PURPOSE The self-controlled risk interval design is commonly used to assess the association between an acute exposure and an adverse event of interest, implicitly adjusting for fixed, non-time-varying covariates. Explicit adjustment needs to be made for time-varying covariates, for example, age in young children. It can be performed via either a fixed or random adjustment. The random-adjustment...

high-dose extended-interval dosage (hded) regimen of aminoglycosides is now considered as the standard dosage strategy in sepsis. although safety and efficacy of this dosing regimen is well studied, but new experiments show increased the risk of resistance development associated with %t>mic less than 60% of the dosing interval following extended interval dosing. moreover, limited information is...