Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India.

BACKGROUND: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. RESULTS: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. CONCLUSION: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Advances in Anti-Cancer Drug Development: Metformin as Anti-Angiogenic Supplemental Treatment for Glioblastoma.

According to the WHO 2016 classification, glioblastoma is the most prevalent primary tumor in the adult central nervous system (CNS) and is categorized as grade IV. With an average lifespan of about 15 months from diagnosis, glioblastoma has a poor prognosis and presents a significant treatment challenge. Aberrant angiogenesis, which promotes tumor neovascularization and is a prospective target for molecular target treatment, is one of its unique and aggressive characteristics. Recently, the existence of glioma stem cells (GSCs) within the tumor, which are tolerant to chemotherapy and radiation, has been linked to the highly aggressive form of glioblastoma. Anti-angiogenic medications have not significantly improved overall survival (OS), despite various preclinical investigations and clinical trials demonstrating encouraging results. This suggests the need to discover new treatment options. Glioblastoma is one of the numerous cancers for which metformin, an anti-hyperglycemic medication belonging to the Biguanides family, is used as first-line therapy for type 2 diabetes mellitus (T2DM), and it has shown both in vitro and in vivo anti-tumoral activity. Based on these findings, the medication has been repurposed, which has shown the inhibition of many oncopromoter mechanisms and, as a result, identified the molecular pathways involved. Metformin inhibits cancer cell growth by blocking the LKB1/AMPK/mTOR/S6K1 pathway, leading to selective cell death in GSCs and inhibiting the proliferation of CD133+ cells. It has minimal impact on differentiated glioblastoma cells and normal human stem cells. The systematic retrieval of information was performed on PubMed. A total of 106 articles were found in a search on metformin for glioblastoma. Out of these six articles were Meta-analyses, Randomized Controlled Trials, clinical trials, and Systematic Reviews. The rest were Literature review articles. These articles were from the years 2011 to 2024. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on metformin use in the treatment of glioblastoma were searched on clinicaltrials.gov. In this article, we examine and evaluate metformin's possible anti-tumoral effects on glioblastoma, determining whether or not it may appropriately function as an anti-angiogenic substance and be safely added to the treatment and management of glioblastoma patients.

Comparative yield of molecular diagnostic algorithms for autism spectrum disorder diagnosis in India: evidence supporting whole exome sequencing as first tier test.

BACKGROUND: Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic architecture of ASD in India. This study aimed to identify the genetic architecture of ASD in India and to assess the use of whole exome sequencing (WES) as a first-tier test instead of chromosomal microarray (CMA) for genetic diagnosis. METHODS: Between 2020 and 2022, 101 patient-parent trios of Indian origin diagnosed with ASD according to the Diagnostic and Statistical Manual, 5th edition, were recruited. All probands underwent a sequential genetic testing pathway consisting of karyotyping, Fragile-X testing (in male probands only), CMA and WES. Candidate variant validation and parental segregation analysis was performed using orthogonal methods. RESULTS: Of 101 trios, no probands were identified with a gross chromosomal anomaly or Fragile-X. Three (2.9%) and 30 (29.7%) trios received a confirmed genetic diagnosis from CMA and WES, respectively. Amongst diagnosis from WES, SNVs were detected in 27 cases (90%) and CNVs in 3 cases (10%), including the 3 CNVs detected from CMA. Segregation analysis showed 66.6% (n = 3 for CNVs and n = 17 for SNVs) and 16.6% (n = 5) of the cases had de novo and recessive variants respectively, which is in concordance with the distribution of variant types and mode of inheritance observed in ASD patients of non-Hispanic white/ European ethnicity. MECP2 gene was the most recurrently mutated gene (n = 6; 20%) in the present cohort. Majority of the affected genes identified in the study cohort are involved in synaptic formation, transcription and its regulation, ubiquitination and chromatin remodeling. CONCLUSIONS: Our study suggests de novo variants as a major cause of ASD in the Indian population, with Rett syndrome as the most commonly detected disorder. Furthermore, we provide evidence of a significant difference in the diagnostic yield between CMA (3%) and WES (30%) which supports the implementation of WES as a first-tier test for genetic diagnosis of ASD in India.

Acute kidney injury requiring kidney replacement therapy in childhood lupus nephritis: a cohort study of the Pediatric Nephrology Research Consortium and Childhood Arthritis and Rheumatology Research Alliance.

BACKGROUND: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited. METHODS: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure. RESULTS: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure. CONCLUSIONS: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

Late infantile form of multiple sulfatase deficiency with a novel missense variant in the SUMF1 gene: case report and review.

BACKGROUND: Multiple sulfatase deficiency (MSD) is a rare lysosomal storage disorder caused due to pathogenic variants in the SUMF1 gene. The SUMF1 gene encodes for formylglycine generating enzyme (FGE) that is involved in the catalytic activation of the family of sulfatases. The affected patients present with a wide spectrum of clinical features including multi-organ involvement. To date, almost 140 cases of MSD have been reported worldwide, with only four cases reported from India. The present study describes two cases of late infantile form of MSD from India and the identification of a novel missense variant in the SUMF1 gene. CASE PRESENTATION: In case 1, a male child presented to us at the age of 6 years. The remarkable presenting features included ichthyosis, presence of irritability, poor social response, thinning of corpus callosum on MRI and, speech regression. Clinical suspicion of MSD was confirmed by enzyme analysis of two sulfatase enzymes followed by gene sequencing. We identified a novel missense variant c.860A > T (p.Asn287Ile) in exon 7 of the SUMF1 gene. In case 2, a two and a half years male child presented with ichthyosis, leukodystrophy and facial dysmorphism. We performed an enzyme assay for two sulfatases, which showed significantly reduced activities thereby confirming MSD diagnosis. CONCLUSION: Overall, present study has added to the existing data on MSD from India. Based on the computational analysis, the novel variant c.860A > T identified in this study is likely to be associated with a milder phenotype and prolonged survival.

Understanding the Molecular Progression of Chronic Traumatic Encephalopathy in Traumatic Brain Injury, Aging and Neurodegenerative Disease.

Traumatic brain injury (TBI) is one of the leading causes of death and disability among children and adults in America. In addition, the acute morbidity caused by TBI is implicated in the development of devastating neuropsychiatric and neurodegenerative sequela. TBI is associated with the development of a neurodegenerative condition termed 'Punch Drunk syndrome' or 'dementia pugilistica', and the more recently renamed 'chronic traumatic encephalopathy'. Chronic traumatic encephalopathy (CTE) is a slowly progressive neurodegenerative condition caused by a single or repetitive blow to the head. CTE was first described in boxers and was later found to be associated with other contact sports and military combat. It is defined by a constellation of symptoms consisting of mood disorders, cognitive impairment, and memory loss with or without sensorimotor changes. It is also a Tauopathy characterized by the deposition of hyperphosphorylated Tau protein in the form of neurofibrillary tangles, astrocytoma tangles, and abnormal neurites found in clusters around small vessels, typically at the sulcal depths. Oxidative stress, neuroinflammation, and glutaminergic toxicity caused due to the insult play a role in developing this pathology. Additionally, the changes in the brain due to aging also plays an important role in the development of this condition. In this review, we discuss the molecular mechanisms behind the development of CTE, as well as genetic and environmental influences on its pathophysiology.

Direct oral anticoagulants to treat left ventricular thrombus-A systematic review and meta-analysis: ELECTRAM investigators.

INTRODUCTION: Though current guidelines currently recommend using warfarin, there is also a growing interest in the utilization of direct oral anticoagulants (DOACs) to treat left ventricular (LV) thrombus. METHODS: We performed a systematic search using PubMed, SCOPUS, EMBASE, Google Scholar, and ClinicalTrials.gov from inception to September 30, 2020, for studies that had reported outcomes in patients with left ventricular thrombus treated with DOACs (PROSPERO registration number CRD42020219761). RESULTS: Twelve studies (n = 867 patients) were included in the analysis. The pooled incidence of the systemic embolic events (SEE) with DOACs was 2.7%, whereas the thrombus resolution rate was 86.6%. The pooled incidence of overall bleeding (composite of major and minor bleeding) and major bleeding with DOACs were 5.6% and 1.1%, respectively. No significant difference was observed in terms of SEE (OR 0.81, 95% confidence interval [CI] 0.44-1.52, p = .54), major bleeding (OR 0.29, 95% CI 0.07-1.26, p = .24), and failure of LV thrombus resolution (OR 0.86, 95% CI 0.28-2.58, p = .68); whereas overall bleeding was significantly low in patients with LV thrombus treated with DOACs compared to vitamin K antagonists (VKAs) (OR 0.33, 95% CI 0.14-0.81, p = .02). CONCLUSION: Our study demonstrates no significant difference in SEE, major bleeding, or failure of LV thrombus resolution between the two groups, thus demonstrating that DOACs are an efficacious and safe alternative for the treatment of LV thrombus compared to VKAs. However, further well-designed prospective trials are needed to answer important clinical questions-optimal dosing/duration of DOACs and its safety in the background of antiplatelet therapy.

Implantable cardioverter-defibrillator in patients with spontaneous coronary artery dissection presenting with sudden cardiac arrest.

INTRODUCTION: The role of secondary prevention implantable cardioverter-defibrillator (ICD) remains uncertain in spontaneous coronary artery dissection (SCAD) patients presenting with sudden cardiac arrest (SCA). METHODS: We aimed at assessing the outcomes following SCA and the role of ICD therapy in SCAD. The meta-analysis was performed using a meta-package for R version 4.0/RStudio version 1.2 and the Freeman-Tukey double arcsine method to establish the variance of raw proportions. Outcomes measured included-(1) incidence of ICD implantation, (2) appropriate and inappropriate ICD therapy, (3) recurrence of SCAD and SCA, and (4) all-cause mortality. RESULTS: Five studies, including 139 SCAD patients with SCA met study inclusion criteria. The mean age was 47.3 ± 12.8 years, mean left ventricular ejection fraction 43.8 ± 10.8%, 88% were female (12% had pregnancy-associated SCAD. Causes of SCA included ventricular arrhythmia (97.9%, n = 136) and pulseless electrical activity (2.1%, n = 3). Overall, 20% patients (95% confidence interval [CI]: 7.1%-36.6%, I2 = 68%) received ICD, of which 1.2% (95% CI: 0%-15.8%, I2 = 0%) and 1% (95% CI: 0%-15.3%, I2 = 0%) patients received appropriate and inappropriate ICD therapies, respectively, during follow-up period (4.1 ± 3.3 years). Incidence of recurrent SCAD was 9% (95% CI: 2.85%-17.5%, I2 = 25%), and recurrent SCA was 3.85% patients (95% CI: 0.65%-8.7%, I2 = 0%; one patient with appropriate ICD therapy). The pooled incidence of all-cause mortality was 6.2% (95% CI: 0.6%-15.1%, I2 = 44%). CONCLUSION: Although ICD therapy is beneficial in patients (all comers) presenting with cardiac arrest; the risk-benefit ratio of secondary prevention ICD arrest remains unclear. Patient-centered shared decision-making and risk-benefit ratio assessment should be performed before consideration for ICD implantation.

Impact of atrial fibrillation on the outcomes of transcatheter mitral valve repair using MitraClip: a systematic review and meta-analysis.

Atrial fibrillation (AF) is a common arrhythmia in patients with mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR). In this systematic review, we aimed to investigate the outcomes of TMVR using MitraClip in AF patients. We performed a systematic search using PubMed, SCOPUS, EMBASE, and Google Scholar, from inception to May 10, 2020, for studies that reported outcomes following MitraClip, in patients with AF versus without AF. Seven studies with a total of 7678 patients met the inclusion criteria. The risk of 1-year all-cause mortality following TMVR was higher in AF patients (RR 1.40, 95% CI 1.27-1.54, p ≤ 0.001). Similarly, the risk of heart failure hospitalization was higher in patients with AF (RR 1.17, 95% CI 1.06-1.30, p = 0.002) and the risk of bleeding was elevated in AF patients (RR 1.29, 95% CI 1.15-1.45, p ≤ 0.001). The risk of procedural failure, in-hospital mortality, cardiovascular mortality, and stroke was not significantly different between the two groups. The higher risk of all-cause mortality, HF hospitalization, and risk of bleeding in AF patients undergoing MitraClip warrants attention.

Renal sympathetic denervation for the treatment of recurrent ventricular arrhythmias-ELECTRAM investigators.

INTRODUCTION: Renal sympathetic denervation (RSDN) is an alternate management approach for refractory ventricular arrhythmias (VAs). We aimed to perform a systematic review of clinical outcomes on the impact of RSDN on refractory VA patients. METHODS: A systematic search without language restriction, using PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov from inception to August 18, 2020, was performed for the studies that reported outcomes in patients who underwent RSDN for VA. The outcomes studied were-(1) recurrent VA; and (2) all-cause mortality. RESULTS: Five studies (from 2014 to 2018) with a total of 51 VA patients met study inclusion criteria. The mean age was 61.92 ± 11.76 years, and 78.4% were men. The pooled incidence of short-term (3 months or less) and long-term (more than 3 months) VA recurrence was 63.85% (95% CI 16.75 to 99.32) and 10.52% (95% CI 0.14 to 28.75), respectively. When stratified by the number of VA episodes, there was a significant reduction in mean VA episodes (SMD -3.79, 95% CI -6.59 to -0.98, p < .01), ICD shocks (SMD -1.71, 95% CI -3.0 to -0.42, p < .01) and anti-tachycardia pacing (SMD -1.21, 95% CI -1.98 to -0.44, p < .01) following RSDN denervation. The pooled incidence of all-cause mortality after RSDN was 10.16% (95% CI 1.08 to 24.12). There were no major vascular complications, one minor vascular complication-small non-flow limiting renal artery dissection (no intervention needed). CONCLUSION: RSDN appears to be a safe and effective treatment strategy in patients with prior failed antiarrhythmic drugs and catheter ablation for recurrent ventricular arrhythmia and electrical storm.

Effect of Neighborhood Food Environment and Socioeconomic Status on Serum Phosphorus Level for Patients on Chronic Dialysis.

BACKGROUND: Elevated blood phosphorus levels are common and associated with a greater risk of death for patients receiving chronic dialysis. Phosphorus-rich foods are prevalent in the American diet, and low-phosphorus foods, including fruits and vegetables, are often less available in areas with more poverty. The relative contributions of neighborhood food availability and socioeconomic status to phosphorus control in patients receiving dialysis are unknown. METHODS: Using longitudinal data from a national dialysis provider, we constructed hierarchical, linear mixed-effects models to evaluate the relationships between neighborhood food environment or socioeconomic status and serum phosphorus level among patients receiving incident dialysis. RESULTS: Our cohort included 258,510 patients receiving chronic hemodialysis in 2005-2013. Median age at dialysis initiation was 64 years, 45% were female, 32% were Black, and 15% were Hispanic. Within their residential zip code, patients had a median of 25 "less-healthy" food outlets (interquartile range, 11-40) available to them compared with a median of four "healthy" food outlets (interquartile range, 2-6). Living in a neighborhood with better availability of healthy food was not associated with a lower phosphorus level. Neighborhood income also was not associated with differences in phosphorus. Patient age, race, cause of ESKD, and mean monthly dialysis duration were most closely associated with phosphorus level. CONCLUSIONS: Neither neighborhood availability of healthy food options nor neighborhood income was associated with phosphorus levels in patients receiving chronic dialysis. Modifying factors, such as nutrition literacy, individual-level financial resources, and adherence to diet restrictions and medications, may be more powerful contributors than food environment to elevated phosphorus.

COVID 19: Diabetes and Obesity API-ICP Recommendations.

Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.

Blood-pressure Lowering Efficacy and Safety of Perindopril / Indapamide / Amlodipine Single-pill Combination in Hypertensive Patients: Phase III Trial in India.

BACKGROUND: Hypertension is the biggest contributor to global burden of disease and mortality. Increasing compliance with antihypertensive treatment and achieving a wide BP control in the population represents a major challenge for clinical practice. The benefits of single pill combination versus free-equivalent combination has been demonstrated in several meta-analyses and is now strongly supported by the latest 2018 ESC/ESH guidelines. The RAAS blocker with CCB and thiazide like diuretic is proposed as the optimal combination in patients inadequately controlled by two drugs. OBJECTIVE: To assess the blood pressure control rate, safety, tolerability and quality of life with triple-drug SPC in patients with grade II/ III hypertension. METHODS: Hypertensive patients uncontrolled (BP ≥ 140/90 mmHg) on two-drug therapy were recruited in an open-label, phase III clinical trial conducted in outpatient setting in India with 6 months treatment period. No other antihypertensive medication except the study medication was received by the patients. RESULTS: Out of 218 evaluable patients the observed average blood pressure reduction achieved from baseline to end of study at 6 months was Systolic Blood Pressure (SBP) 28.5 mm Hg / Diastolic Blood Pressure (DBP) 13.8 mm Hg. The quality of life (QoL) questionnaire demonstrated improvement in QoL for all patients. CONCLUSION: This study showed the clinical efficacy, safety and acceptability of the perindopril/indapamide/amlodipine SPC in patients with grade 2/3 hypertension inadequately controlled with two-drug therapy. The clinical effectiveness was observed in more than 96 % patients. The benefit of single-pill combination (SPC) therapy in hypertension control was reconfirmed in this study.

Screening for Hypertension in Asymptomatic Individuals in India: An Expert Consensus Statement.

INTRODUCTION: Hypertension (HTN) is a rapidly growing epidemic in India. It is no larger restricted to older adults as more young Indians are being diagnosed with HTN. Despite its significant prevalence, the awareness, treatment, and control of HTN remain low in India. Thus, early diagnosis is essential to control HTN and prevent future complications. Screening for HTN can help identify undiagnosed and asymptomatic HTN, and thereby the early use of interventions to control the blood pressure (BP). However, no comprehensive guidelines have been established for effective HTN screening in asymptomatic individuals in an Indian setting. OBJECTIVE: To provide consensus recommendations for hypertension screening in India. CONSENSUS RECOMMENDATIONS: Screening for HTN can provide more effective control of HTN and reduce the complications. Experts recommended that the initial age at screening should be 18 years. In individuals at a high risk of HTN, targeted screening can be undertaken. BP measurement using an electronic BP recorder (with at least two readings) are required for identifying HTN during screening. In asymptomatic adults with BP <130/85 mmHg and BP of 130-139/85- 89 mmHg, rescreening should be conducted every 3-5 years and at least every year, respectively. Screening for HTN can be cost effective even when universal screening of the entire population is undertaken. CONCLUSION: The consensus recommendations would increase the awareness of HTN screening. Screening for HTN can provide more effective control of HTN and reduce the complications.

Circumferential Vault Excision and Reconstruction: Technical Description of Management of Intractable Secondary Vault Hemorrhage after Hysterectomy in Resource-Limited Settings.

Hemorrhage after gynecologic surgery is an infrequent complication. It can be divided based on time of onset into primary and secondary. Secondary hemorrhage is a life-threatening complication with a reported incidence of .17% to .45%. When the etiology cannot be ascertained and when the hemorrhage does not respond to conservative management, it is aptly labeled as an intractable hemorrhage. Numerous techniques have been used to manage secondary hemorrhage, including vaginal exploration and securing of the bleeding vessels, laparotomy and ligation of uterine and internal iliac arteries, and transarterial embolization of uterine or internal iliac vessels using interventional radiologic modalities. Circumferential vault excision and reconstruction is a methodic technique to effectively control this condition using a total laparoscopic route with systematic and easily replicable steps.

Racial Disparities in Nephrology Consultation and Disease Progression among Veterans with CKD: An Observational Cohort Study.

BACKGROUND: Incident rates of ESRD are much higher among black and Hispanic patients than white patients. Access to nephrology care before progression to ESRD is associated with better clinical outcomes among patients with CKD. However, it is unknown whether black or Hispanic patients with CKD experience lower pre-ESRD nephrology consultation rates compared with their white counterparts, or whether such a disparity contributes to worse outcomes among minorities. METHODS: We assembled a retrospective cohort of patients with CKD who received care through the Veterans Health Administration from 2003 to 2015, focusing on individuals with incident CKD stage 4 who had an initial eGFR≥60 ml/min per 1.73 m2 followed by two consecutive eGFRs<30 ml/min per 1.73 m2. We repeated analyses among individuals with incident CKD stage 3. Outcomes included nephrology provider referral, nephrology provider visit, progression to CKD stage 5, and mortality. RESULTS: We identified 56,767 veterans with CKD stage 4 and 640,704 with CKD stage 3. In both cohorts, rates of nephrology referral and visits were significantly higher among black and Hispanic veterans than among non-Hispanic white veterans. Despite this, both black and Hispanic patients experienced faster progression to CKD stage 5 compared with white patients. Black patients with CKD stage 4 experienced slightly lower mortality than white patients, whereas black patients with CKD stage 3 had a small increased risk of death. CONCLUSIONS: Black or Hispanic veterans with CKD are more likely than white patients to see a nephrologist, yet are also more likely to suffer disease progression. Biologic and environmental factors may play a bigger role than nephrology consultation in driving racial disparities in CKD progression.

Evaluation of Clinical Acceptability of Perindopril / Indapamide Single-pill Combination in Moderate to Severe Hypertension.

BACKGROUND: Current European hypertension guidelines recommend to initiate the treatment of patients with moderate to severe hypertension with a Single Pill Combination (SPC) containing two drugs, as SPC use leads to more effective and faster blood pressure control. The guidelines also recommend tighter blood pressure control in hypertensive patients with cardiovascular risk factors such as diabetes mellitus. OBJECTIVE: To evaluate efficacy on blood pressure reduction and acceptability of the single pill combination of Perindopril/Indapamide in patients with moderate to severe hypertension. METHODS: In this multicentre, prospective, observational study, patients with moderate to severe hypertension were prescribed Perindopril 4mg/ Indapamide 1.25 mg for 90 days. The primary outcomes were blood pressure decrease and achievement of BP control. Patients were up-titrated to Perindopril 8 mg/Indapamide 2.5 mg SPC, if target BP control (≤140/90 mm Hg) could not be achieved by day 30. RESULTS: In this study, 173 hypertensive patients, with a mean age of 51 years were enrolled at 3 centres from different geographic areas within India. Mean SBP/DBP decreased significantly from baseline (155.70 (±10.39) / 95.72 (±6.99) mmHg) over 90 days (30.31 (±14.15) / 17.14 (±9.33) mmHg; p < 0.0000). Few side effects were reported during the 90-day period. CONCLUSION: : Perindopril/Indapamide given as a SPC was found to be an effective and well-tolerated antihypertensive combination resulting in rapid blood pressure control in patients with moderate to severe hypertension.

IMPACT India: Insights for Insulin Therapy in Routine Clinical Practice.

OBJECTIVE: Widely used in the management of diabetes, insulin therapy is influenced by several patient preferences and physician choices. This article reports the findings of the IMPACT survey, designed to assess insights on various factors which influence the choice of insulin therapy in India. METHODS: We administered a questionnaire which focused on the practice and patient profiles and the preferred regimens in specific clinical situations using a case scenario. Respondents were asked about preferred insulin regimens for various phases of life, comorbid conditions, dietary choices and psychological factors. RESULTS: Overall, 314 doctors participated in the survey. Majority were general physicians (51%) and diabetologists (37%). In clinical practice, the most preferred regimens included premix insulin BD in adults (59%) and elderly (53%), and basal bolus therapy in pregnant women (>47%) and in acute illness (62%). Both regimens were equally preferred for symptomatic patients (41% basal bolus and 38% premix insulin) and those with renal or hepatic failure (36% each). Premix insulin was preferred for patients with high carbohydrate intake (73%) while basal bolus was preferred for patients with variable meal timings (39%) and in pronounced postprandial glucose excursions (45%). Insulin co-formulation and high-mix insulins were not a part of the survey questionnaire. SUMMARY: Indian physicians exercise logic in the choice of insulin regimens. Preference is based on patient characteristics including glucophenotype, dietary patterns, psychosocial needs, clinical situations, and comorbid conditions.

Management of Diabetes during Fasting and Feasting in India.

Fasting and feasting are integral part of many religions and cultures. As the amount of food and fluid intake are markedly altered during these phases, patients with diabetes are prone to higher risk of complications. Even though several guidelines for fasting and feasting are available; Indian specific recommendations are the need of the hour, because of the distinct dietary habits and the diet content (high carbohydrate) of Indians. To fill this void, the current guidelines have been developed by experts from India who extensively reviewed the literature, shared their practical knowledge and ultimately arrived at a consensus.