Faculty Bibliography

BACKGROUND/UNASSIGNED:Fewer minoritized patients with end-stage kidney disease (ESKD) receive kidney transplantation (KT); efforts to mitigate disparities have thus far failed. Pinpointing the specific stage(s) within the transplant care continuum (being informed of KT options, joining the waiting list, to receiving KT) where disparities emerge among each minoritized population is pivotal for achieving equity. We therefore quantified racial and ethnic disparities across the KT care continuum. METHODS/UNASSIGNED:We conducted a retrospective cohort study (2015-2020), with follow-up through 12/10/2021. Patients with incident dialysis were identified using the US national registry data. The exposure was race and ethnicity (Asian, Black, Hispanic, and White). We used adjusted modified Poisson regression to quantify the adjusted prevalence ratio (aPR) of being informed of KT, and cause-specific hazards models to calculate adjusted hazard ratios (aHR) of listing, and transplantation after listing. FINDINGS/UNASSIGNED:Among 637,951 adults initiating dialysis, the mean age (SD) was 63.8 (14.6), 41.8% were female, 5.4% were Asian, 26.3% were Black, 16.6% were Hispanic, and 51.7% were White (median follow-up in years [IQR]:1.92 [0.97-3.39]). Black and Hispanic patients were modestly more likely to be informed of KT (Black: aPR = 1.02, 95% confidence interval [CI]:1.01-1.02; Hispanic: aPR = 1.03, 95% CI: 1.02-1.03) relative to White patients. Asian patients were more likely to be listed (aHR = 1.18, 95% CI: 1.15-1.21) but less likely to receive KT (aHR = 0.56, 95% CI: 0.54-0.58). Both Black and Hispanic patients were less likely to be listed (Black: aHR = 0.87, 95% CI: 0.85-0.88; Hispanic: aHR = 0.85, 95% CI: 0.85-0.88) and receive KT (Black: aHR = 0.61, 95% CI: 0.60-0.63; Hispanic: aHR = 0.64, 95% CI: 0.63-0.66). INTERPRETATION/UNASSIGNED:Improved characterization of the barriers in KT access specific to each racial and ethnic group, and the interventions to address these distinct challenges throughout the KT care continuum are needed; our findings identify specific stages most in need of mitigation. FUNDING/UNASSIGNED:National Institutes of Health.

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice.

In controlled organ donation after circulatory determination of death (cDCDD), accurate and timely death determination is critical, yet knowledge gaps persist. Further research to improve the science of defining and determining death by circulatory criteria is therefore warranted. In a workshop sponsored by the National Heart, Lung, and Blood Institute, experts identified research opportunities pertaining to scientific, conceptual, and ethical understandings of DCDD and associated technologies. This article identifies a research strategy to inform the biomedical definition of death, the criteria for its determination, and circulatory death determination in cDCDD. Highlighting knowledge gaps, we propose that further research is needed to inform the observation period following cessation of circulation in pediatric and neonatal populations, the temporal relationship between the cessation of brain and circulatory function after the withdrawal of life-sustaining measures in all patient populations, and the minimal pulse pressures that sustain brain blood flow, perfusion, activity, and function. Additionally, accurate predictive tools to estimate time to asystole following the withdrawal of treatment and alternative monitoring modalities to establish the cessation of circulatory, brainstem, and brain function are needed. The physiologic and conceptual implications of postmortem interventions that resume circulation in cDCDD donors likewise demand attention to inform organ recovery practices. Finally, because jurisdictionally variable definitions of death and the criteria for its determination may impede collaborative research efforts, further work is required to achieve consensus on the physiologic and conceptual rationale for defining and determining death after circulatory arrest.

Ionic imbalances and sodium channel dysfunction, well-known sequelae of traumatic brain injury (TBI), promote functional impairment in affected subjects. Therefore, non-invasive measurement of sodium concentrations using ²³Na MRI has the potential to detect clinically relevant injury and predict persistent symptoms. Recently, we reported diffusely lower apparent total sodium concentrations (aTSC) in mild TBI patients compared to controls, as well as correlations between lower aTSC and worse clinical outcomes. The main goal of this study was to determine whether these aTSC findings, and their changes over time, predict outcomes at 3- and 12-month from injury. Twenty-seven patients previously studied with ²³Na MRI and outcome measures at 22 ± 10 days (average ± standard deviation) after injury (visit-1, v1) were contacted at 3- (visit-2, v2) and 12-month after injury (visit-3, v3) to complete the Rivermead post-concussion symptoms questionnaire (RPQ), the extended Glasgow outcome scale (GOSE), and the brief test of adult cognition by telephone (BTACT). Follow-up ¹H and ²³Na MRI were additionally scheduled at v2. Linear regression was used to calculate aTSC in global grey and white matters. Six hypotheses were tested in relation to the serial changes in outcome measures and in aTSC, and in relation to the cross-sectional and serial relationships between aTSC and outcome. Twenty patients contributed data at v2 and fifteen at v3. Total RPQ and composite BTACT z-scores differed significantly for v2 and v3 in comparison to v1 (each P < 0.01), reflecting longitudinally reduced symptomatology and improved performance on cognitive testing. No associations between aTSC and outcome were observed at v2. Previously lower grey and white matter aTSC normalized at v2 in comparison to controls, in line with a statistically detectable longitudinal increase in grey matter aTSC between v1 and v2 (P = 0.0004). aTSC values at v1 predicted a subset of future BTACT subtest scores, but not future RPQ scores nor GOSE-defined recovery status. Similarly, aTSC rates of change correlated with BTACT rates of change, but not with those of RPQ. Tissue aTSC, previously shown to be diffusely decreased compared to controls at v1, was no longer reduced by v2, suggesting normalization of the sodium ionic equilibrium. These changes were accompanied by marked improvement in outcome. The results support the notion that early aTSC from ²³Na MRI predicts future BTACT, but not RPQ scores, nor future GOSE status.

OBJECTIVE:Given the significant disparities in diabetes burden and access to care, this study uses qualitative interviews of Black men having HbA1c levels consistent with previously undiagnosed diabetes or prediabetes to understand their perceptions of the healthcare system. RESEARCH DESIGN AND METHODS/METHODS:We recruited Black men from Black-owned barbershops in Brooklyn, NY, who were screened using point-of-care HbA1c tests. Among those with HbA1c levels within prediabetes or diabetes thresholds, qualitative interviews were conducted to uncover prevalent themes related to their overall health status, health behaviors, utilization of healthcare services, and experiences with the healthcare system. We used a theoretical framework from the William and Mohammed medical mistrust model to guide our qualitative analysis. RESULTS:Fifty-two Black men without a prior history of diabetes and an HbA1c reading at or above 5.7% were interviewed. Many participants stated that their health was in good condition. Some participants expressed being surprised by their abnormal HbA1c reading because it was not previously mentioned by their healthcare providers. Furthermore, many of our participants shared recent examples of negative interactions with physicians when describing their experiences with the healthcare system. Finally, several participants cited a preference for incorporating non-pharmaceutical options in their diabetes management plans. CONCLUSION/CONCLUSIONS:To help alleviate the disparity in diabetes burden among Black men, healthcare providers should take a more active role in recognizing and addressing their own implicit biases, engage in understanding the specific healthcare needs and expectations of each patient, and consider emphasizing non-medication approaches to improve glycemic control.

IMPORTANCE:Emergency department (ED) pediatric readiness is associated with improved survival among children. However, the association between geographic access to high-readiness EDs in US trauma centers and mortality is unclear. OBJECTIVE:To evaluate the association between the proximity of injury location to receiving trauma centers, including the level of ED pediatric readiness, and mortality among injured children. DESIGN, SETTING, AND PARTICIPANTS:This retrospective cohort study used a standardized risk-adjustment model to evaluate the association between trauma center proximity, ED pediatric readiness, and in-hospital survival. There were 765 trauma centers (level I-V, adult and pediatric) that contributed data to the National Trauma Data Bank (January 1, 2012, through December 31, 2017) and completed the 2013 National Pediatric Readiness Assessment (conducted from January 1 through August 31, 2013). The study comprised children aged younger than 18 years who were transported by ground to the included trauma centers. Data analysis was performed between January 1 and March 31, 2022. EXPOSURES:Trauma center proximity within 30 minutes by ground transport and ED pediatric readiness, as measured by weighted pediatric readiness score (wPRS; range, 0-100; quartiles 1 [low readiness] to 4 [high readiness]). MAIN OUTCOMES AND MEASURES:In-hospital mortality. We used a patient-level mixed-effects logistic regression model to evaluate the association of transport time, proximity, and ED pediatric readiness on mortality. RESULTS:This study included 212 689 injured children seen at 765 trauma centers. The median patient age was 10 (IQR, 4-15) years, 136 538 (64.2%) were male, and 127 885 (60.1%) were White. A total of 4156 children (2.0%) died during their hospital stay. The median wPRS at these hospitals was 79.1 (IQR, 62.9-92.7). A total of 105 871 children (49.8%) were transported to trauma centers with high-readiness EDs (wPRS quartile 4) and another 36 330 children (33.7%) were injured within 30 minutes of a quartile 4 ED. After adjustment for confounders, proximity, and transport time, high ED pediatric readiness was associated with lower mortality (highest-readiness vs lowest-readiness EDs by wPRS quartiles: adjusted odds ratio, 0.65 [95% CI, 0.47-0.89]). The survival benefit of high-readiness EDs persisted for transport times up to 45 minutes. The findings suggest that matching children to trauma centers with high-readiness EDs within 30 minutes of the injury location may have potentially saved 468 lives (95% CI, 460-476 lives), but increasing all trauma centers to high ED pediatric readiness may have potentially saved 1655 lives (95% CI, 1647-1664 lives). CONCLUSIONS AND RELEVANCE:These findings suggest that trauma centers with high ED pediatric readiness had lower mortality after considering transport time and proximity. Improving ED pediatric readiness among all trauma centers, rather than selective transport to trauma centers with high ED readiness, had the largest association with pediatric survival. Thus, increased pediatric readiness at all US trauma centers may substantially improve patient outcomes after trauma.

IMPORTANCE:Presentation to emergency departments (EDs) with high levels of pediatric readiness is associated with improved pediatric survival. However, it is unclear whether children of all races and ethnicities benefit equitably from increased levels of such readiness. OBJECTIVE:To evaluate the association of ED pediatric readiness with in-hospital mortality among children of different races and ethnicities with traumatic injuries or acute medical emergencies. DESIGN, SETTING, AND PARTICIPANTS:This cohort study of children requiring emergency care in 586 EDs across 11 states was conducted from January 1, 2012, through December 31, 2017. Eligible participants included children younger than 18 years who were hospitalized for an acute medical emergency or traumatic injury. Data analysis was conducted between November 2022 and April 2023. EXPOSURE:Hospitalization for acute medical emergency or traumatic injury. MAIN OUTCOMES AND MEASURES:The primary outcome was in-hospital mortality. ED pediatric readiness was measured through the weighted Pediatric Readiness Score (wPRS) from the 2013 National Pediatric Readiness Project assessment and categorized by quartile. Multivariable, hierarchical, mixed-effects logistic regression was used to evaluate the association of race and ethnicity with in-hospital mortality. RESULTS:The cohort included 633 536 children (median [IQR] age 4 [0-12] years]). There were 557 537 children (98 504 Black [17.7%], 167 838 Hispanic [30.1%], 311 157 White [55.8%], and 147 876 children of other races or ethnicities [26.5%]) who were hospitalized for acute medical emergencies, of whom 5158 (0.9%) died; 75 999 children (12 727 Black [16.7%], 21 604 Hispanic [28.4%], 44 203 White [58.2%]; and 21 609 of other races and ethnicities [27.7%]) were hospitalized for traumatic injuries, of whom 1339 (1.8%) died. Adjusted mortality of Black children with acute medical emergencies was significantly greater than that of Hispanic children, White children, and of children of other races and ethnicities (odds ratio [OR], 1.69; 95% CI, 1.59-1.79) across all quartile levels of ED pediatric readiness; but there were no racial or ethnic disparities in mortality when comparing Black children with traumatic injuries with Hispanic children, White children, and children of other races and ethnicities with traumatic injuries (OR 1.01; 95% CI, 0.89-1.15). When compared with hospitals in the lowest quartile of ED pediatric readiness, children who were treated at hospitals in the highest quartile had significantly lower mortality in both the acute medical emergency cohort (OR 0.24; 95% CI, 0.16-0.36) and traumatic injury cohort (OR, 0.39; 95% CI, 0.25-0.61). The greatest survival advantage associated with high pediatric readiness was experienced for Black children in the acute medical emergency cohort. CONCLUSIONS AND RELEVANCE:In this study, racial and ethnic disparities in mortality existed among children treated for acute medical emergencies but not traumatic injuries. Increased ED pediatric readiness was associated with reduced disparities; it was estimated that increasing the ED pediatric readiness levels of hospitals in the 3 lowest quartiles would result in an estimated 3-fold reduction in disparity for pediatric mortality. However, increased pediatric readiness did not eliminate disparities, indicating that organizations and initiatives dedicated to increasing ED pediatric readiness should consider formal integration of health equity into efforts to improve pediatric emergency care.

Use of extracorporeal membrane oxygenation (ECMO) in cardiopulmonary resuscitation, termed eCPR, offers the prospect of improving survival with good neurological function after cardiac arrest. After death, ECMO can also be used for enhanced preservation of abdominal and thoracic organs, designated normothermic regional perfusion (NRP), before organ recovery for transplantation. To optimize resuscitation and transplantation outcomes, healthcare networks in Portugal and Italy have developed cardiac arrest protocols that integrate use of eCPR with NRP. Similar dissemination of eCPR and its integration with NRP in the USA raise novel ethical issues due to a non-nationalized health system and an opt-in framework for organ donation, as well as other legal and cultural factors. Nonetheless, eCPR investigations are ongoing, and both eCPR and NRP are selectively employed in clinical practice. This paper delineates the most pressing relevant ethical considerations and proposes recommendations for implementation of protocols that aim to promote public trust and reduce conflicts of interest. Transparent policies should rely on protocols that separate lifesaving from organ preservation considerations; robust, centralized eCPR data to inform equitable and evidence-based allocations; uniform practices concerning clinical decision-making and resource utilization; and partnership with community stakeholders, allowing patients to make decisions about emergency care that align with their values. Proactively addressing these ethical and logistical challenges could enable eCPR dissemination and integration with NRP protocols in the USA, with the potential to maximize lives saved through both improved resuscitation with good neurological outcomes and increased organ donation opportunities when resuscitation is unsuccessful or not in accordance with individuals' wishes.

PURPOSE/OBJECTIVE:H MRS) offers biomarkers of metabolic damage after mild traumatic brain injury (mTBI), but a lack of replicability studies hampers clinical translation. In a conceptual replication study design, the results reported in four previous publications were used as the hypotheses (H1-H7), specifically: abnormalities in patients are diffuse (H1), confined to white matter (WM) (H2), comprise low N-acetyl-aspartate (NAA) levels and normal choline (Cho), creatine (Cr) and myo-inositol (mI) (H3), and correlate with clinical outcome (H4); additionally, a lack of findings in regional subcortical WM (H5) and deep gray matter (GM) structures (H6), except for higher mI in patients' putamen (H7). METHODS:26 mTBI patients (20 female, age 36.5 ± 12.5 [mean ± standard deviation] years), within two months from injury and 21 age-, sex-, and education-matched healthy controls were scanned at 3 Tesla with 3D echo-planar spectroscopic imaging. To test H1-H3, global analysis using linear regression was used to obtain metabolite levels of GM and WM in each brain lobe. For H4, patients were stratified into non-recovered and recovered subgroups using the Glasgow Outcome Scale Extended. To test H5-H7, regional analysis using spectral averaging estimated metabolite levels in four GM and six WM structures segmented from T1-weighted MRI. The Mann-Whitney U test and weighted least squares analysis of covariance were used to examine mean group differences in metabolite levels between all patients and all controls (H1-H3, H5-H7), and between recovered and non-recovered patients and their respectively matched controls (H4). Replicability was defined as the support or failure to support the null hypotheses in accordance with the content of H1-H7, and was further evaluated using percent differences, coefficients of variation, and effect size (Cohen's d). RESULTS:Patients' occipital lobe WM Cho and Cr levels were 6.0% and 4.6% higher than controls', respectively (Cho, d = 0.37, p = 0.04; Cr, d = 0.63, p = 0.03). The same findings, i.e., higher patients' occipital lobe WM Cho and Cr (both p = 0.01), but with larger percent differences (Cho, 8.6%; Cr, 6.3%) and effect sizes (Cho, d = 0.52; Cr, d = 0.88) were found in the comparison of non-recovered patients to their matched controls. For the lobar WM Cho and Cr comparisons without statistical significance (frontal, parietal, temporal), unidirectional effect sizes were observed (Cho, d = 0.07 - 0.37; Cr, d = 0.27 - 0.63). No differences were found in any metabolite in any lobe in the comparison between recovered patients and their matched controls. In the regional analyses, no differences in metabolite levels were found in any GM or WM region, but all WM regions (posterior, frontal, corona radiata, and the genu, body, and splenium of the corpus callosum) exhibited unidirectional effect sizes for Cho and Cr (Cho, d = 0.03 - 0.34; Cr, d = 0.16 - 0.51). CONCLUSIONS:H MRS biomarkers for mTBI may best be achieved by using high signal-to-noise-ratio single-voxels placed anywhere within WM. The biochemical signature of the injury, however, may differ and therefore absolute levels, rather than ratios may be preferred. Future replication efforts should further test the generalizability of these findings.

BACKGROUND:Housing insecurity is prevalent among emergency department (ED) patients. Despite a surge of interest in screening for patients' social needs including housing insecurity, little research has examined ED social needs interventions. We worked together with government and community partners to develop and pilot test a homelessness prevention intervention targeted to ED patients with drug or unhealthy alcohol use. METHODS:We approached randomly sampled patients at an urban public hospital ED, May to August 2019. Adult patients were eligible if they were medically stable, not incarcerated, spoke English, had unhealthy alcohol or any drug use, and were not currently homeless but screened positive for risk of future homelessness using a previously developed risk screening tool. Participants received a three-part intervention: (1) brief counseling and referral to treatment for substance use delivered through a preexisting ED program; (2) referral to Homebase, an evidence-based community homelessness prevention program; and (3) up to three troubleshooting phone calls by study staff. Participants completed surveys at baseline and 6 months. RESULTS:Of 2183 patients screened, 51 were eligible and 40 (78.4%) participated; one later withdrew, leaving 39 participants. Participants were diverse in age, gender, race, and ethnicity. Of the 32 participants reached at 6 months, most said it was very or extremely helpful to talk to someone about their housing situation (n = 23, 71.9%) at the baseline ED visit. Thirteen (40.6%) said their housing situation had improved in the past 6 months and 16 (50.0%) said it had not changed. Twenty participants (62.5%) had made contact with a Homebase office. Participants shared ideas of how to improve the intervention. CONCLUSIONS:This pilot intervention was feasible and well received by participants though it required a large amount of screening to identify potentially eligible patients. Our findings will inform a larger future trial and may be informative for others seeking to develop similar interventions.