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PURPOSE In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapse (so-called CNS prophylaxis) remains controversial. International guidelines continue to recommend HD-MTX in patients deemed ultra high risk (UHR) because of a lack of robust data specific to these subgroups. This study was designed to examine the impact of HD-MTX specifically in UHR patients. METHODS Data from two previous retrospective analyses were combined to produce a cohort of UHR patients (≥1 of the following criteria: CNS international prognostic index score 5-6; testicular, renal/adrenal, or breast involvement; ≥3 extranodal sites), treated with or without HD-MTX. The primary outcome was CNS relapse rate (isolated or concurrent with systemic relapse) measured from diagnosis with additional landmark analysis of all responding patients with no progression event at 6 months. RESULTS Analyses were performed on 1,923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between no HD-MTX (n = 1,051) versus HD-MTX patients (n = 872), including in multivariable analyses adjusting for baseline characteristics (3-year rate, 9.3% v 8.1%; adjusted hazard ratio [HR], 1.13 [95% CI, 0.82 to 1.57]). Analyses restricted to isolated CNS relapse also confirmed no difference (5.9% v 5.7%; adjusted HR, 1.03 [95% CI, 0.69 to 1.53]). In the landmark analysis (no HD-MTX n = 782, HD-MTX n = 773), no difference in 3-year CNS relapse was observed (6.7% v 6.6%, adjusted HR, 0.95 [95% CI, 0.62 to 1.44]). CONCLUSION To our knowledge, this is the largest international comparative data set of patients with LBCL with UHR features showing no significant reduction in CNS relapse with HD-MTX in all UHR or in any individual subgroup. Despite inherent limitations of retrospective analyses, the data strongly support previous studies in suggesting HD-MTX prophylaxis has no meaningful benefit for most patients.

Background Although regional anesthesia (RA) is associated with improved pain control, reduced opioid use, and accelerated recovery after arthroplasty, racial and geographic differences have been identified in hip and knee arthroplasty, with limited data for shoulder and ankle arthroplasty. We examined differences in RA utilization for shoulder, hip, knee, and ankle arthroplasty, based on patient-level and hospital-level characteristics. Methods Using the National Inpatient Sample, we conducted a cross-sectional study of adults who underwent shoulder, hip, knee, and ankle arthroplasties from 2016 to 2020. RA was defined using procedure codes for neuraxial anesthesia and peripheral nerve blocks. Weighted descriptive statistics summarized RA utilization and compared patient-level and hospital-level characteristics using standardized mean differences (SMDs), with ≥0.10 indicating meaningful differences. Results We identified 1132 011 unweighted admissions, representing approximately 5.7 million weighted arthroplasties. RA was used in 7.0% of cases. RA utilization varied by procedure type, with the highest rates in shoulder (11.4%) and ankle arthroplasty (11.4%), followed by knee (9.1%) and hip arthroplasty (2.4%). Variation in RA utilization was observed in ankle arthroplasty based on race (SMD=0.11) and primary payer (SMD=0.12). RA use also varied by hospital size for shoulder (SMD=0.13), hip (SMD=0.29), and knee arthroplasty (SMD=0.22), by hospital location and teaching status for shoulder (SMD=0.17), hip (SMD=0.18), knee (SMD=0.19), and ankle arthroplasty (SMD=0.12), and by geographic region for shoulder (SMD=0.26), hip (SMD=0.45), knee (SMD=0.24), and ankle arthroplasty (SMD=0.17). Conclusions There is notable variation in RA use for inpatient arthroplasty across hospitals and geographic regions, with limited variation based on patient characteristics. These findings highlight the presence of system-level variation in RA use and underscore the need for further research to better understand the drivers of these patterns.

ABSTRACT Inpatient, acute care clinical pharmacists have contributed to many notable improvements in patient outcomes. Several studies have shown a reduction in mortality and other clinical markers when pharmacists are integrated within the care team. Economic analyses of inpatient clinical pharmacy services (CPS) generally demonstrate cost savings related to specific medication classes, prevention of adverse drug events, decreased length of stay, and decreased rehospitalization. Studies also show high satisfaction from other health care professionals, noting improvements in medication‐related patient safety. Finally, studies conducted in tertiary care hospital settings report high levels of patient satisfaction with CPS. As such, the ECHO framework, based on economic, clinical, and humanistic outcomes, is used herein to organize the summary of literature associated with CPS. Given the growing body of evidence, numerous health professional and government organizations recognize the role of pharmacists as an integral part of the inpatient team. Yet implementation of CPS has not been fully realized by hospitals and health systems. This paper briefly describes inpatient CPS, highlights many benefits of and endorsements for clinical pharmacist participation on interdisciplinary teams, and provides high‐level recommendations for health system administrators and the profession of pharmacy to further encourage broader integration of CPS into patient care teams. Effectively positioning inpatient clinical pharmacists as indispensable team members will require intentional work and strategic planning with a focus on high‐impact value, visibility, and leadership.

Abstract Objective This study was undertaken to evaluate the safety and effectiveness of responsive thalamic stimulation as adjunctive therapy for drug‐resistant idiopathic generalized epilepsy (IGE) with generalized tonic–clonic seizures (GTCSs). Methods NAUTILUS is a prospective, multicenter, single‐blind, randomized sham‐controlled pivotal trial. Patients were ≥12 years of age with drug‐resistant IGE and ≥2 GTCSs over a 3‐month baseline. Bilateral depth leads were targeted to the centromedian thalamus. One month later, patients were randomized to Active (responsive stimulation, n = 44) or Sham (no stimulation, n = 43). The effectiveness evaluation period (EEP) began 3 months postimplant through 1 year. After a second GTCS in the EEP, patients transitioned to open‐label active stimulation. The primary safety endpoint was the serious adverse device‐related event (SADE) rate at 84 days postimplant. The primary effectiveness endpoint was time‐to‐second‐GTCS during the EEP. Additional endpoints included median percent change in days with any generalized seizure, GTCS frequency, and responder rate (RR). Results Eighty‐seven patients were implanted across 23 US centers. The SADE rate was significantly below the performance goal (6.9%, p < .0001), with no adverse effects on cognition, mood, or sleep. The prespecified primary effectiveness endpoint was not significant. However, a post hoc mixed‐effects model considering all EEP days demonstrated greater GTCS reduction in the originally randomized Active group (61%) compared to patients originally randomized to Sham (49%, p = .030). Eighteen‐month outcomes included 76.8% median GTCS reduction, 62.5% RR, 40% GTCS‐free at that timepoint, and 77.8% median reduction in days with any generalized seizure. More than 90% of patients and 86% of physicians reported improvement on Global Impression of Change scales. Significance NAUTILUS is the first randomized controlled neuromodulation trial in IGE. Responsive thalamic stimulation provided a clinically meaningful and durable reduction in seizures with an acceptable safety profile, offering a much‐needed option for drug‐resistant IGE.

Background Knee osteoarthritis (OA) is a leading cause of chronic pain and disability, with limited disease modifying therapies. While glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have established cardiometabolic benefits and have been associated with reductions in knee OA related pain, it is unclear whether they can reduce progression to total knee arthroplasty (TKA). Methods We conducted a retrospective cohort study using the TriNetX Global Research Network, identifying adults with knee OA diagnosed between January 1, 2010, and December 31, 2024. Patients were stratified by GLP-1 RA exposure class (any GLP-1 RA or new generation agents, semaglutide or tirzepatide) and treatment duration (1 or 3 years), and then compared with propensity score matched non-exposed cohorts balanced for age, sex, race, musculoskeletal diagnoses, obesity related conditions, body mass index, and proxies for healthcare access. The primary outcome was cumulative incidence of TKA at 1, 3, 5, and 8 years. Hazard ratios (HRs) were estimated by Cox proportional hazards models and absolute risk differences from Kaplan–Meier curves, expressed as exposed minus non-exposed. Results After propensity score matching, cohort sizes ranged from 13 351 (new generation GLP-1 RA, 3 year exposure) to 42 062 patients (any GLP-1 RA, 1 year exposure). GLP-1 RA use was associated with significantly lower cumulative TKA incidence across all exposure classes, durations, and follow-up intervals (all p<0.001). With 1 year exposure to any GLP-1 RA, the absolute risk difference at 8 years was −2.80 percentage points (HR 0.90, 95% CI 0.83 to 0.98). Risk reductions were greater with new generation agents and longer duration: 3 year exposure to semaglutide or tirzepatide gave an absolute risk difference of −4.71 percentage points at 8 years (HR 0.72, 95% CI 0.67 to 0.78). Conclusions In this large, multicenter, real world cohort study, GLP-1 RA use was associated with a significantly reduced long term risk of TKA in patients with knee OA, with effects that were greater with longer treatment duration and newer generation agents. These duration and agent dependent associations are consistent with potential disease modifying activity beyond weight loss alone, although prospective trials are needed to establish causality and define optimal treatment targets.