Background Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is lack of information on epidemiology and progression of CKD in low-middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian CKD patients . Methods ICKD study is prospective, multicentric, cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73m2 or > 60 ml/min/1.73m2 with proteinuria. Clinical details and biological samples are collected at annual visit. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants. Results A total of 4056 patients have been enrolled till March 31, 2020. The age was 50.3 ±11.8 years, 67.2% were males, 2/3 lived in rural areas and median eGFR was 40 ml/min/1.73m2. About 87% were hypertensive, 37% had diabetes, 22% had CVD, 6.7% had past history of acute kidney injury and 23% reported prior use of alternative drugs. Diabetic kidney disease, chronic interstitial nephritis and CKD-cause unknown were the leading causes. Rural participants had more occupational exposure and tobacco use but lower educational status and income. CIN and unknown categories were leading causes in rural participants. Conclusions The ICKD study is the only large cohort study of patients with mild-to-moderate CKD in a lower-middle income country. Baseline characteristics of study population reveal differences as compared to other cohorts.

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Invasive fungal infections (IFIs) are a significant cause of morbidity in solid organ transplant (SOT) recipients. Common causes among them are Aspergillus, Candida, and Cryptococcus. Antifungal prophylaxis has led to decrease in overall incidence of IFI; however, there is very little decline in the incidence of Cryptococcal infections of SOT recipients because effective prophylaxis is not available against this infectious agent. Spectrum of manifestation of Cryptococcal infection varies in immunocompetent and immunocompromised host with subclinical and self-limiting with lungs being the primary site in immunocompetent and central nervous system as the most common site in an immunocompromised host. Other preferred sites are cutaneous, pulmonary, urinary tract (prostate) and the bone. Herein, we describe a young adult renal transplant recipient male diagnosed as a rare case of biopsy proven Cryptococcal infection in transplant kidney manifesting as chronic allograft dysfunction.

Background: Diabetes mellitus (DM) causes serious deterioration in general quality of life (QoL) mainly affecting the health-related quality of life (HRQOL). Routine assessment of QoL improves communication with the patient, helps to predict treatment response, and supports clinical decision-making. QoL can predict an individual's capacity to manage the disease and maintain long-term health and wellbeing. Aims: To find out the QoL and its socio-demographic, anthropometric, and clinical determinants among DM patients attending health institutions from sub-Himalayan region, catering rural population. Settings and Design: This cross-sectional study was conducted in two hospitals mostly catering rural population from 2014 to 2018. Purposive sampling technique was used. Materials and Methods: Socio-demographic, anthropometric, and clinical data of DM patients (N = 300) were collected. They were administeredHindi translation of QoL Instrument for Indian Diabetes Patients (QOLID) and Patient Health Questionnaire-9 (PHQ-9). All statistical analyses were carried out using Statistical Package for Social Sciences (SSPS) (Version 17.0, USA). Results: About 10% had very poor, 13% poor, 11% average, 16% good, and 50% very good QoL on QOLID. General health (GH) and treatment satisfaction (TS) were the most affected domains. Fatigue was the most common symptom (79%) reported in QOLID. Age more than 55 years, rural background, and PHQ-9 score of more than 7 were predictors of poorer QoL. Conclusion: There is a need for a holistic and collaborative care of DM patients, to maintain a good HRQoL. Screening of depression, fatigue, and regular assessment of QoL should be emphasized.

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ObjectivesThe pathophysiology of SARS-Cov-2 is characterized by inflammation, immune dysregulation, coagulopathy, and endothelial dysfunction. No single therapeutic agent can target all these pathophysiologic substrates. Moreover, the current therapies are not fully effective in reducing mortality in moderate and severe disease. Hence, we aim to evaluate the combination of drugs (aspirin, atorvastatin, and nicorandil) with anti-inflammatory, antithrombotic, immunomodulatory, and vasodilator properties as adjuvant therapy in covid- 19.Trial designSingle-centre, prospective, two-arm parallel design, open-label randomized control superiority trial. ParticipantsThe study will be conducted at the covid centre of Dr. Rajendra Prasad Government Medical College Tanda Kangra, Himachal Pradesh, India. All SARS-CoV-2 infected patients requiring admission to the study centre will be screened for the trial. All patients >18years who are RT-PCR/RAT positive for SARS-CoV-2 infection with pneumonia but without ARDS at presentation (presence of clinical features of dyspnoea hypoxia, fever, cough, spo2 <94% on room air and respiratory rate >24/minute) requiring hospital admission and consenting to participate in the trial will be included.Patients with documented significant liver disease/dysfunction (AST/ALT > 240), myopathy and rhabdomyolysis (CPK > 5x normal), allergy or intolerance to statins, allergy or intolerance to aspirin, patients taking medications with significant interaction with statins, prior statin use (within 30 days), prior aspirin use (within 30 days), history of active GI bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, patient unable to take oral or nasogastric medications, patients in altered mental status, shock, acute renal failure, acute coronary syndrome, sepsis and ARDS at presentation will be excluded. Intervention and comparatorAfter randomization, participants in the intervention group will receive aspirin, atorvastatin, and nicorandil. Atorvastatin will be prescribed as 40 mg starting dose followed by 40 mg oral tablets once daily for ten days or till hospital discharge whichever is later. Aspirin dose will be 325 starting dose followed by 75 mg once daily for ten days or till hospital discharge whichever is later. Nicorandil will be given as 10 mg starting dose followed by 5mg twice daily ten days or till hospital discharge whichever is later. All patients in the intervention and control group will receive a standard of care for covid management as per national guidelines. All patients will receive symptomatic treatment with antipyretics, adequate hydration, anticoagulation with low molecular weight heparin, intravenous remdesivir, corticosteroids (intravenous dexamethasone for 5 days or more duration if oxygen requirement increasing or inflammatory markers are raised), and oxygen support. Patients will receive treatment for comorbid conditions as per guidelines.Main outcomesThe patients will be followed up for outcomes during the hospital stay or for ten days whichever is longer. The primary outcome will be in-hospital mortality. Any progression to ARDS, shock, acute kidney injury, impaired consciousness, length of hospital stay, length of mechanical ventilation (invasive plus non-invasive) will be secondary outcomes. Changes in serum markers (CRP, D –dimer, S ferritin) will be other secondary outcomes. The safety endpoints will be hepatotoxicity (ALT/AST > 3x ULN; hyperbilirubinemia), myalgia—muscle ache, or weakness without creatine kinase (CK) elevation, myositis—muscle symptoms with increased CK levels (3-10) ULN, rhabdomyolysis—muscle symptoms with marked CK elevation (typically substantially greater than 10 times the upper limit of normal [ULN]) and with creatinine elevation (usually with brown urine and urinary myoglobin) observed during the hospital stay. RandomizationComputer-generated block randomization will be used to randomize the participants in a 1:1 ratio to the active intervention group A (Aspirin, Atorvastatin, Nicorandil) plus conventional therapy and control group B conventional therapy only. Blinding (masking)The study will be an open-label trial. Numbers to be randomized (sample size)A total of 396 patients will participate in this study, which is randomly divided with 198 participants in each group.Trial statusThe first version of the protocol was approved by the institutional ethical committee on 1st February 2021, IEC /006/2021. The recruitment started on 8/4/2021 and will continue until 08/07/2021. A total of 281 patients have been enrolled till 21/5/2021.Trial registrationThe trial has been prospectively registered in Clinical Trial Registry – India (ICMR- NIMS): CTRI/2021/04/032648 [Registered on: 08/04/2021].Full protocolThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported under the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Objectives The pathophysiology of SARS-Cov-2 is characterized by inflammation, immune dysregulation, coagulopathy, and endothelial dysfunction. No single therapeutic agent can target all these pathophysiologic substrates. Moreover, the current therapies are not fully effective in reducing mortality in moderate and severe disease. Hence, we aim to evaluate the combination of drugs (aspirin, atorvastatin, and nicorandil) with anti-inflammatory, antithrombotic, immunomodulatory, and vasodilator properties as adjuvant therapy in covid- 19. Trial design Single-centre, prospective, two-arm parallel design, open-label randomized control superiority trial. Participants The study will be conducted at the covid centre of Dr. Rajendra Prasad Government Medical College Tanda Kangra, Himachal Pradesh, India. All SARS-CoV-2 infected patients requiring admission to the study centre will be screened for the trial. All patients >18years who are RT-PCR/RAT positive for SARS-CoV-2 infection with pneumonia but without ARDS at presentation (presence of clinical features of dyspnoea hypoxia, fever, cough, spo2 <94% on room air and respiratory rate >24/minute) requiring hospital admission and consenting to participate in the trial will be included. Patients with documented significant liver disease/dysfunction (AST/ALT > 240), myopathy and rhabdomyolysis (CPK > 5x normal), allergy or intolerance to statins, allergy or intolerance to aspirin, patients taking medications with significant interaction with statins, prior statin use (within 30 days), prior aspirin use (within 30 days), history of active GI bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, patient unable to take oral or nasogastric medications, patients in altered mental status, shock, acute renal failure, acute coronary syndrome, sepsis and ARDS at presentation will be excluded. Intervention and comparator After randomization, participants in the intervention group will receive aspirin, atorvastatin, and nicorandil (Fig. 1). Atorvastatin will be prescribed as 40 mg starting dose followed by 40 mg oral tablets once daily for ten days or till hospital discharge whichever is later. Aspirin dose will be 325 starting dose followed by 75 mg once daily for ten days or till hospital discharge whichever is later. Nicorandil will be given as 10 mg starting dose followed by 5mg twice daily ten days or till hospital discharge whichever is later. All patients in the intervention and control group will receive a standard of care for covid management as per national guidelines. All patients will receive symptomatic treatment with antipyretics, adequate hydration, anticoagulation with low molecular weight heparin, intravenous remdesivir, corticosteroids (intravenous dexamethasone for 5 days or more duration if oxygen requirement increasing or inflammatory markers are raised), and oxygen support. Patients will receive treatment for comorbid conditions as per guidelines. Main outcomes The patients will be followed up for outcomes during the hospital stay or for ten days whichever is longer. The primary outcome will be in-hospital mortality. Any progression to ARDS, shock, acute kidney injury, impaired consciousness, length of hospital stay, length of mechanical ventilation (invasive plus non-invasive) will be secondary outcomes. Changes in serum markers (CRP, D –dimer, S ferritin) will be other secondary outcomes. The safety endpoints will be hepatotoxicity (ALT/AST > 3x ULN; hyperbilirubinemia), myalgia—muscle ache, or weakness without creatine kinase (CK) elevation, myositis—muscle symptoms with increased CK levels (3-10) ULN, rhabdomyolysis—muscle symptoms with marked CK elevation (typically substantially greater than 10 times the upper limit of normal [ULN]) and with creatinine elevation (usually with brown urine and urinary myoglobin) observed during the hospital stay. Randomization Computer-generated block randomization will be used to randomize the participants in a 1:1 ratio to the active intervention group A (Aspirin, Atorvastatin, Nicorandil) plus conventional therapy and control group B conventional therapy only. Blinding (masking) The study will be an open-label trial. Numbers to be randomized (sample size) A total of 396 patients will participate in this study, which is randomly divided with 198 participants in each group. Trial status The first version of the protocol was approved by the institutional ethical committee on 1st February 2021, IEC /006/2021. The recruitment started on 8/4/2021 and will continue until 08/07/2021. A total of 281 patients have been enrolled till 21/5/2021. Trial registration The trial has been prospectively registered in Clinical Trial Registry – India (ICMR- NIMS): CTRI/2021/04/032648 [Registered on: 8 April 2021]. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported under the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Cryptococcal infection constitutes around 3% of opportunistic infections in solid organ transplant recipients. Most common organ affected in renal transplant recipients (RTRs) is central nervous system and usually presents with chronic meningoencephalitis (CME). Ischaemic stroke as a consequence of cryptococcal meningoencephalitisis rare and possibly due to the involvement of intracranial vessel by exudates causing vasculitis-related thrombosis. In this context, we describe an unusual case of asymptomatic cryptococcaemia in an RTR, progressing on to acute ischaemic stroke secondary to acute CME with near complete neurological recovery following timely diagnosis, early and appropriate antifungal treatment. The index case attempts to re-emphasise the significance of mandatory screening required to exclude the possibility of dissemination of cryptococcaemia in RTRs besides highlighting the requirement of prolonged induction phase with combination therapy, particularly in presence of stroke.