Faculty Bibliography

BACKGROUND:Some of the most promising strategies to reduce hospital readmissions in heart failure (HF) is through the timely receipt of home health care (HHC), delivered by Medicare-certified home health agencies (HHAs), and outpatient medical follow-up after hospital discharge. Yet national data show that only 12% of Medicare beneficiaries receive these evidence-based practices, representing an implementation gap. To advance the science and improve outcomes in HF, we will test the effectiveness and implementation of an intervention called Improving TRansitions ANd OutcomeS for Heart FailurE Patients in Home Health CaRe (I-TRANSFER-HF), comprised of early and intensive HHC nurse visits combined with an early outpatient medical visit post-discharge, among HF patients receiving HHC. METHODS:This study will use a Hybrid Type 1, stepped wedge randomized trial design, to test the effectiveness and implementation of I-TRANSFER-HF in partnership with four geographically diverse dyads of hospitals and HHAs ("hospital-HHA" dyads) across the US. Aim 1 will test the effectiveness of I-TRANSFER-HF to reduce 30-day readmissions (primary outcome) and ED visits (secondary outcome), and increase days at home (secondary outcome) among HF patients who receive timely follow-up compared to usual care. Hospital-HHA dyads will be randomized to cross over from a baseline period of no intervention to the intervention in a randomized sequential order. Medicare claims data from each dyad and from comparison dyads selected within the national dataset will be used to ascertain outcomes. Hypotheses will be tested with generalized mixed models. Aim 2 will assess the determinants of I-TRANSFER-HF's implementation using a mixed-methods approach and is guided by the Consolidated Framework for Implementation Research 2.0 (CFIR 2.0). Qualitative interviews will be conducted with key stakeholders across the hospital-HHA dyads to assess acceptability, barriers, and facilitators of implementation; feasibility and process measures will be assessed with Medicare claims data. DISCUSSION/CONCLUSIONS:As the first pragmatic trial of promoting timely HHC and outpatient follow-up in HF, this study has the potential to dramatically improve care and outcomes for HF patients and produce novel insights for the implementation of HHC nationally. TRIAL REGISTRATION/BACKGROUND:This trial has been registered on ClinicalTrials.Gov (#NCT06118983). Registered on 10/31/2023, https://clinicaltrials.gov/study/NCT06118983?id=NCT06118983&rank=1 .

BACKGROUND/UNASSIGNED:Electronic health records (EHRs) are increasingly used for epidemiologic research to advance public health practice. However, key variables are susceptible to missing data or misclassification within EHRs, including demographic information or disease status, which could affect the estimation of disease prevalence or risk factor associations. OBJECTIVE/UNASSIGNED:In this paper, we applied methods from the literature on missing data and causal inference to assess whether we could mitigate information biases when estimating measures of association between potential risk factors and diabetes among a patient population of New York City young adults. METHODS/UNASSIGNED:We estimated the odds ratio (OR) for diabetes by race or ethnicity and asthma status using EHR data from NYU Langone Health. Methods from the missing data and causal inference literature were then applied to assess the ability to control for misclassification of health outcomes in the EHR data. We compared EHR-based associations with associations observed from 2 national health surveys, the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health and Nutrition Examination Survey, representing traditional public health surveillance systems. RESULTS/UNASSIGNED:Observed EHR-based associations between race or ethnicity and diabetes were comparable to health survey-based estimates, but the association between asthma and diabetes was significantly overestimated (OREHR 3.01, 95% CI 2.86-3.18 vs ORBRFSS 1.23, 95% CI 1.09-1.40). Missing data and causal inference methods reduced information biases in these estimates, yielding relative differences from traditional estimates below 50% (ORMissingData 1.79, 95% CI 1.67-1.92 and ORCausal 1.42, 95% CI 1.34-1.51). CONCLUSIONS/UNASSIGNED:Findings suggest that without bias adjustment, EHR analyses may yield biased measures of association, driven in part by subgroup differences in health care use. However, applying missing data or causal inference frameworks can help control for and, importantly, characterize residual information biases in these estimates.

OBJECTIVES/OBJECTIVE:The Dietary Approaches to Stop Hypertension (DASH) diet reduces blood pressure, but the mechanisms underlying DASH diet-blood pressure relations are not well understood. Proteomic measures may provide insights into the pathophysiological mechanisms through which the DASH diet reduces blood pressure. METHODS:The DASH (1994-1996) and DASH-Sodium (1997-1999) trials were multicenter, randomized-controlled feeding trials. Proteomic profiling was conducted in serum collected at the end of the feeding period (DASH, N = 215; DASH-Sodium, N = 390). Multivariable linear regression models were used to identify interactions between 71 DASH diet-related proteins and changes in systolic and diastolic blood pressure. Estimates were meta-analyzed across both trials. Elastic net models were used to identify proteins that predict changes in blood pressure. RESULTS:Ten significant interactions were identified [systolic blood pressure: seven proteins; diastolic blood pressure: three proteins], which represented nine unique proteins. A high level of renin at the end of the feeding period was associated with greater reductions in diastolic blood pressure in individuals consuming the control than DASH diets. A high level of procollagen c-endopeptidase enhancer 1 (PCOLCE) and collagen triple helix repeat-containing protein 1 (CTHRC1) were associated with greater reductions in systolic blood pressure in individuals consuming the DASH than control diets, and with elevations in systolic blood pressure in individuals consuming the control diets (P for interaction for all tests < 0.05). Elastic net models identified six additional proteins that predicted change in blood pressure. CONCLUSIONS:Several novel proteins were identified that may provide some insight into the relationship between the DASH diet and blood pressure.

PURPOSE/UNASSIGNED:Immune checkpoint inhibition (ICI) shows benefits in adjuvant (AT) and neoadjuvant melanoma treatments. However, ICI frequently induces severe immune-related adverse events (irAE). Unlike metastatic disease, in which irAEs are a clinical trade-off for treatment that improves survival, the toxicity burden from ICI in the AT setting is a substantial clinical problem urging for irAE-predictive biomarkers. EXPERIMENTAL DESIGN/UNASSIGNED:We assessed postsurgical, pre-ICI treatment peripheral CD4+ and CD8+ T cells from clinical trial patients (CheckMate 915) treated with AT nivolumab (n = 130) or ipilimumab/nivolumab (COMBO, n = 82). Performing RNA sequencing differential gene expression analysis, we tested baseline differences associated with severe (grades 3-5) irAEs and constructed an irAE-predictive model using least absolute shrinkage and selection operator-regularized logistic regression. RESULTS/UNASSIGNED:The analysis of predicted protein-protein interactions among differentially expressed genes in peripheral CD4+ cells revealed significant enrichment of the spleen tyrosine kinase (SYK) pathway, associated with severe irAEs in COMBO-treated patients. This gene expression signature predicted severe-irAE COMBO patients (χ2P value = 0.001) with 73% accuracy and was independent of disease recurrence (P = 0.79). The irAE-predictive model incorporating this gene expression signature demonstrated 82% accuracy (χ2P value = 8.91E-06). CONCLUSIONS/UNASSIGNED:We identified baseline gene expression differences in key immune pathways of peripheral blood T cells from COMBO-treated patients with grades 3 to 5 irAEs and defined a SYK-related gene signature correctly identifying ∼60% of COMBO-treated patients with grades 3 to 5 irAEs. This finding aligns with our previous work linking anti-CTLA4 irAEs with a germline variant associated with high SYK expression. This gene signature may serve as a baseline biomarker of severe grade 3 to 5 irAE risk, which is especially important in AT treatment.

Objective: To identify the current state of knowledge among adolescent and young adults (AYAs) with sickle cell disease (SCD) on fertility, family building, and contraception. We aimed to identify recommendations and guidance for communication strategies and counseling methods in these areas. Design: Full-text publications were included if they focused on individuals with SCD, were published in English in peer-reviewed journals, and addressed patient or family knowledge of fertility, family building, or contraception. A comprehensive search using PubMed, CINAHL, Ovid MEDLINE, Embase, and PsycINFO was performed. Multiple reviewers independently assessed each abstract for inclusion, and a senior librarian resolved disagreements. Results: Of 2,885 publications screened, 314 underwent full review, and 11 were included. Of the included studies, three discussed fertility only, two discussed family building only, two discussed contraception only, two discussed contraception and fertility, one discussed contraception and family building, and one discussed fertility and family building. Two overarching gaps were identified: a lack of counseling related to reproductive healthcare provided to AYAs with SCD and limited knowledge regarding their own disease sequelae. Conclusion: Many AYAs are not counseled and are not knowledgeable about their fertility risks, family building options, and contraception choices. Furthermore, previous counseling guidelines on these subjects are limited, leading to incomplete and highly variable discussions between patient and clinicians on these subjects. This review highlights counseling recommendations and areas in which more concrete guidelines and evidence are important for the standardization of comprehensive reproductive healthcare in the AYA SCD population.

Efforts to bolster the school readiness of Latine children from low-income and immigrant homes have focused on fostering parent engagement in children's education. In assessing parent engagement, most measures center school-based activities in alignment with middle class, European American dominant norms, missing the multiple ways that Latine families engage with their children to support their educational experiences and development. Additionally, studies of predictors of Latine parent engagement have mainly focused on parent demographic and linguistic factors, limiting our understanding of how to support parent engagement equitably. Using a measure of parent engagement sensitive to culturally contextualized behaviors of Latine families, this study describes the ways Latine parents living in historically disinvested neighborhoods in New York City engage in their children's learning at home and in school during a nationally charged anti-immigrant, anti-Latine sociopolitical climate. We also examine whether immigration enforcement threat and parent health are associated with Latine family engagement in home and school-based activities. Data come from a larger study conducted with Latine parents (n=103; 42% immigrant) of pre-K children. Descriptive results indicate that despite a charged sociopolitical context, levels of engagement in children's education and development across multiple domains were comparable with mean levels established by the developers. Findings from regression analyses demonstrated that above and beyond demographic, linguistic and financial factors, immigration enforcement threat and parent health were associated with aspects of family engagement in young children's learning among Latine families in low-income communities. Implications for policy and practice are discussed.

BACKGROUND:Recent data suggest patients with graft failure had better access to repeat kidney transplantation (re-KT) than transplant-naive dialysis accessing first KT. This was postulated to be because of better familiarity with the transplant process and healthcare system; whether this advantage is equitably distributed is not known. We compared the magnitude of racial/ethnic disparities in access to re-KT versus first KT. METHODS:Using United States Renal Data System, we identified 104 454 White, Black, and Hispanic patients with a history of graft failure from 1995 to 2018, and 2 357 753 transplant-naive dialysis patients. We used adjusted Cox regression to estimate disparities in access to first and re-KT and whether the magnitude of these disparities differed between first and re-KT using a Wald test. RESULTS:Black patients had inferior access to both waitlisting and receiving first KT and re-KT. However, the racial/ethnic disparities in waitlisting for (adjusted hazard ratio [aHR] = 0.77; 95% confidence interval [CI], 0.74-0.80) and receiving re-KT (aHR = 0.61; 95% CI, 0.58-0.64) was greater than the racial/ethnic disparities in first KT (waitlisting: aHR = 0.91; 95% CI, 0.90-0.93; Pinteraction = 0.001; KT: aHR = 0.68; 95% CI, 0.64-0.72; Pinteraction < 0.001). For Hispanic patients, ethnic disparities in waitlisting for re-KT (aHR = 0.83; 95% CI, 0.79-0.88) were greater than for first KT (aHR = 1.14; 95% CI, 1.11-1.16; Pinteraction < 0.001). However, the disparity in receiving re-KT (aHR = 0.76; 95% CI, 0.72-0.80) was similar to that for first KT (aHR = 0.73; 95% CI, 0.68-0.79; Pinteraction = 0.55). Inferences were similar when restricting the cohorts to the Kidney Allocation System era. CONCLUSIONS:Unlike White patients, Black and Hispanic patients with graft failure do not experience improved access to re-KT. This suggests that structural and systemic barriers likely persist for racialized patients accessing re-KT, and systemic changes are needed to achieve transplant equity.

In studies with time-to-event outcomes, multiple, inter-correlated, and time-varying covariates are commonly observed. It is of great interest to model their joint effects by allowing a flexible functional form and to delineate their relative contributions to survival risk. A class of semiparametric transformation (ST) models offers flexible specifications of the intensity function and can be a general framework to accommodate nonlinear covariate effects. In this paper, we propose a partial-linear single-index (PLSI) transformation model that reduces the dimensionality of multiple covariates into a single index and provides interpretable estimates of the covariate effects. We develop an iterative algorithm using the regression spline technique to model the nonparametric single-index function for possibly nonlinear joint effects, followed by nonparametric maximum likelihood estimation. We also propose a nonparametric testing procedure to formally examine the linearity of covariate effects. We conduct Monte Carlo simulation studies to compare the PLSI transformation model with the standard ST model and apply it to NYU Langone Health de-identified electronic health record data on COVID-19 hospitalized patients' mortality and a Veteran's Administration lung cancer trial.

INTRODUCTION/BACKGROUND:ChatGPT has shown the ability to answer clinical questions in general medicine but may be constrained by the specialized nature of kidney transplantation. Thus, it is important to explore how ChatGPT can be used in kidney transplantation and how its knowledge compares to human respondents. METHODS:We prompted ChatGPT versions 3.5, 4, and 4 Visual (4 V) with 12 multiple-choice questions related to six kidney transplant cases from 2013 to 2015 American Society of Nephrology (ASN) fellowship program quizzes. We compared the performance of ChatGPT with US nephrology fellowship program directors, nephrology fellows, and the audience of the ASN's annual Kidney Week meeting. RESULTS:Overall, ChatGPT 4 V correctly answered 10 out of 12 questions, showing a performance level comparable to nephrology fellows (group majority correctly answered 9 of 12 questions) and training program directors (11 of 12). This surpassed ChatGPT 4 (7 of 12 correct) and 3.5 (5 of 12). All three ChatGPT versions failed to correctly answer questions where the consensus among human respondents was low. CONCLUSION/CONCLUSIONS:Each iterative version of ChatGPT performed better than the prior version, with version 4 V achieving performance on par with nephrology fellows and training program directors. While it shows promise in understanding and answering kidney transplantation questions, ChatGPT should be seen as a complementary tool to human expertise rather than a replacement.

BACKGROUND AND OBJECTIVES/UNASSIGNED:Exposure to repetitive head impacts (RHI) is linked to the development of chronic traumatic encephalopathy (CTE), which can only be diagnosed at post-mortem. The presence of a cavum septum pellucidum (CSP) is a common finding in post-mortem studies of confirmed CTE and in neuroimaging studies of individuals exposed to RHI. This study examines CSP in living former American football players, investigating its association with RHI exposure, traumatic encephalopathy syndrome (TES) diagnosis, and provisional levels of certainty for CTE pathology. METHODS/UNASSIGNED:Data from the DIAGNOSE CTE Research Project were used to compare the presence and ratio of CSP in former American football players (n = 175), consisting of former college (n = 58) and former professional players (n = 117), and asymptomatic unexposed controls without RHI exposure (n = 55). We further evaluated potential associations between CSP measures and cumulative head impact index (CHII) measures (frequency, linear acceleration, and rotational force), a TES diagnosis (yes/no), and a provisional level of certainty for CTE pathology (suggestive, possible, and probable). RESULTS/UNASSIGNED:Former American football players exhibited a higher CSP presence and ratio than unexposed asymptomatic controls. Among player subgroups, professional players showed a greater CSP ratio than former college players and unexposed asymptomatic controls. Among all football players, CHII rotational forces correlated with an increased CSP ratio. No significant associations were found between CSP measures and diagnosis of TES or provisional levels of certainty for CTE pathology. DISCUSSION/UNASSIGNED:This study confirms previous findings, highlighting a greater prevalence of CSP and a greater CSP ratio in former American football players compared with unexposed asymptomatic controls. In addition, former professional players showed a greater CSP ratio than college players. Moreover, the relationship between estimates of CHII rotational forces and CSP measures suggests that cumulative frequency and strength of rotational forces experienced in football are associated with CSP. However, CSP does not directly correlate with TES diagnosis or provisional levels of certainty for CTE, indicating that it may be a consequence of RHI associated with rotational forces. Further research, especially longitudinal studies, is needed for confirmation and to explore changes over time.