BACKGROUND AND OBJECTIVES:Rituximab (RTX) dosed every 6 months is an affordable and highly effective treatment for relapsing multiple sclerosis (RMS). However, higher cumulative doses are associated with greater risks of infections. Whether extending dosing intervals at a low dose (500 mg) increases the risk of return of disease activity, particularly in those with only 1 year of stability or with significant return of B cells, is uncertain. Our objective was to compare whether extending RTX dosing to every 12 months (q12mo) vs continuing every 6 months (q6mo) dosing in patients with RMS increased the risk of return of disease activity. METHODS:We emulated a target trial comparing the effectiveness of RTX 500 mg q12mo to q6mo starting in year 2 (baseline) among patients with RMS who had active disease at RTX start and no evidence of disease activity (NEDA) during the first year on RTX. Eligible patients were identified from the retrospective cohort of patients with MS treated with RTX between 2008 and 2023 in Kaiser Permanente Southern California. The absence of relapses, MRI disease activity, and disability progression (NEDA-3) were analyzed by intention-to-treat (ITT) and per-protocol (PP) with inverse probability of treatment weighting of receiving q6mo or q12mo dosing. RESULTS:We identified 140 patients (mean age 40.4 years, 73.6% female) who received q12mo dosing and 468 patients (mean age 38.4, 70.9% female) on q6mo dosing after baseline with a median ITT follow-up of 2.6 (interquartile range [IQR] 1.9-3.3) and 3.9 years (IQR 2.4-4.8), respectively. Relapses and/or MRI disease activity (3.5%) and failing NEDA-3 (3.8%) up to 4 years later were uncommon. Extending dosing to q12mo was associated with significant B-cell repopulation (70.5% with ≥80 cells/μL PP, 75.7% ITT) compared with q6mo intervals (23.3% with ≥80 cells/μL PP, 60.2% ITT) but not with an increased risk of failing NEDA-3 up to 4 years after baseline in propensity score-adjusted ITT (hazard ratio [HR] 1.60, 95% CI 0.69-3.68) or PP analyses (HR 1.44, 95% CI 0.45-4.61). DISCUSSION:Extending low-dose RTX treatment intervals after 1 year of stability to q12mo was highly effective and did not result in an increased risk of disease activity despite high B-cell counts compared with continuing q6mo dosing over 2 or more years of follow-up. CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that in persons with RMS with NEDA-3 in the 12 months following RTX, extending the dosing interval to 12 months did not increase the risk of disease activity compared with continuing q6mo dosing.
Clear cell renal cell carcinoma (ccRCC) prognosis is guided by a tumor’s pathological features. While radiomics shows promise for non-invasive tumor characterization, it remains unclear whether incorporating the peritumoral region and leveraging multiphase CT imaging improves model performance beyond standard tumor-region analysis. This study aimed to determine whether radiomic features derived from the peritumoral area in standard four-phase CT protocol improve the prediction of ccRCC stage, grade, and aggressiveness compared to intratumoral features alone. A retrospective cohort of 250 patients with ccRCC was analyzed. Using tumor and 5-mm peritumoral regions on four-phase CT, 1874 radiomic features were extracted per region per phase. Elastic Net and Random Forest models were trained with tenfold cross-validation to predict binarized stage, grade, and aggressiveness outcomes using three feature sets: tumor region, peritumoral region, and a combined region including both the tumor and peritumoral regions. Models using only tumor-region features consistently outperformed those using the peritumoral and combined regions. The best tumor-region model achieved area under the receiver operating characteristic curve (AUC) values of 0.875 for stage, 0.697 for grade, and 0.915 for aggressiveness. Multiphase analysis provided no benefit over a single-phase approach, with the nephrographic phase alone yielding equivalent or superior performance to multiphase models across all outcomes. A simplified radiomic approach using features from the tumor region in the nephrographic phase alone provides optimal performance for predicting key ccRCC characteristics. The added complexity of peritumoral and multiphase analysis did not enhance predictive accuracy, potentially streamlining future ccRCC radiomic research.
BACKGROUND:Purkinje-mediated ventricular fibrillation (VF) may arise from discrete fascicular triggers or diffuse abnormal Purkinje substrate. The relative performance of trigger-based vs substrate-based de-networking remains uncertain. OBJECTIVES:The goal of this study was to compare outcomes of trigger-focused and substrate-based Purkinje de-networking for VF. METHODS:In this retrospective multicenter cohort, 43 patients underwent Purkinje-targeted VF ablation using high-power, short-duration radiofrequency energy (90 W for 4 seconds or 50 W for 10 seconds). Patients were grouped according to ablation strategy: 1) trigger group (n = 19), ablation of the culprit premature ventricular complex-triggering fascicle; or 2) substrate group (n = 24), elimination of all abnormal Purkinje-like potentials. The primary endpoint was recurrence of polymorphic ventricular tachycardia/VF; secondary endpoints included conduction system complications. Median follow-up was 12.2 months (Q1-Q3: 8.8-18.8 months). RESULTS:Baseline characteristics were similar between groups. Freedom from polymorphic ventricular tachycardia/VF was higher with substrate modification (22 of 24 [91.7%]; 95% CI: 73.0%-98.9%) than with trigger-based ablation (12 of 19 [63.2%]; 95% CI: 38.4%-83.7%; HR: 0.20 [95% CI: 0.05-0.76]; log-rank test; P = 0.026). Both approaches significantly reduced arrhythmic burden (trigger group: 3.9 ± 0.8 episodes to 0.4 ± 0.2 episodes [P < 0.001]; substrate group: 4.8 ± 1.2 episodes to 0.1 ± 0.1 episodes [P < 0.001]). Conduction complications differed: new left bundle branch block occurred in 5 of 24 substrate patients (20.8%), whereas one posterior fascicular block occurred in the trigger group (1 of 19 [5.3%]; P < 0.001). CONCLUSIONS:Substrate-based de-networking was associated with greater freedom from ventricular tachycardia/VF but a higher rate of conduction system injury. Trigger-focused ablation may serve as an initial strategy in patients with identifiable premature ventricular complex triggers, with substrate modification reserved for refractory or nontriggered VF.
Objective: We explored the feasibility of integrating a digital mental health intervention (DMHI) for adolescents identified with mild or moderate depressive symptoms during preventive health encounters. Methods: We conducted a quality improvement study at a large integrated health care system in California from August to December 2023. Collaborators included 47 physicians and a nurse practitioner. Results: Of 1200 health encounters with adolescents, 1143 (95%) documented depression screening. Screening identified depressive symptoms at 106 (9%) encounters, including 41 (3%) with mild to moderate symptoms, 14 (1%) with moderately severe or severe symptoms, and 51 (5%) who screened positive with no information on depression severity. Clinicians documented a DMHI referral offer at 17 encounters with mild to moderate symptoms (41%) and 7 encounters with moderately severe or severe symptoms (50%). Over half of youths with depressive symptoms who were offered the DMHI accepted it (52%), but only one-fifth obtained the download instructions. Clinicians appreciated having a DMHI available, but challenges included difficulty identifying adolescents with depressive symptoms and low adolescent interest. Clinicians recommend facilitating adolescent download of the DMHI at the visit and involving parents/guardians. Conclusions: A clinician-focused implementation strategy demonstrated limited success in integrating DMHI into adolescent preventive health visits.
