Objectives/Goals: The overall goal of this project is to determine bacterial transcriptional signatures from clinical sputum and assess their potential to monitor treatment response and predict the outcome of drug therapy in patients with tuberculosis (TB). Methods/Study Population: We are developing a novel transcript capture sequencing (TC-Seq) approach to sequence the mRNA of Mycobacterium tuberculosis (Mtb) and analyze transcriptomes from clinical samples containing minimal amounts of bacterial RNA. This protocol generates single-stranded biotinylated probes from Mtb DNA. Probes are hybridized to and allow enrichment of Mtb-specific mRNA within next-generation RNA sequencing libraries. We will apply TC-Seq to sputum samples collected throughout an 18-month Phase II clinical trial investigating response to TB treatment to compare the transcriptome of Mtb between patients whose treatment results in cure or relapse. Results/Anticipated Results: We have refined a technique to generate biotinylated probes starting from DNA of lab grown Mtb. This protocol achieves robust and unbiased sampling of the Mtb transcriptome from mixed samples containing both human and Mtb RNA. Preliminary sequencing of clinical sputum collected pretreatment has generated 1–4 million Mtb-specific reads, a sequencing depth that allows examination of the entire bacterial transcriptome. We will measure differential gene expression before and during treatment as well as between cure and relapse cases. These results will allow us to characterize bacterial response to treatment and identify bacterial markers that correlate with relapse. Discussion/Significance of Impact: Understanding Mtb activity during treatment will offer new ways to assess the efficacy of different treatment regimens. Crucially, identifying clear bacterial markers that demarcate a cure or relapse outcome will have a significant impact on determining patient eligibility for shorter drug therapy.

Objectives/Goals: Digital recruitment can improve participant engagement in medical research, but its potential to introduce demographic and socioeconomic biases is unclear. This study investigates pathways participants took during a digital recruitment workflow in neurology, examining potential associations with socioeconomic and demographic factors. Methods/Study Population: As part of an ongoing study aiming to remotely capture speech from patients with neurologic disease, most participants seen in neurology on our campus are invited to complete a self-administered speech examination. We exported participant data from Epic (semi-automated identification and invitation), Qualtrics (eligibility screening), the participant tracking database (consent), and the recording platform (completion) for March to July 2024. Data visualization was performed using a Sankey diagram. Socioeconomic status was assessed using the housing-based socioeconomic status (HOUSES) index and area deprivation index (ADI) national rank. Kruskal–Wallis and Wilcoxon rank-sum tests were used to compare the median age, socioeconomic indices, and time taken to reach different steps of the study. Results/Anticipated Results: Of the 5846 invited participants, 57% were from urban areas, 23% from rural areas, and 20% from urban clusters. Most did not read/respond (2739) or declined (1749) the initial invitation via Epic. Of the 1358 interested participants, 415 completed the study. Participants from urban areas completed enrollment steps faster than those from rural areas and urban clusters, though the variance was large (42.6 ± 41.4 days vs. 50.6 ± 42.2 days and 50 ± 43.9 days, respectively; p  =  0.030). Female participants took longer to complete enrollment than males (48.7 ± 44 days vs. 40.5 ± 38.8 days; p  =  0.026). Participants who successfully finished the study had significantly lower ADI national ranks compared to other common pathways (40.6 ± 19; p  =  0.0021). No associations were found with the HOUSES indices. Discussion/Significance of Impact: Our findings support differences in participant engagement, with urban participants and males more likely to complete enrollment steps. Those who finished the study were less disadvantaged suggesting potential bias in digital recruitment. These findings can inform strategies to improve digital recruitment in neurology research.

Objectives/Goals: To present findings from a focus group study that evaluate clinical research professionals’ (CRPs) team science learning preferences. The study aims to better understand CRPs’ experiential perceptions of team science skills, training gaps, team cohesion, conflict, and contributions for their preferred team science training. Methods/Study Population: This study targeted CRPs across various roles in Academic Health Centers via focus groups. The focus groups will assess current skills, identify training gaps, and share experiences on team cohesion, team conflict, team contribution, and their thoughts and perceptions about clinical research professional team science training. The focus groups will be held via Zoom in the Autumn of 2024 with volunteer participants from an initial survey that was conducted earlier in 2024. We will report on combined data from multiple 90-minute focus groups, with approximately 6 participants per session. Results/Anticipated Results: The focus group facilitator’s guide includes questions informed by the CRP team science learning needs assessment results and other questions on team issues that would benefit from focused training. Focus group methods and demographic characteristics of the participants by role and experience level will also be presented. Qualitative analyses of recorded focus-group discussions will present key themes by demographic groups, and as a whole, these data will contribute to the development of CRP team science educational programs and toolkits. Discussion/Significance of Impact: CRPs are vital members of clinical translational science teams. Overlooking CRP team science training can negatively affect the efficiency and effectiveness of the clinical translational science enterprise. CRP team science skills will foster a more collaborative and productive research environment.

The Cox duration model serves as the basis for more complex duration models like competing risks, repeated events, and multistate models. These models make a number of assumptions, many of which can be assessed empirically, sometimes for substantive ends. We use Monte Carlo simulations to show the order in which practitioners assess these assumptions can impact the model’s final specification, and ultimately, can produce misleading inferences. We focus on three assumptions regarding model specification decisions: proportional hazards (PH), stratified baseline hazards, and stratum-specific covariate effects. Our results suggest checking the PH assumption before checking for stratum-specific covariate effects tends to produce the correct final specification most frequently. We reexamine a recent study of the timing of GATT/WTO applications to illustrate our points.

Dientamoeba fragilis (D. fragilis) is an intestinal protozoan parasite with uncertain pathogenic potential. In the United States, data on D. fragilis in the era of molecular detection are limited. The aim of this retrospective chart review was to evaluate the epidemiology and clinical characteristics of D. fragilis cases identified using polymerase chain reaction assays between 2016 and 2024 at our academic medical centre located in Utah. We identified 28 unique cases with varying gastrointestinal symptomatology including diarrhoea, abdominal pain, nausea, vomiting, and bloating. Approximately half (52%) of patients with follow-up data demonstrated improvement in symptoms following initial treatment for D. fragilis. The overall prevalence of D. fragilis was low among those tested (0.6% positivity). Additional research, including case-control studies, is needed to better describe the etiologic role of D. fragilis.

Empirical Bayes methods are shown to provide a practical alternative to standard least squares methods in fitting high dimensional models to sparse data. An example concerning prediction bias in educational testing is presented as an illustration.

Reporting effect size index estimates with their confidence intervals (CIs) can be an excellent way to simultaneously communicate the strength and precision of the observed evidence. We recently proposed a robust effect size index (RESI) that is advantageous over common indices because it’s widely applicable to different types of data. Here, we use statistical theory and simulations to develop and evaluate RESI estimators and confidence/credible intervals that rely on different covariance estimators. Our results show (1) counter to intuition, the randomness of covariates reduces coverage for Chi-squared and F CIs; (2) when the variance of the estimators is estimated, the non-central Chi-squared and F CIs using the parametric and robust RESI estimators fail to cover the true effect size at the nominal level. Using the robust estimator along with the proposed nonparametric bootstrap or Bayesian (credible) intervals provides valid inference for the RESI, even when model assumptions may be violated. This work forms a unified effect size reporting procedure, such that effect sizes with confidence/credible intervals can be easily reported in an analysis of variance (ANOVA) table format.

Control of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa spread in healthcare settings begins with timely and accurate laboratory testing practices. Survey results show most Veterans Affairs facilities are performing recommended tests to identify these organisms. Most facilities report sufficient resources to perform testing, though medium-complexity facilities report some perceived barriers.

Background: We performed a network meta-analysis of randomized controlled trials to assess the comparative effectiveness of available pharmacological prophylaxis for migraines. Methods: We searched MEDLINE, EMBASE, Web of Science, Scopus, PsycINFO and Cochrane CENTRAL up to October 2023 for trials that: (1) enrolled adults diagnosed with chronic migraine, and (2) randomized them to any prophylactic medication vs. another medication or placebo. We performed a random-effects frequentist network meta-analysis for patient-important outcomes. Results: We included 193 randomized trials. Compared to placebo, CGRP monoclonal antibodies (mean difference [MD] -1.7, 95%CI: -1.1 to -2.2), injection of botulinum toxin (MD -1.8, 95%CI: -0.7 to -2.9), calcium channel blockers (MD -1.8, 95%CI: -0.5 to -3.0), beta-blockers (MD -1.4, 95%CI: -0.2 to -2.6), and anticonvulsants (MD -1.1, 95%CI: -0.4 to -1.8) were among the most effective treatments in reducing average number of headache days per months. Anticonvulsants (Risk Ratio [RR] 2.3, 95%CI: 1.8 to 3.0), calcium channel blockers (RR 1.8, 95% CI: 1.1 to 3.1), and tricyclic antidepressants (RR 2.3, 95% CI: 1.3 to 3.8) showed the highest risk of discontinuation due to adverse events. Conclusions: Our findings suggest that CGRP inhibitors, botulinum toxin, and beta-blockers may provide the greatest benefit, and tolerability, for reducing the frequency of migraine headaches.

Monitoring indicators of children`s diet quality at the national level is imperative to examine if a country is on track to achieving children`s global nutrition targets and fulfilling the related Sustainable Development Goals. Despite the importance of diet quality in early life and its impact in health and wellbeing throughout the life course, Aotearoa New Zealand has limited information that is nationally representative or generalizable on children`s diet quality, especially among children under 5 years old. The only national child nutrition survey conducted to date took place two decades ago and involved children 5 years of age and older. We have previously used data collected by the Growing in Up in New Zealand cohort study, which is nationally generalizable, to partially fill historic gaps in knowledge of children`s diet and feeding practices in the first five years of life. Information on breastfeeding initiation, duration and exclusivity, timing of food introduction and whole-of-diet adherence to National Food and Nutrition Guidelines have been previously published 1–3. This work intends to complement information on NZ children`s diet quality by examining the cohort`s dietary patterns (DPs) at 9- (n = 6,259), 24- (n = 6,292), and 54-months (n = 6,131) and their maternal sociodemographic and health behaviour determinants. At all time-points, children`s DPs were identified using principal components analyses. Multivariate linear regressions were performed to examine the associations between each DP and the maternal variables. At 9-, 24- and 54-months two distinct DPs were identified, explaining, 36.4%, 35.3% and 33.6% of children`s intake variability, respectively. The Refined high in sugar and salt DP, at all time-points, was characterised by high positive loadings in white/refined breads and cereals and items with high content of sugar, sodium, and fat. At 24-months, the Refined high in sugar and salt DP also had high positive loading in the protein group. The Fruit/Vegetables DP, at all time-points, had high positive loadings for fruits and vegetables (with type varying across time-points). The Fruit/Vegetables DP had high loading in whole grain options of breads and cereals at 24-months and positive loading in the protein group at 9- and 54-months. High scores on the Refined high in sugar and salt DP at the three time-points were associated with maternal smoking habits, maternal education level, ethnicity, and maternal scores in the “Junk” and “Traditional/White bread” DPs (obtained at the antenatal maternal interview). High children’s scores on the Fruit/Vegetables DP, at all time-points, were associated with the maternal antenatal score in the “Health Conscious” DP. Findings support that policies and interventions aiming to improve early life diets in NZ should be culturally safe and support mothers’ access to formal education, healthy diets, and smoking cessation.

Decreasing the time to contact precautions (CP) is critical to carbapenem-resistant Enterobacterales (CRE) prevention. Identifying factors associated with delayed CP can decrease the spread from patients with CRE. In this study, a shorter length of stay was associated with being placed in CP within 3 days.

OBJECTIVES/GOALS: The objectives of the Academy of Community Reviewers (ACR) serve to: (1) provide comprehensive education and training to community members about clinical research and the community review process for clinical research grants; and (2) collaborate with the community in the development of the training to ensure benefice and meaningful engagement. METHODS/STUDY POPULATION: This training targets community members who will serve as future grant reviewers for The Ohio State University Center for Clinical Translational Science (CCTS) pilot grant submissions, other grant submissions and as expert consultants on other projects needing community perspectives. In 2019 and 2020, this training was offered as a live session. Thirty-eight community reviewers were trained and have served as grant reviewers and consultants on over 70 projects. Based on feedback of former graduates, time demands, logistics, and technology advances warranted transitioning the course to an online learning platform. ACR graduates were consulted in course redesign and updates. Course revisions include material on DEIA, implicit bias and health equity in clinical research with narrated lectures. RESULTS/ANTICIPATED RESULTS: Each of the 7 modules (including a total of 15 submodules) will have a brief summary knowledge check. The module “How to incorporate diversity, equity, inclusion and accessibility in health research” will invite trainees to independently explore their own social identity and biases through a guided exercise. The last (7th) module will have interactive opportunities for submitting grant reviews and participation in an online grant review session, geared to The Ohio State University CCTS. ACR graduates have been invited to consult on educational material and pilot the new course. Demographic, knowledge assessments and module evaluations will be collected. An overall course evaluation and focus group interviews with graduates will also be analyzed for quality improvement and contributions in grant reviews. DISCUSSION/SIGNIFICANCE: The increased accessibility of the ACR course will foster more inclusive community engagement and support the development of clinical and translational research that is innovative, efficient, equitable, and relevant to its beneficiaries. This in depth community reviewer training has been designed to be used and customized to other CTSA Hubs.