Love, Thomas E.

Background: There is growing support for high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS), but escalation (ESC) approaches remain common. Objective: To describe decision-making in a pragmatic trial of early high-efficacy treatment (EHT) versus ESC. Methods: DELIVER-MS is a multi-center, pragmatic, randomized controlled trial (RCT) with a parallel observational study (OBS), which enrolled treatment-naïve people with RRMS in 31 UK/US sites. Primary outcome was as follows: 36-month brain volume loss according to initial treatment approach (EHT vs. ESC). Stepwise multivariable logistic regression was used to predict participation in RCT versus OBS and choice of EHT versus ESC within the OBS cohort. Results: In total, 816 people with MS were enrolled. Participants declined randomization due to preference for a particular DMT (85%), efficacy concerns (20%), and safety concerns (9%). RCT versus OBS participation was associated with lower relapse rate ( p = 0.043) and greater brain parenchymal fraction ( p = 0.002). Among 374 in the OBS cohort, 125 (33%) chose ESC and 249 (67%) chose EHT. People commencing EHT had higher education attainment ( p < 0.001) and relapse rate ( p = 0.025). Conclusion: Baseline DELIVER-MS data demonstrate that participants with milder disease are more likely to participate in RCT. The choice of EHT versus ESC was associated with demographic factors and disease activity. Clinical trial registration: NCT03535298

321 Background: Factors that determine renal function after partial nephrectomy (PN) are not well defined, including the impact of cold vs. warm ischemia and the relative importance of modifiable and non-modifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing PN. Methods: In 1980–2009, 660 PN were performed at 4 centers for tumor in a solitary-functioning kidney under cold (n=300) or warm (n=360) ischemia. Data were collected in IRB-approved registries; follow- up averaged 4.5 years. Pre- and postoperative glomerular filtration rates (GFR) were estimated via CKD-EPI equation. Results: At 3 months after PN, median GFR decreased by equivalent amounts with cold or warm ischemia (21% vs. 22%, respectively, p=0.7) although median cold ischemic times were much longer (45 vs. 22 min. respectively, p<0.001). In multivariable analyses, increasing age, larger tumor size, lower preoperative GFR, and longer ischemia time were associated with decreased postoperative GFR (p<0.05). When percentage of parenchyma spared was incorporated into the analysis, this factor and preoperative GFR proved to be the primary determinants of ultimate renal function, and duration of ischemia lost statistical significance. Conclusions: This non-randomized comparative study suggests that long-term renal function after PN is determined primarily by the quantity and quality of renal parenchyma that can be preserved. Within the relatively strict parameters of conventional practice, i.e. predominantly short ischemic intervals and liberal use of hypothermia, ischemia time was not an independent predictor of ultimate renal function after PN. Nevertheless, type and duration of ischemia remain the most important modifiable factors during PN, and mandate further study. [Table: see text]