Objective: Early prognostic indicators of nonresponse to buprenorphine treatment for opioid use disorder can inform targeted efforts to improve outcomes. Opioid use in the first 2-3 weeks of treatment predicts later outcomes, yet it is unclear what frequency of opioid use confers risk. We aimed to (1) identify thresholds for the frequency of early opioid use that optimally predict later sustained use and (2) quantify associations between thresholds and continuous treatment outcomes. Method: We used data from 2 clinical trials of buprenorphine (N=562; mean age=34 years; 38% female), which were conducted from 2006-2009 and 2007-2011. Area under the receiver operating characteristic curve analyses identified optimal thresholds for opioid frequency during the first 4 weeks in predicting sustained use during weeks 5-12 (ie, 4 consecutive weeks with an opioid-positive or missing urine drug screen). Negative binomial regressions examined associations between early nonresponse and opioid-free and retention weeks. Results: Sustained opioid use was optimally predicted by ≥1 day of opioid use in the first 2 weeks (sensitivity=0.747; specificity=0.688; positive predictive value [PPV]=0.524; negative predictive value [NPV]=0.856) and ≥2 days of use in the first 3 weeks (sensitivity=0.649; specificity=0.810; PPV=0.611; NPV=0.834). Both thresholds were negatively associated with opioid-free and retention weeks. Conclusions: Even very low levels of opioid use in the first 2-3 weeks of buprenorphine treatment signal risk for poor outcomes. Emphasizing abstinence or near abstinence early in treatment might help promote long-term stability. Identified thresholds can be used to identify patients who may benefit from treatment adjustments and close monitoring.
Publications by Year: 2026
2026
Oncolytic viruses (OV) are thought to mediate antitumor activity by killing tumor cells and inducing antitumor immunity, but how this happens is not well understood. In this issue, Ludwig and colleagues show that PVSRIPO, an oncolytic poliovirus being developed for glioblastoma, may induce better immune and therapeutic responses when injected into both tumor and tumor-draining lymph nodes. Dual delivery may be a novel approach to optimize OV treatment and has implications for how we manage patients with solid tumors in the era of local immunotherapy. See related article by Ludwig et al., p. 228.
INTRODUCTION: The genetic basis of sporadic early-onset Alzheimer's disease (EOAD) remains largely unknown, prompting evaluation of late-onset Alzheimer's disease (LOAD) polygenic risk in EOAD.
METHODS: A LOAD polygenic score (PGS) was calculated in the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) study and tested for associations with AD risk, cognitive performance, and imaging and fluid biomarkers.
RESULTS: Though PGS was elevated in LOAD and EOAD, it was not a significant predictor of EOAD adjusting for APOE ε4 carrier status and was not associated with age of EOAD onset (p = 0.106) or with cognitive performance (p = 0.417). In LEADS, greater LOAD PGS was associated with differences in neuroimaging and fluid biomarkers, including elevated synaptosomal-associated protein 25 (SNAP-25) (p = 2.3 × 10-5).
DISCUSSION: While LOAD polygenic risk contributed minimally to EOAD onset and cognitive dysfunction, PGS association with fluid biomarkers in LEADS suggests a role for LOAD polygenic risk in EOAD pathophysiology.
HIGHLIGHTS: LOAD PGSs were elevated in both LOAD and EOAD compared to controls; however, LOAD PGS did not significantly predict EOAD risk, age at onset, or cognitive performance independent of APOE ε4 in the LEADS. Higher LOAD PGS was associated with lower amyloid PET Centiloids (less brain amyloid deposition) as well as lower CSF biomarker Aβ42 in LEADS (proxy marker suggesting higher brain amyloid deposition) in LEADS; these contradictory findings support the need for larger studies to further investigate whether LOAD PGS is associated with increased amyloid deposition in EOAD. Higher LOAD PGS was also associated with higher levels of CSF synaptosomal-associated protein 25 (SNAP-25), a key component of the SNARE complex, suggesting that LOAD genetic factors may contribute to dysregulation of synaptic transmission and/or pathological protein aggregation in EOAD.
PURPOSE: The purpose of this study was to evaluate the accuracy of large language model (LLM) LLaMA 2-70B in summarizing glaucoma clinic notes into patient-friendly language and generating educational material.
METHODS: A random sample of 147 clinic notes from unique patients who visited Glaucoma Service at a tertiary center was analyzed. LLaMA 2 generated paragraph and bullet-point summaries in five subjects: (1) glaucoma diagnosis and type, (2) disease progression, (3) treatment plan, (4) treatment changes, and (5) surgical/laser interventions. Two ophthalmologists reviewed responses for accuracy and categorized them as "correct," "partially correct," or "incorrect." Discrepancies were adjudicated by a glaucoma specialist. A comparison using identical prompts was performed on a subset (n = 50) with ChatGPT-4.
RESULTS: LLaMA 2 correctly summarized 97 notes (66%) in paragraph and 103 (70%) in bullet format. Another 44 (30%) and 41 (28%) were partially correct, respectively. Paragraph summaries were more accurate and complete for glaucoma suspects than diagnosed patients (82% vs. 53%, P < 0.001). For targeted clinical questions, LLaMA 2 accurately identified glaucoma diagnosis in 118 notes (80%), disease stability/progression in 129 (88%), treatment plans in 127 (87%), treatment changes in 134 (91%), and surgical/laser interventions in 124 (84%). ChatGPT-4 achieved 46% correct paragraph summaries, 50% correct bullet summaries, and accuracies of 96%, 88%, 64%, 78%, and 82%, respectively, for targeted questions.
CONCLUSIONS: Although LLaMA 2 is not yet reliable as a standalone clinical tool, it shows promise to improve clinical communication.
TRANSLATION RELEVANCE: LLMs may enhance patient experience and health literacy by standardizing patient-friendly language in clinical care.
Sharing research code in an open access version-controlled repository offers significant benefits for both science as a whole and for individual researchers. In this article, we focus on this practice, which is fully aligned with the NIH's Gold Standard Science (GSS) program as well as FAIR (findable, accessible, interoperable, reusable) and TRUST (transparency, responsibility, user focus, sustainability, technology) principles. Gold Standard Science supports open science by emphasizing transparency, reproducibility, and the use of best practices that enable others to verify and extend research. Pairing a research article's cited data snapshot with a versioned, environment-specific code release, deposited in a companion code repository, ensures that, upon submission to a medical journal, readers and reviewers can directly verify results. An executable and updatable companion code repository complements, rather than replaces, established research data repositories. When code underlying medical research results is made openly available, then other scientists can inspect, run, and validate analyses. These activities enhance reproducibility, which is a core aim of GSS. Shared code also facilitates collaborative innovation by allowing researchers to extend the utility of the code to new datasets and applications. For researchers, code sharing can increase visibility, credibility, and citation impact. Demonstrating transparency through shared executable and updatable code builds trust with journal readers, peer reviewers, funders, and peers. Shared code in an open access repository signals adherence to high standards of scientific integrity and attracts opportunities for collaboration. A researcher who shares code receives recognition as a leader in reproducible, trustworthy research consistent with NIH's GSS principles.
BACKGROUND: Spontaneous coronary artery dissection is a cause of myocardial infarction, which predominantly affects middle-aged women. There are limited data on men with spontaneous coronary artery dissection.
METHODS: Information on demographics, presenting characteristics, in-hospital outcomes including major adverse cardiovascular events (composite of myocardial infarction, cerebrovascular accident, or heart failure), length of stay, and discharge medications in men and women were obtained from the multicenter iSCAD (International Spontaneous Coronary Artery Dissection) registry.
RESULTS: Of 1252 patients enrolled from 2019 to 2023, 80 (6.4%) were men. Mean age did not significantly differ between sexes (men, 50.2±10.3 versus women 49.7±10.4; P=0.792). Women reported more emotional stress preceding spontaneous coronary artery dissection (10.2% versus 2.5% men; P=0.025). Men reported more physical stress (22.5% versus 7.7% women; P<0.001), both isometric exertion (12.5% versus 2.4% women; P<0.001) and aerobic exertion (12.5% versus 5.6% women, P<0.013). Chest discomfort was the major symptom, although women reported more non-chest discomfort, shortness of breath, and nausea/vomiting. Men had fewer autoimmune conditions, systemic inflammatory disorders, and fibromuscular dysplasia but more recreational drug use. In-hospital major adverse cardiovascular events did not significantly differ (4.1% men versus 8.5% women; P=0.178). The median length of stay was 3.0 (interquartile range, 3.0-4.0) days for males versus 4.0 (interquartile range, 3.0-5.0) days for women (P=0.003). At discharge, more men were prescribed statins (72.5% men versus 55.3% women; P=0.003) and dual antiplatelet therapy (66.3% men versus 53.7% women) (P=0.049).
CONCLUSIONS: In a large spontaneous coronary artery dissection registry, there were significant sex differences in presentation, baseline medical conditions, and triggers. In-hospital outcomes were similar, but length of stay was longer for women. Men were more often discharged on statins and dual antiplatelet therapy.
BACKGROUND: Activity Measure for Post-Acute Care (AM-PAC) score is used in discharge planning for patients with acute ischemic stroke from a large vessel occlusion (AIS-LVO). Prolonged venous transit (PVT) is a binary, qualitative measure visually ascertained from computed tomography perfusion imaging time-to-maximum (Tmax) maps. PVT has been associated with unfavorable recovery and mortality.
OBJECTIVE: To assess the robustness of PVT by evaluating its association with AM-PAC.
METHODS: Consecutive adult patients with AIS-LVO treated successfully with reperfusion therapy were retrospectively reviewed. PVT+ is defined as Tmax ≥ $$ \ge $$ 10 seconds timing on at least one of the following: superior sagittal sinus and/or torcula. PVT- lacks this in both regions. Primary outcome was favorable AM-PAC score, defined as having both Basic Mobility Score ≥ $$ \ge $$ 17 and Daily Activity Score ≥ $$ \ge $$ 19. Logistic regressions in unmatched and 1:1 propensity score-matched cohorts were performed.
RESULTS: Among 121 patients, the median age was 72 (interquartile range, 64-81) years. Favorable AM-PAC scores occurred less often in PVT+ than PVT- patients (10.5% vs. 45.8%). PVT+ was associated with significantly reduced odds of favorable AM-PAC score in multivariable regressions (PVT+ vs. PVT- odds ratio [OR]: 0.11, 95% confidence interval [CI]: 0.03-0.48, p = .01); the significant association furthermore persisted in the matched cohort analysis (PVT+ vs. PVT- OR: 0.73, 95% CI: 0.60-0.88, p < .001).
CONCLUSION: PVT+ is independently associated with lower odds of favorable AM-PAC scores at discharge. Logistically-consistent associations with short-term and long-term clinical outcomes augment our understanding of PVT and further establish the potential of this novel imaging parameter as an informative metric in clinical practice.
INTRODUCTION: We evaluated the clinical performance of the fully automated, high-throughput, prototype Elecsys® Phospho-Tau (217P) plasma immunoassay (Roche Diagnostics) for detecting amyloid pathology.
METHODS: Plasma tau phosphorylated at threonine 217 (pTau217) levels were determined in samples from cognitively impaired and unimpaired individuals from five cohorts (N = 2148) using the pTau217 plasma immunoassay. Clinical performance was evaluated against amyloid positron emission tomography.
RESULTS: For cognitively impaired, mean plasma pTau217 levels for amyloid-positive (A+) individuals were higher (n = 394; 0.835 pg/mL) than amyloid-negative (A-) individuals (n = 144; 0.361 pg/mL); similarly, for cognitively unimpaired, A+ (n = 224; 0.516 pg/mL) and A- individuals (n = 1386; 0.220 pg/mL). Area under the curve was 0.878 (95% confidence interval [CI] 0.840, 0.915; impaired) and 0.907 (95% CI 0.885, 0.929; unimpaired). A cutoff < 0.189 pg/mL reliably ruled out individuals without amyloid pathology. High negative predictive values (92.51% [impaired]; 98.60% [unimpaired]) were observed with sensitivity/specificity of 98.98%/29.17% and 95.54%/50.72%, respectively.
DISCUSSION: The pTau217 plasma immunoassay accurately detects amyloid pathology, irrespective of cognitive status.
TRIAL REGISTRATION NUMBER: A4, NCT02008357; SKYLINE, NCT05256134; AIBL, SAGE Project ID Number: 2022/PID06188; SVHM Local Ref ID: HREC 028/06; CREAD, NCT02670083; CREAD2, NCT03114657 HIGHLIGHTS: The Elecsys® pTau217 plasma immunoassay (Roche Diagnostics) was evaluated across five cohorts. The pTau217 plasma immunoassay demonstrated high performance in detecting amyloid pathology in both cognitively impaired and unimpaired individuals. The pTau217 plasma immunoassay had a high negative predictive value which supports its utility as a pre-screening tool for Alzheimer's disease (AD). The pTau217 plasma immunoassay cutoffs identified are suitable for use as rule-out pre-screener tools in clinical trials. These findings reinforce the value of the high-throughput pTau217 plasma immunoassay measurements to aid AD diagnosis.
Radioligand therapy (RLT) has reshaped the treatment landscape of advanced prostate cancer (PCa), offering a precision medicine approach that integrates molecular imaging with targeted radionuclide delivery, in which radioactive isotopes are bound to molecules that aim to selectively target cancer cells. The approval of 177Lu-prostate-specific membrane antigen (PSMA)-617 for metastatic castration-resistant prostate cancer marked a major milestone, with randomized trials (VISION, PSMAfore) demonstrating significant improvements in overall and progression-free survival compared to standard therapies. Beyond beta-emitting agents, next-generation alpha emitters such as actinium-225 and beta/Auger electron-emitting isotopes like terbium‑161 are in active development, aiming to overcome resistance and target micrometastases with greater potency. Combination approaches, pairing RLT with poly(ADP-ribose) polymerase inhibitors, immune checkpoint blockade, or androgen receptor pathway inhibitors, for example, are under intense investigation, with early phase data indicating potential efficacy. Technical advances in imaging, personalized dosimetry, and molecular diagnostics may enable more precise patient selection and adaptive treatment strategies, such as dose adjustment based on dosimetry or target expression. Emerging RLT platforms target additional tumor markers, including human kallikrein 2 and six-transmembrane epithelial antigen of the prostate-2 as well as bispecific ligands, addressing disease heterogeneity and expanding therapeutic reach. Nonetheless, challenges remain around long-term hematologic and renal safety, radionuclide supply, protocol standardization, and global accessibility. Ongoing and future multicenter trials, collaborative consortia, and innovations in theranostics will be critical to defining optimal patient selection, sequencing with existing therapies, and embedding RLT as a key pillar in the management of advanced PCa.