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Objective To determine whether a chemokine receptor type 2 antagonist, DMX-200 (repagermanium), in combination with an angiotensin receptor blocker, candesartan, improves clinical outcomes in people with COVID-19.Design Prospective, multicentre, double-blind, placebo-controlled trial.Setting Ten acute care hospitals in India.Participants Adults

The development of chronic kidney disease and its progression to End Stage Renal Disease requiring renal replacement therapy remains a significant source of reduced quality of life and premature mortality. The global dialysis population and treatment gap is growing, especially in low- and middle- income countries. In India, 70% of those starting dialysis, die or discontinue treatment in the initial period due to the high cost of treatment and lack of access to dialysis therapy. Achieving health equity requires ensuring access to the resources that needs to be healthy, and addressing social determinants of health involves needs factors that influence the health outcomes. Universal Health Coverage requires an alternate model to address the substantial Out-Of-Pocket-Expenditure borne by these patients for traveling and medications.

An isolated multilevel bidirectional dc–dc converter is presented in this article to interface the low-voltage (LV) battery and the high-voltage (HV) propulsion inverter in electric vehicles. The proposed topology achieves a HV step-up ratio in the motoring mode by reconfiguring two split capacitor half-bridge circuits in series/parallel through the symmetrical modulation of a voltage bidirectional, two quadrant switch. This reconfiguration generates a high-frequency multilevel voltage output at the dc-bus side of the inverter, which reduces the output filter volume. The dc-bus voltage is regulated by the duty cycle modulation of the intermediary switch in the motoring mode, simplifying the sensing and control. During regenerative braking, the converter is operated with phase shift modulation between the HV half bridges and the LV full bridge to regulate the battery voltage. The presented modulation strategies achieve zero voltage switching for the full-bridge devices over a wide load range. A comprehensive analysis of the proposed multilevel converter in motoring and braking modes along with the design constraints and soft switching boundary conditions is presented in this article. Detailed experimental results on a 1.5-kW laboratory prototype are presented to verify the design approach and illustrate the converter performance. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) not associated with known risk factors, called CKD of unknown etiology (CKDu), has been reported from several geographically distinct regions across the world. This study reports the clinical and epidemiological profile of patients with CKDu from a new hotspot in central India. Materials and Methods: This cross-sectional study describes the sociodemographic, clinical, and laboratory profile of the patients diagnosed with CKDu visiting a tertiary care public hospital in the state of Chhattisgarh in central India between June 2019 and June 2021. CKDu was diagnosed as progressive CKD, minimal proteinuria, absence of hematuria, diabetes, severe hypertension, systemic illness, glomerulonephritis or other urinary tract diseases, and presence of symmetrically contracted kidneyon ultrasound. Results: A total of 166 (3.1%) out of 5365 patients with CKD were diagnosed with CKDu. The mean age was 53.6 ± 11.8 years. The patients were predominantly male (n = 113, 68.1%), belonged to rural areas (n = 147, 88.6%), and were engaged in farming (n = 105, 63.3%). The estimated glomerular filtration rate (eGFR) at presentation was 21.5 ± 15.1 ml/min/1.73m². Forty-four (26.5%) had stage 3 CKD, 57 (34.3%) had stage 4 CKD, and 65 (39.2%) had stage5 CKD. There was an over-representation of CKDu cases in patients with CKD from Gariyaband (36.0%) and Mahasamund (25%) districts of Chhattisgarh and Nuapada (35.0%) and Balangir (30.0%) districts of Odisha. Conclusion: The study suggests clustering of cases of CKDu in certain districts of Orissa and Chhattisgarh. [ABSTRACT FROM AUTHOR]

This article proposes a multilevel dc–dc converter topology for fast charging of electric and plug-in hybrid electric vehicles (EVs and PHEVs). The proposed dc–dc converter topology converts the front end ac–dc converter output and provides regulated supply to the EV propulsion battery. The proposed topology consists of full-bridge converter at the primary, while the secondary side consists of voltage doubler rectifier units and combination of diodes and mosfet for reconfiguration of the voltage doubler rectifiers to generate the multilevel voltage. The multilevel voltage at the output helps in reducing the output filter size and increases the power density of the converter. The topology utilizes the resonance between leakage inductor of high frequency transformer, parasitic output capacitors of full-bridge mosfets and voltage doubler capacitors to achieve soft switching (ZVS turn-on) for all the full-bridge devices and soft turn-offfor the rectifier diodes. The load limited ZVS turn on capability of conventional full-bridge topologies is mitigated through the use of resonance between magnetizing inductance of transformer and mosfet output capacitors. The converter is designed for 650 V dc bus input and 200–400 V EV battery output at 100 kW rated charging power. The analysis of the proposed converter in continuous and discontinuous modes of operation, soft switching operation, and the component design guidelines are presented in this article. The proposed converter is validated through detailed PLECS simulation results for 100 kW charging power. Experimental results from laboratory prototype of 500 W power are also presented to validate the design methodology and converter performance. [ABSTRACT FROM AUTHOR]

Background: A phase 3 study to assess the efficacy and safety of the desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, against the epoetin alfa for the treatment of anemia in patients with chronic kidney disease (CKD) with dialysis dependency. Methods: DREAM-D was a phase 3, multicenter, open-label, randomized, active-controlled clinical study conducted across 38 centers in India. A total of 392 patients with clinical diagnosis of anemia due to CKD with dialysis need (Erythrocyte Stimulating Agent [ESA] naïve or prior ESA users) and with baseline hemoglobin levels of 8.0–11.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat oral tablets (thrice a week) or epoetin alfa subcutaneous injection for 24 weeks to maintain a hemoglobin level of 10–12 g/dL. The primary endpoint was to assess the change in the hemoglobin level between the desidustat and the epoetin alfa groups from the baseline to evaluation period week 16–24. The key secondary efficacy endpoint was the number of patients with hemoglobin response. Results: The least square mean (standard error) change in hemoglobin from the baseline to week 16–24 was 0.95 (0.09) g/dL in the desidustat group and 0.80 (0.09) g/dL in the epoetin alfa group (difference: 0.14 [0.14] g/dL; 95% confidence interval: −0.1304, 0.4202), which met the prespecified noninferiority margin. The number of hemoglobin responders was significantly higher in the desidustat group (106 [59.22%]) when compared to the epoetin alfa group (89 [48.37%]) (p = 0.0382). The safety profile of the desidustat oral tablet was comparable with the epoetin alfa injection. There were no new risks or no increased risks seen with the use of desidustat compared to epoetin alfa. Conclusion: In this study, desidustat was found to be noninferior to epoetin in the treatment of anemia in CKD patients on dialysis and it was well-tolerated. Clinical Trial Registry Identifier: CTRI/2019/12/022312 (India). [ABSTRACT FROM AUTHOR]

The CLARITY trial (Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease) is a two-arm, multi-centre, randomised controlled trial being run in India and Australia that investigates the effectiveness of angiotensin receptor blockers in addition to standard care compared to placebo (in Indian sites) with standard care in reducing the duration and severity of lung failure in patients with COVID-19. The trial was designed as a Bayesian adaptive sample size trial with regular planned analyses where pre-specified decision rules will be assessed to determine whether the trial should be stopped due to sufficient evidence of treatment effectiveness or futility. Here, we describe the statistical analysis plan for the trial and define the pre-specified decision rules, including those that could lead to the trial being halted. The primary outcome is clinical status on a 7-point ordinal scale adapted from the WHO Clinical Progression scale assessed at day 14. The primary analysis will follow the intention-to-treat principle. A Bayesian adaptive trial design was selected because there is considerable uncertainty about the extent of potential benefit of this treatment.Trial registrationClinicalTrials.gov NCT04394117 . Registered on 19 May 2020Clinical Trial Registry of India CTRI/2020/07/026831Version and revisionsVersion 1.0. No revisions. [ABSTRACT FROM AUTHOR]

Horseshoe kidney is a common congenital renal fusion anomaly. Acute kidney injury occurs secondary to urinary infection or obstructive uropathy, but glomerular involvement is rarely reported. A 47-year-old female presented with symptoms of urinary infection and was hospitalized in the urology clinic. Investigations revealed renal dysfunction and active urine sediments. The patient did not respond to antibiotics and eventually became anuric after 3 weeks of initiation of symptoms. Abdominal ultrasound was suggestive of horseshoe kidney. Workup for rapidly progressive glomerulonephritis and kidney biopsy confirmed the diagnosis of anti-glomerular basement membrane disease. The patient responded to immunosuppression and plasmapheresis. The above case highlights the importance of timely renal biopsy in diagnosis and management of glomerular disease even in patients with horseshoe kidney. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel antidiabetic agents with overwhelming cardiorenal protection. Recent trials focusing on the nephroprotective role of SGLT2i have underscored its success as a phenomenal agent in halting the progression of kidney disease in patients with and without Type 2 diabetes mellitus. Multitudes of pleiotropic effects on tubules have raised hopes for reasonable nephroprotection beyond the purview of the hyperglycemic milieu. This review summarizes various animal and human data as evidence for the utility of SGLT2i in non-diabetic chronic kidney disease (CKD). Web-based medical database entries were searched. On the premise of existing evidence, we have discussed mechanisms likely contributing to nephroprotection by SGLT2i in patients with non-diabetic CKD. Further elucidation of mechanisms of nephroprotection offered by SGLT2i is required to extend its use as a nephroprotective agent. The use of non-traditional markers of kidney damage in future studies would improve the evaluation of their role in attenuating CKD progression. Emerging animal data support the early use of SGLT2i in states of modest proteinuria for superior outcomes. Future long-term trials in patients should aim to address the time of intervention with SGLT2i during the natural disease course of CKD for best outcomes. [ABSTRACT FROM AUTHOR]

Patients with hemato-oncologic diseases are particularly vulnerable to severe infections. Adult patients with blood cancers infected with SARS-CoV-2 had poorer treatment outcomes and higher mortality than patients with COVID-19 without burden. However, in pediatric patients with hemato-oncologic diseases the course of COVID-19 is milder than in adults in the same group of patients. In this report, we describe the case of our patient with acute lymphoblastic leukemia infected with SARS-CoV-2 and treated with remdesivir. We also review the existing literature of pediatric patients who have been diagnosed with both hemato-oncologic diseases and COVID-19., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)