Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients

OBJECTIVE: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). METHODS: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). RESULTS: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3-14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3-24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19-52%, p<0.001) overall, 63% (95%CI=35-79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2-44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. CONCLUSION: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results

Selective maintenance for multi-state systems considering the benefits of repairing multiple components simultaneously

NoMany industrial systems such as aircrafts, ships, manufacturing systems, etc. are required to perform several missions with finite breaks between missions. Maintenance is only available within the breaks. Due to the limitation of resources, all components in the system may not be maintained as desired. The selective maintenance problem helps the decision makers figure out what critical components to select and how to perform maintenance on these components. This paper studies the selective maintenance for multi-state series-parallel systems with the benefit of repairing multiple components simultaneously. Both time and cost savings can be acquired when several components are simultaneously repaired in a selective maintenance strategy. As the number of repaired components increases, the saved time and cost will also increase due to the share of setting up between components and another additional reduction amount from the repair of multiple identical components. A non-linear optimization model is developed to find the most reliable system subjected to time and cost constraints. Genetic algorithm is used to solve the optimization model. An illustrative example will be provided.Natural Sciences and Engineering Research Council of Canada (NSERC) and Vietnam International Education Development (VIED

Condition-based maintenance for systems with aging and cumulative damage based on proportional hazards model

This paper develops a condition-based maintenance (CBM) policy for systems subject to aging and cumulative damage. The cumulative damage is modeled by a continuous degradation process. Different from previous studies which assume that the system fails when the degradation level exceeds a specific threshold, this paper argues that the degradation itself does not directly lead to system failure, but increases the failure risk of the system. Proportional hazards model (PHM) is employed to characterize the joint effect of aging and cumulative damage. CBM models are developed for two cases: one assumes that the distribution parameters of the degradation process are known in advance, while the other assumes that the parameters are unknown and need to be estimated during system operation. In the first case, an optimal maintenance policy is obtained by minimizing the long-run cost rate. For the case with unknown parameters, periodic inspection is adopted to monitor the degradation level of the system and update the distribution parameters. A case study of Asphalt Plug Joint in UK bridge system is employed to illustrate the maintenance policy