Molecular Hydrogen for Outpatients with COVID-19 (Hydro-COVID): A Phase 3 Randomised, Triple-Blinded, Pragmatic, Placebo-Controlled, Multicentre Trial.

Background. Due to its antioxidant, anti-inflammatory, anti-apoptosis, and anti-fatigue properties, molecular hydrogen (H2) is potentially a novel therapeutic nutrient for patients with coronavirus acute disease 2019 (COVID-19). We determined the efficacy and safety profile of hydrogen-rich water (HRW) to reduce the risk of COVID-19 progression. Methods: We also conducted a phase 3, triple-blind, randomised, placebo-controlled trial to evaluate treatment with HRW initiated within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19. Participants were randomised to receive HRW or placebo twice daily for 21 days. The incidence of clinical worsening and adverse events were the primary endpoints. Results: A total of 675 participants were followed up to day 30. HRW was not superior to placebo in preventing clinical worsening at day 14: in H2 group, 46.1% in the H2 group, 43.5% in the placebo group, hazard ratio 1.09, 90% confidence interval [0.90-1.31]. One death was reported at day 30 in the H2 group and two in the placebo group at day 30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants, respectively. Conclusions: HRW taken twice daily from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening.

[Implementing an operating room pharmacy satellite in an university hospital]. / Mise en place d'une antenne pharmaceutique de blocs opératoires dans un centre hospitalier universitaire.

OBJECTIVES: An operating room pharmaceutical unit centralizes medical devices and drugs for various surgical specialities. The aim of this work is to present the methodology used in our establishment to set up the operating room pharmaceutical unit. METHODS: This approach involved the formation of multi-professional working groups. The needs of operating theatres were defined based on an analysis of healthcare product consumption and stock inventories. Material sheets were defined for each procedure. On the basis of simulations, material supply arrangements were selected, specifying material flows, equipment, workstations and information systems. RESULTS: Over 3200 healthcare product references were identified and 862 equipment files were created. Local stocks have been limited to medical trolleys for nursing staff. Emergency operating packs have been deployed for unforeseen operations. Cabinets have been dedicated to transporting re-sterilizable medical devices, and carts have been purchased for programmed operating packs. The equipment is made available by logistics agents and pharmacy assistants under pharmaceutical responsibility. CONCLUSIONS: This innovative approach is a model for facilities desiring to centralize and secure the logistics of healthcare products in the operating room. Ongoing adjustments will be required to meet new operating rooms needs.

An ethically guided preclinical device for phenotyping H2 production in laboratory rodents.

BACKGROUND: Dihydrogen (H2) is produced endogenously by the intestinal microbiota through the fermentation of diet carbohydrates. Over the past few years, numerous studies have demonstrated the significant therapeutic potential of H2 in various pathophysiological contexts, making the characterization of its production in laboratory species of major preclinical importance. METHODS: This study proposes an innovative solution to accurately monitor H2 production in free-moving rodents while respecting animal welfare standards. The developed device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained, and the H2 concentration was continuously analyzed. After the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked, tests were carried out on rats and mice with different metabolic phenotypes, over 12 min to 1-h experiments and repeatedly. H2 production rates (HPR) were obtained using an easy calculation algorithm based on a first-order moving average. RESULTS: HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats, respectively, 2.64 and 1.27 nmol.s-1 per animal. In addition, the ingestion of inulin, a dietary fiber, stimulated H2 production in mice. HPRs were 0.46 nmol.s-1 for animals under control diet and 1.99 nmol.s-1 for animals under inulin diet. CONCLUSIONS: The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H2 production.

Hydrogen inhalation: in vivo rat genotoxicity tests.

Preclinical and clinical studies have shown that molecular hydrogen (H2) has anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Safety data are available in the literature and acute toxicity has been tested in isolated cells and laboratory animals. We have evaluates the genotoxicity of H2 in vivo in rats after 72 h exposure, following the International Council for Harmonization guidelines ICH S2 (R1). The study was conducted on three groups of male Wistar rats: a negative control group, a positive control group receiving methyl methanesulfonate, and a H2-treated group receiving a 3.1% H2 gas mixture for 72 h. Alkaline comet, formamidopyrimidine DNA glycosylase (Fpg)-modified comet and bone marrow micronucleus assays were performed. H2 exposure increased neither comet-tail DNA intensity (DNA damage) nor frequency of "hedgehogs" in blood, liver, lungs, or bronchoalveolar lavage fluid. No increase in Fpg-sensitive sites in lungs, no induction of micronucleus formation, and no imbalance of immature erythrocyte to total erythrocyte ratio (IME%) was observed in rats exposed to H2. The ICH S2 (R1) test-battery revealed no in vivo genotoxicity in Wistar rats after 72 h inhalation of a mixture containing 3.1% H2.

Unexpected overdose blood concentration of tacrolimus: Keep in mind the role of inflammation.

Tacrolimus is the cornerstone of the therapeutic immunosuppressive strategy in liver transplantation. The inter-individual and intra-individual variability of its trough blood concentrations is a surrogated biomarker of allograft rejection. Here we described two cases of patients with liver transplant who exhibited increases of tacrolimus blood trough concentration adjusted on the dose while experiencing acute inflammatory episodes. These case reports highlight the inhibitory effect of acute inflammation on tacrolimus metabolism and show that it accounts for the longitudinal intra-individual variability of tacrolimus blood concentrations, beyond drug-drug interaction and observance.