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Background: With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening.Methods: The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥ 65 years with COVID-19 (diagnosed within the preceding 3 days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age ≥ 75 years, or SpO2 ≤ 94% in room air, or PaO2/FiO2 ≤ 300 mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation > 800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000 IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000 IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28 days. The primary outcome measure is all-cause mortality within 14 days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7.Discussion: COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments.Trial Registration: ClinicalTrials.gov NCT04344041 . Registered on 14 April 2020 TRIAL STATUS: Recruiting. Recruitment is expected to be completed in April 2021. [ABSTRACT FROM AUTHOR]

Background: Glucose is widely used as an osmotic agent in peritoneal dialysis (PD), but exerts untoward effects on the peritoneum. The potential protective effect of a reduced exposure to hypertonic glucose has never been investigated.Methods: The cohort of PD patients attending our center which tackled the challenge of a restricted use of hypertonic glucose solutions has been prospectively followed since 1992. Small-solute transport was assessed using an equivalent of the glucose peritoneal equilibration test after 6 months, and then every year. Study was stopped on July 1st, 2008, before use of biocompatible solutions. Repeated measures in patients treated with PD for 54 months were analyzed by using (1) the slopes of the linear regression for D4/D0 ratios over time computed for each individual, and (2) a linear mixed model.Results: In the study period, 44 patients were treated for a total of 2376 months, 2058 without hypertonic glucose. There was one episode of peritoneal infection every 18 patient-months. The mean of slopes of the linear regression for D4/D0 ratios was found to be significantly positive (Student's test, p < .001) and the results of the mixed model reflected a similar significant increase for D4/D0 ratios over time. These results reflected a significant decrease of small-solute transport.Conclusion: In this large series, minimizing the use of hypertonic glucose solutions was associated in patients on long term PD with an overall decrease of small-solute transport within 54 months, despite a high rate of peritoneal infection. [ABSTRACT FROM AUTHOR]

Background: Although chronic kidney disease (CKD) affects a growing number of people, epidemiologic data on incident CKD in the general population are scarce. Screening strategies to increase early CKD detection have been developed. Methods: From a community-based sample of 4,409 individuals residing in a well-defined geographical area, we determined the number of patients having a first serum creatinine value ≥1.7 mg/dL and present for at least 3 months that allowed us to calculate an annual incidence rate of CKD (stages 3 to 5). CKD (stages 3 to 5) was defined by estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We also described the primary care, outcomes and risk factors associated with outcomes using competing risks analyses for these CKD patients. Results: A total of 631 incident CKD patients (stages 3 to 5) were followed-up until the occurrence of death and dialysis initiation for more than 3 years. The annual incidence rate of CKD (stages 3 to 5) was estimated at 977.7 per million inhabitants. Analyses were performed on 514 patients with available medical data. During the study, 155 patients (30.2 %) were referred to a nephrologist, 193 (37.5 %) died and 58 (11.3 %) reached end-stage renal disease and initiated dialysis. A total of 139 patients (27.6 %) had a fast decline of their renal function, 92 (18.3 %) a moderate decline and the 272 remaining patients had a physiological decline (21.1 %) or a small improvement of their renal function (33.0 %). Predictors of death found in both Cox and Fine-Gray multivariable regression models included age at diagnosis, anemia, active neoplasia and chronic heart failure, but not a low glomerular filtration rate (GFR). Age at diagnosis, anemia and a low GFR were independently associated with dialysis initiation in Cox model, but anemia was not found to be a risk factor for dialysis initiation in Fine-Gray model. Conclusions: This large cohort study provided useful epidemiological data on incident CKD (stages 3 to 5) and stressed the need to improve the hands-on implementation of clinical practice guidelines for the evaluation and the management of CKD in primary care. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions and adverse drug events (ADEs) are major public health issues. Many different prospective tools for the automated detection of ADEs in hospital databases have been developed and evaluated. The objective of the present study was to evaluate an automated method for the retrospective detection of ADEs with hyperkalaemia during inpatient stays. Methods: We used a set of complex detection rules to take account of the patient’s clinical and biological context and the chronological relationship between the causes and the expected outcome. The dataset consisted of 3,444 inpatient stays in a French general hospital. An automated review was performed for all data and the results were compared with those of an expert chart review. The complex detection rules’ analytical quality was evaluated for ADEs. Results: In terms of recall, 89.5% of ADEs with hyperkalaemia “with or without an abnormal symptom” were automatically identified (including all three serious ADEs). In terms of precision, 63.7% of the automatically identified ADEs with hyperkalaemia were true ADEs. Conclusions: The use of context-sensitive rules appears to improve the automated detection of ADEs with hyperkalaemia. This type of tool may have an important role in pharmacoepidemiology via the routine analysis of large inter-hospital databases. [ABSTRACT FROM AUTHOR]

Background: Reasons underlying dialysis decision-making in Octogenarians and Nonagenarians have not been further explored in prospective studies. Methods: This regional, multicentre, non-interventional and prospective study was aimed to describe characteristics and quality of life (QoL) of elderly (≥80 years of age) with advanced chronic kidney disease (stage 3b-5 CKD) newly referred to nephrologists. Predictive factors of death and dialysis initiation were also assessed using competing-risk analyses. Results: All 155 included patients had an estimated glomerular filtration rate (eGFR) below 45 ml/min/1.73m2. Most patients had a non anaemic haemoglobin level (Hb) with no iron deficiency, and normal calcium and phosphate levels. They were well-fed and had a normal cognitive function and a good QoL. The 3-year probabilities of death and dialysis initiation reached 27% and 11%, respectively. The leading causes of death were cardiovascular (32%), cachexia (18%), cancer (9%), infection (3%), trauma (3%), dementia (3%), and unknown (32%). The reasons for dialysis initiation were based on uncontrolled biological abnormalities, such as hyperkalemia or acidosis (71%), uncontrolled digestive disorders (35%), uncontrolled pulmonary or peripheral oedema (29%), and uncontrolled malnutrition (12%). No patients with acute congestive heart failure or cancer initiated dialysis. Predictors of death found in both multivariate regression models (Cox and Fine & Gray) included acute congestive heart failure, age, any walking impairment and Hb <10 g/dL. Regarding dialysis initiation, eGFR <23 mL/min/1.73m2 was the only predictor found in the Cox multivariate regression model whereas eGFR <23 mL/min/1.73m2 and diastolic blood pressure were both independently associated with dialysis initiation in the Fine & Gray analysis. Such findings suggested that death and dialysis were independent events. Conclusions: Octogenarians and Nonagenarians newly referred to nephrologists by general practitioners were highly selected patients, without any symptoms of the common geriatric syndrome. In this population, nephrologists' dialysis decision was based exclusively on uremic criteria. [ABSTRACT FROM AUTHOR]

Background: In survival analysis, patients on peritoneal dialysis are confronted with three different outcomes: transfer to hemodialysis, renal transplantation, or death. The Kaplan-Meier method takes into account one event only, so whether it adequately considers these different risks is questionable. The more recent competing risks method has been shown to be more appropriate in analyzing such situations. Methods: We compared the estimations obtained by the Kaplan-Meier method and the competing risks method (namely the Kalbfleisch and Prentice approach), in 383 consecutive incident peritoneal dialysis patients. By means of simulations, we then compared the Kaplan-Meier estimations obtained in two virtual centers where patients had exactly the same probability of death. The only difference between these two virtual centers was whether renal transplantation was available or not. Results: At five years, 107 (27.9%) patients had died, 109 (28.4%) had been transferred to hemodialysis, 91 (23.8%) had been transplanted, and 37 (9.7%) were still alive on peritoneal dialysis; before five years, 39 (10.2%) patients were censored alive on peritoneal dialysis. The five-year probabilities estimated by the Kaplan-Meier and the competing risks methods were respectively: death: 50% versus 30%; transfer to hemodialysis: 59% versus 32%; renal transplantation: 39% versus 26%; event-free survival: 12% versus 12%. The sum of the Kaplan-Meier estimations exceeded 100%, implying that patients could experience more than one event, death and transplantation for example, which is impossible. In the simulations, the probability of death estimated by the Kaplan-Meier method increased as the probability of renal transplantation increased, although the probability of death actually remained constant. Conclusion: The competing risks method appears more appropriate than the Kaplan-Meier method for estimating the probability of events in peritoneal dialysis in the context of univariable survival analysis. [ABSTRACT FROM AUTHOR]