Publications by Year: 2026

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.

BACKGROUND: YouTube is an open-access platform increasingly used for both medical and patient education, but its user-generated content is not subject to peer review and shows wide variability in accuracy and quality. Celiac plexus blocks are technically complex procedures that are presented on YouTube, yet the educational quality of these instructional videos has not yet been systematically evaluated.

OBJECTIVE: To evaluate the educational quality of YouTube videos on celiac plexus blocks and to explore the utility of ChatGPT-4o as a secondary, adjunctive tool for assessing video quality.

METHODS: YouTube was searched on June 2nd, 2025 using the keywords "celiac plexus neurolysis," "celiac block for cancer pain," "celiac plexus block," and "celiac plexus injection." The 17 most-viewed videos were independently evaluated by two board-certified chronic pain physicians and by ChatGPT-4o using a modified DISCERN scale (mDISCERN), the Global Quality Scale (GQS), and a usefulness classification.

RESULTS: Based on human expert ratings, only 18 % of videos contained highly reliable information as assessed by the mDISCERN scale, and 24 % demonstrated moderate to excellent information quality on the Global Quality Scale. Overall, 65 % of videos were classified as useful. Inter-rater reliability between human experts ranged from poor to moderate across the three scales of evaluation, while agreement between human expert and ChatGPT-4o assessment was poor.

CONCLUSIONS: The educational quality of YouTube videos on celiac plexus blocks was generally poor. Unlike similar studies investigating other procedures, the quality of videos produced by physician and hospital sources was not better than that of videos by nonacademic sources. These findings highlight the need to improve the quality of educational content produced by physicians, hospitals, and professional societies.

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.

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.

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.

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.

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.

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.

IMPORTANCE: The ongoing opioid-related overdose crisis in the US is increasingly affecting adolescents and is exacerbated by the widespread availability of illicitly manufactured fentanyl. Adolescents face significant gaps in care for prevention and treatment of opioid use and opioid-related harms. Regulatory changes have impacted the availability of 2 lifesaving medications, naloxone and buprenorphine. This narrative review summarizes the current knowledge of opioid use, overdoses, and opioid use disorder (OUD) among US adolescents in the context of fentanyl, and reviews the use of naloxone and buprenorphine, for overdose reversal and OUD treatment, respectively.

OBSERVATIONS: Owing to their developmental stage, adolescents are uniquely vulnerable to initiating substances, experiencing substance-related harms, and developing substance use disorders. From 2018 through 2023, morbidity and mortality have increased from use of opioids, particularly fentanyl, among youth. Naloxone and buprenorphine are safe and highly effective medications for opioid overdose reversal and OUD treatment, respectively. Regulations for these medications have changed to address the worsening overdose epidemic. Naloxone is approved for over-the-counter sales (including by adolescents younger than 18 years). Any clinician with a US Drug Enforcement Administration-controlled substance license can now prescribe buprenorphine for OUD without a waiver. These policy changes present critical opportunities to save lives and reduce inequities among adolescents.

CONCLUSION AND RELEVANCE: Harms from opioids are increasingly affecting adolescents with a notable rise in overdose fatalities in the past 5 years. Regulatory changes for naloxone and buprenorphine have occurred to improve access to both these medications. Despite these changes, adolescents continue to have low access to these life-saving interventions. Ensuring that clinicians have the knowledge to provide both medications to adolescents is a key step to addressing the epidemic of adolescent drug overdoses and reducing opioid-related harms.