Background Older adult delirium is often unrecognized in the emergency department (ED), yet the most compelling research questions to overcome knowledge‐to‐practice deficits remain undefined. The Geriatric Emergency care Applied Research (GEAR) Network was organized to identify and prioritize delirium clinical questions. Methods GEAR identified and engaged 49 transdisciplinary stakeholders including emergency physicians, geriatricians, nurses, social workers, pharmacists, and patient advocates. Adhering to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses for Scoping Reviews, clinical questions were derived, medical librarian electronic searches were conducted, and applicable research evidence was synthesized for ED delirium detection, prevention, and management. The scoping review served as the foundation for a consensus conference to identify the highest priority research foci. Results In the scoping review, 27 delirium detection “instruments” were described in 48 ED studies and used variable criterion standards with the result of delirium prevalence ranging from 6% to 38%. Clinician gestalt was the most common “instrument” evaluated with sensitivity ranging from 0% to 81% and specificity from 65% to 100%. For delirium management, 15 relevant studies were identified, including one randomized controlled trial. Some intervention studies targeted clinicians via education and others used clinical pathways. Three medications were evaluated to reduce or prevent ED delirium. No intervention consistently prevented or treated delirium. After reviewing the scoping review results, the GEAR stakeholders identified ED delirium prevention interventions not reliant on additional nurse or physician effort as the highest priority research. Conclusions Transdisciplinary stakeholders prioritize ED delirium prevention studies that are not reliant on health care worker tasks instead of alternative research directions such as defining etiologic delirium phenotypes to target prevention or intervention strategies.

Predicting how species will respond to selection pressures requires understanding the factors that constrain their evolution. We use genome engineering of Drosophila to investigate constraints on the repeated evolution of unrelated herbivorous insects to toxic cardiac glycosides, which primarily occurs via a small subset of possible functionally-relevant substitutions to Na+,K+-ATPase. Surprisingly, we find that frequently observed adaptive substitutions at two sites, 111 and 122, are lethal when homozygous and adult heterozygotes exhibit dominant neural dysfunction. We identify a phylogenetically correlated substitution, A119S, that partially ameliorates the deleterious effects of substitutions at 111 and 122. Despite contributing little to cardiac glycoside-insensitivity in vitro, A119S, like substitutions at 111 and 122, substantially increases adult survivorship upon cardiac glycoside exposure. Our results demonstrate the importance of epistasis in constraining adaptive paths. Moreover, by revealing distinct effects of substitutions in vitro and in vivo, our results underscore the importance of evaluating the fitness of adaptive substitutions and their interactions in whole organisms.

Compared with drip-and-ship, the trip-and-treat model demonstrated shorter treatment times for endovascular therapy in our series. The trip-and-treat model offers a valid alternative to current interhospital stroke transfers in urban environments.

Predicting how species will respond to selection pressures requires understanding the factors that constrain their evolution. We use genome engineering of Drosophila to investigate constraints on the repeated evolution of unrelated herbivorous insects to toxic cardiac glycosides, which primarily occurs via a small subset of possible functionally-relevant substitutions to Na + ,K + -ATPase. Surprisingly, we find that frequently observed adaptive substitutions at two sites, 111 and 122, are lethal when homozygous and adult heterozygotes exhibit dominant neural dysfunction. We identify a phylogenetically correlated substitution, A119S, that partially ameliorates the deleterious effects of substitutions at 111 and 122. Despite contributing little to cardiac glycoside-insensitivity in vitro, A119S, like substitutions at 111 and 122, substantially increases adult survivorship upon cardiac glycoside exposure. Our results demonstrate the importance of epistasis in constraining adaptive paths. Moreover, by revealing distinct effects of substitutions in vitro and in vivo, our results underscore the importance of evaluating the fitness of adaptive substitutions and their interactions in whole organisms.