is 79·3% in Bangladesh, 85·2% in Pakistan, and 99·8% in Sri Lanka. INTERPRETATION: The low cost of scale-up and the cost-effectiveness of COBRA-BPS suggest that this programme is a viable strategy for responding to the growing cardiovascular disease epidemic in rural communities in low-income and middle-income countries where community health workers are present, and that it should qualify as a priority intervention across rural settings in south Asia and in other countries with similar demographics and health systems to those examined in this study. FUNDING: The UK Department of Health and Social Care, the UK Department for International Development, the Global Challenges Research Fund, the UK Medical Research Council, Wellcome Trust

Patients' experiences on accessing health care services for management of hypertension in rural Bangladesh, Pakistan and Sri Lanka: A qualitative study.

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

Experimental evolution of adaptive divergence under varying degrees of gene flow

Adaptive divergence is the key evolutionary process generating biodiversity by means of natural selection. Yet, the conditions under which it can arise in the presence of gene flow remain contentious. To address this question, we subjected 132 sexually reproducing fission yeast populations, sourced from two independent genetic backgrounds, to disruptive ecological selection and manipulated the level of migration between environments. Contrary to theoretical expectations, adaptive divergence was most pronounced when migration was either absent (allopatry) or maximal (sympatry), but was much reduced at intermediate rates (parapatry and local mating). This effect was apparent across central life-history components (survival, asexual growth and mating) but differed in magnitude between ancestral genetic backgrounds. The evolution of some fitness components was constrained by pervasive negative correlations (trade-off between asexual growth and mating), while others changed direction under the influence of migration (for example, survival and mating). In allopatry, adaptive divergence was mainly conferred by standing genetic variation and resulted in ecological specialization. In sympatry, divergence was mainly mediated by novel mutations enriched in a subset of genes and was characterized by the repeated emergence of two strategies: an ecological generalist and an asexual growth specialist. Multiple loci showed consistent evidence for antagonistic pleiotropy across migration treatments providing a conceptual link between adaptation and divergence. This evolve-and-resequence experiment shows that rapid ecological differentiation can arise even under high rates of gene flow. It further highlights that adaptive trajectories are governed by complex interactions of gene flow, ancestral variation and genetic correlations

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury