tbuckley/cabot-search huggingface dataset:
Abstract 4137479: Integrating Ambulatory Care Pharmacists into Value-Based Primary Care: A Scalable Model for Addressing Cardiometabolic Disease
Authors: Alexander Blood, Harry Saag, Adam Chesler, Dalia Ameripour, Max Gutierrez, Van Nguyen, Cassandra Richardson, Clive Fields, Jen Clair, Aaron Yao, Sashidaran Moodley
Journal: Circulation (2024)

Background: Chronic disease is common, costly, and complicated. In the shift to value-based payment models, interventions to engage patients and improve disease control are necessary to reduce morbidity, mortality, and cost. The use of ambulatory pharmacists has demonstrated improved management of chronic diseases. Traditionally, ambulatory pharmacists are employed by healthcare systems. In this study, we test if integrating ambulatory pharmacists hired, trained, and managed by a retail pharmacy into value-based primary care (VBPC) clinics improves care. Hypothesis: Integrating a Walgreens pharmacist empowered by collaborative drug therapy management agreements (CDTM) into Village Medical (VMD) clinics will improve indicators of chronic disease control. Aims: Improve hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2D) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in patients with hypertension (HTN). Methods: An ambulatory pharmacist was embedded into VMD clinics in Phoenix, Arizona under the supervision of VMD primary care providers via a CDTM. The pharmacist provided education, coaching, and medication management by prescribing and titrating therapies for treating T2D and HTN - enabled by access to pharmacy dispensing data. β was generated from difference-in-differences (DID) analyses with propensity score matched controls. Results: 125 patients had T2D, and 43 patients had HTN in the intervention group with 250 and 86 in the matched control group, respectively. The mean age was 65 years, 54% were female, 2% non-English speaking, and 29% racial/ethnic minorities. The average baseline HbA1c was 9% in the intervention group and 10% in the matched cohort. The average baseline SBP was 146 mmHg in the intervention group and 142 mmHg in the matched cohort. The β in the T2D group was -1.61% (p&lt;0.001) while the β in the HTN group was -10.2 mmHg (p&lt;0.01) for SBP and -2.0 mmHg (p=0.42) for DBP. Conclusion: We saw significant reductions in SBP and HbA1c in the pharmacist-managed group compared with matched controls. These results demonstrate that pharmacist integration into VBPC clinics may improve measures of chronic disease known to be associated with morbidity and mortality.
Abstract 4137989: Notched P-wave by digital ECG analysis was associated with new-onset atrial fibrillation onset and ischemic stroke
Authors: Tomoyuki Kabutoya, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2024)

Background: A bimodal P wave in lead II reflects left atrial remodeling and is described as a notched P wave. A notched P wave is usually defined as a dip over the smallest unit of electrocardiography (ECG) recording paper, 40 ms, but automated analysis of ECGs has shown that even a notch of 20 ms is associated with cardiovascular events. A notched P wave is also known to predict atrial fibrillation (AF) after catheter ablation. However, the relationship between automatically assessed notched P waves and new-onset AF and ischemic stroke in patients without documented AF has not been clarified. Hypothesis: A notched P-wave by digital ECG analysis was associated with both new-onset AF and ischemic stroke. Methods: We enrolled 4,216 subjects from the Cardiovascular Prognostic Coupling Study in Japan (Coupling Registry) who had one or more cardiovascular risk factors. Twelve-lead electrocardiography was conducted, and the peak-to-peak distance in the M shape was calculated automatically using a 12-lead ECG analysis system. We compared two definitions: P-waves defined as “notched” at the the peak-to-peak (“M shape”) distance in lead II of ≥20 ms or ≥40 ms. New-onset AF was confirmed through routine medical care as well as annual ECGs. We defined the primary endpoint as new-onset AF and the secondary endpoint as ischemic stroke. Results: The mean follow-up period was 53 ± 17 months, during which 17 AF cases developed. When a notched P-wave was defined as ≥20 ms (n = 319), it was a significant predictor of both new-onset AF (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.41–6.01, p=0.004) and ischemic stroke (HR 3.02, 95% CI 1.56–5.83, P=0.001). A notched P-wave defined as ≥40 ms (n = 63) was also a predictor of new-onset AF (HR 4.57; 95% CI:1.42–14.71, p = 0.011) and ischemic stroke (HR 3.84, 95% CI 1.20–12.29, P=0.024). Conclusions: A notched P-wave by digital ECG analysis was associated with ischemic stroke as well as the new-onset AF.
Implementation of ePROs Into Multidisciplinary Tumor Board Discussions for Patients With Pancreatic Cancer: The INSPIRE Intervention
Authors: Nicole L. Henderson, Etzael Ortiz-Olguin, Garrett Bourne, Cameron Pywell, J. Bart Rose, Grant R. Williams, Ryan D. Nipp, Gabrielle B. Rocque
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: The incorporation of electronic patient-reported outcomes (ePROs), such as the Geriatric Assessment (GA) and treatment preferences, into decision-making for pancreatic cancer has been limited by clinician- and system-level barriers concerning workflow. We hypothesized that ePRO inclusion within multidisciplinary tumor boards (MDTBs) would circumvent barriers and provide a venue for systematic consideration of critical patient-provided information. Patients and Methods: The INtegrating Systematic PatIent-Reported Evaluations (INSPIRE) intervention consists of (1) patient survey completion, including GA and patient preferences, and (2) screensharing patient ePROs during MDTBs. Proctor et al’s implementation outcomes were assessed, with penetration (the proportion of consented patients who were presented at MDTBs) acting as the primary outcome (considered successful at 70%). Secondary outcomes included adoption, feasibility, acceptability, appropriateness, cost, and sustainability, assessed by clinician post-MDTB exit surveys, clinician postintervention surveys, clinician postintervention semistructured interviews, and time-coding analysis of recorded and transcribed historical (November 2021–February 2022) and intervention (September 2022–June 2023) MDTBs. Results: A total of 50 patients completed surveys and all were presented at MDTBs (penetration=100%). All eligible clinicians (n=9) enrolled patients (adoption=100%) and reported that ePROs were useful in 90% and led to a change in treatment plan in 30% of cases. In postintervention surveys and interviews, clinicians primarily responded positively to feasibility, acceptability, and appropriateness questions. Time-coding analysis found a modest time cost of an additional 51.1 seconds in mean discussion time-per-patient between preintervention (mean [SD], 172.7 [111.4] seconds) and intervention patients (mean [SD], 223.8 [107.1] seconds); 86% of clinicians reported the intervention did not take too much time. All surveyed clinicians reported interest in continuing the intervention and suggested adaptations to further promote sustainability. Conclusions: The integration of ePROs into pancreatic MDTBs was feasible and acceptable, providing a potential approach to increase the utilization of ePROs by clinical teams in their management of patients with pancreatic cancer.
Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation
Authors: Lihua Shu, Alexi Vasbinder, Tonimarie Catalan, Kristen Machado, Anis Ismail, Christina Hutten, Ian Pizzo, Yiyuan Huang, Pennelope Blakely, Mousumi Banerjee, Monika Leja, Salim Hayek
Journal: Circulation (2024)

Background: Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (&lt;440ms), Grade 1 (440-480ms), and Grade ≥2 (&gt;480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score. Results: Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc. Conclusions: In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation
Abstract 4137342: Prolonged Bazett’s corrected QT interval is associated with cardiovascular events and sudden death in Japanese patients with cardiovascular risk
Authors: Yuki Hirata, Tomoyuki Kabutoya, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2024)

Background: QT durations are sex-dependent, with women having longer QT durations than men. In addition to congenital long-QT syndrome, prominent QTc prolongation is a risk for sudden death. There are several correction formulas for the QTc interval, but the association between the QTc interval and cardiovascular events by type of correction in patients at cardiovascular risk remains unclear. Hypothesis: Prolonged QTc duration is associated with cardiovascular events and sudden death in patients at high cardiovascular risk. Methods: We enrolled 4,654 subjects from the Cardiovascular Prognostic Coupling Study in Japan (Coupling Registry), who had one or more cardiovascular risk factors. We used two different definitions of QT prolongation: Bazett’s corrected QT interval (QTcB) and Fridericia’s corrected QT interval (QTcF). QTc was divided into quartiles by gender, and quartile associations with the primary endpoint (composite cardiovascular events: cardiovascular death, nonfatal myocardial infarction/stroke) and secondary endpoint (sudden death) were compared. Results: QTc duration in females (QTcB: median 428 [IQR 414–444] ms, QTcF 422 [IQR 409–436] ms) was slightly longer than that in males (QTcB: median 419 [IQR 405–435] ms and QTcF 415 [IQR 402–430], both p&lt;0.001). The mean follow-up period was 53 ± 17 months, during which 159 primary endpoints and 14 secondary endpoints occurred. The longest QTcB group (Q4: ≥ 435 ms in men, ≥ 444 ms in women) had significantly more cardiovascular events than the other quartiles (vs. Q1: p=0.016, vs. Q2: p=0.037, and vs. Q3 p=0.141), and sudden death was more common than in Q2 and Q3 (vs. Q2 0.003, vs. Q3: p=0.032). On the other hand, the longest QTcF group (Q4) (≥430 ms for men, 436 ms for women) had significantly more cardiovascular events than the Q1 and Q2 groups but not the Q3 group (vs. Q1: p=0.016, vs. Q2: p=0.037, and vs. Q3: p=0.141); sudden death was not significantly different among quartiles (all P&gt;0.05). Conclusions: In Japanese patients at cardiovascular risk, prolonged QTcB was associated with cardiovascular events as well as sudden death.
Abstract 4137500: The Histone Methyltransferase MLL1 Regulates Notch Signaling and T Cell Phenotype During Pathologic Abdominal Aortic Aneurysm Development
Authors: Brennan Callow, Xiaobing He, Kevin Mangum, Tyler Bauer, Amrita Joshi, Andrea Obi, Katherine A Gallagher, Frank Davis
Journal: Circulation (2024)

Objective: Abdominal aortic aneurysms (AAA) are characterized by pathological vascular remodeling and an imbalance between anti-inflammatory regulatory T H cells (Tregs) and pro-inflammatory T H 17 cells within the aortic wall. The mechanisms regulating CD4 + T H cell differentiation during AAA development remain unknown. Recently, the histone methyltransferase, mixed lineage leukemia 1 (MLL1), has been shown to influence T H cell phenotype by directly altering key transcription factors for T H 17 (RORγ) and Treg (FOXp3) differentiation in varying disease states. As such the objective of this study was to evaluate the role of MLL1 in promoting T H 17 activity within AAA development and to determine key T H 17 cell signaling pathways that are altered Methods: Single-cell sequencing was conducted on human AAAs and control tissue samples. For our murine model, C57BL/6 mice were injected with an AAV encoding a PCSK9 gain-of-function mutation and fed a saturated fat diet followed by either AngII infusion to induce AAAs (1 µg/kg/min) or saline. Mice with T-cell specific deletion of Notch1 signaling (Notch1 f/f CD4 cre+ ) or MLL1 ( Mll1 f/f CD4 cre+ ) were subjected to the AngII-induced AAA model and AAA diameters quantified. CD4+ T-cells were isolated by MACs and gene expression analyzed by qPCR as well as T-cell phenotype by flow cytometry. ChIP was used to evaluate histone 3 lysine trimethylation (H3K4me3). Results: Single-cell RNA sequencing of human aortic tissue revealed that the epigenetic enzyme MLL1 and Notch1 signaling were profoundly upregulated in human AAA CD4+ cells compared to non-aneurysmal control samples. Congruently, CD4 + T H cells isolated from the murine AngII-induced AAA model displayed a predominance of T H 17 phenotype and elevated expression of MLL1. Histone methylation was evaluated by ChIP in AngII-induced AAA CD4+ cells and demonstrated increased levels of the MLL1-mediated activation histone methylation mark, H3K4me3, on the Notch 1 promoter. Mice deficient in CD4 + T H cell Notch signaling ( Notch1 f/f CD4 cre+ ) or MLL1 ( Mll1 f/f CD4 cre+ ) subjected to the AngII-induced murine model displayed significant reduction AAA development (n=10/group, p&lt;0.05) with decreased CD4+ T H 17 cell activity and reciprocal increase in Treg expression. Conclusions: MLL1, a histone methyltransferase, regulates Notch1 signaling and T-cell differentiation in AAA development, causing pathologic inflammation. This pathway may serve as a potential therapeutic target to prevent aortic dilation.
Abstract 4137448: Systemic Heparin Administration Does Not Inhibit microRNA Amplification in Patients with Myocardial Infarction
Authors: Kurt Barringhaus, Sarah Slone, George Prousi, Stephanie Samani, Lisa Freeburg, Amelia Churillo, Francis Spinale
Journal: Circulation (2024)

Purpose: MicroRNAs (miRs) have been proposed as biomarkers of myocardial infarction (MI), but prior evidence has demonstrated that heparin, commonly administered to patients presenting with MI, inhibits amplification during quantitative PCR (qPCR). The purpose of this study was to determine whether qPCR amplification of miRs is reduced in plasma of patients receiving heparin and if heparinase reverses this effect. Methods: Blood samples were collected and plasma recovered from patients with normal coronary arteries who had undergone CT coronary angiography ( N=5 ) or who had received intravenous heparin at the time of invasive coronary angiography( N=8 ). Blood was also collected at the time of invasive coronary angiography from patients presenting with ST elevation MI ( N=9 ). RT-qPCR was performed to quantify levels of 84 cardiac miRs, and Cel-miR-39-3p was utilized as a spike-in control. MiR qPCR was also performed following the addition of heparinase to plasma from 2 patients without MI treated with heparin and 2 patients presenting with MI who had received heparin. Results: Mean age of patients was 57 years, and 55% of patients were male. As compared with control patients, the cycle number for cel-miR-39-3p was significantly increased for patients receiving heparin (Figure 1a). No difference was seen in levels of cel-39-3p in heparin-treated patients with respect to the presence or absence of MI. Cel-miR-39-3p cycle times decreased when heparinase was added to samples from heparin-treated patients (Figure 1b). In contrast, heparin did not increase cycle times in any of the cardiac miRs tested, and cycle times decreased even further for miRs 499a-5p and 208b-3p in patients with MI (Figure 2). Conclusions: Systemic heparin treatment inhibits qPCR amplification of cel-mir-39-3p but does not inhibit endogenous miR amplification under these conditions. MiRs 499a-5p and 208b-3p are potentially important candidates for MI detection and quantification.
Abstract 4137423: Can Machine Learning Help Prioritise Who to Screen for Elevated Lipoprotein(a) (Lp[a]) in the General Population vs a Screen all Approach? An Analysis from UK Biobank
Authors: Christophe Stevens, Fotis Barkas, Julia Brandts, Sunganani Kwilasi, Alireza Mahani, Antonio J. Vallejo-Vaz, Mansour Taghavi Azar Sharabiani, Kausik Ray
Journal: Circulation (2024)

Background: Elevated lipoprotein(a) [Lp(a)] is an inherited, currently non-modifiable risk marker that increases lifetime ASCVD risk. Guidance vary on Lp(a) levels at which risk increases; hence prevalence of “elevated” Lp(a) depends on putative thresholds e.g. &gt;1.3 billion people globally have Lp(a)≥125 nmol/L. Lp(a) levels are &gt;90% genetically determined and stable throughout life; hence measurement once in adulthood is recommended. Awareness of Lp(a) levels may change patient management with more intensive control of traditional risk factors. However, testing all adults is costly and the test is not universally available. Research Question: Can Machine Learning (ML) models reduce the number needed to screen (NNS) compared to population universal screening for identifying individuals with elevated Lp(a)? Aims&amp;Objectives: To derive a model from ML to help prioritise individuals likely to have high levels for Lp(a) testing and compare its yield to universal screening at different Lp(a) cut-points. This approach could enable automatic screening of large databases like EHRs for Lp(a) testing. Method: We conducted a cross-sectional predictive analysis using UK Biobank, including individuals ≥40 years old with Lp(a) measurements, split into feature importance, derivation, and validation datasets. Eight ML classification algorithms were used for feature importance analysis and model derivation. Models' performance was evaluated in the validation set using sensitivity and NNS in comparison with the discrimination ability of the following guidelines across different populations: The 2019’s Heart UK and European Atherosclerosis Society (EAS) and Society of Cardiology guidelines, the 2022 EAS Consensus Statement, and threshold used in clinical trial —respective cut-offs: 90,430,125,200nmol/L. Results: 438,579 patients were included. The best ML models were neural networks with different weights. Regardless of the Lp(a) threshold used, ML models resulted in higher rates of high Lp(a) cases identified per million tests with lower NNS compared to universal screening (Table 1). Using higher Lp(a) thresholds (200-430nmol/L) increased models sensitivity with far fewer tests required to identify those with high Lp(a). Conclusion: ML models could reduce the number of tests needed to identify individuals with high Lp(a), increasing efficiency and potentially helping to prioritize Lp(a) testing, with a potentially scalable cost-effective option for health systems. Work supported by Novartis
Abstract 4137823: Influence of Hospital and Cardiac Rehabilitation Facility Proximity on Enrollment Rates Among Medicare Beneficiaries
Authors: Usman Khan, Jie Yang, Robert Hawkins, Steven Keteyian, Donald Likosky, Mike Thompson, Whitney Fu, Devraj Sukul
Journal: Circulation (2024)

Background: Participation in cardiac rehabilitation (CR) is enhanced by proximity to CR facilities and communication between inpatient and outpatient settings but may become fragmented when patients are distant from their discharging hospital and nearest CR facility. Research Question: This study investigates how patient distance to both hospitals and CR facilities impacts the rates of CR participation. Methods: This study included 100% Medicare fee-for-service claims for beneficiaries with 12 months of continuous Part A/B coverage who had coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or surgical or transcatheter aortic valve replacements (SAVR or TAVR) between 07/2016-12/2018, excluding patients discharged to hospice or died within 30 days. Google Maps defined travel distances from the patient to hospital and CR facility locations using geographic centroids of ZIP codes, which were then categorized into quartiles. CR enrollment was defined as attending at least one session within one year of discharge. Logistic regression models estimated marginal CR enrollment rates across both hospital and CR facility distance categories adjusting for patient, hospital, and regional factors. Results: The study included a total sample of 501,049 beneficiaries undergoing PCI (62%), CABG (19%), SAVR (7%), and/or TAVR (15%). The median travel distance to the hospital was 18.6 miles (IQR 8.2-43.3 miles) and to the CR facility was 7.7 miles (IQR 2-15.3 miles). A total of 188,963 (37.7%) beneficiaries attended at least one CR session, which varied across categories of distance to hospital (Q1: 36.8% to Q4: 37.5%) and CR facility (Q1: 44.7% to Q4: 30.0%, p&lt;0.01). Adjusted CR enrollment rates improved when beneficiaries lived farther from their admitting hospitals but closer to CR facilities (Figure 1), with the highest enrollment for those located farthest from their admitting hospital but closest to the CR facility (47.5%) and lowest enrollment among those closest to the hospital but farthest from the CR facility (20.6%). Conclusions: Greater distance to the admitting hospital was associated with higher CR enrollment, while greater distance to the CR facility was associated with lower enrollment among eligible Medicare beneficiaries. Addressing geographic barriers to CR participation may require tailored solutions based on patient proximity to hospitals and CR facilities.