Faculty Bibliography

BACKGROUND/UNASSIGNED:Chronic kidney disease (CKD) impacts more than 800 million people. It causes significant suffering and disproportionately impacts marginalized populations in the United States. Kidney palliative care has the potential to alleviate this distress, but has not been tested. This pilot study evaluates the feasibility of a randomized clinical trial (RCT) testing the efficacy of integrated kidney palliative and CKD care in an urban safety-net hospital. METHODS/UNASSIGNED:, and are receiving care at our safety net hospital. Participants will be randomized in permuted blocks of two or four to either the intervention group, who will receive monthly ambulatory care visits for six months with a palliative care provider trained in kidney palliative care, or to usual nephrology care. Primary outcomes are feasibility of recruitment, retention, fidelity to the study visit protocol, and the ability to collect outcome data. These outcomes include symptom burden, quality of life, and engagement in advance care planning. DISCUSSION/UNASSIGNED:This pilot RCT will provide essential data on the feasibility of testing integrated palliative care in CKD care in an underserved setting. These outcomes will inform a larger, fully powered trial that tests the efficacy of our kidney palliative care approach. CLINICAL TRIAL REGISTRATION/UNASSIGNED:NCT04998110.

BACKGROUND:Venous thromboembolism (VTE) is a significant preventable cause of postoperative morbidity and mortality after major abdominopelvic surgery that calls for extended VTE prophylaxis (eVTEp). Literature suggests that significant racial disparities may exist in post-operative care. OBJECTIVE:The study sought to examine if racial disparities exist in the administration of eVTEp after hysterectomy in a statewide collaborative. METHODS:We conducted a retrospective cohort study of post-hysterectomy patients across 69 hospitals in the Michigan Surgical Quality Collaborative from January 2016 to February 2020. The variable of interest was race (Black/African or White American). The primary outcome was administration or absence of eVTEp. Descriptive statistics and mixed effects logistic regression were performed for risk adjustment with covariates such as age, cancer occurrence, inflammatory bowel disease, American Society of Anesthesiologists physical status classification, perioperative VTE prophylaxis, postoperative VTE prophylaxis, surgical approach, and surgical duration, among other variables. RESULTS:In total, 24,513 patients underwent hysterectomy. Of these patients, 1,107 (4.45%) received eVTEp, 153 (13.24%) of which were Black and 954 (82.53%) of which were White. Mixed effects logistic regression analysis suggested that Black patients were significantly less likely to receive eVTEp than White patients (odds ratio = 0.776; 95% CI: 0.615-0.979; P = 0.039). Additionally, tobacco use, coronary artery disease, bleeding disorder, cancer occurrence, functional status, perioperative VTE prophylaxis, surgical duration, length of stay, and surgical approach were associated with a higher likelihood of receiving eVTEp. CONCLUSION/CONCLUSIONS:eVTEp is recommended for the prevention of post-discharge VTE in select patients after hysterectomy. Regression analysis showed that, compared to their White counterparts, Black females were significantly less likely to receive eVTEp. The underlying reasons for this disparity require further investigation into possible socioeconomic influences and inherent biases.

PURPOSE/OBJECTIVE:To determine the robustness of randomized controlled trials (RCTs) supporting the current rhinosinusitis guideline; International Consensus Statement on Allergy and Rhinology: rhinosinusitis (ICAR-RS). MATERIALS & METHODS/METHODS:RCTs referenced by ICAR-RS with primary dichotomous outcomes were analyzed. The Fragility Index (FI) was calculated for trials with statistically significant findings. Trial characteristics, the FI, and FI minus number lost to follow-up (LTF) were assessed for associations. RESULTS:A total of 317 RCTs were identified, with 38 trials possessing a primary dichotomous outcome. Thirty-one percent evaluated surgical interventions and 24 % were industry-sponsored. The mean sample size was 116 with 9 patients, on average, LTF. Sixty-three percent were eligible for FI calculation and had a median FI of 2.5 (IQR 1, 4.25). Sixty-seven percent of trials had an FI ≤ 3, indicating low robustness. No difference in FI was observed between trials with and without industry support (p = 0.577). The FI was less than or equal to the number of patients LTF in 33 % of trials (n = 8). Higher FI was strongly correlated with higher sample size, total number of events, p-value, and grade of recommendation (p < 0.001). After adjusting for covariates, higher sample size and total number of events were associated with higher FI. CONCLUSION/CONCLUSIONS:The RCTs used to support the ICAR-RS have an overall low robustness and future rhinosinusitis trials should report FI measures to provide improved context of their results.

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.

Cardiometabolic comorbidities, diabetes (DM), hypertension (HTN), and obesity, contribute to cardiovascular disease (CVD). Circulating biomarkers facilitate prognostication for patients with CVD. We explored the relationship between cardiometabolic comorbidity burden in patients with chronic coronary disease (CCD) and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the ISCHEMIA Trials biorepository with plasma biomarkers (NT-proBNP, hs-cTnT, hs-CRP, IL-6, sCD40L, and GDF-15) and clinical risk factors [hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body mass index (BMI)] at baseline. We defined cardiometabolic comorbidities as DM, HTN, and obesity at baseline. Comorbidity burden characterized by number and severity of comorbidities. Controlled comorbidities were defined as HbA1c <7% for those with DM, SBP <130 mmHg for those with HTN and BMI <30 kg/m². Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mmHg, and BMI ≥35 kg/m². We performed linear regression analyses to examine the association between comorbidity burden and log-transformed biomarker levels adjusting for age, sex, eGFR controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 individuals (mean age 66, 19% female, 84% white) were included in this analysis. Self-reported Black race, current smokers, history of MI and HF had greater cardiometabolic comorbidity burden. The presence of ≥ 1 severely uncontrolled comorbidity was associated with significantly higher baseline levels of hs-cTnT, hs-CRP, IL-6, and GDF-15 compared to participants with no comorbidities. In conclusion, increasing cardiometabolic comorbidity burden in patients with CCD is associated with higher levels of circulating biomarkers of myocardial injury and inflammation.

KEY POINTS:Regardless of race and ethnicity, older adults with kidney failure residing in or receiving care at dialysis facilities located in high-segregation neighborhoods were at a 1.63-fold and 1.53-fold higher risk of dementia diagnosis, respectively. Older adults with kidney failure residing in minority-predominant high-segregation neighborhoods had a 2.19-fold higher risk of dementia diagnosis compared with White individuals in White-predominant neighborhoods. BACKGROUND:a form of structural racism recently identified as a mechanism in numerous other health disparities. METHODS:We identified 901,065 older adults (aged ≥55 years) with kidney failure from 2003 to 2019 using the United States Renal Data System. We quantified dementia risk across tertiles of residential neighborhood segregation score using cause-specific hazard models, adjusting for individual- and neighborhood-level factors. We included an interaction term to quantify the differential effect of segregation on dementia diagnosis by race and ethnicity. RESULTS: CONCLUSIONS:Residing in or receiving care at dialysis facilities located in high-segregation neighborhoods was associated with a higher risk of dementia diagnosis among older individuals with kidney failure, particularly minoritized individuals.

INTRODUCTION/BACKGROUND:Adults residing in deprived neighborhoods face various socioeconomic stressors, hindering their likelihood of receiving live-donor kidney transplantation (LDKT) and preemptive kidney transplantation (KT). We quantified the association between residential neighborhood deprivation index (NDI) and the likelihood of LDKT/preemptive KT, testing for a differential impact by race and ethnicity. METHODS:We studied 403 937 adults (age ≥ 18) KT candidates (national transplant registry; 2006-2021). NDI and its 10 components were averaged at the ZIP-code level. Cause-specific hazards models were used to quantify the adjusted hazard ratio (aHR) of LDKT and preemptive KT across tertiles of NDI and its 10 components. RESULTS:: LDKT < 0.001; Preemptive KT = 0.002). All deprivation components were associated with the likelihood of both LDKT and preemptive KT (except median home value): for example, higher median household income (LDKT: aHR = 1.08, 95% CI: 1.07-1.09; Preemptive KT: aHR = 1.10, 95% CI: 1.08-1.11) and educational attainments (≥high school [LDKT: aHR = 1.17, 95% CI: 1.15-1.18; Preemptive KT: aHR = 1.23, 95% CI: 1.21-1.25]). CONCLUSION/CONCLUSIONS:Residence in socioeconomically deprived neighborhoods is associated with a lower likelihood of LDKT and preemptive KT, differentially impacting minority candidates. Identifying and understanding which neighborhood-level socioeconomic status contributes to these racial disparities can be instrumental in tailoring interventions to achieve health equity in LDKT and preemptive KT.

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.

RATIONALE & OBJECTIVE/UNASSIGNED:This study aimed to assess the effect of exposure to organic pollutants in adults with chronic kidney disease (CKD). STUDY DESIGN/UNASSIGNED:This was a cross-sectional and longitudinal analysis. SETTING AND PARTICIPANTS/UNASSIGNED:Forty adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC). EXPOSURES/UNASSIGNED:Exposure at baseline and longitudinally to various organic chemical pollutants. OUTCOMES/UNASSIGNED:The outcomes were as follows: death; composite of congestive heart failure, myocardial infarction, and stroke; event-free survival from kidney failure or ≥50% decline in estimated glomerular filtration rate (eGFR); and longitudinal trajectory of eGFR. ANALYTICAL APPROACH/UNASSIGNED:We used high-performance liquid chromatography with tandem mass spectrometry to measure urinary concentrations of bisphenols, phthalates, organophosphate pesticides, polycyclic aromatic hydrocarbons, melamine, and cyanuric acid at years 1, 3, and 5 after enrollment in the CRIC. Univariate and multivariable logistic regression were used to examine the association of individual compounds and classes of pollutants with the outcomes. The Cox proportional hazards model and Kaplan-Meier method were used to calculate hazard ratios and 95% CIs for each class of pollutants. RESULTS/UNASSIGNED:and 0.58 mg/g, respectively. Of 52 compounds assayed, 30 were detectable in ≥50% of participants. Urinary chemical concentrations were comparable in patients with CKD and healthy individuals from contemporaneous National Health and Nutrition Examination Survey cohorts. Phthalates were the only class with a trend toward higher exposure in patients with CKD. There was an inverse relationship between exposure and the eGFR slopes for bisphenol F, mono-(3-carboxypropyl) phthalate, mono-benzyl phthalate, mono-[2-(carboxymethyl)hexyl] phthalate, and melamine. There were no associations between organic pollutant exposure and cardiovascular outcomes. LIMITATIONS/UNASSIGNED:Small sample size, evaluation of single rather than combined exposures. CONCLUSIONS/UNASSIGNED:Simultaneous measurement of multiple organic pollutants in adults with CKD is feasible. Exposure levels are comparable with healthy individuals. Select contaminants, especially in the phthalate class, may be associated with more rapid deterioration in kidney function.

The surtvep package is an open-source software designed for estimating time-varying effects in survival analysis using the Cox non-proportional hazards model in R. With the rapid increase in large-scale time-to-event data from national disease registries, detecting and accounting for time-varying effects in medical studies have become crucial. Current software solutions often face computational issues such as memory limitations when handling large datasets. Furthermore, modeling time-varying effects for time-to-event data can be challenging due to small at-risk sets and numerical instability near the end of the follow-up period. surtvep addresses these challenges by implementing a computationally efficient Kronecker product-based proximal algorithm, supporting both unstratified and stratified models. The package also incorporates P-spline and smoothing spline penalties to improve estimation (Eilers & Marx, 1996). Cross-validation and information criteria are available to determine the optimal tuning parameters. Parallel computation is enabled to further enhance computational efficiency. A variety of operating characteristics are provided, including estimated time-varying effects, confidence intervals, hypothesis testing, and estimated hazard functions and survival probabilities. The surtvep package thus offers a comprehensive and flexible solution to analyzing large-scale time-to-event data with dynamic effect trajectories.