The overuse and inappropriate use of antimicrobials have led to environmental waste and drug shortages. This challenges the ecological and economical sustainability of our healthcare system and worsens antimicrobial resistance.

Antimicrobial stewardship programs (ASP) commonly consider the cost of drug acquisition but may be failing to recognize the hidden costs of multi-dose intravenous regimens including additional nursing administration time, tubing and fluids, and potentially increased hospital length of stay. They also rarely consider the environmental impact of medical waste creation and disposal, which contributes to the global antimicrobial resistance crisis. These costs are harder to calculate but crucial to a comprehensive assessment of a medication’s total impact. In this invited commentary, we provide an example of a stewardship evaluation at our institution focused on changing from meropenem (MER) to ertapenem (ETP) for infections caused by extended-spectrum beta-lactamase producing organisms. We found that despite an increase in acquisition costs, changing from MER to ETP is associated with overall savings and decreased waste production. A secondary analysis suggests that stay length may also be improved with this substitution.

We present a holistic approach to antimicrobial stewardship that considers the total cost of an antimicrobial. By broadening their view to include hidden costs and secondary effects, ASPs can further demonstrate their value to the healthcare system, reduce resistance, and improve their environmental impact.

Working memory encompasses the limited incoming information that can be held in mind for cognitive processing. To date, we have little information on the effects of bilingualism on working memory because, absent evidence, working memory tasks cannot be assumed to measure the same constructs across language groups. To garner evidence regarding the measurement equivalence in Spanish and English, we examined second-grade children with typical development, including 80 bilingual Spanish–English speakers and 167 monolingual English speakers in the United States, using a test battery for which structural equation models have been tested – the Comprehensive Assessment Battery for Children – Working Memory (CABC-WM). Results established measurement invariance across groups up to the level of scalar invariance.

OBJECTIVES/GOALS: Fluid boluses are administered to hypotensive, critically ill children but may not reverse hypotension, leading to delay of vasoactive infusion, end-organ damage, and mortality. We hypothesize that a machine learning-based model will predict which children will have sustained response to fluid bolus. METHODS/STUDY POPULATION: We will conduct a single-center retrospective observational cohort study of hypotensive critically ill children who received intravenous isotonic fluid of at least 10 ml/kg within 72 hours of pediatric intensive care unit admission between 2013 and 2023. We will extract physiologic variables from stored bedside monitors data and clinical variables from the EHR. Fluid responsive (FR) will be defined as a MAP increase by 310%. We will construct elastic net, random forest, and a long short-term memory models to predict FR. We will compare complicated course (multiple organ dysfunction on day 7 or death by day 28) between: 1) FRs and non-FRs, 2) predicted FRs and non-FRs, 3), FRs and non-FRs stratified by race/ethnicity, and 4) FRs and non-FRs stratified by sex as a biologic variable. RESULTS/ANTICIPATED RESULTS: We anticipate approximately 800 critically ill children will receive 2,000 intravenous isotonic fluid boluses, with a 60% rate of FR. We anticipate being able to complete all three models. We hypothesize that the model with the best performance will be the long short-term memory model and the easiest to interpret will be the tree-based random forest model. We hypothesize non-FRs will have a higher complicated course than FRs and that predicted non-FRs will have a higher rate of complicated course than FRs. Based on previous adult studies, we hypothesize that there will be a higher rate of complicated course in patients of black race and/or Hispanic ethnicity when compared to non-Hispanic white patients. We also hypothesize that there will be no difference in complicated course when comparing sex as a biologic variable. DISCUSSION/SIGNIFICANCE: We have a critical need for easily-deployed, real-time prediction of fluid response to personalize and improve resuscitation for children in shock. We anticipate the clinical application of such a model will decrease time with hypotension for critically ill children, leading to decreased morbidity and mortality.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Participant recruitment for research is a persistent bottleneck that can be improved by leveraging electronic health records (EHRs). Despite emerging evidence for various EHR-driven approaches, guidance for those attempting to select and use such approaches is limited. The national Recruitment Innovation Center established the EHR Recruitment Consult Resource (ERCR) service line to support multisite studies through implementation of EHR-driven recruitment strategies. As the ERCR, we evolved a guide through 17 consultations over 3 years with multisite studies recruiting in diverse biomedical research domains. We assessed literature and engaged domain experts to identify five key EHR-driven recruitment strategies: direct to patient messages, candidate lists for mailings/calls, direct to research alerts, point of care alerts, and participant registries. Differentiating factors were grouped into factors of study population, study protocol and recruitment workflows, and recruitment site capabilities. The decision matrix indicates acceptable or preferred strategies based on the differentiating factors. Across the ERCR consultations, candidate lists for mailing or calls were most common, participant registries were least frequently recommended, and for some studies no EHR-driven recruitment was recommended. Comparative effectiveness research is needed to refine further evidence for these and potentially new strategies to come.

Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.

Cities around the world are responding to aging populations and equity concerns for older people by developing age-friendly communities plans, following the World Health Organization’s guidelines. Such plans, however, often fail to account for the wide diversity of older people in cities, with the result that some older people, including Indigenous older people, do not see their needs reflected in age-friendly planning and policies. This article reports on a study involving 10 older First Nations and Métis women in the city of Prince George, Canada, comparing the expressed needs of these women with two age-friendly action plans: that of the city of Prince George, and that of the Northern Health Authority. Four main categories were raised in a group discussion and interview with these women at the Prince George Native Friendship Centre: availability of health care services, accessibility and affordability of programs and services, special roles of Indigenous Elders, and experiences of racism and discrimination. There are many areas of synergy between the needs expressed by the women and the two action plans; however, certain key areas are missing from the action plans; in particular, specific strategies for attending to the needs of Indigenous and other older populations who often feel marginalized in health care and in age-friendly planning.