Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

Background: Antibiotics are frequently prescribed in patients with COVID-19 infections to treat secondary bacterial pneumonia. The pneumonia panel (PNP) is a molecular diagnostic tool that rapidly detects 33 bacterial and viral targets. The utility of this panel in COVID-19 patients and how it may direct antibiotic use is unknown. We sought to understand the utilization of PNP in patients with COVID-19 pneumonia over time by comparing clinical parameters, microbiologic results, and antibiotic use between May–December 2020 and January–July 2022. Methods: We implemented the PNP in May 2020 with antimicrobial stewardship guidance, provider education, and order restriction to critical care and infectious disease clinicians. From February–July 2021 prescribers received regular structured antimicrobial stewardship feedback regarding PNP results; from August 2021 to January 2022, no antimicrobial stewardship feedback was provided; from February to July 2022, intermittent feedback was provided. We compared PNP and culture results from sputum or bronchoalveolar lavage samples and antibiotic use and modification within 24 hours of PNP result from patients with confirmed COVID-19 pneumonia between May–December 2020 and January–July 2022. Clinical data and antibiotic use were abstracted through chart review. We excluded patients who died within 72 hours of PNP, those who had concurrent nonpulmonary infections, and those whose COVID-19 test was >30 days prior. Results: We included 114 patients in 2020 and 71 patients in 2022. The overall median age was 61 years, 71% were male, and 66% were mechanically ventilated without statistical differences between the cohorts, including their comorbidities. Acute or worsening hypoxia remained the predominant indication for PNP (77% in 2020 vs 75% in 2022, NS). The median number of days between admission and PNP was 4 (IQR, 1–8) in 2020 versus 3 (IQR, 1–7), and the difference was not significant. PNP and culture results in Table 1 show that Staphylococcus aureus and Hemophilus influenzae were the pathogens most commonly identified. Table 2 describes empiric prescribing and modifications for commonly prescribed antibiotics. Prescribers used empiric cefepime and ceftriaxone more in 2020 and vancomycin more in the 2022 group; however, these were not statistically significant. Cefepime de-escalation was more common in 2022 (53% vs 28%; P = .03). Antibiotic modifications within 24 hours of PNP remained similar in 2020 vs 2022. Although vancomycin cessation was more common in 2020 (78%) versus 2022 (57%), the difference was not statistically significant. Conclusions: With ASP guidance, PNP may be a useful tool to stop or target antibiotics for secondary bacterial pneumonia in COVID-19 pneumonia. Early vancomycin cessation (prior to culture results) may be an enduring consequence of PNP implementation.

Disclosures: None

People often use tools for tasks, and sometimes there is uncertainty about whether a given task can be completed with a given tool. This project explored whether, when, and how people’s optimism about successfully completing a task with a given tool is affected by the contextual salience of a better or worse tool. In six studies, participants were faced with novel tasks. For each task, they were assigned a tool but also exposed to a comparison tool that was better or worse in utility (or sometimes similar in utility). In some studies, the tool comparisons were essentially social comparisons, because the tool was assigned to another person. In other studies, the tool comparisons were merely counterfactual rather than social. The studies revealed contrast effects on optimism, and the effect worked in both directions. That is, worse comparison tools boosted optimism and better tools depressed optimism. The contrast effects were observed regardless of the general type of comparison (e.g., social, counterfactual). The comparisons also influenced discrete decisions about which task to attempt (for a prize), which is an important finding for ruling out superficial scaling explanations for the contrast effects. It appears that people fail to exclude irrelevant tool-comparison information from consideration when assessing their likelihood of success on a task, resulting in biased optimism and decisions.

Neurobiological and social-contextual influences shape children’s adjustment, yet limited biopsychosocial studies have integrated temporal features when modeling physiological regulation of emotion. This study explored whether a common underlying pattern of non-linear change in respiratory sinus arrhythmia (RSA) across emotional scenarios characterized 4–6 year-old children’s parasympathetic reactivity (N = 180). Additionally, we tested whether dynamic RSA reactivity was an index of neurobiological susceptibility or a diathesis in the association between socioeconomic status, authoritarian parenting, and the development of externalizing problems (EP) and internalizing problems over two years. There was a shared RSA pattern across all emotions, characterized by more initial RSA suppression and a subsequent return toward baseline, which we call vagal flexibility (VF). VF interacted with parenting to predict EP. More authoritarian parenting predicted increased EP two years later only when VF was low; conversely, when VF was very high, authoritarian mothers reported that their children had fewer EP. Altogether, children’s patterns of dynamic RSA change to negative emotions can be characterized by a higher order factor, and the nature by which VF contributes to EP depends on maternal socialization practices, with low VF augmenting and high VF buffering children against the effects of authoritarian parenting.

The expansion of the Umayyad and Abbasid Caliphates (seventh to ninth centuries AD) brought diverse regions from the Indus Valley to the Eurasian Steppe under hegemonic control. An overlooked aspect of this political process is the subsequent translocation of species across ecological zones. This article explores species introduction in the early Islamic world, presenting the first archaeological evidence for domestic water buffalo in the Caucasus—identified using zooarchaeological and ZooMS methods on material from the historical site of Bardhaʿa in Azerbaijan. We contextualise these finds with historical accounts to demonstrate the exploitation of medieval marginal zones and the effects of centralised social reorganisation upon species dispersal.