Publications

The purpose of this study was to determine the healthcare utilization patterns in a national sample of older adults across several factors (ethnicity, gender, race, education) with normal and dementia/impaired cognition. We used datasets from the Health and Retirement Study (HRS, 2018) to evaluate healthcare utilization, including metrics such as hospital and nursing home stays, hospice care, and the number of visits to the doctor. Logistic models were used to predict healthcare utilization separately in those with normal cognition and dementia. Our final sample comprised 15,607 adults (mean age: 65.2 normal cognition, mean age 71.5 dementia). Hispanics with normal cognition were less likely to stay in a hospital than non-Hispanic respondents (OR: 0.52-0.71, p < 0.01). Being female was associated with a higher risk for shorter nursing home days (OR: 1.41, p < 0.01) and doctor visits (OR: 1.63-2, p < 0.01) in cognitively normal older adults. Being female was associated with a lower risk for hospital stay in those with dementia (OR: 0.50-0.78, p < 0.01). Respondents identifying as Black or other races with dementia were less likely to experience nursing home days (OR: 0.42, p < 0.04). Black respondents with normal cognition were less likely to experience doctor visits (OR: 0.32-0.37, p < 0.01). Those with more than a high school education in both groups were more likely to experience doctors' visits. The study points to the continued disparities in healthcare utilization linked to participants' characteristics and cognition.

Peer support services in which people with lived experience provide non-clinical, mutualistic support are effective in improving health outcomes for people with serious mental health challenges. Despite its demonstrated effectiveness, there is limited research on peer supporters' experiences with training, service delivery, and supervision across diverse global contexts. This explanatory mixed methods study explored these perspectives through a survey (N = 101), key informant interviews (N = 13), and focus group discussions (N = 14). Quantitative data from the survey was summarized descriptively, and qualitative data were analyzed using thematic content analysis. Participants reported high use of peer-specific competencies including sharing lived experience (89.1%), collaboration and care (81.2%), and communication (78.2%). Themes emerging from qualitative data emphasized role clarity, collaboration with non-peers, accessible training, and peer supervision. Challenges identified included stigma, inequitable compensation, limited career pathways, and inconsistent training quality. Many participants preferred peer-led or co-supervision models. In contexts without formalized peer support infrastructures, grassroots and faith-based organizations played a critical role in delivering peer support services. These findings highlight common foundations and context-specific nuances necessary for strengthening peer support across contexts, including standardized training competencies, sustainable and inclusive training, equitable compensation, and peer supervision models.

BACKGROUND: Stressor-associated atrial fibrillation (AF), defined as newly diagnosed AF in the setting of a reversible physiological stressor, is common. However, risk factors, outcomes, and current management practices remain poorly understood.

METHODS: We analyzed data from VITAL-AF, a pragmatic, cluster-randomized AF screening trial conducted in 2018 and 2019 comprising adults ≥65 years of age across 16 primary care practices affiliated with Massachusetts General Hospital. All participants had longitudinal follow-up for adjudicated incident AF (including whether stressor-associated versus nonstressor-associated ["primary"]) and clinical outcomes. We compared associations between clinical AF risk factors and incident AF group (stressor-associated versus primary) using Fine-Gray models handling death and each AF group as competing risks. We also quantified oral anticoagulant initiation rates after AF diagnosis. We then fit Cox proportional hazards models to quantify associations between incident AF group (as a time-varying covariate) and a composite end point of major bleeding, stroke, and all-cause mortality, with adjustment for CHA₂DS₂-VASc (congestive heart failure, hypertension, age >74, diabetes, stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74, sex category; stroke) and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation; bleeding) scores and time-varying oral anticoagulant exposure.

RESULTS: We analyzed 30 265 patients (41% men, 83% White, and mean age 74 years). Of 988 incident AF events, 290 (29%) were stressor associated. Clinical risk factors, including age, hypertension, and heart failure, showed similar associations with both primary and stressor-associated AF. Oral anticoagulant initiation within 90 days of new AF diagnosis was lower for stressor-associated versus primary AF (56% versus 75%, P<0.001). The incidence of the composite end point was 2.30 per 100 person-years (95% CI, 2.17-2.44) for no AF, 15.09 (95% CI, 12.22-18.42) for primary AF, and 22.71 (95% CI, 16.91-29.87) for stressor-associated AF. In adjusted models and using no AF as the referent, both primary AF (hazard ratio [HR], 3.91 [95% CI, 2.89-5.28]) and stressor-associated AF (HR, 6.13 [95% CI, 4.31-8.72]) were associated with substantially higher risk of the composite end point.

CONCLUSIONS: Among >30 000 primary care patients with adjudicated AF events, nearly one-third of incident AF cases were stressor associated. Despite similar risk factor profiles and comparably high rates of adverse outcomes, oral anticoagulant initiation is lower when AF is stressor associated. Future work is needed to define optimal approaches to prevention, surveillance, and management of stressor-associated AF.

STUDY DESIGN: Retrospective study.

OBJECTIVE: To determine the prevalence of new chronic pain conditions within one-year of whiplash and factors associated with chronic pain following whiplash exposure.

SUMMARY OF BACKGROUND DATA: Whiplash is among the most common injuries that occur following motor vehicle accidents. Many have postulated that whiplash is a progenitor for the development of chronic pain. Prior research in this arena has been limited.

METHODS: We retrospectively identified TRICARE beneficiaries who sustained a whiplash injury between 2017-2023. The records of eligible beneficiaries were abstracted to obtain age at the time of injury, race, sex, US census region, sponsor rank, mental health diagnoses, environment of care, beneficiary status, time-period of injury and number of co-morbidities. We considered junior enlisted sponsor rank indicative of lower socioeconomic strata. The primary outcome was development of a chronic pain condition. We used multivariable logistic regression with re-weighting to account for confounders. We examined interactions between sex/mental health conditions, sex/socio-economic status and sex/time-period to address secular trends.

RESULTS: The development of new chronic pain conditions occurred in 23.4%. After adjusting for confounders, we found that women (OR 1.57, 95% CI 1.49, 1.65), pre-existing mental health conditions (OR 1.35; 95% CI 1.28, 1.42) and our proxy for lower socioeconomic status (OR 1.15; 95% CI 1.04, 1.27) were significantly associated with the likelihood of developing chronic pain disorders within 1-year of whiplash injury. There were interactions between women and mental health conditions, as well as women and socio-economic status.

CONCLUSIONS: This represents the largest study that longitudinally surveys for the development of chronic pain conditions following whiplash. The incidence of chronic pain after whiplash is lower than has been previously postulated. We believe these findings can inform management in the post-injury time-period and recommendations for surveillance.

Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8+ cells, CD4+ T cells capable of regulating inflammation show promise in reducing pathology and improving cognitive outcomes in mouse models of AD and in aging. Here, we sought to exploit the beneficial properties of CD4+ T cells while circumventing the need for TCR and peptide-MHC antigen discovery, thereby providing a potential universal therapeutic approach. To achieve this, we engineered CD4+ T cells with chimeric antigen receptors (CARs) targeting fibrillar forms of aggregated amyloid-β. Our findings demonstrate that optimized CAR-T cells can alter amyloid deposition in the dura and reduce parenchymal pathology in the brain. Furthermore, we observed that CAR-T treatment promotes the expansion and recruitment of endogenous CD4+ T cells into the brain parenchyma and leptomeninges. In summary, we established the feasibility of amyloid plaque-specific CAR-T cells as a potential therapeutic avenue for AD. These findings highlight the potential of CD4+ CAR-T therapy not only to modify amyloid pathology but also to reshape the immune landscape of the CNS, paving the way for future development of cellular immunotherapies for neurodegenerative disease.

BACKGROUND AND OBJECTIVES: Neonatal encephalopathy (NE)-including hypoxic-ischemic encephalopathy (HIE)-is associated with significant morbidity and mortality worldwide. While data registries provide hypothesis-generating data, aid in quality improvement, and track management/outcomes over time, we recently demonstrated that only 4 of 1,281 (0.3%) variables were collected by all 22 international NE/HIE registries: birth weight, gestational age, and 1- and 5-minute Apgar scores. In response, our team set out to develop a set of common inpatient data elements to enable future harmonization of NE/HIE registry data.

METHODS: Using a modified Delphi method, a panel of 14 international NE experts voted to separate the 1,281 variables from our previous study into "core elements," "supplemental elements," or those that "do not need to be collected." Based on the anonymous survey results, we created draft lists of core and supplemental common data elements (CDEs). These lists were further revised through group consensus meetings and external feedback from global registry leaders and attendants at 2 international conferences.

RESULTS: The final data forms include 164 core elements and 225 supplemental elements stratified into 11 domains: demographics; pregnancy, labor, and delivery; delivery room; transport; acid-base; therapeutic hypothermia; neuromonitoring and seizures; neuroimaging; laboratory values (other than acid-base); hospital course; and discharge.

DISCUSSION: The CDEs are the first of several important steps to further standardize research and reporting of NE/HIE investigations to perform more efficient and powerful clinical research in the field moving forward. Future studies need to establish a clinical and research definition of HIE and develop CDEs for collecting long-term, family-centered follow-up data postdischarge.

Frailty is a syndrome of decreased reserve across multiple physiologic systems that is associated with greater risk for hospitalizations, disability, institutionalization, and other adverse outcomes, including mortality. Patients with frailty, most of whom are older adults, may be more likely to experience adverse outcomes due to iatrogenic causes, such as higher-risk medications or procedures. Guidelines recommend frailty screening for both chronic disease management and in-hospital care, as identification of frailty allows for risk mitigation and alignment of care with patients' goals. In addition, some interventions may delay or reverse frailty, thus increasing physiologic reserve and improving day-to-day function. This article reviews frailty definitions, approaches to assessment in different care settings, and management.

Acute pancreatitis is among the most frequent gastroenterologic reasons for hospitalization in the United States. This condition is associated with significant morbidity, including recurrent acute pancreatitis and chronic pancreatitis. Although most patient cases are due to biliary disease and ethanol, approximately 18% are idiopathic. Diagnostic and management options for idiopathic acute pancreatitis include genetic testing for a number of associated mutations and cholecystectomy to treat subclinical or undetected biliary disease. Endoscopic retrograde cholangiopancreatography, often with concomitant endoscopic sphincterotomy, is also sometimes considered in the management of idiopathic recurrent acute pancreatitis, although the role of this invasive procedure is generally limited. Here, 2 pancreatologists and coauthors of a recent American College of Gastroenterology guideline on the management of acute pancreatitis discuss issues related to genetic testing, cholecystectomy, and endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy for patients with acute idiopathic pancreatitis in general, and for a young woman recently diagnosed with this condition.

AIMS: To evaluate diabetic ketoacidosis (DKA) risk among new users of ertugliflozin versus sulfonylureas (SU) or thiazolidinediones (TZD) and incretin-based drugs in patients with type 2 diabetes.

METHODS: We used Medicare and Medicaid fee-for-service adjudicated claims within the Innovation in Medical Evidence and Development Surveillance network to identify three new-user cohorts: (1) ertugliflozin; (2) SU/TZD; and (3) incretin-based drugs. The outcome was a principal hospital discharge diagnosis for DKA. Adjusted hazard ratios (HRs) were estimated after 1:1 propensity score (PS) matching, separately for ertugliflozin vs. SU/TZD and vs. incretin-based drugs. Subgroup analyses were performed based on baseline insulin use.

RESULTS: After PS matching, baseline characteristics were similarly distributed in each cohort. For ertugliflozin (n = 42,907) vs. SU/TZD (n = 42,907), the incidence rates of DKA per 1000 person-years (PY) were 2.95 and 1.49, respectively. For ertugliflozin (n = 42,247) vs. incretin-based drugs (n = 42,247), the incidence rates of DKA per 1000 PY were 2.76 and 1.06, respectively. For ertugliflozin vs. SU/TZD, the HR [95% confidence interval (CI)] was 1.88 [1.17-3.02]; in non-insulin users, 2.34 [1.27-4.31]; and in insulin users, 1.17 [0.54-2.52]. For ertugliflozin vs. incretin-based drugs, the HR [95% CI] was 2.40 [1.40-4.11]; in non-insulin users, 2.84 [1.42-5.66]; and in insulin users, 1.87 [0.79-4.46].

CONCLUSIONS: Ertugliflozin was associated with a higher risk of DKA relative to comparators. HRs were higher among new users with no-concomitant insulin use than those with concomitant insulin use. Results were consistent with prior SGLT2i data and highlighted the importance of caution by both patients and physicians.