Low- and middle-income countries (LMICs) face significant challenges in the control of COVID-19, given limited resources, especially for inpatient care. In a parallel effort to that for vaccines, the identification of therapeutics that have near-term potential to be available and easily administered is critical. Using the United States, European Union, and WHO clinical trial registries, we reviewed COVID-19 therapeutic agents currently under investigation. The search was limited to oral or potentially oral agents, with at least a putative anti-SARS-CoV-2 virus mechanism and with at least five registered trials. The search yielded 1,001, 203, and 1,128 trials, in the United States, European Union, and WHO trial registers, respectively. These trials covered 13 oral or potentially oral repurposed agents that are currently used as antimicrobials and immunomodulatory therapeutics with established safety profiles. The available evidence regarding proposed mechanism of actions, potential limitations, and trial status is summarized. The results of the search demonstrate few published studies of high quality, a low proportion of trials completed, and the vast majority with negative results. These findings reflect limited investment in COVID-19 therapeutics development compared with vaccines. We also identified the need for better coordination of trials of accessible agents and their combinations in LMICs. To prevent COVID-19 from becoming a neglected tropical disease, there is critical need for rapid and coordinated effort in the evaluation and deployment of those agents found to be efficacious.

Low- and middle-income countries (LMICs) face significant challenges in the control of COVID-19, given limited resources, especially for inpatient care. In a parallel effort to that for vaccines, the identification of therapeutics that have near-term potential to be available and easily administered is critical. Using the United States, European Union, and World Health Organization clinical trial registries, we reviewed COVID-19 therapeutic agents currently under investigation. The search was limited to oral or potentially oral agents, with at least a putative anti-SARS-CoV-2 virus mechanism, and with at least 3 registered trials. We describe the available evidence regarding agents that met these criteria and additionally discuss the need for additional investment by the global scientific community in large well-coordinated trials of accessible agents and their combinations in LMICs. The search yielded 636, 175, and 930 trials, in the US, EU, and WHO trial registers, respectively. These trials covered 17 oral or potentially oral repurposed agents that are currently used as antimicrobials and immunomodulatory therapeutics and therefore have established safety. The available evidence regarding proposed mechanism of actions, clinical efficacy, and potential limitations is summarized. We also identified the need for large well-coordinated trials of accessible agents and their combinations in LMICs. Several repurposed agents have potential to be safe, available, and easily administrable to treat COVID-19. To prevent COVID-19 from becoming a neglected tropical disease, there is critical need for rapid and coordinated effort in their evaluation and the deployment of those found to be efficacious.

Background:The evaluation and treatment of children with septic arthritis (SA) is challenging and requires an organized approach to address the spectrum of pathogens which appear to aggregate in age-specific groups. Although evidence-based guidelines have recently been published for the evaluation and treatment of children with acute hematogenous osteomyelitis, there is a relative dearth of literature devoted exclusively to SA. Methods: Recently published guidance for the evaluation and treatment of children with SA was reviewed and evaluated with respect to pertinent clinical questions to summarize what is new in this area of practice for pediatric orthopaedic surgeons. Results: Evidence suggests that there is a profound difference between children with primary SA and those who have contiguous osteomyelitis. This disruption of the commonly accepted paradigm of a continuum of osteoarticular infections has important implications in the evaluation and treatment of children with primary SA. Clinical prediction algorithms have been established to help determine the applicability of magnetic resonance imaging during the evaluation of children suspected to have SA. Antibiotic duration for SA has been recently studied with some evidence in favor of short-course parenteral followed by short-course oral therapy may be successful if the pathogen is not methicillin-resistant Staphylococcus aureus. Conclusion: Recent studies of children with SA have provided better guidance for evaluation and treatment to improve diagnostic accuracy, processes of evaluation, and clinical outcomes. Level of Evidence: Level 4.