Alexandra M. Klomhaus

Background: Early in the children’s COVID-19 rollout in the United States, racial and ethnic vaccination rate disparities were evident. Based on COVID-19 communication literature and qualitative interviews with Hispanic parents, we developed a mobile phone–delivered digital intervention to address factors associated with low vaccine confidence. Objective: We conducted a community-based randomized controlled trial of a digital intervention called MiVacunaLA/MyShotLA to increase COVID-19 vaccine uptake among Hispanic children. The fully automated digital intervention was designed in collaboration with community organizations and linguistically and culturally tailored to meet the informational needs of Hispanic caregivers. The intervention focused on families with unvaccinated children 5 to 11 years old but was offered to families with any unvaccinated children 17 years or younger. Methods: Participants were recruited with community organization partners and trained parent ambassadors via an open online screener. The 4-week intervention consisted of 3 SMS text messages with culturally and linguistically tailored educational information weekly. Intervention materials were delivered digitally through a closed online platform. Study team members were blinded. We used a difference-in-difference model with an intention-to-treat approach. The primary outcome was self-reported COVID-19 vaccine uptake among household children collected via online questionnaires. Secondary outcomes included COVID-19 vaccine knowledge, vaccine trust, and measures of participant engagement. We conducted a sensitivity analysis using the treatment-on-the-treated approach. Results: In total, 254 participants completed the baseline survey (128 control and 126 intervention). The average participant age was 34 (SD 6.3) years with an average of 1.7 (SD 0.8) minors in the household, and among households, 62.2% (n=158) reported having children aged 5 to 11 years old. Most participants (n=207, 81.5%) reported English as their primary language. We found a statistically significant difference of 13.3% (95% CI 0.3%-26.4%; P =.04) points in self-reported vaccine uptake between intervention and control groups among caregivers of Hispanic children aged 5 to 11 years old. We also found a statistically significant point difference of 14.3% (95% CI 0%‐23.7%; P =.003) between intervention and control groups in trust of governmental approval processes for the children’s COVID-19 vaccine. Most participants reported that the weekly digital videos and educational information were “very” (892/1031, 86.5%) or “extremely” (888/1019, 87.1%) useful. Conclusions: MiVacunaLA demonstrates that a culturally tailored, community-based, mobile phone–delivered vaccine educational intervention can increase COVID-19 vaccine uptake among Hispanic children and improve caregivers’ trust in governmental vaccine processes. MiVacunaLA is innovative in its integration of community-informed design with a fully automated, mobile phone–centric format and builds on prior literature by prospectively evaluating a culturally tailored, SMS text messaging–linked web curriculum in a community setting. Findings provide evidence that scalable, low-cost, digital strategies can measurably improve trust and uptake in a population facing persistent vaccination gaps. Real-world implications include the portability and adaptability of this approach across diverse communities and settings to support timely, community-engaged vaccination efforts for broader applicability and scalability in public health.

Background: Suicide is the second-leading cause of US childhood mortality after 9 years of age. The accurate measurement of pediatric emergency service use for self-injurious thoughts and behaviors (SITB) remains challenging, as diagnostic codes undercount children. This measurement gap impedes public health and prevention efforts. Current research has not established which combination of electronic health record data elements achieves both high detection accuracy and consistent performance across youth populations. Objective: This study aims to (1) compare the detection accuracy of electronic health record−based methods for identifying SITB-related pediatric emergency department (ED) visits: basic structured data ( International Classification of Diseases Version 10, Clinical Modification codes, chief concern), comprehensive structured data, clinical note text with natural language processing, and hybrid approaches combining structured data with notes; and (2) for each method, measure variability in detection by youth demographics and underlying mental health diagnosis. Methods: Multiple human experts reviewed clinical records of 3828 pediatric mental health emergency visits (28,861 clinical notes) to a large health system with 2 EDs (June 2022-October 2024). The reviewers used the Columbia Classification Algorithm for Suicide Assessment to label the presence of SITB at the visit. Random forest classifiers were developed using 3 data modalities: (1) structured data (low-dimensional [International Classification of Diseases codes and chief concerns], medium-dimensional [adding Columbia Suicide Severity Rating Scale screening or mental health diagnoses], and high-dimensional [all structured data or augmented case surveillance, aCS]); (2) text data (general-purpose natural language processing, medical text-specific trained natural language processing, and Large Language Model Meta AI−derived scores), and (3) hybrid data (combining aCS with each text approach). Model performance was evaluated using area under the receiver operating characteristic curve (AUROC). Results: Of the 3828 visits, 1760 (n=1760, 46.0%) were SITB-related. Detection performance improved with dimensionality: low-dimensional (AUROC=0.865), medium-dimensional (AUROC=0.934‐0.935), and high-dimensional (AUROC=0.965). Low-dimensional structured (International Classification of Diseases codes and chief concerns) showed high variability in detection, with lower accuracy among preadolescents (AUROC=0.821 vs 0.880 for adolescents); male participants (AUROC=0.817 vs 0.902 for females); and patients with neurodevelopmental (AUROC=0.568‐0.809), psychotic (AUROC=0.718), and disruptive disorders (AUROC=0.703). Hybrid modality (aCS+Large Language Model Meta AI) achieved optimal performance (AUROC=0.977), with AUROC ≥0.90 for all 20 demographic and 12/15 diagnostic subgroups. Conclusions: This cross-sectional retrospective study identified that, relative to diagnostic codes and chief concern alone, hybrid structured-text detection methods improved accuracy and mitigated unwanted detection variability. The findings offer a scaffold for future clinical deployment of improved information retrieval of pediatric suicide and self-harm−related emergencies.

Background: Appendicitis in children can be treated with operative management (OM) or non-operative management (NOM) depending on patient risk factors. Our goal was to evaluate for differences in being offered NOM before and after the implementation of a standardized clinical pathway among patients of different demographic backgrounds. Methods: This was a single center retrospective study of patients under the age of 18 years with appendicitis. Univariate regression was used to assess for associations between demographic factors and patients who were offered NOM. Results: There were 730 unique patient encounters for appendicitis during the study period. Qualified patients had significantly increased odds of being offered NOM in the post-pathway period than in the pre-pathway period (OR = 2.21, 95 ^th CI 1.28-3.82). In the post-pathway period, Hispanic/Latino patients (OR = 0.47, 95 ^th CI 0.28-0.78) and patients in the 4 ^th social vulnerability index quartile (OR = 0.46, 95 ^th CI 0.23-0.94) had decreased odds of being offered NOM. Patients with private insurance (OR = 2.25, 95 ^th CI 1.33-3.79) had increased odds of being offered NOM. When restricted to patients who qualified for NOM, female patients (OR = 2.66, 95 ^th CI 1.02-6.93) and patients with private insurance (OR = 3.26 95 ^th CI 1.31-8.15) were more likely to be offered NOM. Conclusion: A clinical pathway for appendicitis increased the odds that qualified patients were offered NOM. However, differences in who was offered NOM based on demographic features were seen. More research on the effect of clinical pathways and factors impacting differential care is needed.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to decrease blood glucose levels, promote weight loss, and prevent cardiovascular events. However, evidence is limited regarding their effect on dementia, although emerging observational studies, some with serious methodological limitations, have suggested large reductions in dementia associated with GLP-1RAs that may not be entirely causally related. To compare the effect of GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP4is) as second-line therapy for type 2 diabetes on risk for dementia among older adults. Target trial emulation. United States from January 2016 to December 2020. Medicare fee-for-service beneficiaries aged 66 years or older with diabetes who used metformin and did not have dementia at baseline and initiated GLP-1RAs or DPP4is between January 2017 and December 2018. Onset of dementia was defined as 1 year before the date of a new dementia diagnosis. Risks were calculated at 30 months in GLP-1RA and DPP4i groups matched in a 1:2 ratio on an estimated propensity score and compared via ratios and differences. Among 2418 patients initiating GLP-1RAs and 4836 matched patients initiating DPP4is, the mean age was 71 years, and 55% were female. Over a median follow-up of 1.9 years, the outcome occurred in 96 patients in the GLP-1RA group and 217 in the DPP4i group. The estimated risk difference at 30 months was -0.93 (95% CI, -2.33 to 0.23) percentage points, and the estimated risk ratio was 0.83 (95% CI, 0.61 to 1.05). The estimated risk ratios were 0.64 (95% CI, 0.46 to 0.93) and 1.22 (95% CI, 0.74 to 1.66) among those younger than 75 years and aged 75 years or older, respectively. Potential residual confounding (no data on body mass index, glycemic control, or duration of diabetes), outcome misclassification, and short follow-up. Among older adults with diabetes, no clear evidence was found that the incidence of dementia differed overall between patients using GLP-1RAs versus DPP4is. Under conventional statistical criteria, an effect of GLP-1RAs between a 39% decrease and a 5% increase in risk for dementia was highly compatible with the data, although estimates differed by age. Randomized trials are needed to quantify the effect of GLP-1RAs on dementia. Gregory Annenberg Weingarten, GRoW @ Annenberg.

Adoptive transfer of genetically engineered T cells expressing a tumor-antigen-specific transgenic T cell receptor (TCR) can result in clinical responses in a variety of malignancies. However, these responses are frequently short-lived, and patients typically relapse within several months. This phenomenon is largely due to poor persistence of the transgenic T cells, as well as a progressive loss of their functionality and terminal differentiation in vivo. This underscores the need for cell therapy approaches able to sustain the initial antitumor efficacy and lead to long-term antitumor efficacy. Herein, we report the use of tandem cell therapies involving autologous T cells and hematopoietic stem cells engineered to express the NY-ESO-1 TCR for the treatment of solid tumors in a first-in-human phase I clinical trial (NCT03240861). This therapy is shown to be safe, feasible, and leads to initial tumor regression activity. T cell progeny from the HSC progenitors is shown to provide circulating transgenic NY-ESO-1 TCR-T cells, which display tumor-antigen-specific antitumor functionality, without any evidence of anergy or exhaustion. These results demonstrate the utility of transgenic HSCs to generate a self-renewing source of tumor-specific cellular immunotherapy in human participants. Clinicaltrials.gov: NCT NCT03240861

PURPOSE: The perspective of all stakeholders involved in clinical trials is critical to addressing disparities in racial/ethnic minority (REM) clinical trial participation. Little is known about clinical trial investigator perspectives. To our knowledge, there are no published studies assessing differences in investigator perspectives on the basis of their primary role in clinical trials (ie, principal investigator [PI] or subinvestigator [sub-I]). Differences likely exist in investigator perspectives on the basis of having a more design-oriented (PI) or recruitment-oriented (sub-I) role. MATERIALS AND METHODS: We conducted a cross-sectional, anonymous, pilot survey of 107 oncology clinical trial investigators at an academic center. The survey assessed five domains about disparities in REM clinical trial participation. We performed a subgroup analysis of mid- and late-career investigators (≥10 years of experience) comparing PIs (opened ≥one clinical trial in the past year) with sub-Is (did not). RESULTS: Among 60 respondents, a majority (83%) strongly agreed disparities exist in REM clinical trial participation and that this is problematic (75%). Notably, 45% agreed they cannot directly address this problem. In the subgroup analysis, PIs were more likely to have received training about barriers/facilitators to REM clinical trial participation and strategies to increase participation. They were also more likely to endorse wanting help in this area. CONCLUSION: Our results suggest clinical trial investigators are aware of disparities in REM clinical trial participation but do not feel they can address them. PIs are more likely to have received previous training on this topic and to want help to improve their ability to address disparities. More studies are needed to inform targeted interventions and structural improvements to enhance investigators' self-efficacy for improving REM participation in oncology clinical trials.

We developed and tested MivacunaLA/MyshotLA, a community-informed mobile phone intervention, to increase COVID-19 vaccination among Latino parents/caretakers of minors in under-resourced areas of Los Angeles by addressing misinformation and building trust. We recruited Latino parents/caregivers with at least one unvaccinated child in East and South Los Angeles in the summer of 2021 and evaluated MivacunaLA as a randomized controlled trial with a wait-list control group. A difference-in-difference analysis showed Latino parents/caregivers that participated in MivacunaLA (n = 246), in comparison to the control group, were 15 percentage points more likely (p = 0.04) to report vaccination of minors aged 12–17 years, and 12 percentage points more likely (p = 0.03) to report a positive intention to vaccinate minors aged 2–11 years (when COVID-19 vaccines became available). Mobile phone-delivered digital interventions using videos and culturally tailored educational material to promote COVID-19 vaccine confidence can be an effective way to combat misinformation and deliver timely information to marginalized communities. Community-based participatory research approaches are crucial to advance health equity among minority communities, especially immigrant Spanish-speaking underserved communities.