tbuckley/cabot-search huggingface dataset:
AI-Generated Clinical Summaries—Reply
Authors: Katherine E. Goodman, Daniel J. Morgan
Journal: JAMA (2024)

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Medical Assistant Health Coaching for Type 2 Diabetes in Primary Care: Results From a Pragmatic Cluster Randomized Controlled Trial
Authors: Addie L. Fortmann, Emily C. Soriano, Linda C. Gallo, Taylor L. Clark, Samantha R. Spierling Bagsic, Haley Sandoval, Jennifer A. Jones, Scott Roesch, Todd Gilmer, James Schultz, Thomas Bodenheimer, Athena Philis-Tsimikas
Journal: Diabetes Care (2024)

This cluster (clinic-level) randomized controlled trial (RCT) compared medical assistant (MA) health coaching (MAC) with usual care (UC) among at-risk adults with type 2 diabetes in two diverse real-world primary care environments: a federally qualified health center (FQHC; Neighborhood Healthcare) and a large nonprofit private insurance-based health system (Scripps Health).
Clinical and healthcare use outcomes after cessation of long term opioid treatment due to prescriber workforce exit: quasi-experimental difference-in-differences study
Authors: Adrienne H Sabety, Hannah T Neprash, Marema Gaye, Michael L Barnett
Journal: BMJ (2024)

To examine the association between prescriber workforce exit, long term opioid treatment discontinuation, and clinical outcomes. Quasi-experimental difference-in-differences study SETTING: 20% sample of US Medicare beneficiaries, 2011-18. People receiving long term opioid treatment whose prescriber stopped providing office based patient care or exited the workforce, as in the case of retirement or death (n=48 079), and people whose prescriber did not exit the workforce (n=48 079). Discontinuation from long term opioid treatment, drug overdose, mental health crises, admissions to hospital or emergency department visits, and death. Long term opioid treatment was defined as at least 60 days of opioids per quarter for four consecutive quarters, attributed to the plurality opioid prescriber. A difference-in-differences analysis was used to compare individuals who received long term opioid treatment and who had a prescriber leave the workforce to propensity-matched patients on long term opioid treatment who did not lose a prescriber, before and after prescriber exit. Discontinuation of long term opioid treatment increased from 132 to 229 per 10 000 patients who had prescriber exit from the quarter before to the quarter after exit, compared with 97 to 100 for patients who had a continuation of prescriber (adjusted difference 1.22 percentage points, 95% confidence interval 1.02 to 1.42). In the first quarter after provider exit, when discontinuation rates were highest, a transient but significant elevation was noted between the two groups of patients in suicide attempts (adjusted difference 0.05 percentage points (95% confidence interval 0.01 to 0.09)), opioid or alcohol withdrawal (0.14 (0.01 to 0.27)), and admissions to hospital or emergency department visits (0.04 visits (0.01 to 0.06)). These differences receded after one to two quarters. No significant change in rates of overdose was noted. Across all four quarters after prescriber exit, an increase was reported in the rate of mental health crises (0.39 percentage points (95% confidence interval 0.08 to 0.69)) and opioid or alcohol withdrawal (0.31 (0.014 to 0.58)), but no change was seen for drug overdose (-0.12 (-0.41 to 0.18)). The loss of a prescriber was associated with increased occurrences of discontinuation of long term opioid treatment and transient increases in adverse outcomes, such as suicide attempts, but not other outcomes, such as overdoses. Long term opioid treatment discontinuation may be associated with a temporary period of adverse health impacts after accounting for unobserved confounding.
Immunotherapy-activated T cells recruit and skew late-stage activated M1-like macrophages that are critical for therapeutic efficacy
Authors: Marit J. van Elsas, Jim Middelburg, Camilla Labrie, Jessica Roelands, Gaby Schaap, Marjolein Sluijter, Ruxandra Tonea, Vitalijs Ovcinnikovs, Katy Lloyd, Janine Schuurman, Samantha J. Riesenfeld, Thomas F. Gajewski, Noel F.C.C. de Miranda, Thorbald van Hall, Sjoerd H. van der Burg
Journal: Cancer Cell (2024)

Total tumor clearance through immunotherapy is associated with a fully coordinated innate and adaptive immune response, but knowledge on the exact contribution of each immune cell subset is limited. We show that therapy-induced intratumoral CD8+ T cells recruited and skewed late-stage activated M1-like macrophages, which were critical for effective tumor control in two different murine models of cancer immunotherapy. The activated CD8+ T cells summon these macrophages into the tumor and their close vicinity via CCR5 signaling. Exposure of non-polarized macrophages to activated T cell supernatant and tumor lysate recapitulates the late-stage activated and tumoricidal phenotype in vitro. The transcriptomic signature of these macrophages is also detected in a similar macrophage population present in human tumors and coincides with clinical response to immune checkpoint inhibitors. The requirement of a functional co-operation between CD8+ T cells and effector macrophages for effective immunotherapy gives warning to combinations with broad macrophage-targeting strategies.
Abstract P519: Sleep as a Cardiometabolic Risk Factor Following Release From Carceral Facilities
Authors: Johanna Elumn, Inessa Cohen, Jenerius Aminawung, Lisa Puglisi, Nadine Horton, Hsiuju Lin, Henry K Yaggi, Emily Wang
Journal: Circulation (2024)

Background: Approximately 2 million people are incarcerated, and 11 million cycle in and out of U.S. jails and prisons annually. Cardiovascular disease (CVD) morbidity and mortality are higher among people with a history of incarceration, especially in the weeks following release from prison. Sleep is an underexplored factor that may contribute to CVD disparities among people with a history of incarceration. Population-specific risk factors in the social and physical environment may contribute to poor sleep and CVD risk during imprisonment and after release from a carceral facility. Methods: The Sleep Justice study, an ancillary study to an ongoing prospective cohort recruiting individuals with known cardiovascular risk factors within three months of release from incarceration, the Justice-Involved Individuals Cardiovascular Disease Epidemiology (JUSTICE) study, aimed to describe sleep and examine the connections between sleep and CVD risk factor control among people released from a carceral facility. Sleep was assessed using subjective and objective measures. The Pittsburgh Sleep Quality Index (PSQI), the STOP-Bang, and the Brief Index of Sleep Control were used, and wrist-worn actigraphy was used to measure sleep objectively in a subsample of 80 participants. We will examine sleep and its association with CVD in this sample of people recently released from a carceral facility. Results: Most participants were male (92%), non-Hispanic Black (51%) or Hispanic (27%), were incarcerated 2-5 times, and were living in transitional housing (78%) at baseline. All participants had a CVD risk factor as a requirement of the study inclusion criteria: hypertension (78%), hyperlipidemia (47%), obesity (59%), diabetes (29%), and history of CVD (19%). Most reported low (24%) or some control (35%) over their sleep. Participants were at increased risk for sleep apnea, with 47% at moderate risk and 23% at high risk. Most participants reported poor sleep quality (65%) on the PSQI. We conducted logistic regression examining the relationship between sleep and CVD risk and found that poor sleep quality was associated with HTN (p=0.02), even after adjusting for age, race and ethnicity, and gender (AOR 2.44, 95% CI 1.14-5.29). Discussion: Given the disproportionate incarceration of racial and ethnic minoritized groups, the impact of incarceration on sleep health and CVD are areas that urgently need to be examined. This study is the first to examine sleep after release from a carceral facility and highlights the need for interventions targeting sleep health and CVD in this population.
Abstract P503: Syphilis Infection and Increased Odds of Cardiovascular Morbidity
Authors: Aaron Briggs, Joseph Risser, Bernard Newman
Journal: Circulation (2024)

Background: Cardiovascular disease (CVD) is the number one cause of death in the United States and around the world. Syphilis is a sexually transmitted infection conferred by the spirochete Treponema pallidum which demonstrates a unique affinity for the human CV system. It is understood that Treponemal invasion of vascular and cardiac tissue, in the absence of treatment, may result in the CV manifestations of late, tertiary syphilis including: aortic aneurysm, aortic insufficiency, coronary artery disease (CAD), and stroke. Recent literature has suggested that chronic kidney disease (CKD) may also be among these sequalae. It is the current understanding that syphilitic CVD morbidity is effectively prevented and treated with the standard of care (SOC) antimicrobial therapy dictated for early and late syphilis, however, there is a relative paucity of data to support this. In light of the ongoing syphilis epidemic in the United States, our group sought to revisit and evaluate these central tenets of syphilis care. Methods: A preliminary, 10-year retrospective analysis (01/2013-12/31/2022) of deidentified electronic medical records (EMR) from a California-based academic health system was undertaken. The study population consisted of all health system patients &gt;18 who were seen during the study period. The exposure of interest consisted of ICD-10 codes representative of syphilis infection with CVD outcomes defined as ICD-10 diagnoses reflective of the known, principle clinical manifestations of tertiary syphilis as well as CKD and HTN. Unadjusted, bivariate analysis was performed for preliminary assessment of exposure-outcome association. Results: 3,559,370 unique EMR were included in final analysis. 5,915 patients were found to have a diagnosis of syphilis. The majority of patients diagnosed with syphilis had documentation of treatment. Patients with history of syphilis infection had significantly higher odds of aortic aneurysm (OR = 6.17; 95%CI = 5.07-7.5), CAD (OR = 5.81; 95%CI = 5.37-6.27), aortic insufficiency (OR = 5.52; 95%CI = 4.47-6.81), stroke (OR = 5; 95%CI = 4.58-5.46), HTN (OR = 8.38; 95%CI = 7.94-8.85), and CKD (OR = 10.94; 95%CI = 10.28-11.64) relative to uninfected patients. Conclusion: Preliminary analysis indicates syphilis infection to be associated with significantly increased odds of CVD morbidity across all outcomes measured including CKD. These data suggest that the CV impact of syphilis may be broader than previously understood and raise concern for a clinically significant limitation to the current SOC in protection against CVD morbidity. A follow-up study is underway which will utilize multivariate logistic regression analysis to determine the independent effect of syphilis infection adjusting for multiple confounders to further clarify our preliminary results.
Abstract P225: Heartfelt Savings: Health Savings Accounts Assist in Alleviating Financial Burdens and Prompt Timely Treatment for Patients With Cardiovascular Disease
Authors: Daniel Won, James Walker, Connor Workman, James W Guo, Elizabeth Zordani, Anna Chorniy, S. Christopher Malaisrie, Donald M Lloyd-Jones
Journal: Circulation (2024)

Background: Cardiovascular diseases (CVD) are among most costly in the U.S, with a significant portion of CVD patients unable to afford care. Use of health savings accounts (HSA) to increase financial savings for medical expenditures is controversial. While HSA have shown to not decrease medical expenditures, the financial impact of HSA on patients with CVD remains unknown. Methods: This cross-sectional study used data from the Medical Expenditure Panel Survey for 2014-19 and included patients aged 18-64 who reported having at least one CVD (i.e., hypertension, angina, myocardial infarction, heart failure, stroke, or all other CVD). A survey-weighted model was utilized to determine the adjusted odds ratios (OR) for associations between CVD patients with HSA and 1) demographics factors and 2) metrics associated with financial difficulty by adjusting for age, sex, race, total out of pocket (OOP) yearly premiums, total yearly medical expenditures, total OOP yearly medical expenditures, total yearly income, annual deductibles, and other demographic factors (Figure 1) . Results: CVD patients with HSA were significantly less likely to experience financial difficulties such as affording medical care (OR 0.586, 95% CI 0.344-0.998, p = 0.049) and trouble paying medical bills (OR 0.762, 95% CI 0.582-0.996, p = 0.047). Furthermore, CVD patients with HSA were significantly less likely to delay medical care (OR 0.614, 95% CI 0.389-0.970, p = 0.037) and preventive medicine (OR 0.575, 95% CI 0.336-0.983, p = 0.046) due to cost. However, CVD patients who earn lower income, self-identify as Hispanic or Black, from the South or West, or have lower years of education were significantly less likely to benefit from an HSA (Figure 1) . Conclusions: CVD patients with HSA were significantly associated with decreased financial difficulties and were less likely to delay care. Policies intended to support minority and lower-income CVD patients such as increased financial education may reduce healthcare disparities and promote access to care.
Abstract P461: Concordance of Hypoglycemia Symptoms Reported in Real-Time via Smartphone and Hypoglycemia Detected Using Continuous Glucose Monitoring (CGM) in Adults With Type 2 Diabetes
Authors: Joseph Sartini, Michael Fang, Scott Mu, Dan Wang, Casey M Rebholz, Christine M Mitchell, Lawrence J Appel, Scott Zeger, Scott Pilla, Elizabeth Selvin
Journal: Circulation (2024)

Introduction: Understanding the association between low glucose readings (hypoglycemia) detected by CGM and hypoglycemic symptoms experienced by people with diabetes is critically important for diabetes management. However, tools that capture hypoglycemic symptoms in real-time are lacking. Objective: Implement a real-time hypoglycemia symptom reporting tool and examine agreement between self-reported hypoglycemia symptoms and CGM-detected hypoglycemia. Methods: We developed a survey tool for real-time reporting of symptoms via smartphone ( Fig. 1A ) using REDCap, and implemented this tool in an ongoing, randomized clinical trial of adults with type 2 diabetes, the Dietary Approaches to Stop Hypertension for Diabetes (DASH4D) trial. DASH4D participants wore a CGM sensor (Abbott Libre Pro) for up to 5 periods (max 2-weeks per period), and we offered the option to report symptoms using the real-time survey tool during each CGM wear. We examined the concordance of real-time reported symptoms and CGM-detected hypoglycemia (glucose &lt;70 mg/dL for &gt; 15 minutes) ( Fig. 1B ). Concordance was defined as CGM-detected hypoglycemia occurring within 30 minutes before or after a reported symptom. Results: Of 159 participants who wore a CGM, 114 (72%; mean age 64 years; 86% Black; 64% female) used the real-time symptom reporting tool (the remainder used a paper-based booklet). Across all CGM wear-periods (N=280), participants reported a mean 1.94 symptoms per period. Fatigue was the most common (37 occurrences); unsteadiness and passing out were not reported ( Fig. 1C ). The overall concordance between self-reported symptoms and CGM-detected hypoglycemia was 3% ( Fig. 1D ). Conclusion: We developed a simple and secure smartphone-based tool allowing patients with diabetes to report hypoglycemic symptoms in real-time. Concordance of CGM-detected hypoglycemia with symptoms was low, indicating substantial disconnect between perceived symptoms and CGM-detected hypoglycemic events among adults with type 2 diabetes. [NCT04286555]
Abstract MP55: The Cardioprotective Feature of High-Density Lipoprotein Function Diminishes as Women Transition Through Menopause: The Swan HDL Study
Authors: Samar R El Khoudary, James Matuk, Jeffrey Billheimer, Maria M Brooks, Trevor Orchard, Imke Janssen, Dan McConnell, Sybil Crawford, Karen A Matthews, Dan Rader
Journal: Circulation (2024)

Objective: HDL cholesterol efflux capacity (CEC) is a key metric of the cardioprotective HDL functionality. CEC generally rises as women traverse the menopause but it is unclear whether this rise reduces future CVD risk. We tested whether the association between CEC and subclinical CVD burden, measured using a composite subclinical CVD score based on carotid-intima media thickness (c-IMT), carotid-femoral pulse wave velocity (cf-PWV) and presence of coronary artery calcium (CAC score ≥10), varies by time relative to the final menstrual period (FMP). Design: We included 279 women (at baseline: age 51±2.8 years; 68.5% White; 31.5% Black; 60.6% Pre-/perimenopausal) who had HDL metrics and subclinical CVD outcome measures measured once (N=115 [41.2%]) or twice (N=164 [58.8%]). The composite subclinical CVD score was computed using a factor analysis for mixed data approach (FactoMineR R package), which combines principal component analysis for continuous (c-IMT, cf-PWV) and multiple correspondence analysis for categorical data (CAC≥10). A linear mixed effects model was used to model the composite score of subclinical CVD and estimates were back transformed to the individual observed components. We tested the interaction between CEC and time relative to FMP in this model. Results: Higher CEC was associated with a lower composite subclinical CVD score at FMP in unadjusted analyses (Illustration). This association was negligible after adjustment for confounders. In all models, association of CEC varied by time relative to FMP such that the pre-FMP protective association of CEC diminishes after the FMP. This pattern was consistent across all components of the composite score (Illustration). Conclusions: In women, higher CEC is associated with a lower risk of subclinical CVD burden before but not after menopause. High CEC is not a consistent indicator of CVD protection in women traversing menopause.
Abstract P333: Plasma Proteins, Structural Brain Reserve, and Onset of Alzheimer’s Disease: Proteome-Wide Mendelian Randomization
Authors: Yang Pan, Xiao Sun, Zhijie Huang, Ruiyuan Zhang, Brenna Kirkpatrick, Avi Aronov, Changwei Li, Tanika N Kelly
Journal: Circulation (2024)

Introduction: While the emergence of amyloid-clearing treatments for Alzheimer’s disease is promising, the identification of additional therapeutic options for Alzheimer’s disease and related dementia syndromes (AD/ADRD) remains urgent. Plasma proteins represent a class of actionable drug targets AD/ADRD treatment. Yet, the role of the blood proteome in influencing structural brain reserve, and consequently, cognitive performance and the development of AD, remains elusive. Hypothesis: Plasma proteins may causally associate with changes in structural brain reserve and cognition phenotypes. Methods: We conducted proteome-wide Mendelian randomization (MR) to identify potentially causal associations of plasma proteins with changes in brain reserve, proxied by brain imaging-derived phenotypes (IDPs), cognitive performance, and AD onset. Genetic instruments for plasma proteins were previously developed by integrating summary data from five genome-wide association studies (GWASs) of plasma proteome. Summary statistics from large GWASs of 12 AD-associated IDPs (N=33,224), cognitive performance (N=257,841), and two AD cohorts (IGAP consortium, N=63,926, and FinnGen study, N=309,154) are obtained to perform two-sample MR. Causal estimates from two AD outcomes are meta-analyzed to improve statistical power. Correction for multiple testing and sensitivity analyses are performed. Results: Among 956 proteins with genetic instruments that satisfied MR assumptions, genetically determined levels of 14 plasma proteins were associated with at least one of the 10 AD-related IDPs at a false discovery rate of 5%. Six of these proteins were associated with white matter hyperintensities, an IDP known to be involved in cognitive decline. In addition, 26 plasma proteins were associated with cognitive performance, and four were causally linked to AD. Notably, four identified proteins were associated with structural brain reserve and either cognition or AD. Specifically, ADAM12, CREB3L4, and UROS were associated with distinct IDPs and cognitive performance, while TMEM106B, a protein that forms age-dependent amyloid filaments, was associated with increased hippocampal tail volume and AD. Conclusions: This study identified potential causal plasma proteins underlying structural brain reserve, cognitive performance, and AD, offering insights into the molecular etiology of these conditions and potential targets for drug development.