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.govNCT04344041. Registered on 14 April 2020 Trial status Recruiting. Recruitment is expected to be completed in April 2021.
Background In France, emergency departments (EDs) are the fastest and most common means for general practitioners (GPs) to cope with the complex issues presented by elderly patients with multiple conditions. EDs are overburdened, and studies show that being treated in EDs can have a damaging effect on the health of elderly patients. Outpatient care or planned hospitalizations are possible solutions if appropriate geriatric medical advice is provided. In 2013, France’s regional health authorities proposed creating direct telephone helplines, “geriatric hotlines,” staffed by geriatric specialists to encourage interactions between GP clinics and hospitals. These hotlines are designed to improve health care pathways and the health status of the elderly. Objective This study aims to describe the health care pathways and health status of patients aged 75 years and older hospitalized in short-stay geriatric wards following referral from a geriatric hotline. Methods The study will be conducted over 24 months in seven French university hospital centers. It will include all patients aged 75 and older, living in their own homes or nursing homes, who are admitted to short-stay geriatric wards following hotline consultation. Two questionnaires will be filled out by medical staff at specific time points: (1) after conducting the telephone consultation and (2) on admitting the patient to a short-stay geriatric medical care. The primary endpoint will be mean hospitalization duration. The secondary endpoints will be intrahospital mortality rate, the characteristics of patients admitted via the hotline, and the types of questions asked and responses given via the hotline. Results The study was funded by the National School for Social Security Loire department (École Nationale Supérieure de Sécurité Sociale) and the Conference for funders of prevention of autonomy loss for the elderly of the Loire department in November 2017. Institutional review board approval was obtained in April 2018. Data collection started in May 2018; the planned end date for data collection is May 2020. Data analysis will take place in the summer of 2020, and the first results are expected to be published in late 2020. Conclusions The results will reveal whether geriatric hotlines provide the most effective management of elderly patients, as indicated by shorter mean hospitalization durations. Shorter hospital durations could lead to a reduced risk of complications—geriatric syndromes—and the domino chain of geriatric conditions that follow. We will also describe different geriatric hotlines from different cities and compare how they function to improve the health care of the elderly and pave the way toward new advances, especially in the organization of the care path. Trial Registration ClinicalTrials.gov NCT03959475; https://clinicaltrials.gov/ct2/show/NCT03959475 International Registered Report Identifier (IRRID) DERR1-10.2196/15423
The purpose of the present study was to investigate the possible role of intrafollicular amino acids in the human ovarian follicle. Follicular fluid (FF) and oocytes were obtained from 12 women for in vitro fertilization. Follicular development was induced with clomiphene citrate and human menopausal gonadotropin. Thirty-six FF samples, free of visible blood contamination and containing mature oocytes were used to measure free amino acids, steroids and gonadotropins. The FF were divided into three groups: (1) follicles yielding oocytes that were unfertilized (n = 12); (B) follicles containing oocytes that were fertilized and cleaved to less than four cells (n = 12); (C) follicles yielding oocytes that were fertilized and cleaved to four or more cells (n = 12). The concentrations of histidine, phenylalanine and asparagine in FF were significantly greater than those in plasma at the time of follicle aspiration. However, amino acid concentrations in FF did not differ significantly between the three groups studied. No significant relationships were found between intrafollicular levels of amino acids and those of LH, FSH, estradiol, progesterone and testosterone. These results suggest that intrafollicular amino acids are not involved in the regulation of human preovulatory follicle.
A specific gravity, column gradient method was coupled with a tissue punch technique to measure regional edema in the traumatized spinal cord of the cat at 1 and 2 hours after a 500-g/cm impact injury. A significant increase in water content was observed at the injury site in the posterior, anterior, and lateral white columns by 1 hour after injury and extended 2 mm above and below the site by 2 hours after injury.
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