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The search for clinically effective antivirals against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is ongoing. Repurposing of drugs licensed for non–coronavirus disease 2019 (COVID-19) indications has been extensively investigated in laboratory models and in clinical studies with mixed results.

Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs).

The suboptimal sensitivity and specificity of available diagnostic methods for scabies hampers clinical management, trials of new therapies and epidemiologic studies. Additionally, parasitologic diagnosis by microscopic examination of skin scrapings requires sample collection with a sharp scalpel blade, causing discomfort to patients and difficulty in children. Polymerase chain reaction (PCR)-based diagnostic assays, combined with non-invasive sampling methods, represent an attractive approach.

Households are known to be high-risk locations for the transmission of communicable diseases. Numerous modelling studies have demonstrated the important role of households in sustaining both communicable diseases outbreaks and endemic transmission, and as the focus for control efforts. However, these studies typically assume that households are associated with a single dwelling and have static membership.

Despite several calls for greater inclusion of pregnant people in non-obstetric clinical trials, their systematic exclusion remains common practice. Excluding pregnant individuals from clinical trials may result in unintended consequences such as inadequate treatment of medical conditions in pregnancy, inappropriate dosing of medications, and investigational therapies being used off-label outside of the context of a clinical trial, risking adverse events in the absence of demonstrated efficacy.

SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have limited the utility of traditional approaches to randomised controlled trials.

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%-30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection.

Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. The objective was to determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children.

Obesity was a risk factor for severe COVID-19 in children during early outbreaks of ancestral SARS-CoV-2 and the Delta variant. However, the relationship between obesity and COVID-19 severity during the Omicron wave remains unclear.

Life-threatening invasive infections caused by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis (SDSE) are unpredictable, frequently fatal, and are increasing in incidence globally. In the absence of evidence from randomized controlled trials (RCTs), clinical management for these conditions varies. Understanding current management approaches and areas of clinical equipoise will inform planning of feasible high-impact RCTs.