Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment.

INTRODUCTION: In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing. METHODS: COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases. FINDINGS: Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities. CONCLUSION: Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.

Training and academic demands are associated with sleep quality in high-performance "dual career" student swimmers.

Dual career collegiate athletes, who combine sporting endeavours with academic studies, are commonplace in high-performance sport. Sleep is an important aspect of physical and psychological recovery for athletes, plays a role in memory and learning and is associated with academic achievement. The aim of this study was to assess variations in sleep characteristics of collegiate swimmers to understand the incidence of poor sleep, and which stressors might contribute towards this. A total of 22 (male n = 13, female n = 9) high-performance student swimmers (mean ± SD; age 20 ± 2 years) participated in this study. Sleep/wake behaviour was assessed using the Pittsburgh Sleep Quality Index each month over a 12-month period. Additionally, academic and sporting commitments were quantified on a monthly basis and summarised as 4 stressors: average weekly training hours, total number of competitive races, total number of academic assessments, and average weekly learning hours. On average across the 12-month period, 41.7% of athletes reported poor sleep. The latest bedtimes, wake times and longest sleep durations were found in the months where academic and training demands were lowest. A statistically significant positive association was identified between median sleep quality scores and mean number of academic assessments (ρ(12) = 0.71, p=0.005). Hierarchal linear modelling analysis determined that number of academic assessments best predicted sleep quality within this cohort. The present study highlights the need for those working with athletes who have competing academic demands to consider sleep quality, and its potential impact on performance and wellbeing.

Normobaric hyperoxia training in elite female hockey players.

BACKGROUND: Supplemental oxygen use may offer recovery benefits to team sport athletes both in training and match play. A blinded independent measures study was used to investigate the effect of supplementary oxygen use during recovery from high-intensity exercise on performance. METHODS: Fifteen female international hockey players underwent a 6 week running based training program with a 2:1 work to rest ratio. The subjects were split into 3 groups; normobaric hyperoxia (HXA), normoxia (NXA) and control (CTR). In between exercise sets HXA received 100% oxygen for 1 minute whilst NXA received a placebo in the same manner. CTR received no treatment and were not supervised. Maximal aerobic speed (MAS) was measured pre and post. Distance covered was measured along with peak heart rate (HRpeak), peak blood lactate concentration ([La-]peak) and rate of perceived exertion (RPE). RESULTS: MAS improved in HXA, NXA and CTR. However, distance ran in training was not different between groups. There was a likely positive effect on HRpeak in HXA (lower in HXA). RPE and [La-]peak response was not different between groups. CONCLUSIONS: Inhaling supplementary oxygen during recovery between high-intensity intervals did not improve physiological performance of high-level team sport players. The normobaric hyperoxia treatment had no effect on maximal aerobic (distance covered), metabolic ([La-]peak), and perception (RPE) parameters. It is not recommended as an ergogenic aid to training at sea level.