Faculty Bibliography

The rs6923761 (Gly168Ser) missense variant in the glucagon-like peptide-1 receptor (GLP-1R) has been associated with favorable anthropometric and metabolic parameters in individuals with obesity but decreased responsiveness to incretin-based therapies. Here, we performed a pre-specified analysis of a randomized-controlled trial in individuals with obesity and pre-diabetes comparing treatment with the GLP-1R agonist liraglutide, the dipeptidyl peptidase 4 inhibitor sitagliptin or hypocaloric diet, and evaluated the effects of the rs6923761 variant on outcomes. We found significantly greater weight loss to liraglutide with each copy of the variant allele present, indicating a gene dose effect. In addition, individuals with the variant allele exhibited a significant reduction in the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 after liraglutide treatment. There was no effect of genotype on fasting glucose after liraglutide treatment, yet individuals with the variant allele exhibited decreased responsiveness to liraglutide and hypocaloric diet in measurements of fasting insulin, C-peptide, glucagon, and HOMA-IR. In conclusion, we found that the GLP-1R rs6923761 variant exerts a dual impact on liraglutide efficacy-enhancing weight loss while diminishing metabolic benefits. The observed associations could be consistent with the constitutive activation of the GLP-1R in the presence of this variant with reduced activation/signaling in response to pharmacologic agents, a pattern that has been observed with the rs10305492 variant in animal models. Future studies are needed to investigate the molecular mechanisms of associations with the rs6923761 variant.

BACKGROUND:To encourage high-quality, reduced-cost care for total joint arthroplasty (TJA), the Centers of Medicare & Medicaid Services mandated a pay-for-performance model, the Comprehensive Care for Joint Replacement (CJR), as part of the Patient Protection and Affordable Care Act (PPACA). The CJR incentivizes cost containment, and it was anticipated that its implementation would reduce access to TJA for high-cost populations. Patients with end-stage kidney disease (ESKD) undergoing kidney replacement therapy (dialysis and kidney transplant) are costly compared with healthier patients, but it was unknown whether this population lost access to hip and knee replacement because of CJR implementation. This population allows study of whether TJA is accessible for medically complex patients whose risk of surgical complications has been mitigated, as kidney transplantation improves outcomes compared with dialysis, allowing evaluation as to whether access improved when patients crossed over from dialysis to transplantation. Because all patients with ESKD are included in a mandated national registry, we can quantify whether access changed for patients who underwent dialysis and transplantation. QUESTIONS/PURPOSES/OBJECTIVE:(1) How did the rate of TJA change amid the shift to bundled payments for patients with ESKD receiving dialysis? (2) How did the rate of TJA change amid the shift to bundled payments for patients with ESKD after kidney transplant? METHODS:This was an observational cohort study from 2008 to 2018 using the United States Renal Data System, a mandatory national registry that allows for the opportunity to study all individuals with ESKD. During the study period, we identified 1,324,614 adults undergoing routine dialysis and 187,212 adult kidney transplant recipients; after exclusion for non-Medicare primary insurance (n = 785,224 for dialysis and 78,011 for transplant), patients who were 100 years or older (n = 79 and 0, respectively), those who resided outside of 50 US states and Puerto Rico (n = 781 and 87, respectively), missing dialysis status for the dialysis cohort (n = 8658), and multiorgan transplant recipients for the transplant cohort (n = 2442), our study population was 40% (529,872) of patients who underwent routine dialysis and 57% (106,672) of adult kidney transplant recipients, respectively. TJA was ascertained using Medicare Severity Diagnosis Related Groups and ICD-9 and ICD-10 codes. We divided the study period by PPACA (January 1, 2014, to March 31, 2016) and CJR (April 1, 2016, to December 31, 2018) implementation and compared the incidence of TJA by era using mixed-effects Poisson regression adjusting for calendar time and clinical and demographic variables. RESULTS:After adjustment for linear temporal trend and patient case mix, there was no evidence of association between policy implementation and the incidence of TJA. In the dialysis cohort, the adjusted incidence rate ratio (IRR) for TJA was 1.06 (95% confidence interval [CI] 0.98 to 1.14; p = 0.2) comparing PPACA with the previous period and 1.02 (95% CI 0.96 to 1.08; p = 0.6) comparing CJR with the previous periods. Similarly, in the transplant cohort, the adjusted IRR for TJA was 0.82 (95% CI 0.67 to 1.02; p = 0.07) comparing PPACA with the previous period and 1.10 (95% CI 0.94 to 1.28; p = 0.9) comparing CJR with the previous periods. CONCLUSION/CONCLUSIONS:There was no loss in access to TJA for medically complex patients receiving kidney replacement therapy. The increase in TJA incidence for patients after kidney transplant and decrease for patients receiving dialysis suggest that surgeons continued to provide care for higher risk patients whose risk of morbidity or mortality with total joint replacement has been maximally improved after transplantation. LEVEL OF EVIDENCE/METHODS:Level III, prognostic study.

IMPORTANCE/UNASSIGNED:Despite evidence of clinical benefits and guidelines recommending first-line treatment intensification (TI) for metastatic castration-sensitive prostate cancer (mCSPC), the majority of patients do not receive it. OBJECTIVE/UNASSIGNED:To identify barriers to and facilitators of first-line TI. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The IMPLEMENT study (December 2022 to August 2024) comprised 3 phases and used a mixed-methods, qualitative and quantitative approach. US-based urologists and oncologists who were primary treaters for 1 or more patients with mCSPC in the past 6 months, had been practicing for 2 to 35 years, spent 50% or more of their time in direct patient care, and were able to provide informed consent were included. EXPOSURE/UNASSIGNED:Phase 1 consisted of semistructured interviews based on the Theoretical Domains Framework. Phase 2 consisted of a discrete choice experiment to identify priority barriers and helpful resources. Phase 3 consisted of cocreation sessions to ideate potential solutions to underutilization based on the findings of the previous phases. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome in phase 1 was barriers to and facilitators of first-line TI, as identified through thematic analysis. The primary outcome of phase 2 was perceived helpfulness of potential resources for first-line TI decisions, measured with a coefficient of helpfulness [CoH] for each resource. The primary outcome of phase 3 was potential solutions to increase TI uptake, as cocreated and ranked by urologists and oncologists. RESULTS/UNASSIGNED:In total, 352 participants were included in IMPLEMENT, with 36 in phase 1 (33 men [92%]; mean [range] years in practice, 19 [5-34]), 302 in phase 2 (253 men [84%]; mean [range] years in practice, 18 [4-35]), and 14 in phase 3 (12 men [86%]; mean [range], years in practice, 20 [8-35]). In each phase, one-half of participants were oncologists and one-half were urologists (18 urologists and 18 oncologists in phase 1, 151 urologists and 151 oncologists in phase 2, and 7 urologists and 7 oncologists in phase 3). In phase 1, 5 domains had the greatest perceived influence on intensification: memory, attention, and decision processes; environmental context and resources; knowledge; beliefs about consequences; and social or professional role. Urologists more commonly reported barriers to intensification, while oncologists more commonly reported facilitators. In phase 2, urologists found decision-support tools most helpful (CoH, 3.27; 95% CI, 2.90-3.65), while oncologists preferred databases of posttreatment options (CoH, 2.58; 95% CI, 2.29-2.89) and clinical trial summaries (CoH, 2.41; 95% CI, 2.14-2.69). In phase 3, cross-specialty tumor boards were ranked by both specialties as the best solution to address TI underutilization. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study using a mixed-methods approach with quantitative and qualitative components found that the issues underlying TI underutilization were numerous and multifactorial; the barriers encountered by physicians and the resources to help address them varied by specialty. These findings offer insights into physician-supported strategies that could help improve rates of first-line TI for mCSPC in the US.

The objective of this study was to explore the buffering effect of support on the association between stress and postpartum depression (PPD) among immigrant women. We surveyed 223 Chinese pregnant or postpartum (within one year post-delivery) immigrant women in New York City. Surveys were conducted in English, Simplified Chinese or Mandarin, March-June 2021. PPD was measured with the Edinburgh PPD scale (EPDS); scores of 13 or higher indicate probable depression. Perceived stress was measured with one question, "How often did you feel stressed in the past week?"; responses were collapsed into a binary measure: Never/Rarely and Sometimes/Often/Always. Support was assessed with a general question about perception of receiving needed support and the Patient-Reported Outcomes Measurement Information System (PROMIS) V2.0 Short Form Informational, Instrumental, and Emotional Support measures. Bivariate and multivariable general linear regression models assessed the relationship among stress, support, and PPD. The EPDS mean score was 11.9 (95%CI:11.1-12.7) and 50% (95%CI: 42-57%) had EPDS scores ≥ 13, indicative of serious symptoms; 56% felt stressed in the past week and 37% reported getting needed support. Among women without perceived needed support, mean EPDS scores were higher among women who were stressed compared with women who were not (adjusted mean difference (aMD) 5.4; 95%CI:3.3-7.5); the association between stress and EPDS score was attenuated among women with needed support (aMD 1.1; 95%CI:-1.0, 3.1). Similar patterns held for emotional and instrumental support. Perceived and social support attenuated the association between perceived stress and depression symptoms among Chinese immigrant women. Enhancing support may be effective in countering the impact of stressors on PPD.

BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP1RA) provide survival benefits in people with diabetes, including kidney transplant (KT) recipients with pre-existing diabetes. Post-transplant diabetes mellitus (PTDM) is common, but the benefits of GLP1RAs remain undefined in this population. We aim to describe current usage practices and outcomes in PTDM. METHODS:We used USRDS and Medicare claims data (2013-2022) to conduct a drug utilization profile of GLP1RA among 7681 first-time adult KT recipients with PTDM. We used survival analysis to estimate GLP1RA initiation incidence and associated patient, graft, and safety outcomes. RESULTS:A total of 430 adult KT recipients with PTDM were prescribed GLP1RA. Dulaglutide was the most commonly prescribed medication (46.1%). The 5-year cumulative incidence of GLP-1 receptor agonists prescription was 9.8%. Median (interquartile range) time from PTDM diagnosis to first prescription was 1.7 (0.6, 3.4) years. GLP1RA use was not associated with a difference in the risk of mortality or graft failure but was associated with a 1.80-fold (95% confidence interval [CI]: 1.11-2.91) increased risk of diabetic retinopathy. No increased risk of pancreatitis, biliary complications, or medullary thyroid cancer were identified. CONCLUSIONS:GLP1RA use in KT recipients with PTDM was not associated with graft or patient survival, though longer follow-up is necessary. GLP1RA use was associated with an increased risk of diabetic retinopathy, and care should be taken when initiating these agents.

Cardiovascular disease (CVD) and cancer remain the leading causes of mortality in the United States, where poor diet has surpassed smoking as the leading risk factor for death, and life expectancy has hit a plateau as CVD mortality has stagnated over the past decade. Although the pathophysiology of CVD and cancer is complex and multifactorial, lifestyle factors including diet often contribute significantly to their pathogenesis. There is a wealth of observational data as well as emerging trial data supporting the benefits of a predominantly whole-food plant-based diet in the prevention of CVD and cancer. However, there is a need for implementation science to effectuate existing knowledge. Given the shortcomings of the standard American diet, characterized by excessive intake of red meat and ultraprocessed foods, while deficient in fiber and phytonutrients, it will be necessary to shift default patterns of eating to make healthy choices the path of least resistance.

The 2024 revisions of the McDonald diagnostic criteria include the optic nerve as a fifth anatomical location within the CNS for the diagnosis of multiple sclerosis, in addition to periventricular, juxtacortical or cortical, infratentorial, and spinal cord lesions. Demonstration of dissemination in space can now be achieved with the detection of typical lesions in at least two of these five locations. We review the evidence supporting the use of optical coherence tomography (OCT) and visual evoked potentials (VEPs) to show optic nerve involvement in the diagnosis of multiple sclerosis. We also report consensus recommendations for their use. Provided there is no better explanation for optic nerve involvement and that rigorous quality control is applied, OCT-derived peripapillary retinal nerve fibre layer inter-eye differences of 6 μm or greater or composite macular ganglion cell and inner plexiform layer inter-eye differences of 4 μm or greater support optic nerve injury. Delayed VEP latency, which depends on technical and methodological factors, and is centre and device dependent, supports demyelinating optic nerve injury when done with appropriate technical knowledge and interpretation.

BACKGROUND AND OBJECTIVES/UNASSIGNED:Burnout is a pervasive occupational hazard for neurologists-undermining their well-being, jeopardizing patient safety and satisfaction, limiting access to care, and inflating health care costs. Well-designed appreciation and recognition practices may help mitigate some of its key drivers. This pilot study evaluates faculty perspectives on appreciation strategies in an academic neurology department. We used the Moffitt Provider Appreciation Assessment (MPAA), which assesses the types of appreciation methods respondents value, regardless of whether those practices are currently implemented in their workplace. METHODS/UNASSIGNED:A cross-sectional survey was conducted among full-time clinical faculty in the Department of Neurology at NYU Grossman School of Medicine. The survey included demographics, the MPAA, the single-item Mini-Z burnout inventory to assess self-reported burnout levels, and an intent-to-leave question. MPAA responses were analyzed for frequencies, and the association between burnout and intent to leave was examined. RESULTS/UNASSIGNED:< 0.00001). Because the scores for self-reported burnout and intent to leave reflect current work conditions while MPAA scores capture enduring personal values, MPAA rankings cannot be compared directly with burnout or turnover metrics. DISCUSSION/UNASSIGNED:Neurology clinical faculty prioritized appreciation methods that directly address clinical work, underscoring the value of implementing tailored recognition practices that may reduce burnout. The methodology used in this pilot study can be adapted for broader application in other settings. After identifying faculty preferences, health care organizations can implement meaningful, transparent, and inclusive appreciation strategies that have the potential to strengthen physician relationships, promote well-being, and support a sustainable workforce.

BACKGROUND/UNASSIGNED:In 2024, the US Environmental Protection Agency tightened the Mercury and Air Toxics Standards (MATS) for emissions of filterable particulate matter (fPM) from coal-fired power plants to 0.010 lb/MMBtu. In April 2025, a presidential proclamation stated that 47 specific power plant companies received a 2-year exemption from the new requirements. The proclamation provided no estimates of the resulting health impacts. METHODS/UNASSIGNED:: 1.095, 95% confidence interval (CI) = 1.064, 1.127; in sensitivity analyses, we employ other CRFs); (4) aggregate results (e.g., by US state). RESULTS/UNASSIGNED:emissions to ~6,900 tons, from ~4,400 tons. We estimate that the additional ~2,500 tons emitted will lead to 32 (95% CI = 22, 43) deaths. The highest mortality is in St. Louis, Missouri, (population: 2.2 million) with an estimated 14 (95% CI = 10,19) deaths. The increased mortality is, for some states (e.g., Missouri, and Pennsylvania), caused by mostly in-state emissions; for other states (e.g., Illinois, Maryland, New Jersey, and Virginia), the cause is out-of-state emissions. DISCUSSION/UNASSIGNED:Results here quantify a portion of the health impacts but leave unquantified nonmortality impacts, impacts from hazardous air pollutant (HAP) exposures, and noninhalation pathways. The reduced computational demands of the air pollution model employed here allows for more timely investigation of government actions than would traditional air dispersion modeling. Sensitivity analyses yielded mortality results that ranged from 47% lower to 169% higher than the core findings. CONCLUSIONS/UNASSIGNED:at the exempted coal-fired power plants will lead to 32 (95% CI = 22, 43) additional deaths.