Global variability of vascular and peritoneal access for chronic dialysis.

AIM: Vascular and peritoneal access are essential elements for sustainability of chronic dialysis programs. Data on availability, patterns of use, funding models, and workforce for vascular and peritoneal accesses for dialysis at a global scale is limited. METHODS: An electronic survey of national leaders of nephrology societies, consumer representative organizations, and policymakers was conducted from July to September 2018. Questions focused on types of accesses used to initiate dialysis, funding for services, and availability of providers for access creation. RESULTS: Data from 167 countries were available. In 31 countries (25% of surveyed countries), >75% of patients initiated haemodialysis (HD) with a temporary catheter. Seven countries (5% of surveyed countries) had >75% of patients initiating HD with arteriovenous fistulas or grafts. Seven countries (5% of surveyed countries) had >75% of their patients starting HD with tunnelled dialysis catheters. 57% of low-income countries (LICs) had >75% of their patients initiating HD with a temporary catheter compared to 5% of high-income countries (HICs). Shortages of surgeons to create vascular access were reported in 91% of LIC compared to 46% in HIC. Approximately 95% of participating countries in the LIC category reported shortages of surgeons for peritoneal dialysis (PD) access compared to 26% in HIC. Public funding was available for central venous catheters, fistula/graft creation, and PD catheter surgery in 57%, 54% and 54% of countries, respectively. CONCLUSION: There is a substantial variation in the availability, funding, workforce, and utilization of vascular and peritoneal access for dialysis across countries regions, with major gaps in low-income countries.

A Mobile Clinical Decision Support System for High-Risk Pregnant Women in Rural India (SMARThealth Pregnancy): Pilot Cluster Randomized Controlled Trial.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in women in India. Early identification is crucial to reducing deaths. Hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) carry independent risks for future CVD, and antenatal care is a window to screen and counsel high-risk women. In rural India, community health workers (CHWs) deliver antenatal and postnatal care. We developed a complex intervention (SMARThealth Pregnancy) involving mobile clinical decision support for CHWs and evaluated it in a pilot cluster randomized controlled trial (cRCT). OBJECTIVE: The aim of the study is to co-design a theory-informed intervention for CHWs to screen, refer, and counsel pregnant women at high risk of future CVD in rural India and evaluate its feasibility and acceptability. METHODS: In phase 1, we used qualitative methods to explore community priorities for high-risk pregnant women in rural areas of 2 diverse states in India. In phase 2, informed by behavior change theory and human-centered design, we used these qualitative data to develop the intervention components and implementation strategies for SMARThealth Pregnancy in an iterative process with end users. In phase 3, using mixed methods, we evaluated the intervention in a cRCT with an embedded qualitative substudy across 4 primary health centres: 2 in Jhajjar district, Haryana, and 2 in Guntur district, Andhra Pradesh. RESULTS: SMARThealth Pregnancy embedded a total of 15 behavior change techniques and included (1) community awareness programs; (2) targeted training, including point-of-care blood pressure and hemoglobin measurement; and (3) mobile clinical decision support for CHWs to screen women in their homes. The intervention focused on 3 priority conditions: anemia, HDP, and GDM. The evaluation involved a total of 200 pregnant women, equally randomized to intervention or enhanced standard care (control). Recruitment was completed within 5 months, with minimal loss to follow-up (4/200, 2%) at 6 weeks postpartum. A total of 4 primary care doctors and 54 CHWs in the intervention clusters took part in the study. Fidelity to intervention practices was 100% prepandemic. Over half the study population was affected by moderate to severe anemia at baseline. The prevalence of HDP (2.5%) and GDM (2%) was low in our study population. Results suggest a possible improvement in mean hemoglobin (anemia) in the intervention group, although an adequately powered trial is needed. The model of home-based care was feasible and acceptable for pregnant or postpartum women and CHWs, who perceived improvements in quality of care, self-efficacy, and professional recognition. CONCLUSIONS: SMARThealth Pregnancy is an innovative model of home-based care for high-risk pregnant women during the transitions between antenatal and postnatal care and adult health services. The use of theory and co-design during intervention development facilitated acceptability of the intervention and implementation strategies. Our experience has informed the decision to initiate a larger-scale cRCT. TRIAL REGISTRATION: ClinicalTrials.gov NCT03968952; https://clinicaltrials.gov/ct2/show/NCT03968952. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3389/fgwh.2021.620759.

SMARThealth Pregnancy: Feasibility and Acceptability of a Complex Intervention for High-Risk Pregnant Women in Rural India: Protocol for a Pilot Cluster Randomised Controlled Trial.

Introduction: India is in the process of a major epidemiological transition towards non-communicable diseases. Cardiovascular disease (CVD) is the leading cause of death in women in India. Predisposing independent risk factors include pregnancy-related conditions, e.g., hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM) - also associated with significant perinatal mortality and morbidity. Early identification, referral and management of pregnant women at increased risk of future CVD may offer opportunities for prevention. In rural India, Community Health Workers (CHWs) provide most antenatal and postnatal care. Innovative solutions are required to address integrated care for rural women during transitions between antenatal, postnatal and general health services. The George Institute's SMARThealth Programme has shown that CHWs in rural India screening non-pregnant adults for cardiovascular risk, using a decision support system, is feasible. Building on this, we developed a targeted training programme for CHWs and a complex system-level intervention that uses mobile clinical decision support for CHWs and primary care doctors to screen high-risk pregnant women. In addition to addressing HDP and GDM, the intervention also screens for anaemia in pregnancy. Methods/Design: A pilot study will be undertaken in two diverse rural districts of India: Jhajjar (Haryana) and Guntur (Andhra Pradesh). Two Primary Health Centre clusters will be randomised to intervention or control groups at each study site. The primary objective of this pilot study is to explore the feasibility and acceptability of the SMARThealth Pregnancy intervention. Secondary objectives are to estimate: (a) prevalence rates of moderate to severe anaemia, HDPs and GDM at the study sites; (b) referral and follow-up rates, and (c) mean haemoglobin and blood pressure values at the routine 6 week postnatal visit. A process evaluation will be conducted to explore the acceptability of the SMARThealth Pregnancy intervention for pregnant women and healthcare workers using qualitative methods. Discussion: It is anticipated that the findings of this pilot study will help determine the feasibility and acceptability of the SMARThealth Pregnancy intervention, and highlight how the intervention might be further developed for evaluation in a larger, cluster randomised controlled trial. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03968952.

Cardiometabolic Risk Factors in Pregnancy and Implications for Long-Term Health: Identifying the Research Priorities for Low-Resource Settings.

Cardiometabolic disorders (CMDs), including ischemic heart disease, stroke and type 2 diabetes are the leading causes of mortality and morbidity in women worldwide. The burden of CMDs falls disproportionately on low and middle-income countries (LMICs), placing substantial demands on already pressured health systems. Cardiometabolic disorders may present up to a decade earlier in some LMIC settings, and are associated with high-case fatality rates. Early identification and ongoing postpartum follow-up of women with pregnancy complications such as hypertensive disorders of pregnancy (HDPs), and gestational diabetes mellitus (GDM) may offer opportunities for prevention, or help delay onset of CMDs. This mini-review paper presents an overview of the key challenges faced in the early identification, referral and management of pregnant women at increased risk of CMDs, in low-resource settings worldwide. Evidence-based strategies, including novel diagnostics, technology and innovations for early detection, screening and management for pregnant women at high-risk of CMDs are presented. The review highlights the key research priorities for addressing cardiometabolic risk in pregnancy in low-resource settings.

Usefulness of mycophenolate mofetil in Indian patients with C3 glomerulopathy.

BACKGROUND: C3 glomerulopathy (C3G) is a heterogeneous disease caused by alternative complement pathway abnormalities without any standardized treatment. An immunosuppressive agent, mycophenolate mofetil (MMF), has been recently shown to be useful in treating C3G, mainly in studies from the west. We report the clinical outcome of 17 Indian C3G patients treated with MMF with or without steroids. METHODS: The clinical and histology details of the C3G patients treated with MMF for at least 6 months with a follow-up of at least 12 months were retrieved from the medical records of our center. RESULTS: The median serum creatinine and proteinuria at presentation were 0.8 mg/dL and 3.7 g/day, respectively, with the majority (88.2%) presenting as nephrotic syndrome. The mean dose of MMF was 1.65 (±0.56) g/day, and the median duration of MMF therapy was 18 months. Two-thirds (64%) of the patients responded to the treatment, with complete remission in 4 (23%) and partial remission in 7 (41%) (median time: 9 months). Three patients progressed to end-stage renal disease (ESRD) on follow-up. Of the three patients, one (33%) had an initial response in proteinuria to MMF but did not respond after a relapse and subsequently progressed to ESRD and two (67%) other patients were nonresponsive to MMF from the start of the therapy. CONCLUSION: Despite a small sample size and lack of a control arm, this study describes the effectiveness of MMF in treating C3G patients from Asia and forms a basis for future randomized trials.

Secretome proteins regulate comparative osteogenic and adipogenic potential in bone marrow and dental stem cells.

INTRODUCTION: Dental stem cells (DMSC) have been studied extensively since their early discovery. However, the data regarding osteogenic potential of DMSC with other cell types is sparse and the secretome proteins underlying these differences have not been explored. In this study, we have compared the osteogenic and adipogenic potential of DMSC with Bone Marrow Stem cells (BMSC) and reported the contribution of secretome proteins in controlling their differentiation. METHODS: Osteogenic potential of these stem cells was compared by mineralization assay, alkaline phosphatase (ALP) assay, immunofluorescence of dentine sialo phosphoprotein (DSPP) & qPCR for osteogenic genes. Adipogenic potential was compared by Oil Red O staining and qPCR for PPAR-γ, leptin & adipsin. Proteomic analysis of secretome was performed by employing WATERS nano Lc-MS/MS system. RESULTS: We observed a higher osteogenic potential in DMSC, especially dental pulp stem cells (DPSC) as compared to BMSC population but adipogenic potential was found to be better in BMSC as compared to DMSC. Deeper investigations into secretome of these cells by Lc-MS/MS revealed the presence of proteins pertaining to osteogenic and adipogenic lineage. Presence of some important proteins regulating osteogenic (DSPP, BMP7, DDR2, USP9X) and adipogenic differentiation (NCOA2, PEG10, LPA) in secretome of BMSC and DMSC reflected the role of paracrine factors during differentiation. CONCLUSION: Our study provides first evidence regarding regulation of osteogenic/adipogenic potential by secretome proteins in DMSC and BMSC. DMSC especially DPSC and its secretome show an inherent tendency for higher osteogenic differentiation and lower adipogenic differentiation, these may be potential candidates for effective future therapy in osteoporosis where disturbance of osteocyte/adipocyte homeostasis is reported.

Molecular spectrum of secretome regulates the relative hepatogenic potential of mesenchymal stem cells from bone marrow and dental tissue.

Liver regeneration is a spontaneous process that occurs after liver injury, but acute liver failure is a complex and fatal disease which is difficult to treat. Cell-based therapies are promising alternative therapeutic approach for liver failure and different cell sources have been tested in this regard. We investigated the comparative hepatogenic potential of human bone marrow stem cells (BMSC) with stem cells derived from human dental pulp (DPSC), apical papilla (SCAP) and follicle (DFSC) during this study. Hepatogenic potential of stem cells was assessed by functional assays at both genetic and protein level. We observed higher expression of most of the hepatic markers post differentiation in DPSCs compared to other cell types. LC-MS/MS analysis of stem cell secretome revealed the presence of different proteins related to hepatogenic lineage like growth arrest specific protein 6, oncostatin M, hepatocyte growth factor receptor etc. Interactome and Reactome pathway analysis revealed the interaction of DPSC/SCAP secretome proteins and these proteins were found to be associated with various pathways involved in lipid transport and metabolism. To the best of our knowledge, this is the first study regarding detailed investigation of hepatogenic potential of BMSCs v/s DMSCs (DPSC, SCAP & DFSC) along-with secretome characterization.

Radon emanation from backfilled mill tailings in underground uranium mine.

Coarser mill tailings used as backfill to stabilize the stoped out areas in underground uranium mines is a potential source of radon contamination. This paper presents the quantitative assessment of radon emanation from the backfilled tailings in Jaduguda mine, India using a cylindrical accumulator. Some of the important parameters such as (226)Ra activity concentration, bulk density, bulk porosity, moisture content and radon emanation factor of the tailings affecting radon emanation were determined in the laboratory. The study revealed that the radon emanation rate of the tailings varied in the range of 0.12-7.03 Bq m(-2) s(-1) with geometric mean of 1.01 Bq m(-2) s(-1) and geometric standard deviation of 3.39. An increase in radon emanation rate was noticed up to a moisture saturation of 0.09 in the tailings, after which the emanation rate gradually started declining with saturation due to low diffusion coefficient of radon in the saturated tailings. Radon emanation factor of the tailings varied in the range of 0.08-0.23 with the mean value of 0.21. The emanation factor of the tailings with moisture saturation level over 0.09 was found to be about three times higher than that of the absolutely dry tailings. The empirical relationship obtained between (222)Rn emanation rate and (226)Ra activity concentration of the tailings indicated a significant positive linear correlation (r = 0.95, p < 0.001). This relationship may be useful for quick prediction of radon emanation rate from the backfill material of similar nature.

Metabolic syndrome in chronic kidney disease and renal transplant patients in North India.

AIM: The cluster of biochemical and clinical abnormalities known as metabolic syndrome (MS) has become a public health problem even in developing countries. Previous studies have shown a graded relationship between MS components and worsening renal function in the general population. The prevalence of MS in non-dialysis-dependent CKD (NDD-CKD) and kidney transplant recipients in the North Indian population is unknown. METHODS: We studied all patients with stable CKD and with renal transplantation attending the nephrology clinic in a large centre in North India over an eight-week period. All transplant patients had stable graft function for 3 months prior to recruitment. MS was defined according to the International Diabetes Federation (IDF) 2007 guidelines. A total of 252 (155 NDD-CKD and 97 renal transplant recipients) patients were studied. RESULTS: MS was present in 86 (34%) patients. The prevalence of MS was similar in NDD-CKD and transplant patients [60 (39%) vs. 26 (27%), P = 0.052]. Patients with MS were older than those without MS (48 ± 12 years-old vs. 40 ± 14 years-old, P < 0.001) and MS was more common in women than in men (59% vs. 26%, P < 0.001). Female gender was an independent risk factor for MS in this population [adjusted OR 5.25 (95% CI: 2.74-10.06)]. With advancing CKD, the prevalence of MS decreased in the NDD-CKD patients. Impaired glucose tolerance and hypertriglyceridemia were independent predictors of MS. Hypertension was not a predictor of MS in NDD-CKD. In transplant recipients, hypertriglyceridemia, hypertension and low HDL cholesterol predicted the risk for MS. CONCLUSION: MS is common in CKD and renal transplant patients in North India. The risk of MS decreases with declining eGFR in CKD patients. Female gender and hypertriglyceridemia independently predict the risk of MS in both NDD-CKD and transplant recipients.

Heavy-chain deposition disease: a morphological, immunofluorescence and ultrastructural assessment.

Heavy-chain deposition disease (HCDD) is the least common of the monoclonal immunoglobulin deposition diseases with only 24 reported cases in English literature, including the present case. The rarity of this disease merits its documentation. We present a case of HCDD from our archival material, who presented with rapidly progressive renal failure and nephrotic syndrome and was found to have nodular glomerulosclerosis on renal biopsy which on immunofluorescence and electron microscopy confirmed HCDD of immunoglobulin G1 type without any light-chain deposition. We also present an in-depth literature review on HCDD.

Acute pyelonephritis with renal vein and inferior vena cava thrombosis in a case of hyperhomocysteinemia.

Acute pyelonephritis is not considered a common cause of renal vein (RVT) and inferior vena caval thrombosis (IVCT). Apart from malignancy, RVT is not an uncommon condition amongst patients with nephrotic syndrome, most commonly seen in patients with membranous glomerulonephritis. However, RVT occurring in association to acute pyelonephritis is rare. Clinically, it is difficult to distinguish between acute pyelonephritis and RVT because both present with fever, flank pain, and hematuria. We report a case of acute pyelonephritis with RVT and IVCT with underlying hyperhomocysteinemia. The patient was treated with systemic anticoagulation, antibiotics, and B complex therapy. At 3 months follow-up, there was complete resolution of thrombus but the left kidney was nonfunctioning.