Faculty Bibliography

INTRODUCTION/BACKGROUND:The coronavirus disease 2019 (COVID-19) pandemic caused unprecedented disruptions to healthcare systems worldwide, significantly affecting patients with chronic kidney disease (CKD). In this study, we evaluated the impact of the pandemic on healthcare-seeking behavior and CKD progression among patients in New York City. METHODS:Using electronic health records from PCORnet's INSIGHT Clinical Research Network, we conducted a retrospective cohort study focused on 84,062 patients with CKD aged 50 years or older with multiple chronic conditions seen between 2017 and 2022. Patients were identified using pre-pandemic CKD diagnostic codes, and confirmed by estimated glomerular filtration rate (eGFR) measurements. Care disruption was defined as receiving fewer visits than recommended by Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. We used linear mixed-effects models to estimate annual eGFR changes and analyze trends in care visits stratified by CKD stage and care disruption. RESULTS:. Care visits declined sharply in 2020 across patients at all but the end stage, with incomplete recovery by 2022. Patients with adequate pre-pandemic care maintained their visits above KDIGO levels, while those with inadequate care increased visits during the pandemic. Pronounced eGFR decline occurred in 2020 (10.6%), with slower declines observed thereafter. CONCLUSION/CONCLUSIONS:The COVID-19 pandemic disrupted CKD care, potentially leading to reduced healthcare-seeking behavior and accelerated kidney function decline in 2020. Slower decline post-2020 may reflect improved healthcare utilization, better medication adherence, and new therapies, and other factors.

BACKGROUND:Prior authorizations could hinder the filling of life-saving heart failure (HF) medications, such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2is). OBJECTIVES/OBJECTIVE:The aim of the study was to determine whether prior authorizations were associated with delayed or decreased filling for ARNI and SGLT2i. METHODS:This was a retrospective cohort study using electronic health record, pharmacy fill, and neighborhood-level data from a large, academic health system. We included patients with HF and a new prescription for ARNI or SGLT2i between April 1, 2021, and April 30, 2023, and assessed for presence of prior authorization requirement. Outcomes included days to first fill and never filling the prescription. Analyses were conducted using inverse probability weighting methods. RESULTS:Among 2,183 patients, 12.2% (152/1,243) and 14.3% (165/1,150) had a prior authorization requirement for ARNI or SGLT2i, respectively. Patients requiring prior authorization tended to be younger, identify as non-Hispanic Black or Hispanic, have non-Medicare insurance, and have fewer comorbidities. In weighted models, patients requiring prior authorization took 3.03 (95% CI: 2.16-4.25) times longer to fill ARNI, 6.75 (95% CI: 4.44-10.3) times longer to fill SGLT2i, and were 2.23 (95% CI: 1.37-3.65) times more likely to never fill SGLT2i prescriptions (all P < 0.001). CONCLUSIONS:Prior authorization requirements were more common for patients identifying as Black or Hispanic and were associated with decreased and delayed filling of ARNI and SGLT2i. Our findings highlight an important barrier to mortality-reducing, guideline-recommended medications for HF.

Phthalates are widely used in consumer products and are recognized as endocrine disruptors. Prenatal exposure to phthalates has been associated with various adverse health outcomes, including preterm birth and impaired fetal growth, and growing attention is being paid to their potential impact on child neurodevelopment. However, previous epidemiological studies examining prenatal phthalate exposure and child neurodevelopment have produced inconsistent or inconclusive findings, and evidence on phthalate mixtures remains limited. In this study, we utilized data from the Environmental influences on Child Health Outcomes (ECHO) Cohort to investigate associations between urinary biomarkers of prenatal phthalate exposure, both individually and as a mixture, and likelihood of neurodevelopmental delay (NDD) in offspring at ages 1 to 3 years. This study included 2378 pregnant person-child dyads from 10 ECHO cohorts who had measurements of NDD odds assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3). Our single-pollutant analyses revealed mixed findings. Higher prenatal exposure to certain phthalates was associated with higher odds of NDD across multiple domains, including motor and problem-solving skills, with evidence of effect modification by child sex. Conversely, we observed negative associations between specific prenatal phthalate concentrations and lower odds of NDD, particularly in communication domain. From mixture analyses, however, no significant associations were observed between the overall phthalate mixture and NDD odds in most domains, except for negative association for the personal-social domain. Further investigation into the biological mechanisms underlying these relationships, as well as more detailed evaluations of phthalate mixtures, will help advance our understanding of how prenatal phthalate exposure may influence early childhood neurodevelopment.

Maternal psychological distress during pregnancy and the early postpartum period is a risk factor for dysregulated affective and regulatory function in young infants. Animal models suggest that perinatal stress may alter offspring development via allopregnanolone (ALLO) exposure. For example, variations in placentally derived ALLO in preterm infants have been linked with altered fetal neurodevelopment. However, no studies have investigated naturalistic variations in ALLO concentrations in maternal milk as a potential moderator of associations between maternal distress and infant temperament during the postnatal period. The current study assesses associations among ALLO concentrations in human milk, maternal psychological distress, and infant temperament in 81 mother-infant dyads (31 females) measured at approximately 6.5 months postpartum (M = 6.55 months, range = 5.5-8 months). Results indicated that human milk ALLO concentration moderated effects of maternal psychological distress on infant regulatory capacity. Specifically, there was a negative association between maternal psychological distress and regulatory capacity in infants of mothers with below-mean ALLO concentrations, but not in infants of mothers with above-mean ALLO concentrations. However, there were no effects of ALLO on infant negative affect or surgency/positive affect. This study provides some of the first preliminary evidence that ALLO concentrations in human milk may moderate associations between maternal psychological distress and infant regulatory capacity.

Health literacy and language impact comprehension of and adherence to written educational materials, including those for gastrostomy tubes (g-tubes). Our objective was to evaluate the readability, understandability, actionability, content, and language availability of a national sample of written g-tube educational materials. We conducted a cross-sectional study of g-tube educational materials from top 20 children's hospitals (US News and World Report) obtained via a systematic online search and provided by the institutions. We assessed material: (1) readability, (2) understandability and actionability (Patient Education Materials Assessment Tool for Printable Materials, (3) content, and (4) language availability. Mean (standard deviation [SD]) reading grade level was 8.3 (1.9). Mean (SD) understandability and actionability scores were 81.6% (12.1%) and 65.9% (23.2%), respectively. Materials covered a mean (SD) of 46.1% (25.3%) of content items; 20% of institutions provided materials in non-English languages. Future research should examine how to improve educational materials for children with g-tubes.

INTRODUCTION/BACKGROUND:Following implementation of the U.S. Kidney Allocation System (KAS) in 2014, deceased donor kidneys with a kidney donor profile index (KDPI) < 35% are prioritized for allocation to pediatric candidates. Early post-KAS data suggested this prioritization may have led to more frequent delayed graft function compared to pre-KAS, when pediatric allocation priority was based on donor age < 35 years. We sought to understand the impact of this allocation change on longer-term pediatric kidney transplant outcomes. METHODS:We used SRTR data to identify all deceased donor kidney transplants with pediatric recipients during two eras: "Pre-KAS" (12/1/2009-11/30/2014) and "KAS" (12/1/2015-11/30/2020). We used Cox proportional hazards models to calculate the association between study era and all-cause graft failure (graft failure or death) after adjusting for recipient characteristics. RESULTS:, p = 0.001). Results were similar in sensitivity analyses limited to recipients < 10 years old and recipients alive with a functioning graft 90 days post-transplant. CONCLUSIONS:KDPI-based prioritization of kidneys for pediatric allocation was associated with a lower risk of graft failure compared to donor age-based prioritization. Further refining donor risk scores may enable additional improvements in graft survival.

OBJECTIVE:This study aimed to characterize bariatric surgery-induced changes in serum metabolites while accounting for changes in glomerular filtration rate (GFR) to understand the metabolic benefits to the kidney of bariatric surgery. METHODS:This was a prospective, single-center cohort of 27 adults with severe obesity who underwent bariatric surgery. Serum metabolomics and measured GFR (mGFR) were performed 1-3 months prior to and 6 months after surgery. In generalized estimating equation (GEE) models, we examined bariatric surgery- and mGFR-associated changes in serum metabolites. We used MetaboAnalyst to perform pathway analyses. RESULTS:Bariatric surgery was significantly associated with changes in 223 serum metabolites after adjustment. Following bariatric surgery, several pathways were downregulated (alpha-linoleic acid and linoleic acid, methionine, kynurenine, and alanine-glucose metabolism pathways; raw p < 0.05) or upregulated (phenylacetate, bile acid biosynthesis, taurine and hypo-taurine metabolism, porphyrin metabolism pathways; raw p < 0.05). Creatinine demonstrated a significant mGFR-independent decrease following surgery. The top metabolites significantly associated with mGFR included N,N,N-trimethyl-alanyl proline betaine (TMAP), followed by creatinine. CONCLUSIONS:We discovered several GFR-independent metabolomic changes after bariatric surgery which may underlie its beneficial kidney effects including decreased inflammation, oxidation, and insulin resistance. Further studies are needed to investigate the potential mechanistic role of identified metabolites to clarify mechanisms of obesity-related kidney disease.

PURPOSE/OBJECTIVE:Prediction models can contribute to disparities in care by performing unequally across demographic groups. While fairness-aware methods have been explored for binary outcomes, applications to survival analysis remain limited. This study compares two fairness-aware deep learning survival models to mitigate racial disparities in predicting survival after radical prostatectomy for prostate cancer. METHODS:We used the National Cancer Database to train deep Cox proportional hazards models for overall survival. Two fairness-aware approaches, Fair Deep Cox Proportional Hazards Model (Fair DCPH) and Group Distributionally Robust Optimization Deep Cox Proportional Hazards Model (GroupDRO DCPH), were compared against a standard Deep Cox model (Baseline). Model fairness was assessed via cross-group and within-group concordance indices (C-index). RESULTS:Among 418,968 included patients, 78.5% were White, with smaller proportions of Black (13.2%), Hispanic (4.5%), Asian (1.9%), and Other (2.0%) patients. The baseline DCPH model achieved a cross-group C-index of 0.699 for White patients but showed reduced performance for Black (0.678) and Hispanic (0.689) patients. Fairness-aware models improved cross-group C-indices; for Black patients, cross-group C-index increased to 0.692 (Fair DCPH) and 0.696 (GroupDRO DCPH); for Hispanic patients, to 0.693 and 0.697, respectively. Cross-group C-index also improved in the Asian subgroup, where the C-index rose from 0.696 (Baseline DCPH) to 0.702 (Fair DCPH) and 0.707 (GroupDRO DCPH), with minimal performance loss observed for White patients. CONCLUSION/CONCLUSIONS:We benchmark two fairness-aware survival models that address racial disparities in post-prostatectomy survival prediction. These methods can be extended to other time-to-event models to ensure equitable care supported by fair prediction models.