Performance of a Provider-Assigned Functional Outcome Score in Critically Ill Children.

OBJECTIVES: Determine agreement between Pediatric Cerebral Performance Category (PCPC) scores integrated into clinical workflow and traditional investigator-assigned scores. DESIGN: Longitudinal study. SETTING: A single-center quaternary-care academic institution. SUBJECTS: Children admitted to the PICU between November 2019 and April 2020. INTERVENTIONS: Providers assigned PCPC scores as part of daily workflow. Investigators assigned scores using retrospective chart review. MEASUREMENTS AND MAIN RESULTS: Of 803 patients admitted to the PICU, 782 survived and were included. Admission and discharge scores were recorded in 95% and 90% of patients, respectively. Agreement between provider- and investigator-assigned scores was excellent, with a weighted kappa of 0.87 (95% CI, 0.84-0.90) and 0.80 (95% CI, 0.76-0.84) for admission and discharge. CONCLUSIONS: Provider-assigned PCPC scores, documented as standard of care, are largely concordant with retrospective investigator-assigned scores. Measurement of cognitive functional status can be successfully integrated into daily provider workflow for use in the clinical, quality improvement, and research arenas.

Lack of detectable short-term effects of a single dose of ivermectin on the human immune system.

BACKGROUND: Ivermectin is widely used in human and animal medicine to treat and prevent parasite nematode infections. It has been suggested that its mode of action requires the host immune system, as it is difficult to reproduce its clinical efficacy in vitro. We therefore studied the effects of a single dose of ivermectin (Stromectol®-0.15 mg/kg) on cytokine levels and immune cell gene expression in human volunteers. This dose reduces bloodstream microfilariae rapidly and for several months when given in mass drug administration programmes. METHODS: Healthy volunteers with no travel history to endemic regions were given 3-4 tablets, depending on their weight, of either ivermectin or a placebo. Blood samples were drawn immediately prior to administration, 4 h and 24 h afterwards, and complete blood counts performed. Serum levels of 41 cytokines and chemokines were measured using Luminex® and expression levels of 770 myeloid-cell-related genes determined using the NanoString nCounter®. Cytokine levels at 4 h and 24 h post-treatment were compared to the levels pre-treatment using simple t tests to determine if any individual results required further investigation, taking p = < 0.05 as the level of significance. NanoString data were analysed on the proprietary software, nSolver™. RESULTS: No significant differences were observed in complete blood counts or cytokine levels at either time point between people given ivermectin versus placebo. Only three genes showed a significant change in expression in peripheral blood mononuclear cells 4 h after ivermectin was given; there were no significant changes 24 h after drug administration or in polymorphonuclear cells at either time point. Leukocytes isolated from those participants given ivermectin showed no difference in their ability to kill Brugia malayi microfilariae in vitro. CONCLUSIONS: Overall, our data do not support a direct effect of ivermectin, when given at the dose used in current filarial elimination programmes, on the human immune system. Trial registration ClinicalTrials.gov NCT03459794 Registered 9th March 2018, Retrospectively registered https://clinicaltrials.gov/ct2/show/NCT03459794?term=NCT03459794&draw=2&rank=1 .

Hypoxia and Anoxia Tolerance in the Annual Killifish Austrofundulus limnaeus.

Embryos of the annual killifish Austrofundulus limnaeus are routinely exposed to oxygen limitation during development and are extremely tolerant of anoxia. Importantly, tolerance of anoxia is not strictly associated with entrance into metabolic dormancy associated with diapause II, but rather any embryo will respond to anoxia by entering into a state of anoxia-induced quiescence. Hypoxia causes a reduction in the rate of development, reduced heart rates, and reduced capacities for metabolic enzyme activity in both aerobic and anaerobic pathways. Embryos of A. limnaeus begin life as oxyconformers, and transition into oxyregulators near the completion of embryonic development. As this transition occurs, extreme anoxia tolerance is lost. The rate of early development is independent of oxygen partial pressure, despite the fact that the embryos are oxyconformers. This suggests a contribution from anaerobic pathways to support early development. However, the specific pathways supporting this metabolism are unknown. The response of A. limnaeus embryos to hypoxia and anoxia is unique compared to other fishes and most other vertebrates, and thus future studies on this species may lend insight into novel mechanisms that support survival during prolonged oxygen limitation.