No abstract

Background and objectives: Fat-based energy-dense nutritional supplements may offer benefits over protein or carbohydrate dense supplements for patients receiving dialysis because of the adverse metabolic consequences of the latter. We conducted a randomized controlled trial to assess the effects of the short-term use of a fat-based nutritional supplement on various measures of nutritional status in patients receiving maintenance hemodialysis who have low dietary energy intake. Design, setting, participants, and measurements: We enrolled nondiabetic patients receiving hemodialysis for more than 3 months and had inadequate dietary energy intake (<30kcal/kg/d). The participants were randomly assigned in a 1:1 ratio to receive an oral fat-based energy-dense supplement (300kcal daily) or routine care for 12 weeks (n=120 per group). The primary outcome was the change in phase angle, measured by bioelectrical impedance analysis, a marker of cell integrity and body cell mass, from the baseline to week 12. The secondary outcomes were changes in quality of life. Other outcomes included laboratory nutritional indicators and physical examinations. Results: The average age of the total population was 47 (SD: 12) years and 55% were male. The median of dialysis vintage was 43.4 (22.5, 76.3) months. 240 participants were randomly assigned to the intervention (n=120) or control group (n=120). In total, 228 (95%) participants completed the trial. The change in phase angle did not differ significantly between the intervention and the control groups (estimate (95% confidence interval [CI]): 0.0 (-0.1, 0.1) vs. 0.0 (-0.1, 0.1); estimated difference, 0.0; 95% [CI], −0.2 to 0.2; P=0.99). None of the 19 domains of quality of life differed between the groups. Adverse events were reported in 23 (19%) participants in the control group and 40 (33%) participants in the intervention group. Conclusions: In nondiabetic maintenance hemodialysis patients, short-term administration of fat-based energy-dense nutritional supplement has no clinically significant effect on nutritional status as measured by phase angle.

In Feb 2020, we developed a physiologically-based pharmacokinetic (PBPK) model of hydroxychloroquine (HCQ) and integrated in vitro anti-viral effect to support dosing design of HCQ in the treatment of COVID-19 patients in China. This, along with emerging research and clinical findings, supported broader uptake of HCQ as a potential treatment for COVID-19 globally at the beginning of the pandemics. Therefore, many COVID-19 patients have been or will be exposed to HCQ, including specific populations with underlying intrinsic and/or extrinsic characteristics that may affect the disposition and drug actions of HCQ. It is critical to update our PBPK model of HCQ with adequate drug absorption and disposition mechanisms to support optimal dosing of HCQ in these specific populations. We conducted relevant in vitro and in vivo experiments to support HCQ PBPK model update. Different aspects of this model are validated using PK study from 11 published references. With parameterization informed by results from monkeys, a permeability-limited lung model is employed to describe HCQ distribution in the lung tissues. The updated model is applied to optimize HCQ dosing regimens for specific populations, including those taking concomitant medications. In order to meet predefined HCQ exposure target, HCQ dose may need to be reduced in young children, elderly subjects with organ impairment and/or coadministration with a strong CYP2C8/CYP2D6/CYP3A4 inhibitor, and be increased in pregnant women. The updated HCQ PBPK model informed by new metabolism and distribution data can be used to effectively support dosing recommendations for clinical trials in specific COVID-19 patients and treatment of patients with malaria or autoimmune diseases.