Brock, Guy

Background Higher scores for the American Heart Association Life's Essential 8 (LE8) metrics, blood pressure, cholesterol, glucose, body mass index, physical activity, smoking, sleep, and diet, are associated with lower risk of chronic disease. Socioeconomic status (SES; employment, insurance, education, and income) is associated with LE8 scores, but there is limited understanding of potential differences by sex. This analysis quantifies the association of SES with LE8 for each sex, within Hispanic Americans, non‐Hispanic Asian Americans, non‐Hispanic Black Americans, and non‐Hispanic White Americans. Methods and Results Using cross‐sectional data from the National Health and Nutrition Examination Survey, years 2011 to 2018, LE8 scores were calculated (range, 0–100). Age‐adjusted linear regression quantified the association of SES with LE8 score. The interaction of sex with SES in the association with LE8 score was assessed in each racial and ethnic group. The US population representatively weighted sample (13 529 observations) was aged ≥20 years (median, 48 years). The association of education and income with LE8 scores was higher in women compared with men for non‐Hispanic Black Americans and non‐Hispanic White Americans ( P for all interactions <0.05). Among non‐Hispanic Asian Americans and Hispanic Americans, the association of SES with LE8 was not different between men and women, and women had greater LE8 scores than men at all SES levels (eg, high school or less, some college, and college degree or more). Conclusions The factors that explain the sex differences among non‐Hispanic Black Americans and non‐Hispanic White Americans, but not non‐Hispanic Asian Americans and Hispanic Americans, are critical areas for further research to advance cardiovascular health equity.

Background Socioeconomic status (SES) is associated with cardiovascular health (CVH). Potential differences by sex in this association remain incompletely understood in Black Americans, where SES disparities are posited to be partially responsible for cardiovascular inequities. The association of SES measures (income, education, occupation, and insurance) with CVH scores was examined in the Jackson Heart Study. Methods and Results American Heart Association CVH components (non–high‐density‐lipoprotein cholesterol, blood pressure, diet, tobacco use, physical activity, sleep, glycemia, and body mass index) were scored cross‐sectionally at baseline (scale: 0–100). Differences in CVH and 95% CIs (Estimate, 95% CI) were calculated using linear regression, adjusting for age, sex, and discrimination. Heterogeneity by sex was assessed. Participants had a mean age of 54.8 years (SD 12.6 years), and 65% were women. Lower income, education, occupation (non‐management/professional versus management/professional occupations), and insurance status (uninsured, Medicaid, Veterans Affairs, or Medicare versus private insurance) were associated with lower CVH scores (all P <0.01). There was heterogeneity by sex, with greater magnitude of associations of SES measures with CVH in women versus men. The lowest education level (<high school) versus highest (>high school) was associated with 8.8‐point lower (95% CI: −10.2 to −7.3) and 5.4‐point lower (95% CI: −7.2 to −3.6) CVH scores in women and men, respectively (interaction P =0.003). The lowest (<25 000) versus highest level of income (≥$75 000) was associated with a greater reduction in CVH scores in women than men (interaction P =0.1142). Conclusions Among Black Americans, measures of SES were associated with CVH, with a greater magnitude in women compared with men for education and income. Interventions aimed to address CVH through SES should consider the role of sex.

Background The American Heart Association's Life's Essential 8 (LE8) are 8 risk factors for cardiovascular disease, with poor attainment across all racial, ethnic, and socioeconomic groups. Attainment is lowest among Americans of low socioeconomic status (SES). Evidence suggests the association of SES with LE8 may vary by race and ethnicity. Methods and Results The association of 4 SES categories (education, income‐to‐poverty line ratio, employment, insurance) with LE8 was computed in age‐adjusted linear regression models, with an interaction term for race and ethnicity, using National Health and Nutrition Examination Survey data, years 2011 to 2018. The sample (n=13 529) had a median age of 48 years (51% female) with weighting to be representative of the US population. The magnitude of positive association of college education (relative to ≤high school) with LE8 was greater among non‐Hispanic White Americans (NHWA) compared with non‐Hispanic Black Americans, Hispanic Americans, and non‐Hispanic Asian Americans (all interactions P <0.001). NHWA had a greater magnitude of positive association of income‐to‐poverty line ratio with LE8, compared with non‐Hispanic Black Americans, Hispanic Americans, and non‐Hispanic Asian Americans (all interactions P <0.001). NHWA with Medicaid compared with private insurance had a greater magnitude of negative association with LE8 compared with non‐Hispanic Black Americans, non‐Hispanic Asian Americans, or Hispanic Americans (all interactions P <0.01). NHWA unemployed due to disability or health condition (compared with employed) had a greater magnitude of negative association with LE8 than non‐Hispanic Black Americans, non‐Hispanic Asian Americans, or Hispanic Americans (all interactions P <0.05). Conclusions The magnitude of association of SES with LE8 is greatest among NHWA. More research is needed on SES's role in LE8 attainment in minority group populations.

Abstract Introduction Advanced Practice Providers (APPs; Advanced practice registered nurses, physician assistants) and physicians-in-training (residents, fellows) receive inadequate education on obstructive sleep apnea (OSA)/perioperative OSA risks. However, they are front-line providers assessing these patients. Failure to mitigate this risk has led to significant postoperative morbidity/mortality. We assessed these providers’ perceptions to OSA/perioperative OSA training. Methods Surveys were sent to three provider roles, APPs, residents, and fellows, in four categories of practice at nine academic institutions between May 9-June 30, 2021. Chi-square and Fisher’s exact tests assessed association between survey responses and participant characteristics. False discovery rate adjustment accounted for multiple comparisons, threshold of q&lt;0.05 for statistical significance. Cochran-Mantel-Haenzsel tests evaluated associations stratified by institution. Results 2236 of 6724 (33.3%) participants responded: 48.4% APPs, 11% Fellows and 40.6% Residents. Primary category of practice included: 20.3% Anesthesiology, 8.9% Family Medicine, 34.1%, Internal Medicine (IM)/IM subspecialties, 6.7% Obstetrics/Gynecology/Gynecologic Oncology, 25.9% Surgery/Surgery subspecialties, 4.1% Other.While 93.2% of respondents believed OSA is a risk factor for perioperative complications, fewer respondents reported that they felt adequately trained to assess for OSA (50.9%) in general, with significant differences noted by provider role (range 42-70%, q=0.001) and across the categories of practice (range 12-82%, q=0.001). Even fewer felt adequately trained to assess for OSA in perioperative patients (38.2%) with significant differences noted by provider role (range 31-52%, q=0.001) and across the categories of practice (range 15-84%, q=0.001).Across all categories of practice, respondents indicated that they would like additional educational training about OSA (76.7%). This varied by clinical role (range 64-82%, q=0.003), but not categories of practice (range 73-84%, q=0.13). Furthermore, respondents indicated they also desired additional education about OSA in the perioperative patient (75.5%). This extended across all clinical roles (range 68-77%, q=0.09) and categories of practice (range 72-80%, q=0.09). Conclusion We found significant differences in APP and physician-in-training perceptions of the adequacy of their current training and desire for further OSA/perioperative OSA education. Our study identifies a critical gap and opportunity to improve provider understanding and patient care. Support (If Any) American Academy of Sleep Medicine Foundation (AASMF) award.

BACKGROUND: Liberal oxygenation during mechanical ventilation is harmful in critically ill patients and in certain subsets of patients, including those with stroke, acute myocardial infarction, and cardiac arrest. Surveillance through electronic medical records improves safety of mechanical ventilation in the ICU. To date, this practice has not been used for oxygen titration ( F IO 2 ) in adults. We hypothesize that a surveillance system based on the electronic medical record to alert respiratory therapists to titrate F IO 2 is feasible, safe, and efficacious. METHODS: In this pilot study, mechanically ventilated subjects were randomized to respiratory therapist-driven F IO 2 titration after an electronic alert versus standard of care (ie, titration based on physician order). An automated surveillance system utilizing a hyperoxemia-detection algorithm generated an electronic alert to a respiratory therapist’s pager. Hyperoxemia was defined as F IO 2 > 0.5 and S pO 2 > 95% for > 30 min. No other aspects of treatment were changed. We assessed feasibility, safety, and preliminary efficacy. Primary outcome was duration of hyperoxemia during mechanical ventilation. An unsafe outcome was identified as hypoxemia ( S pO 2 < 88%) within 1 h after titration per alert. Feasibility was assessed by a survey of respiratory therapists. RESULTS: Of 226 randomized subjects, 31 were excluded (eg, programming errors of the electronic alerts, no consent, physician discretion). We included 195 subjects, of whom 86 were in the intervention arm. Alert accuracy was 78%, and respiratory therapists responded to 64% of the alerts. During mechanical ventilation, exposure to hyperoxemia significantly decreased in the intervention group (median 13.5 h [interquartile range 6.2–29.4] vs 18.8 h [interquartile range 9.6–37.4]). No episodes of significant hypoxemia were registered. Most respiratory therapists agreed that the alert was helpful in reducing excessive oxygen exposure. CONCLUSIONS: Use of an electronic surveillance system to titrate F IO 2 was safe and feasible and showed preliminary efficacy in reducing hyperoxemia. Our study serves to justify larger randomized controlled trials for F IO 2 titration.

Abstract The first two authors and last two authors contributed equally. Genome-wide association studies (GWAS) have identified risk loci for Acute Lymphoblastic Leukemia (ALL), Chronic Lymphoblastic Leukemia (CLL) and Non-Hodgkin Lymphoma, however an Acute Myeloid Leukemia (AML) GWAS has not been published to date. We performed a GWAS to identify AML and Myelodysplastic Syndrome (MDS) risk loci using a nested case-control study design in the DISCOVeRY-BMT cohorts which includes almost 2000 AML and MDS patients as cases and 2813 unrelated donors as controls. Genotyping was performed using the Illumina Human OmniExpress BeadChip and imputed using the Haplotype Reference Consortium, yielding > 8 million high-quality variants for statistical analysis. Logistic regression models with AML (de novo AML with normal cytogenetics, de novo AML with abnormal cytogenetics and therapy-related AML) and MDS cases and European American healthy donor controls adjusted for age and sex were used to test the association of each SNP with disease status. To identify the strongest association signal with disease we conducted a summary statistic SNP-based association analysis (ASSET) using non-overlapping AML and MDS cases implemented in R statistical software. ASSET uses an exhaustive search for SNPs with small but common pleiotropic effects across groups of traits while accounting for the multiple tests required by the subset search, as well as any shared controls between groups. This approach allowed us to further investigate the heterogeneity within AML subtypes and to gain increased power by pooling subtypes that show pleiotropic effects. ASSET genome wide (GW) significance is defined as P<5.0x10-8, however, we present results of each subset analysis. ASSET analyses identified an association of T allele at rs12203592, Interferon Regulatory Factor 4 (IRF4), with increased risk of de novo AML and MDS (Figure 1) (OR=1.37; 95% CI, 1.25-1.51, Pmeta=1.59x10-10). The variant has been reported significant in GWAS of skin pigmentation, hair color, non-melanoma skin cancer, squamous cell carcinoma, actinic keratosis, and childhood ALL; GW case-control studies of neuroblastoma and breast cancer show suggestive association signals (P<5 x 10-6). IRF4 belongs to the IRF family of transcription factors and is a key regulator of differentiation stages in hematopoiesis. The T allele at rs12203592 is associated with significantly increased expression of IRF4 in whole blood and lung tissue and in vitro mouse studies have shown the T allele to be associated with higher levels of IRF4 transcription. rs12203592 is <80bp from an IRF4 transcription start site and in an important position within NF-κB motifs in multiple blood and immune cell lines, supporting the hypothesis that this SNP modulates NF-κB repression of IRF4 expression. Another variant in the IRF4 regulatory region, rs62389423 (A allele), showed a putative association with subsets of de novo AML and MDS (OR=1.36; 95% CI,1.21-1.52, Pmeta=1.2x10-7). Although not in linkage disequilibrium with rs12203592, the A allele has also been previously associated with susceptibility to skin cancer and melanoma in multiple GWAS. Analysis of 596 UKbiobank CLL cases and >300,000 controls, shows the A allele correlates with a 50% increased risk of CLL (95% CI, 1.32-1.73, P= 2.4x10-9).Several other GWAS also show an association between additional IRF4 variants and CLL. Analyses in individual subtypes also revealed an intronic variant, rs10098598, in RAD21 to be associated with de novo AML (OR=2.18; 95% CI, 1.60-2.97; Pmeta=8.9x10-7). RAD21, on8q24, a region known to be associated with multiple cancer types, is involved in DNA double-stranded break repair and in chromatid cohesion in mitotic cells. Loss of function would theoretically lead to chromosomal instability and tumorigenesis. Components of the cohesion complex (including RAD21) are somatically mutated in ~12% of de novo AML and MDS patients, where it is frequently an early event. We provide the first GW evidence of association between a common variant and AML susceptibility. This SNP has been shown to be associated with multiple phenotypes, suggesting that there are pleiotropic effects at work. Our RAD21 finding is consistent with the role of cohesion in leukemogenesis and provides some evidence of its role in de novo AML susceptibility. Replication and further subset analyses with genome-wide data in >2000 AML cases are ongoing. Disclosures Griffiths: Alexion Inc.: Honoraria, Research Funding; Astex/Otsuka Pharmaceuticals: Honoraria, Research Funding; Celgene, Inc: Honoraria, Research Funding; Novartis, Inc.: Research Funding; Pfizer, Inc.: Research Funding. McCarthy:Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

Key PointsCandidate SNP associations with survival outcomes after URD transplant are most likely false-positive findings. Over 85% of candidate SNPs are not linked to a biochemical function; of those that are, about half are not linked to the candidate gene.