Adjustment For Race Research Articles

PTSD is associated with accelerated transcriptional aging in World Trade Center responders

Posttraumatic stress disorder (PTSD) is associated with shortened lifespan and healthspan, which suggests accelerated aging. Emerging evidence suggests that methylation age may be accelerated in PTSD. It is important to examine whether transcriptional age is also accelerated because transcriptome is highly dynamic, associated with age-related outcomes, and may offer greater insight into the premature aging in PTSD. This study is the first reported investigation of the relationship between transcriptional age and PTSD. Using RNA-Seq data from our previous study on 324 World Trade Center responders (201 never had PTSD, 81 with current PTSD, and 42 with past PTSD), as well as a transcriptional age calculator (RNAAgeCalc) recently developed by our group, we found that responders with current PTSD, compared with responders without a PTSD diagnosis, showed accelerated transcriptional aging (p = 0.0077) after adjustment for chronological age and race. We compared our results to the epigenetic aging results computed from several epigenetic clock calculators on matching DNA methylation data. GrimAge methylation age acceleration was also associated with PTSD diagnosis (p = 0.0097), and the results remained significant after adjustment for the proportions of immune cell types. PhenoAge, Hannum, and Horvath methylation age acceleration were not reliably related to PTSD. Both epigenetic and transcriptional aging may provide biological insights into the mechanisms underpinning aging in PTSD.

Analysis of patterns of care and benefit of thoracic radiotherapy for patients with stage IV NSCLC in the immunotherapy-era from a national hospital-based registry.

9123 Background: Metastatic non-small cell lung cancer (mNSCLC) has classically been treated with platinum-doublet chemotherapy. Recent studies have established immunotherapy as an integral part of therapy for mNSCLC without targetable mutations. There are limited data on the role of consolidative thoracic radiotherapy (TRT) for patients with mNSCLC in the immunotherapy-era. A secondary analysis of KEYNOTE-001 showed significant improvement in overall survival in patients who received radiotherapy with pembrolizumab compared to patients not previously receiving radiotherapy. Methods: We queried the National Cancer Database (NCDB) for patients with metastatic presentation, stage IVA/IVB non-small cell lung cancer between the ages of 18-90 years treated between 2012-2017 with a combination of chemotherapy, immunotherapy, and thoracic radiotherapy. Patients with unknown treatment status, follow up time, or vital status were excluded. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between treatment groups utilizing log-rank testing. A 3:1 nearest-neighbor propensity-score matching was performed utilizing clinical and demographic covariates to reduce the impact of potential confounders of overall survival on the probability of receipt of TRT. Cox proportional hazards regression was used to identify predictors of overall survival. Results: A total of 81,382 patients were identified that met inclusion criteria. The median age was 68 (18-90) years. The majority of patients (n = 51,681, 64%) had chemotherapy, while 7,929 (10%) patients received immunotherapy, and 15,984 (20%) received TRT. The median follow-up was 6.18 (range 0-76.9) months. For the entire cohort of patients receiving immunotherapy, 2 year OS was 29.4% with TRT compared to 32.7% without. Following propensity matching by age, sex, race, and comorbidity score, a total number of 4,264 patients receiving immunotherapy were matched. The 2 year OS was 27.7% in patients receiving TRT and immunotherapy vs. 22.2% in patients with immunotherapy alone (p = 0.004). On multivariable analysis receipt of TRT was a significant predictor of OS after adjustment for age, race, comorbidity score, sex, and median income (p = 0.0003, HR 0.87, 95% CI 0.80 - 0.94). For patients receiving BED10 > 39 Gy (equivalent to 30 Gy in 10 fractions), 2 year OS was significantly improved at 37.0% vs 18.1% (p < 0.0001). Conclusions: In patients with mNSCLC, the addition of TRT to immunotherapy is associated with improved overall survival at 2 years. Receipt of a higher BED10 is associated with further improved survival. Selection of mNSCLC patients receiving immunotherapy for TRT approaching definitive doses warrants further investigation. Data from prospective, randomized trials may better elucidate this benefit and identify a potential mechanism.

The relationship between chronic arsenic exposure and body measures among US adults: National Health and Nutrition Examination Survey 2009-2016

BackgroundCurrent research on the relationship between arsenic and body measures is inconclusive. We explored the relationship between arsenic and body measures in a large cohort representative of the United States population. MethodsData were analyzed from the 2009–2016 National Health and Nutrition Examination Survey (NHANES). We examined the relationship between quartiles of urinary arsenic metabolites and BMI as a continuous variable, BMI by obesity category, and waist circumference, using linear regression models without and with adjustment for gender, age, diabetes, hypertension, race, smoking, and alcohol use. A piecewise linear spline model with a knot at 4.26 μg/L/day, the urinary-flow-rate-adjusted dimethylarsinic acid median, modeled a non-linear relationship between dimethylarsinic acid and BMI. ResultsThe 6,848 participants were 51.4 % female, 13.6 % diabetic, 37.7 % hypertensive, 40.3 % white, 38 % obese, 20.3 % non-drinkers, and 56.0 % never-smokers. Compared to the lowest quartile, the highest quartile of daily excretion of all urinary arsenic metabolites was associated with lower BMI, waist circumference, and obesity except for dimethylarsinic acid in unadjusted and adjusted analyses. The same relationship was found with analysis of BMI and waist circumference as continuous variables. Urinary-flow-rate-adjusted dimethylarsinic acid was found to have a non-linear relationship with BMI with increasing excretion up to the median (4.78, 95 %CI = 0.30, 9.27; p = 0.04), and decreasing excretion beyond (-0.69, 95 %CI=-1.23, -0.16; p = 0.01). ConclusionWe found a strong inverse relationship between body measures and daily excretion of all urinary arsenic metabolites except dimethylarsinic acid, which had a positive relationship with BMI up to 4.26 μg/L/day, and an inverse relationship beyond it.

Clinical Characteristics and Outcomes Among COVID 19 Hospitalized Patients in a Community Hospital in New York City

Background: COVID-19 has disproportionally affected communities of color in the US. These communities exhibit higher prevalence of chronic preventable disease including type 2 diabetes mellitus (DM2) and obesity. DM2 and obesity have been linked to higher morbidity and mortality in the setting of COVID-19 infection (1). Methods: We query data collected from 521 patients with laboratory-confirmed Covid-19 infection admitted to an inner-city community hospital in Brooklyn, New York between March 20 2020 and May 15 2020. Demographics, pre-infection medical comorbidities, laboratory data at admission and clinical outcomes including in-hospital mortality were analyzed. Results: Patients were 61 years on average (+/-17.2), 42.8% were female, 53.9% were Hispanic and 33% were African-American. Most common comorbidities included: hypertension (62%), chronic kidney disease (20.8%), diabetes (45 %). Mean BMI was 29.9 (+/- 8.2). Among patients with no prior diagnosis of diabetes mean A1c was 5.8% (+/-1.2) and 8.7 (+/-2.5) amongst those with a previous diagnosis of diabetes. Patients hospitalized with moderate to severe COVID-19 infection and a previous diagnosis of DM2 had significantly higher prevalence of CKD and HTN. Amongst those with T2DM, 19.1% presented with DKA. After adjustment for age, gender, race, BMI and creatinine obese patients, compared with normal-weight patients had significantly higher mortality rate (BMI > 30 kg/m2 [OR: 2.29, CI: 95%, P-value: <0.002]) however this association was not observed for DM2 ([OR: 1.25, CI: 95%, P-value: <0.002]). Conclusion: Our cohort represents a particular population affected by the first wave of Covid-19 infection in an urban inner-city community in NYC. The population studied had a larger proportion of African-American, Hispanic and younger patients compared to national averages; these differences are related to the demographics of the communities served by our hospital. Obesity is a negative prognostic factor in the course of Covid-19 infection in comparison to normal-weight patients. Obesity is a proinflammatory condition, associated with high levels of prothrombotic factors including angiotensin-II, also elevated in COVID-19. Understanding that link may yield valuable knowledge on the role obesity plays in numerous disease states beyond COVID-19.

SARS-CoV-2 Cardiac Involvement in Young Competitive Athletes.

Cardiac involvement among hospitalized patients with severe coronavirus disease 2019 (COVID-19) is common and associated with adverse outcomes. This study aimed to determine the prevalence and clinical implications of COVID-19 cardiac involvement in young competitive athletes. In this prospective, multicenter, observational cohort study with data from 42 colleges and universities, we assessed the prevalence, clinical characteristics, and outcomes of COVID-19 cardiac involvement among collegiate athletes in the United States. Data were collected from September 1, 2020, to December 31, 2020. The primary outcome was the prevalence of definite, probable, or possible COVID-19 cardiac involvement based on imaging definitions adapted from the Updated Lake Louise Imaging Criteria. Secondary outcomes included the diagnostic yield of cardiac testing, predictors for cardiac involvement, and adverse cardiovascular events or hospitalizations. Among 19 378 athletes tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 3018 (mean age, 20 years [SD, 1 year]; 32% female) tested positive and underwent cardiac evaluation. A total of 2820 athletes underwent at least 1 element of cardiac triad testing (12-lead ECG, troponin, transthoracic echocardiography) followed by cardiac magnetic resonance imaging (CMR) if clinically indicated. In contrast, primary screening CMR was performed in 198 athletes. Abnormal findings suggestive of SARS-CoV-2 cardiac involvement were detected by ECG (21 of 2999 [0.7%]), cardiac troponin (24 of 2719 [0.9%]), and transthoracic echocardiography (24 of 2556 [0.9%]). Definite, probable, or possible SARS-CoV-2 cardiac involvement was identified in 21 of 3018 (0.7%) athletes, including 15 of 2820 (0.5%) who underwent clinically indicated CMR (n=119) and 6 of 198 (3.0%) who underwent primary screening CMR. Accordingly, the diagnostic yield of CMR for SARS-CoV-2 cardiac involvement was 4.2 times higher for a clinically indicated CMR (15 of 119 [12.6%]) versus a primary screening CMR (6 of 198 [3.0%]). After adjustment for race and sex, predictors of SARS-CoV-2 cardiac involvement included cardiopulmonary symptoms (odds ratio, 3.1 [95% CI, 1.2, 7.7]) or at least 1 abnormal triad test result (odds ratio, 37.4 [95% CI, 13.3, 105.3]). Five (0.2%) athletes required hospitalization for noncardiac complications of COVID-19. During clinical surveillance (median follow-up, 113 days [interquartile range=90 146]), there was 1 (0.03%) adverse cardiac event, likely unrelated to SARS-CoV-2 infection. SARS-CoV-2 infection among young competitive athletes is associated with a low prevalence of cardiac involvement and a low risk of clinical events in short-term follow-up.

Risk of Symptomatic Kidney Stones During and After Pregnancy

There are several well-known anatomical and physiological changes during pregnancy that could contribute to kidney stone formation, but evidence that they increase the risk of kidney stones during pregnancy is lacking. We determined whether there was an increased risk of a first-time symptomatic kidney stone during and after pregnancy. A population-based matched case-control study. 945 female first-time symptomatic kidney stone formers aged 15-45 years and 1,890 age-matched female controls in Olmsted County, MN, from 1984-2012. The index date was the date of onset of a symptomatic kidney stone for both the case and her matched controls. The primary exposure was pregnancy with assessment for variation in risk across different time intervals before, during, and after pregnancy. Medical records were manually reviewed to determine the conception and delivery dates for pregnancies. Medical record-validated first-time symptomatic kidney stone. Conditional and unconditional multivariable logistic regression analysis. Compared with nonpregnant women, the odds of a symptomatic kidney stone forming in women was similar in the first trimester (OR, 0.92; P=0.8), began to increase during the second trimester (OR, 2.00; P=0.007), further increased during the third trimester (OR, 2.69; P=0.001), peaked at 0 to 3 months after delivery (OR, 3.53; P<0.001), and returned to baseline by 1year after delivery. These associations persisted after adjustment for age and race or for diabetes mellitus, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies. Having a prior pregnancy (delivery date>1year ago) was also associated with a first-time symptomatic kidney stone (OR, 1.27; P=0.01). Observational study design in a predominantly White population. The exact timing of stone formation cannot be determined. Pregnancy increases the risk of a first-time symptomatic kidney stone. This risk peaks close to delivery and then improves by 1 year after delivery, though a modest risk of a kidney stone still exists beyond 1 year after delivery.

POS-233 COMPARISON OF GLOMERULAR FILTRATION RATE EQUATIONS IN A RURAL NEW MEXICO COHORT

Estimated glomerular filtration rate (eGFR) equations use plasma filtration markers to predict kidney function. There are scarce data regarding the performance of various eGFR equations in Indigenous and Hispanic populations. Serum creatinine (SCr) has been historically used to estimate eGFR, but Cystatin C (CysC) and beta-2 microglobulin (B2M) may have less inter-person variability based on muscle mass, age and gender. We hypothesized that the various SCr, CysC or B2M-based eGFR equations will evaluate kidney function differently among Hispanics and Native Americans residing in rural New Mexico (NM). We studied 210 participants from the Community-Based Study of the Epidemiology of Chronic Kidney Disease (CKD) in Cuba, NM and Surrounding Areas (COMPASS). At study enrollment clinical measurements, questionnaires and serum blood specimens were obtained. Samples were analyzed at University of New Mexico’s Clinical Translational Sciences Center and TriCore Reference Laboratories. The method comparison between three eGFR equations was tested using Bland-Altman plots. Participants were racially diverse (American Indian 31.43%), but predominantly white (39.05%), Hispanic (53.81%), women (61.43%) and overweight (BMI 30.29 ± 6.84) (see Table below). The mean difference between CysC-eGFR and SCr-eGFR was 25.4 ml/min/1.73m2, and that between CysC-eGFR and B2M-eGFR was 25.3 ml/min/1.73m2. Agreement between CysC-eGFR and B2M-eGFR was excellent, with a mean difference of -0.12 ml/min/1.73m2 (Figure). Tabled 1Characteristics of Study PopulationSummary (Number of Participants = 210)Age49.80 ± 17.86GenderMales81 (38.57 %)Females129 (61.43 %)EthnicityHispanic or Latino113 (53.81 %)Not Hispanic or Latino96 (45.71 %)Unknown/not reported1 (0.48 %)RaceAmerican Indian/Alaska Natives66 (31.43 %)More than one race6 (2.86 %)Unknown/Not reported56 (26.67 %)White82 (39.05 %)Highest Degree of EducationK-1245 (21.43 %)High School degree87 (41.43 %)Higher than High School degree77 (36.66 %)Not disclosed1 (0.48 %)Health Insurance TypeMedicare34 (16.19 %)Medicaid52 (24.76 %)Other51 (24.29 %)2+ type of insurance55 (26.19 %)Uninsured/not disclosed18 (8.57 %)Blood Pressure (BP)Mean ± stdSystolic BP127 ± 14Diastolic BP77 ± 11Laboratory Values (serum)Body Mass Index (BMI)30.29 ± 6.84Serum glucose levels (mg/dL)121.27 ± 58.84Hemoglobin A1C (%)6.2% ± 0.02Serum Creatinine (mg/dL)0.9 ± 0.25Cystatin C (mg/L)0.72 ± 0.35High Sensitivity C-Reactive Protein (mg/L)4.97 ± 6.47BUN (mg/dL)13.83 ± 4.92Albumin (mg/dL)4.20 ± 0.36Hemoglobin (gm/dL)15.01 ± 1.56Hematocrit (%)44.63 ± 3.96Phosphorous (mg/dL)3.4 ± 0.68Uric Acid (mg/dL)5.12 ± 1.33Calcium (mg/dL)9.51 ± 0.53 Open table in a new tab View Large Image Figure ViewerDownload Hi-res image Download (PPT) As the replacement of race-adjusted, SCr-eGFR with CysC-eGFR gains momentum, it is important to understand potential analytical biases introduced by CysC in other racial and ethnic groups. B2M-eGFR does not require adjustment for age, race, or gender thus may be a more optimal method to calculate GFR. Further studies with objective measurements of kidney function are needed to validate these findings.

Race Adjustment in eGFR Equations Does Not Improve Estimation of Acute Kidney Injury Events in Patients with Cirrhosis.

Accuracy of glomerular filtration rate estimating (eGFR) equations has significant implications in cirrhosis, potentially guiding simultaneous liver kidney allocation and drug dosing. Most equations adjust for Black race, partially accounted for by reported differences in muscle mass by race. Patients with cirrhosis, however, are prone to sarcopenia which may mitigate such differences. We evaluated the association between baseline eGFR and incident acute kidney injury (AKI) in patients with cirrhosis with and without race adjustment. We conducted a retrospective national cohort study of veterans with cirrhosis. Baseline eGFR was calculated using multiple eGFR equations including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), both with and without race adjustment. Poisson regression was used to investigate the association between baseline eGFR and incident AKI events per International Club of Ascites criteria. We identified 72,267 patients with cirrhosis, who were 97.3% male, 57.8% white, and 19.7% Black. Over median follow-up 2.78years (interquartile range 1.22-5.16), lower baseline eGFR by CKD-EPI was significantly associated with higher rates of AKI in adjusted models. For all equations this association was minimally impacted when race adjustment was removed. For example, removal of race adjustment from CKD-EPI resulted in a 0.1% increase in the association between lower eGFR and higher rate of AKI events per 15mL/min/1.73m2 change (p < 0.001). Race adjustment in eGFR equations did not enhance AKI risk estimation in patients with cirrhosis. Further study is warranted to assess the impacts of removing race from eGFR equations on clinical outcomes and policy.

Insurance disparity in cardiovascular mortality among non-elderly cancer survivors

BackgroundInsurance status plays a vital role in cancer diagnosis, treatments and survival. Cancer patients have higher cardiovascular disease (CVD) mortality than the general population.MethodsThe Surveillance, Epidemiology and End Results (SEER) program 2007–2016 was used to estimate the CVD mortality among cancer patients aged 18 to 64 years at the time of diagnosis of an initial malignancy with the eight most prevalent cancers. Standardized mortality ratios (SMRs) were calculated for each insurance (Non-Medicaid vs Medicaid vs Uninsured) using coded cause of death from CVD with adjustment of age, race, and gender. The Fine-Grey Model was used to estimate adjusted Hazard Ratios (HR) of each insurance in CVD mortality.ResultsA total of 768,055 patients were included in the final analysis. CVD death in patients with Medicaid insurance remained higher than in those with Non-Medicaid insurance (HR = 1.71; 95%CI, 1.61–1.81; p < 0.001). Older age, male gender, and black race were all associated with increased CVD mortality in the multivariable model. Compared to the general population, patients with Medicaid had the highest SMRs of CVD mortality, regardless of year of cancer diagnosis, follow-up time, cancer site, and race. Non-Medicaid insured patients had similar CVD mortality to the general population after 2 years out from their cancer diagnosis.ConclusionCancer patients with Non-Medicaid insurance have significantly lower CVD mortality than those with no insurance or Medicaid. The insurance disparity remained significant regardless of type of CVD, cancer site, year of diagnosis and follow-up time.

Outcomes of coronavirus disease-2019 among veterans with pre-existing diagnosis of heart failure.

AimsPre‐existing cardiovascular disease in general and related risk factors have been associated with poor coronavirus disease‐2019 (COVID‐19) outcomes. However, data on outcomes of COVID‐19 among people with pre‐existing diagnosis of heart failure (HF) have not been studied in sufficient detail. We aimed to perform detailed characterization of the association of pre‐existing HF with COVID‐19 outcomes.Methods and resultsA retrospective cohort study based on Veterans Health Administration (VHA) data comparing 30 day mortality and hospital admission rates after COVID‐19 diagnosis among Veterans with and without pre‐existing diagnosis of HF. Cox‐regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for covariates. Among 31 051 veterans (97% male) with COVID‐19, 6148 had pre‐existing diagnosis of HF. The mean (SD) age of patients with HF was 70 (13) whereas the mean (SD) age of patients without HF was 57 (17). Within the HF group with available data on left ventricular ejection fraction (EF), 1844 patients (63.4%) had an EF of >45%, and 1063 patients (36.6%) had an EF of ≤45%. Patients in the HF cohort had higher 30 day mortality (5.4% vs. 1.5%) and admission (18.5% vs. 8.4%) rates after diagnosis of COVID‐19. After adjustment for age, sex, and race, HRs (95% CIs) for 30 day mortality and for 30 day hospital admissions were 1.87 (1.61–2.17) and 1.79 (1.66–1.93), respectively. After additional adjustment for medical comorbidities, HRs for 30 day mortality and for 30 day hospital admissions were 1.37 (1.15–1.64) and 1.27 (1.16–1.38), respectively. The findings were similar among HF patients with preserved vs. reduced EF, among those taking vs. not taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, and among those taking vs. not taking anticoagulants.ConclusionsPatients with COVID‐19 and pre‐existing diagnosis of HF had a higher risk of 30 day mortality and hospital admissions compared to those without history of HF. The findings were similar by EF categories and by angiotensin‐converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors or anticoagulant use.

Physical activity is associated with lower pulsatile stress but not carotid stiffness in children.

The cardiovascular disease (CVD) process may begin early in life when accompanied by atherosclerotic risk factors. CVD risk factors in children are associated with stiffening of the large elastic arteries, a reflection of subclinical atherosclerosis. Physical activity is a preventative lifestyle strategy that may benefit arterial stiffness by attenuating the hemodynamic stress on the artery wall. This study examined the relations between physical activity, carotid pulsatile stress, and carotid stiffness in children. One hundred and forty children (9-11 yrs; 50.0% male, 57.9% African American, 42.10% Caucasian, body mass index (BMI) 20.1±4.7 kg/m2) participated in this study. Physical activity counts were measured using a wrist-worn accelerometer and averaged over 7 days. Carotid artery β-stiffness and pulse pressure (calibrated to brachial mean and diastolic pressure) were assessed as via ultrasound and tonometry, respectively. Pulsatile stress was calculated as the product of carotid pulse pressure and heart rate. Physical activity counts were correlated with pulsatile stress (r= -0.27), and BMI (r= -0.23), but were unrelated to carotid stiffness. In multivariate models, associations between physical activity counts and pulsatile stress remained (B= -1.3 [95%CI, -2.4, -0.2], β= -0.20, p<0.05) after covariate adjustment for age, race, sex, pubertal stage and BMI. Carotid pulsatile stress was related to regional carotid stiffness (r=0.45, p<0.05). These data suggest that higher levels of physical activity at young age are associated with lower hemodynamic stress in the carotid artery. Findings are discussed in the context of an inverse relationship between hemodynamic pulsatile stress and carotid stiffness in children.

Does the false-negative rate for 1 or 2 negative sentinel nodes after neo-adjuvant chemotherapy translate into a high local recurrence rate?

Prospective trials demonstrate that sentinel node (SN) biopsy after neo-adjuvant chemotherapy (NACT) has a significant false-negative rate (FNR) when only 1 or 2 SNs are removed. It is unknown whether this increased FNR correlates with an elevated risk of recurrence. Tumor Registry data at an NCI-Designated Comprehensive Cancer Center were reviewed from 2004 to 2018 for patients having a negative SN biopsy after NACT. Among 190 patients with histologically negative nodes after NACT having 1 (n=42), 2 (n=46), and ≥3 (n=102) SNs, axillary recurrences occurred in 7.14%, 0%, and 1.96% (p=0.09), breast recurrences occurred in 2.38%, 6.52%, and 0.98% (p=0.12), and distance recurrences occurred in 16.67%, 8.70%, and 7.84% (p=0.27), respectively. Time to first recurrence did not differ by SN count (p=0.41). After adjustment for age, race, clinical stage, and receptor status, there were no differences in the rates of axillary (p=0.26), breast (p=0.44), or distance recurrence (p=0.24) by numbers of SNs harvested. Median follow-up was 46.8months. Despite higher post-NACT FNRs reported in randomized trials for patients having <3 sentinel nodes, recurrence rates were not significantly different for 1 versus 2 versus ≥3 SNs. This suggests that patients having 1 or 2 post-NACT SNs identified may not necessitate axillary dissection.

Racial Adjustment Adversely Affects Glomerular Filtration Estimates in African Americans Living with HIV

Background: The creatinine-based CKD EPI equation is the most widely used method to estimate glomerular filtration rate (eGFRcr) in clinical practice. The eGFRcr adjusts for sex, age, and race (Black vs non-Black) and was derived and validated in aggregated datasets from US-based research studies in which GFR was measured directly. However, in prior work, we found eGFRcr performed worse in people living with HIV (PLWH) compared to HIV negative counterparts which may be due to differences in muscle mass, the major source of creatinine. Here, we focus on African American (AA) participants to determine whether the race eGFRcr calibration factor contributes to poor accuracy and bias in AAs living with HIV. Methods: Beginning in 2010, we enrolled and followed an AA cohort of PLWH and HIV-negative participants in Baltimore Maryland. Annually, we measured GFR by iohexol disappearance from plasma (iGFR) and serum concentrations of creatinine and cystatin C. This analysis was restricted to AA participants. We calculated eGFRcr and the creatinine-cystatin C combination equation (eGFRcr-cys) with and without race adjustment. Accuracy was defined as the fraction of eGFR values within +/- 30% of iGFR. Bias was defined as eGFR minus iGFR, with positive and negative values representing overestimation and underestimation of iGFR, respectively. We used multilevel mixed models to account for the within-visit linked structure of the multiple GFR measures, further nested within repeated observations for individuals. We examined the association between lean mass, HIV status, and eGFRcr bias in a subset with body composition measures. Findings: 207 HIV-positive and 107 HIV-negative AA participants contributed 781 and 376 study visits, respectively, with valid measures of iGFR, creatinine, and cystatin C. Among PLWH, omitting the race adjustment (compared with retaining it) changed average eGFRcr bias from 9.1 to -3.9 ml/min/1.73 m2. Moreover, estimation accuracy improved significantly when race adjustment was omitted rather than retained: 86% vs. 78% for eGFRcr (P<0.001) and 91% vs. 88% for eGFRcr-cys (P=0.045). Lean mass (but not other measures of body size or composition) was correlated with eGFRcr bias and, in adjusted analyses, lean mass was significantly lower in PLWH compared with HIV-negative AAs compatible with not using the race coefficient. Interpretation: We found that the standard, widely used eGFRcr equation as well as eGFRcr-cys overestimate iGFR and has poor accuracy in AAs living with HIV. Omitting the race coefficient improved both bias and accuracy. HIV clinicians should be aware that race adjustment may worsen the performance of creatinine based GFR estimates in AAs. Funding Statement: This study was supported by the National Institute on Drug Abuse of the National Institutes of Health (R01 DA026770, K24 DA035684) and by the Johns Hopkins University Center for AIDS Research (P30 AI094189). MGA was supported by National Institute of Diabetes and Digestive and Kidney Diseases (P01 DK056492). GE Healthcare provided iohexol to the study free of charge. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Johns Hopkins University School of Medicine Institutional Review Board, and participants provided written informed consent.

Care received by rural and urban patients with newly diagnosed prostate cancer: Results from a population-based prospective cohort.

203 Background: Rural residence is a source of disparity in cancer access and outcomes. It is not known to what extent rurality affects access to care in patients with prostate cancer. Methods: The North Carolina Prostate Cancer Comparative Effectiveness &amp; Survivorship Study (NC ProCESS) is a population-based cohort of newly-diagnosed prostate cancer patients. Patients were enrolled from 2011-2013 through collaboration with the state cancer registry at diagnosis and followed prospectively. Urban/rural residence was defined by the rural urban continuum code (RUCC): 1-3 (urban) and 4-9 (rural). Medical records were collected and abstracted for prostate cancer care received. Individual-level sociodemographic information was collected by patient report. Results: Among 1,456 NC ProCESS participants with a median age of 65 years, 1089 were categorized as urban and 367 (25%) rural. This is a sociodemographically diverse cohort with 30.2% non-White (including 26.9% Black), 34.1% with high school education or less, and 37.3% with household income &lt; = $40,000. The distance to travel for diagnostic scans was greater for rural patients (miles): CT (7.5 urban vs 17.1 rural, p = 0.07), MRI (8.1 vs 12.0, p = 0.04) and bone scan (6.8 vs 14.1, p = 0.009). However, there was no difference in the percent of patients who underwent CT (15.9% urban vs 12.8% rural, p = 0.15), MRI (7.8% vs 8.2%, p = 0.81) and bone scan (15.9% vs 19.4%, p = 0.13); or the percentage of patients with high risk or metastatic disease who had any staging scan (64.2% vs 66.6% p = 0.8). While all patients consulted with a urologist, rural patients were less likely to have had consultation with a radiation oncologist (42.4% vs 35.8%, p = 0.04). Rural patients were also more likely to report that treatment was more difficult due to travel, including robotic prostatectomy (6.8% vs 13.9% p = 0.001) and radiation therapy (8.01% vs 16.07%, p = 0.001). In patients with low risk cancer, rural patients were more likely to have reported treatment at 12 months (68.2% vs 58.7% p = 0.04) instead of surveillance or observation. For high risk patients, both rural and urban patients reported high rates of treatment by 3 months (96.3% vs 91.3%, p = 0.40). After adjustment for age, income, race, education and insurance, rural residence was associated with increased likelihood of receiving treatment at 1 year (OR 1.54, CI 0.99 – 2.39) in low risk patients, but not associated with receiving treatment at 3 months (OR 3.63, CI 0.24 -54.5) among high risk patients. Conclusions: In a population-based cohort, rural patients with prostate cancer have greater barriers such as travel distance, but similar proportions of rural and urban patients received staging scans and timely treatment for high-risk prostate cancer. Rural patients were less likely to receive multidisciplinary consultation prior to treatment, and were less likely to have surveillance for low risk disease.

Association of insurance disparities and survival in adults with multiple myeloma: A non-concurrent cohort study

BackgroundMultiple myeloma (MM) accounts for 10 % of all hematological malignancies. As recent advances in MM treatment continue to improve survival rates, socioeconomic barriers need to be identified to ensure equal treatment. This study evaluates the association between insurance status and survival in patients with MM. MethodsThis study analyzed patients with MM from the 2007–2016 Surveillance, Epidemiology, and End Results (SEER) Program database. Insurance status was categorized as uninsured, Medicaid, private insurance, and other insurance. Cancer-specific survival was measured at one- and five-years post diagnosis. ResultsFrom 2007–2016, there were 41,846 patients with MM extracted from the SEER database. Those with private insurance had a higher proportion of participants that identified as married (65.5 %), resided in metropolitan cities (90.1 %), and identified as white (76 %) and non-Hispanic (90.8 %). The uninsured group had the highest proportion of Black participants compared to other insurance groups (37.4 %). After adjustment for age, sex, race, ethnicity, marital status, and residence, the likelihood of five-year survival was significantly lower in those respondents with Medicaid (adjusted (adj) Hazard Ratio (HR): 1.44; 95 % Confidence Interval (CI): 1.36−1.53), when compared with private insurance holders. Those who were uninsured had a 26 % increased mortality hazard than those with private insurance (95 % CI 1.04−1.53). ConclusionAfter adjustment, insurance status can influence the survival of adults with MM. As treatment modalities for MM continue to advance, the insurance status of a patient should not hinder their ability to receive the most effective and timely therapies.

Association between Lifetime History of Traumatic Brain Injury, Prescription Opioid Use, and Persistent Pain: A Nationally Representative Study.

Pain is common among adults with traumatic brain injury (TBI), yet little data exist regarding prevalence of opioid use in this population. The objective of this retrospective cohort study was to evaluate the association between lifetime TBI exposure, opioid use, and pain in a nationally representative sample of 1022 adults aged 50+ who participated in the Health and Retirement Study (HRS). Our primary exposure was lifetime TBI history measured via the Ohio State University TBI Identification Method. We evaluated three alternate TBI exposures (years since most recent TBI, age at first TBI, and number of lifetime TBIs) in sensitivity analyses. We evaluated two outcomes: recent opioid medication use, and moderate-to-severe pain measured over two HRS waves. We classified three pain groups (persistent, intermittent, and no pain). Prevalences of opioid use among individuals with and without TBI were 19.7% and 13.6%, respectively. After adjustment for age, sex, and race, individuals with TBI had a 52% increased risk for opioid use compared with individuals without TBI (relative risk = 1.52, 95% confidence interval: 1.11, 2.04). Individuals with recent TBI (1-10 years ago), first TBI after age 40+, and 2+ lifetime TBIs had greatest risk for opioid use. Compared with individuals without TBI, individuals with TBI had 4.9-times increased odds for persistent versus no pain, and 1.9-times increased odds of intermittent versus no pain. Persistent pain among adults with lifetime TBI is elevated compared with the general population, which may contribute to increased opioid use among persons with TBI, particularly those with recent injuries or multiple lifetime TBIs.

316 Preeclampsia severity after spontaneous or IVF conception in women age 40 and over

Preeclampsia (PE) is more common in women who conceived by in vitro fertilization (IVF). However, it is unclear if PE severity is worse in IVF pregnancies as prior studies have not fully controlled for age and other confounding factors. We sought to determine if PE severity is worse in women age 40 and over with IVF compared to spontaneous conception. Cohort study of women age 40 and over, who had PE and delivered at our institution from 1/1/13 to 12/31/17. This cohort, chosen due to the high prevalence of IVF conception in women 40 and over, was identified using ICD-10 codes and chart validation. Exclusions were maternal age <40, fetal demise, and non-IVF fertility treatments. The primary exposure was IVF conception (vs. spontaneous) and the primary outcome was PE with severe features (vs. PE without severe features). Secondary outcomes included severe symptoms, laboratory measures, and adverse maternal outcomes (see footnote Table 2). Analyses by t-test, Chi-squared or Fisher’s exact test, and logistic regression (α=0.05). We identified 237 women age 40 and over with PE (mean 42±2 years); 138 (58%) conceived spontaneously and 99 (42%) conceived by IVF. Women with IVF pregnancy were more often older, nulliparous, White, with multifetal gestation and lower BMI (Table 1). Compared to women with spontaneous conception, those with IVF pregnancy were not more likely to have PE with severe features (90% vs. 82%, P=0.09) (Table 2). The odds of PE with severe features was not increased in IVF pregnancies even after adjustment for age, race, BMI, nulliparity and multifetal gestation (aOR 1.9, 95% CI 0.7-5.1). Adverse maternal outcomes were increased with IVF pregnancy (36% vs. 23%, P=0.03), but this was not significant after multivariable adjustment (aOR 0.64, 95% CI 0.3-1.4). In women 40 and over, IVF pregnancy was not independently associated with an increase in preeclampsia severity or adverse maternal outcomes. However, most women 40 and over had PE with severe features, suggesting that age may drive disease severity regardless of mode of conception.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

1166 Short interpregnancy interval and risk of severe maternal morbidity in the United States

Short interpregnancy interval (IPI) increases risk of preterm birth and other adverse pregnancy outcomes. This study aims to investigate whether short IPI, a modifiable risk factor, increases risk of severe maternal morbidity, which is an antecedent to maternal mortality. Retrospective population-based cohort study of all US live births using birth certificate records, 2012-2016. Study population was limited to multiparous mothers with data on IPI since the most recent prior birth. Exposure variables were short IPI defined as < 6 and <12 months. Severe maternal morbidity, a marker for maternal mortality risk, was defined as maternal ICU admission, blood transfusion, uterine rupture or unplanned hysterectomy during delivery hospitalization. Logistic regression estimated risk of SMM with short IPI, after adjustment for maternal race, age, obesity, no prenatal care, and Medicaid. There were 19,844,580 live births in the US during the study period, of which 10,714,861 were in multiparous women with data on IPI. The frequency of short IPI was 5.7% and 16.7% for births at <6 and <12 months, respectively. The frequency of composite severe maternal morbidity was 44 per 10,000 live births, and among women with the shortest IPI of <6 months was 52 per 10,000. After adjusting for the coexisting risks for SMM, short IPI <6 months was associated with 22% increased risk of SMM, adjRR 1.22 (95% CI 1.12,1.33) and short IPI <12 months had no significant increase in risk of SMM, adjRR 1.04 (CI 0.99, 1.10). Pregnancies that occur < 6 months following a recent birth increase the risk of severe maternal mortality in the US. Access to immediate postpartum highly effective contraception may help to prevent unintended pregnancy in the postpartum period. This could help to minimize very short IPIs in the US in effort to minimize the occurrence of serious maternal adverse events that lead to maternal mortality.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

722 Perinatal outcomes among women living in at-risk areas identified by a community health needs assessment

As a recent Community Health Needs Assessment (CHNA) identified geographic areas within our county with substantial health disparities, the aim of this study was to evaluate maternal and infant outcomes within the region. We hypothesized that perinatal outcomes would differ for women living in areas with the higher social needs compared to those living in other regions of the county. This was a retrospective cohort study of pregnant women delivering at a large inner-city county hospital, which serves as the safety net hospital for the county. Perinatal outcomes were analyzed for women living within a target region of ten zip codes, identified during a recent CHNA, and compared to those women living outside the target region. Statistical analysis included student’s t-test, chi square, and logistic regression to adjust for demographics. Between January 2015 and July 2020, 66,936 women delivered at the county hospital. Of these, a total of 7,585 (11%) resided in the CHNA target region. The women living in the target region were younger (26.8 + 6.5 vs 27.9 + 6.4 years, p<.001), more likely to be black (37% vs 13%, p<.001), and had a higher BMI (33.3 + 7.0 vs 32.6 + 6.4 kg/m2,p <.001). The rates of preeclampsia and abruption were higher in the target region (Table). Adverse infant outcomes were also more common including preterm birth, neonatal ICU admission, and neonatal death. Increased risk for all maternal and neonatal adverse outcomes persisted after adjustment for age, race, and BMI (figure). Women living in areas with higher health disparity and more social needs identified in a recent CHNA are at greater risk of adverse perinatal outcomes. Efforts to improve obstetric outcomes in this at-risk area should focus on achieving health equity by eliminating social disparities through targeted education and outreach.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Association of the Estimated Glomerular Filtration Rate With vs Without a Coefficient for Race With Time to Eligibility for Kidney Transplant

Kidney transplant is associated with improved survival and quality of life among patients with kidney failure; however, significant racial disparities have been noted in transplant access. Common equations that estimate glomerular filtration rate (eGFR) include adjustment for Black race; however, how inclusion of the race coefficient in common eGFR equations corresponds with measured GFR and whether it is associated with delayed eligibility for kidney transplant listing are unknown. To compare eGFR with measured GFR and evaluate the association between eGFR calculated with vs without a coefficient for race and time to eligibility for kidney transplant. This prospective cohort study used data from the Chronic Renal Insufficiency Cohort, a multicenter cohort study of participants with chronic kidney disease (CKD). Self-identified Black participants from that study were enrolled between April 2003 and September 2008, with follow-up through December 2018. Statistical analyses were completed on November 11, 2020. Estimated GFR, measured annually and estimated using the creatinine-based Chronic Kidney Disease-Epidemiology (CKD-EPI) equation with and without a race coefficient. Iothalamate GFR (iGFR) measured in a subset of participants (n = 311) and time to achievement of an eGFR less than 20 mL/min/1.73 m2, an established threshold for kidney transplant referral and listing. Among 1658 self-identified Black participants, mean (SD) age was 58 (11) years, 848 (51%) were female, and mean (SD) eGFR was 44 (15) mL/min/1.73 m2. The CKD-EPI eGFR with the race coefficient overestimated iGFR by a mean of 3.1 mL/min/1.73 m2 (95% CI, 2.2-3.9 mL/min/1.73 m2; P < .001). The mean difference between CKD-EPI eGFR without the race coefficient and iGFR was of smaller magnitude (-1.7 mL/min/1.73 m2; 95% CI, -2.5 to -0.9 mL/min/1.73 m2). For participants with an iGFR of 20 to 25 mL/min/1.73 m2, the mean difference in eGFR with vs without the race coefficient and iGFR was 5.1 mL/min/1.73 m2 (95% CI, 3.3-6.9 mL/min/1.73 m2) vs 1.3 mL/min/1.73 m2 (95% CI, -0.3 to 2.9 mL/min/1.73 m2). Over a median follow-up time of 4 years (interquartile range, 1-10 years), use of eGFR calculated without vs with the race coefficient was associated with a 35% (95% CI, 29%-41%) higher risk of achieving an eGFR less than 20 mL/min/1.73 m2 and a shorter median time to this end point of 1.9 years. In this cohort study, inclusion of the race coefficient in the estimation of GFR was associated with greater bias in GFR estimation and with delayed achievement of a clinical threshold for kidney transplant referral and eligibility. These findings suggest that nephrologists and transplant programs should be cautious when using current estimating equations to determine kidney transplant eligibility.