Faculty Bibliography

Teclistamab (Tec) is a first-in-class BCMA X CD3 bispecific T-cell engager antibody approved for treating multiple myeloma progressing after at least 4 lines of therapy. The objective of this study was to evaluate the rate of cytokine release syndrome (CRS) in patients who were treated with commercial Tec and had prior exposure to other T-cell redirection therapies. A retrospective chart review was performed to identify patients who completed the Tec step-up dosing phase between November 2022 and November 2023. Patients were divided into 2 cohorts based on prior exposure to T-cell redirection therapy (cohort 1: T-cell redirection therapy experienced; cohort 2: T-cell redirection therapy naïve). The primary objective was to compare the differences in the rates of CRS between the two cohorts. Univariate and multivariate logistic regression analyses were performed to assess the association between CRS rates with Tec and prior treatment with T-cell redirection therapy. A total of 72 patients were included in the analysis (27 in cohort 1 and 45 in cohort 2). The CRS rates were significantly lower in cohort 1 (37%, n=10) compared to cohort 2 (80%, n=36; p=0.0004). Based on multivariate logistic regression analysis, patients without prior exposure to T-cell redirection therapy (cohort 2) had about a 4-fold increase in the incidence of CRS (95% CI: 1.40-14.90, p=0.0002) with Tec. In our study, prior exposure to T-cell redirection therapy reduced the risk of CRS with Tec during the step-up dosing phase. This observation will allow for the optimization of CRS prophylactic strategies for Tec.

Teclistamab, a B-cell maturation antigen (BCMA)- and CD3-targeting bispecific antibody, is an effective novel treatment for relapsed/refractory multiple myeloma (R/RMM), but efficacy in patients exposed to BCMA-directed therapies and mechanisms of resistance have yet to be fully delineated. We conducted a real-world retrospective study of commercial teclistamab, capturing both clinical outcomes and immune correlates of treatment response in a cohort of patients (n = 52) with advanced R/RMM. Teclistamab was highly effective with an overall response rate (ORR) of 64%, including an ORR of 50% for patients with prior anti-BCMA therapy. Pretreatment plasma cell BCMA expression levels had no bearing on response. However, comprehensive pretreatment immune profiling identified that effector CD8+ T-cell populations were associated with response to therapy and a regulatory T-cell population associated with nonresponse, indicating a contribution of immune status in outcomes with potential utility as a biomarker signature to guide patient management.

OBJECTIVES/OBJECTIVE:National societies recommend against performing routine daily laboratory testing without a specific indication. Unnecessary testing can lead to patient harm, such as hospital-acquired anemia. The objective of this study was to reduce repeat complete blood counts (CBCs) after initial testing. METHODS:This was a quality improvement initiative implemented across 11 safety net hospitals in New York City. A best practice advisory (BPA) was implemented that asked the user to remove a CBC if the last 2 CBCs within 72 hours had normal white blood cell and platelet counts and unchanged hemoglobin levels. The outcome measure was the rate of CBCs per 1000 patient days preintervention (January 8, 2020, to December 22, 2020) to postintervention (December 23, 2020, to December 7, 2021). The process measure was the acceptance rate of the BPA, defined as the number of times the repeat CBC order was removed through the BPA divided by the total number of times the BPA triggered. RESULTS:Across 11 hospitals, repeat CBC testing decreased by 12.3% (73.05 to 64.04 per 1000 patient days, P < .001). Six of the 11 hospitals exhibited statistically significant decreases, ranging from a 10% to 48.9% decrease of repeat CBCs. The overall BPA action rate was 20.0% (24,029 of 119,944 repeat CBCs). CONCLUSIONS:This low-effort, electronic health record-based intervention can effectively reduce unnecessary laboratory testing.

Precision education (PE) uses personalized educational interventions to empower trainees and improve learning outcomes. While PE has the potential to represent a paradigm shift in medical education, a theoretical foundation to guide the effective implementation of PE strategies has not yet been described. Here, the authors introduce a theoretical foundation for the implementation of PE, integrating key learning theories with the digital tools that allow them to be operationalized. Specifically, the authors describe how the master adaptive learner (MAL) model, transformative learning theory, and self-determination theory can be harnessed in conjunction with nudge strategies and audit and feedback dashboards to drive learning and meaningful behavior change. The authors also provide practical examples of these theories and tools in action by describing precision interventions already in use at one academic medical center, concretizing PE's potential in the current clinical environment. These examples illustrate how a firm theoretical grounding allows educators to most effectively tailor PE interventions to fit individual learners' needs and goals, facilitating efficient learning and, ultimately, improving patient and health system outcomes.

IMPORTANCE/UNASSIGNED:Identifying the mechanisms of structural racism, such as racial and ethnic segregation, is a crucial first step in addressing the persistent disparities in access to live donor kidney transplantation (LDKT). OBJECTIVE/UNASSIGNED:To assess whether segregation at the candidate's residential neighborhood and transplant center neighborhood is associated with access to LDKT. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:In this cohort study spanning January 1995 to December 2021, participants included non-Hispanic Black or White adult candidates for first-time LDKT reported in the US national transplant registry. The median (IQR) follow-up time for each participant was 1.9 (0.6-3.0) years. MAIN OUTCOME AND MEASURES/UNASSIGNED:Segregation, measured using the Theil H method to calculate segregation tertiles in zip code tabulation areas based on the American Community Survey 5-year estimates, reflects the heterogeneity in neighborhood racial and ethnic composition. To quantify the likelihood of LDKT by neighborhood segregation, cause-specific hazard models were adjusted for individual-level and neighborhood-level factors and included an interaction between segregation tertiles and race. RESULTS/UNASSIGNED:Among 162 587 candidates for kidney transplant, the mean (SD) age was 51.6 (13.2) years, 65 141 (40.1%) were female, 80 023 (49.2%) were Black, and 82 564 (50.8%) were White. Among Black candidates, living in a high-segregation neighborhood was associated with 10% (adjusted hazard ratio [AHR], 0.90 [95% CI, 0.84-0.97]) lower access to LDKT relative to residence in low-segregation neighborhoods; no such association was observed among White candidates (P for interaction = .01). Both Black candidates (AHR, 0.94 [95% CI, 0.89-1.00]) and White candidates (AHR, 0.92 [95% CI, 0.88-0.97]) listed at transplant centers in high-segregation neighborhoods had lower access to LDKT relative to their counterparts listed at centers in low-segregation neighborhoods (P for interaction = .64). Within high-segregation transplant center neighborhoods, candidates listed at predominantly minority neighborhoods had 17% lower access to LDKT relative to candidates listed at predominantly White neighborhoods (AHR, 0.83 [95% CI, 0.75-0.92]). Black candidates residing in or listed at transplant centers in predominantly minority neighborhoods had significantly lower likelihood of LDKT relative to White candidates residing in or listed at transplant centers located in predominantly White neighborhoods (65% and 64%, respectively). CONCLUSIONS/UNASSIGNED:Segregated residential and transplant center neighborhoods likely serve as a mechanism of structural racism, contributing to persistent racial disparities in access to LDKT. To promote equitable access, studies should assess targeted interventions (eg, community outreach clinics) to improve support for potential candidates and donors and ultimately mitigate the effects of segregation.

The goal of medical education is to produce a physician workforce capable of delivering high-quality equitable care to diverse patient populations and communities. To achieve this aim amidst explosive growth in medical knowledge and increasingly complex medical care, a system of personalized and continuous learning, assessment, and feedback for trainees and practicing physicians is urgently needed. In this perspective, the authors build on prior work to advance a conceptual framework for such a system: precision education (PE).PE is a system that uses data and technology to transform lifelong learning by improving personalization, efficiency, and agency at the individual, program, and organization levels. PE "cycles" start with data inputs proactively gathered from new and existing sources, including assessments, educational activities, electronic medical records, patient care outcomes, and clinical practice patterns. Through technology-enabled analytics, insights are generated to drive precision interventions. At the individual level, such interventions include personalized just-in-time educational programming. Coaching is essential to provide feedback and increase learner participation and personalization. Outcomes are measured using assessment and evaluation of interventions at the individual, program, and organizational level, with ongoing adjustment for repeated cycles of improvement. PE is rooted in patient, health system, and population data; promotes value-based care and health equity; and generates an adaptive learning culture.The authors suggest fundamental principles for PE, including promoting equity in structures and processes, learner agency, and integration with workflow (harmonization). Finally, the authors explore the immediate need to develop consensus-driven standards: rules of engagement between people, products, and entities that interact in these systems to ensure interoperability, data sharing, replicability, and scale of PE innovations.

Previous eras of assessment in medical education have been defined by how assessment is done, from knowledge exams popularized in the 1960s to the emergence of work-based assessment in the 1990s to current efforts to integrate multiple types and sources of performance data through programmatic assessment. Each of these eras was a response to why assessment was performed (e.g., assessing medical knowledge with exams; assessing communication, professionalism, and systems competencies with work-based assessment). Despite the evolution of assessment eras, current evidence highlights the graduation of trainees with foundational gaps in the ability to provide high-quality care to patients presenting with common problems, and training program leaders report they graduate trainees they would not trust to care for themselves or their loved ones. In this article, the authors argue that the next era of assessment should be defined by why assessment is done: to ensure high-quality, equitable care. Assessment should place focus on demanding graduates possess the knowledge, skills, attitudes, and adaptive expertise to meet the needs of all patients and ensuring that graduates are able to do this in an equitable fashion. The authors explore 2 patient-focused assessment approaches that could help realize the promise of this envisioned era: entrustable professional activities (EPAs) and resident sensitive quality measures (RSQMs)/TRainee Attributable and Automatable Care Evaluations in Real-time (TRACERs). These examples illustrate how the envisioned next era of assessment can leverage existing and new data to provide precision education assessment that focuses on providing formative and summative feedback to trainees in a manner that seeks to ensure their learning outcomes prepare them to ensure high-quality, equitable patient outcomes.

BACKGROUND:While recognized as a key HIV prevention strategy, preexposure prophylaxis (PrEP) availability and accessibility are not well documented globally. We aimed to describe PrEP drug registration status and the availability of PrEP services across HIV care sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium. METHODS:We used country-level PrEP drug registration status from the AIDS Vaccine Advocacy Coalition and data from IeDEA surveys conducted in 2014, 2017 and 2020 among participating HIV clinics in seven global regions. We used descriptive statistics to assess PrEP availability across IeDEA sites serving adult patients in 2020 and examined trends in PrEP availability among sites that responded to all three surveys. RESULTS:Of 199 sites that completed the 2020 survey, PrEP was available in 161 (81%). PrEP availability was highest at sites in North America (29/30; 97%) and East Africa (70/74; 95%) and lowest at sites in Central (10/20; 50%) and West Africa (1/6; 17%). PrEP availability was higher among sites in countries where PrEP was officially registered (146/161; 91%) than where it was not (14/32; 44%). Availability was higher at health centers (109/120; 90%) and district hospitals (14/16; 88%) compared to regional/teaching hospitals (36/63). Among the 94 sites that responded to all three surveys, PrEP availability increased from 47% in 2014 to 60% in 2017 and 76% in 2020. CONCLUSION/CONCLUSIONS:PrEP availability has substantially increased since 2014 and is now available at most IeDEA sites. However, PrEP service provision varies markedly across global regions.