Faculty Bibliography

BACKGROUND:Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain. METHODS:To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee-for-Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims-based frailty index (CFI) over a 5-year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes. RESULTS:There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non-White race. In total, 60% had frailty progression and 40% frailty regression over median follow-up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31-1.31), all-cause mortality (HR 1.34, 95% CI 1.34-1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07-1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29-1.30), ischemic stroke (HR 1.14, 95% CI 1.14-1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001). CONCLUSIONS:In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression.

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.

RATIONALE & OBJECTIVE/UNASSIGNED:The prevalence of chronic kidney disease (CKD) is known to increase with age; however, creatinine may be a less reliable filtration marker in older adults. Few studies have investigated the prevalence and progression of CKD using different filtration markers for estimating glomerular filtration rate (GFR). STUDY DESIGN/UNASSIGNED:A prospective observational cohort study. SETTING & PARTICIPANTS/UNASSIGNED:6,393 White and African American participants aged 65-100 years from the Atherosclerosis Risk in Communities Study (ARIC) at Visit 5, followed longitudinally at Visits 6 and 7. EXPOSURE AND OUTCOME/UNASSIGNED:The eGFR was estimated either by creatinine (eGFRcr), cystatin C (eGFRcys), creatinine and cystatin C (eGFRcr-cys), or using creatinine, cystatin C, and β-2-microglobulin (eGFRcr-cys-b2m). CKD progression was defined as 30% decline in eGFR at follow-up visits. ANALYTICAL APPROACH/UNASSIGNED:Logistic regression models, adjusted for sex, race and study center, diabetes, blood pressure, body mass index, prevalent cardiovascular disease, and heart failure. RESULTS/UNASSIGNED:when using eGFRcys (33%) compared with eGFRcr-cys (12%) or eGFRcr-cys-b2m (18%). The proportion with 30% eGFR decline was lowest with eGFRcr and highest with eGFRcys, with greater incidence in older age groups for all markers. LIMITATIONS/UNASSIGNED:No direct measurement of GFR. Not all participants survived or attended subsequent follow-up visits. CONCLUSIONS/UNASSIGNED:The prevalence and progression of CKD increase with age, but estimates vary with the filtration marker used. The eGFRcr gave the lowest estimate of CKD at 15% for people aged 65-69 years at Visit 5 while eGFRcys gave the highest estimates of CKD at 26% for that same population.

INTRODUCTION/BACKGROUND:Same-day surgical case cancellation consumes resources, disrupts patient care, and has a global prevalence of 18%. A retrospective analysis found that 44% of scheduled elective surgeries were canceled at a public tertiary hospital in Lilongwe, Malawi. To better characterize these cancellations, this study defines a process map for surgical case completion and investigates hospital staff and patient perspectives on contributing factors and burdens of cancellation. METHODS:We conducted participatory process mapping and in-depth interviews with hospital staff (n = 23) and patients (n = 10) to detail perioperative processes and perspectives on cancellations. We used purposive sampling to recruit staff by hospital role and patients whose surgery had been canceled. Interviews were audio-recorded, translated, and transcribed for process mapping accuracy and thematic analysis using the constant comparative method and NVivo software. RESULTS:Staff delineated specific steps of the perioperative process, generating a process map that identifies inefficiencies and opportunities for intervention. Hospital staff described unavoidable causes of case cancellation, such as unreliable water supply and material shortages. Modifiable causes linked to wasted time and resources were also evident, such as chronic tardiness, communication barriers, and inadequate preoperative assessment. Thematic analysis of perceived impacts of cancellation revealed compromised provider-patient relationships, communication breakdown, and emotional distress. Staff and patients expressed frustration, embarrassment, fear, and demoralization when planned surgeries were canceled. CONCLUSIONS:We demonstrate the use of process mapping as a tool to identify implementation targets for reducing case cancellation rates. Hospital systems can adapt this approach to address surgical case cancellation in their specific setting.

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 AIMS:The potential impact of peripheral artery disease (PAD) on kidney outcomes is not well understood. The aim of this study was to explore the association between PAD and end-stage kidney disease (ESKD) and chronic kidney disease (CKD). METHODS:with a ≥25 % decline from the baseline) using multivariable Cox proportional hazards models. RESULTS:Over ∼30 years of follow-up, there were 598 cases of incident ESKD and 4686 cases of incident CKD. After adjusting for potential confounders, both symptomatic PAD and asymptomatic PAD conferred a significantly elevated risk of ESKD (hazard ratio 2.28 [95 % confidence interval 1.23-4.22] and 1.75 [1.19-2.57], respectively). Corresponding estimates for CKD were 1.54 (1.14-2.09) and 1.63 (1.38-1.93). Borderline low ABI 0.91-1.00 also showed elevated risk of adverse kidney outcomes after adjustment for demographic variables. Largely consistent results were observed across demographic and clinical subgroups. CONCLUSIONS:Symptomatic PAD and asymptomatic PAD were independently associated with an elevated risk of ESKD and CKD. These results highlight the importance of monitoring kidney function in persons with PAD, even when symptoms are absent.

PURPOSE/OBJECTIVE:Prior to cancer treatment, patients make decisions on whether to undergo fertility preservation (FP) and the method of FP. We sought to learn more about counseling and decision-making on the method of cancer-related FP. METHODS:A cross-sectional 26-item online survey was administered to patients with ovaries who underwent cancer-related FP. Associations between demographics and the FP method were made through estimates of risk difference, with a 95% confidence interval. Open-ended responses were analyzed using the constant comparative method. RESULTS:A total of 240 respondents completed the survey: 52% underwent oocyte cryopreservation (OC), 29% underwent embryo cryopreservation (EC), and 19% underwent both oocyte and embryo cryopreservation (OC/EC). Most respondents agreed that if they were to go through the process again, they would make the same decision about FP (80% EC, 72% OC, 59% OC/EC). Women ≥ 35 years reported being counseled more that embryos were superior compared to younger women (risk difference 46%, CI 32.8, 59.1), however were not more likely to freeze embryos (risk difference 6.2%, CI - 9.8, 22.2). Women in long-term relationships reported they were counseled more that embryos were superior compared to those single/dating (risk difference 27%, CI 18.1, 35.9). All women in long-term relationships reported undergoing EC, while the majority of single/dating women reported undergoing OC (74.6%). CONCLUSION/CONCLUSIONS:Most women who have undergone cancer-related FP reported they would choose the same FP method again. Women in long-term relationships or ≥ 35 years reported they were more likely to be counseled that EC is superior; however, only women in long-term relationships were more likely to freeze embryos.

OBJECTIVE/UNASSIGNED:The objective of this study is to determine whether a sleep and health improvement programme (SHIP) to promote healthy sleep, eating and physical activity would be feasible, acceptable and have a positive impact on lifestyle behaviours for prostate cancer survivors and caregivers. METHODS/UNASSIGNED:We recruited 50 participants for a single group 3-month pre-post pilot study. The SHIP intervention included (1) website about sleep, nutrition and physical activity (≥1 view/week), (2) two email newsletters with goal-setting exercises and resources and (3) midpoint health coach call. The primary outcome was changes in validated sleep scales; secondary outcomes included changes in diet, physical activity and concentration from baseline to 3 months. RESULTS/UNASSIGNED: = 0.07). There were no statistically significant improvements in sleep quality or physical activity, but there were improvements in healthy eating (e.g., increase in cruciferous vegetables and reduction in dairy) and in fatigue-related problems and concentration. Exit interview feedback was positive. CONCLUSIONS/UNASSIGNED:A web-based sleep and healthy lifestyle programme for patients with prostate cancer and their caregivers is feasible and acceptable. A randomized controlled trial is planned to test whether a refined SHIP improves sleep and lifestyle in patients with prostate cancer and caregivers.

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.