Citations

Abstract Introduction Once-nightly sodium oxybate (ON-SXB [LUMRYZ™]) is approved to treat excessive daytime sleepiness (EDS) or cataplexy in patients ≥7 years of age with narcolepsy. Real-world demographic/clinical characteristics and treatment adherence in patients with narcolepsy who received ON-SXB from a specialty pharmacy were assessed. Methods Baseline demographic/clinical data were collected from Optum Frontier Therapies pharmacy for patients with ≥1 filled ON-SXB prescription, ≥1 ON-SXB-related clinical assessment, and baseline Epworth Sleepiness Scale (ESS) score from 6/1/2023-9/30/2024. Adherence (≥80% of days covered) was assessed for patients with ≥3 months of ON-SXB use. Data were stratified by narcolepsy subtype (narcolepsy type 1 [NT1] and 2 [NT2] when available) and prior oxybate use (transitioned from prior oxybate therapy to ON-SXB ≤30 days of index [switch]/were oxybate-naive or discontinued oxybate >30 days before index [not-on-oxybate]). Data were analyzed descriptively. Results 452 patients were identified (NT1, 55%; NT2, 37%; NT unknown, 9%; switch, 40%; not-on-oxybate, 60% [oxybate-naive, n=147/271]). Mean (range) age was 38.9 (16.0-88.0) years. Most patients were female (68%) and had commercial insurance (78%). Overall, 67% of patients had prior oxybate use (NT1, 72% [n=179/247]; NT2, 59% [n=98/166]; switch, 100%; not-on-oxybate, 46% [n=124/271]); for these patients, the most common oxybate (65%) was mixed-salt oxybates (NT1, 61%; NT2, 70%; switch, 61%; not-on-oxybate, 70%). Overall, 64% of patients used stimulants/wake-promoting agents (WPAs) (NT1, 64%; NT2, 65%; switch, 60%; not-on-oxybate, 67%). Overall, the mean (SD) baseline ESS score was 12.0 ([5.5]; NT1, 11.7 [5.5]; NT2, 12.5 [5.3]; switch, 11.0 [5.7]; not-on-oxybate, 12.7 [5.3]). At baseline, 29% of patients experienced severe EDS (ESS score ≥16: NT1, 26%; NT2, 30%; switch, 20%; not-on-oxybate, 34%). Of 269 patients with ON-SXB use ≥3 months, 84% (NT1, 84%; NT2, 89%; switch, 94%; not-on-oxybate, 76%) demonstrated adherence. Conclusion Patients not on an oxybate had the highest baseline ESS scores and proportion with severe EDS, despite greater stimulant/WPA utilization. Patients with NT1 used oxybates more frequently than those with NT2 despite those with NT2 having higher baseline ESS scores and a greater proportion having severe EDS, suggesting oxybates merit earlier consideration in patients with NT2. Most patients demonstrated ON-SXB adherence, indicating they would likely receive full therapeutic benefit. Support (if any) Avadel Pharmaceuticals

Abstract Human genomic studies link reduced CUB domain-containing protein 1 (CDCP1) expression with myocardial recovery in heart failure. While CDCP1 regulates cardiac fibroblast proliferation in vitro, it’s in vivo role in cardiac fibrosis remains unclear. Using a Cdcp1 -knockout (KO) angiotensin II/phenylephrine mouse model, we show that Cdcp1 deletion reduces echocardiographic left ventricular mass, histologic cardiac fibrosis, and pro-fibrotic gene expression, along with decreased fibroblast activation and inflammatory markers. Spatial transcriptomics identified a pressure overload–expanded fibroblast subpopulation enriched for growth factor and TGF-β signaling (FB5), which was markedly attenuated in Cdcp1 -KO hearts, alongside reduction of a pro-inflammatory cardiomyocyte subtype (CM4). Complementary studies in human ventricular fibroblasts demonstrate that CDCP1 knockdown reduced extracellular matrix gene expression and collagen I deposition. These findings establish CDCP1 as a regulator of cardiac fibrotic remodeling in vivo and open avenues for its further investigation as a potential therapeutic target.

This multicenter, single-arm, phase 1/2 study evaluated the safety and efficacy of CD19-directed allogeneic chimeric-antigen-receptor (CAR) immunotherapy CTX110 in adult patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL). Patients received 1 or 2 treatment courses: standard lymphodepletion, followed by 1 CTX110 infusion at dose levels (DLs) 1-4 (3-60 × 107 CAR T-cells; dose escalation, N=32), or 2 infusions at DL4 on days 1 and 35 (cohort expansion, N=31). Primary endpoints in dose escalation and cohort expansion were incidence of dose-limiting toxicities and objective response rate, respectively. CTX110 was administered to 63 heavily pretreated patients: 59% primary refractory, 43% with ≥3 prior treatment lines. Among 57 patients whose first infusion was DL≥3, rates of objective and complete response (CR) were 65% and 39%, respectively. Among 22 patients achieving CR, 5 (23%) had ongoing CR at data cutoff, with 15-50 (median 34) months follow-up. The 2-infusion regimen appeared to prolong response duration compared to 1 infusion (hazard ratio 0.65). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 54% and 13% of treated patients, respectively, including 2 grade ≥3 cases each. The most common grade ≥3 adverse events were neutropenia (59%), and anemia and thrombocytopenia (35% each). Serious adverse events occurred in 32% of treated patients, including CRS (14%), ICANS (8%), and febrile neutropenia (6%). In this r/r NHL population, CTX110 was well-tolerated, resulting in clinically meaningful responses at DL≥3, with a second infusion demonstrating evidence of further clinical benefit. This trial (NCT04035434) was registered at www.clinicaltrials.gov.

Objective: To evaluate the effectiveness of a standardized hazardous medication surveillance program and identify occupational factors associated with adverse health outcomes among healthcare workers (HCWs). Methods: We analyzed data from 2,625 HCWs enrolled in a multi-site surveillance program (2020–2022). Participants completed a standardized questionnaire and underwent complete blood count testing. Exposure was categorized by weekly time handling hazardous medications. Associations were evaluated using univariate and multivariable analyses. Results: Higher exposure (>8 hours/week) was associated with increased symptom reporting, hazardous medication spills, and adverse reproductive outcomes. Female sex, older age, and spill exposure independently predicted symptom reporting and reproductive outcomes. No significant association was observed between exposure intensity and abnormal blood counts. Conclusion: Questionnaire-based surveillance effectively identified exposure-related health risks, whereas routine complete blood count testing showed limited utility.

Abstract Background Postoperative spinal implant infections (PSIIs) are a serious complication of instrumented spinal fusion. Although debridement with implant retention is standard for early infection, the optimal duration of antimicrobial therapy remains uncertain. Methods We conducted a multicenter retrospective cohort study across 10 US academic centers, including adults with early PSII (≤90 days after fusion surgery) from 2017 to 2021. We excluded patients who experienced treatment failure within 6 weeks of debridement. The primary outcome was treatment failure. Antibiotic therapy effect was analyzed as a time-varying exposure using adjusted Cox proportional hazards models. Secondary analyses included 12-week landmark and clone-censor-weighted models to compare durations ≤ 12 weeks versus >12 weeks. Results A total of 116 patients out of 499 (23.2%) experienced treatment failure during a median follow-up of 3.2 years. Among patients who remain failure-free 6 weeks from debridement, being on antibiotics was not associated with treatment failure (adjusted hazard ratio [aHR] 0.71; 95% CI .48–1.07; P = .10). In a 12-week landmark analysis limited to 359 patients who were not on indefinite suppressive antibiotic therapy, treatment durations > 12 weeks did not significantly reduce the risk of failure (aHR 1.01; 95% CI .62–1.64; P = .99). Results were consistent in the clone-censor-weight sensitivity analysis (aHR 0.85; 95% CI .62–1.16; P = .30). Conclusions Prolonged antibiotic therapy was not associated with improved outcomes in early PSII managed with debridement and implant retention. These results support shorter, individualized antibiotic courses in patients with adequate surgical source control.

INTRODUCTION: Online patient education materials are essential in improving access to and understanding of clinical information. Artificial intelligence (AI), specifically ChatGPT, offers a novel way to synthesize complex information and is increasingly being used for patient education, including in obstetrics and gynecology. This study compares the understandability and actionability of patient education materials about hysterectomy and uterine fibroids generated by ChatGPT with those published by the American College of Obstetricians & Gynecologists (ACOG). METHODS: In a randomized cross-sectional study, participants were allocated to one of four groups: ACOG–Fibroids, ChatGPT–Fibroids, ACOG–Hysterectomy, or ChatGPT–Hysterectomy. The ACOG groups reviewed the corresponding ACOG FAQ webpage, while the ChatGPT groups reviewed responses generated by ChatGPT to the same FAQs. Participants then completed demographic questions and the Patient Education Materials Assessment Tool (PEMAT). The primary outcome was the equivalence of PEMAT scores between ACOG and ChatGPT. RESULTS: Equivalence was not demonstrated between ChatGPT and ACOG for either topic. For fibroid material, ACOG was rated higher on both understandability (86.3 versus 82.6 points, P =.039) and actionability (65.4 versus 53.2 points, P =.003) on superiority testing. For hysterectomy content, no significant difference was observed. No interaction was found between material type and either education level or personal history of fibroids/hysterectomy. CONCLUSIONS/IMPLICATIONS: PEMAT scores for ACOG were superior to ChatGPT for fibroid content, but neither equivalent nor superior for hysterectomy content. While ChatGPT offers a responsive, iterative source of information, its understandability and actionability may depend on topic-specific factors, highlighting both the promise and limitations of AI for patient education.

Abstract INTRODUCTION Sleep and circadian rest–activity rhythm (RAR) disruption may bidirectionally relate to Alzheimer's disease (AD). Down syndrome (DS), the most common genetic cause of AD, presents sleep disorders, yet RAR patterns across the DS‐associated AD continuum remain uncharacterized. METHODS We analyzed 7‐day wrist actigraphy in 140 adults with DS (108 asymptomatic; 32 AD dementia) and 41 unimpaired controls. General linear models, adjusted for age, sex, sleep efficiency, and obstructive sleep apnea (OSA) severity, tested group differences, with interaction terms included to evaluate group‐specific associations. RESULTS DS showed lower relative amplitude and higher nocturnal activity, already in asymptomatic individuals. Rhythm strength declined further with AD progression, while regularity and phase timing remained preserved until dementia. Findings were independent of sleep duration and OSA. DISCUSSION Adults with DS showed early RAR disturbance that progressed across the AD continuum, paralleling sporadic AD. Circadian RAR features may be scalable biomarkers of AD progression.

Background: Tablet splitting is widely used to individualize dosing of metoprolol tartrate when low-dose formulations are unavailable. However, splitting may lead to variability in dose accuracy, which can be clinically relevant at low dose strengths. This study compared the accuracy and precision of manual tablet splitting versus automated 3D printing for producing low-dose metoprolol tartrate tablets in a hospital setting. Methods: Commercial 25 mg metoprolol tartrate tablets from two manufacturers were manually split at Mayo Clinic into 12.5 mg halves and 6.25 mg quarters following established procedures. CurifyLabs’ Compounding System, including the Pharma Printer and CuraBlend®-based formulations, was used at two hospital pharmacy sites and a compounding pharmacy to produce 6.25 mg and 12.5 mg tablets via 3D printing. Mass variation and content uniformity were evaluated using USP <905> criteria and validated HPLC methods. Results: Manually split tablets showed high variability, with 6.25 mg quarters ranging from 24.9% to 142.8% API content and 12.5 mg halves from one manufacturer averaging only 66.6%, indicating frequent underdosing. In contrast, 3D-printed tablets achieved mean API contents within 90–103%, standard deviations below 5%, and acceptance values under 15 across all sites and formulations. Conclusion: Manual tablet splitting may not reliably meet pharmacopeial expectations for dose accuracy and content uniformity at lower dose strengths. Automated 3D printing produced consistent low-dose tablets and may offer a validated alternative where available.

Background: Given the faster onset and shorter duration of action of ultra-rapid insulin lispro-aabc (URLi, Lyumjev™ insulin), compared with insulin lispro (a rapid-acting insulin [RAI]), the present study investigated the safety and glycemic outcomes of MiniMed™ 780G advanced hybrid closed-loop (AHCL) use with URLi in youths and adults with T1D. Methods: This 19-site, single-arm, clinical trial enrolled children and adolescents (aged 7–17 years) and adults (aged 18–80 years) with T1D who underwent a run-in period (∼2 weeks) using open loop or automated basal only with an RAI (aspart or lispro), followed by a 3-month study period using URLi with AHCL (AHCL + URLi). End-of-study glycemic metrics and A1c were compared to predefined thresholds and to data from baseline/run-in. Use of recommended optimal settings (ROS, 100 mg/dL glucose target with an active insulin time [AIT] of 2 h) was also assessed. Results: In an intention-to-treat population ( N = 101 pediatric and N = 110 adult participants), percentage of time in range (%TIR) during the last ∼6 weeks of the study period was significantly greater than the predefined thresholds for both the pediatric and adult participants. A1c was unchanged in the pediatric cohort but significantly reduced in the adult cohort (from 7.4 ± 0.9% to 6.9 ± 0.6% [ P < 0.001]). Compared with run-in, study period %TIR and percentage of time in tight target range (%TITR) were significantly increased (pediatric mean %TIRΔ [17.4%] and %TITRΔ [16.0%], respectively, and adult mean %TIRΔ [10.6%] and %TITRΔ [11.6%], respectively; P < 0.001 for all). Additionally, % time above range for both groups was significantly reduced. Use of ROS allowed more participants to achieve recommended glycemic targets. There were no severe hypoglycemia or diabetic ketoacidosis events. Most caregivers agreed that mealtime versus premeal URLi delivery simplified pediatric meal management. Conclusions: Similar to previous studies investigating automated URLi delivery, URLi use in the MiniMed™ 780G system was safe, and glycemic outcomes were favorable for pediatric and adult participants.

Abstract Background Anxiety is a common symptom experienced by patients with cancer, who are increasingly interested in non-pharmacologic symptom management. Acupressure, a noninvasive intervention thought to impact the neurohormonal axis, has shown promise in reducing anxiety. However, research on acupressure for anxiety in patients with cancer has been limited. Methods Individuals receiving chemotherapy, who reported baseline anxiety, were eligible for this study. Consenting participants received one 15-minute nurse-led acupressure session and completed pre- and post-intervention surveys. The primary endpoint was a change in anxiety. Participants were also asked about symptoms of nausea, pain, well-being, relaxation, worry, and distress. Participants were invited to learn self-acupressure techniques. These participants were asked to complete a final survey 1-week post-intervention. Results Thirty adult patients participated in this study. Mean baseline anxiety was 5 on a 0 to 10 Likert scale. Immediate post-intervention anxiety scores significantly improved for all thirty patients to an average of 2.0 (P &lt; .001). Mean nausea scores improved from 1.5 at baseline to 0 post-intervention (P &lt; .001), and pain scores improved from 2.0 at baseline to 1.0 post-intervention (P = .001). Participants reported significant improvement in sense of wellbeing (P = .0004), distress (P &lt; .001), ability to achieve relaxation (P &lt; .001), and ability to control their worries (P &lt; .001). The improvement in anxiety, well-being, and relaxation was sustained at one week. 100% of participants stated that they would recommend acupressure for symptom management. Conclusion Acupressure is a promising non-pharmacologic intervention for the management of cancer-associated anxiety.