14 research outputs found
Toxin-Based Models to Investigate Demyelination and Remyelination.
Clinical myelin diseases, and our best experimental approximations, are complex entities in which demyelination and remyelination proceed unpredictably and concurrently. These features can make it difficult to identify mechanistic details. Toxin-based models offer lesions with predictable spatiotemporal patterns and relatively discrete phases of damage and repair: a simpler system to study the relevant biology and how this can be manipulated. Here, we discuss the most widely used toxin-based models, with a focus on lysolecithin, ethidium bromide, and cuprizone. This includes an overview of their respective mechanisms, strengths, and limitations and step-by-step protocols for their use
The impact of reproductive issues on preferences of women with relapsing multiple sclerosis for disease modifying treatments
Background
Relapsingâremitting multiple sclerosis (RRMS) is an incurable disease characterised by relapses (periods of function loss) followed by full or partial recovery, and potential permanent disability over time. Many disease-modifying treatments (DMTs) exist that help reduce relapses and slow disease progression. Most are contraindicated during conception/pregnancy and some require a discontinuation period before trying to conceive. Although around three-quarters of people with RRMS are women, there is limited knowledge about how reproductive issues impact DMT preference.
Objective
The aim of this study was to measure the preferences for DMTs of women with RRMS who are considering pregnancy.
Design
An online discrete choice experiment (DCE).
Methods
Participants chose between two hypothetical DMTs characterised by a set of attributes, then indicated if they preferred their choice to no treatment. Attributes were identified from interviews and focus groups with people with RRMS and MS professionals, as well as literature reviews, and included the probability of problems with pregnancy, discontinuation of DMTs, and breastfeeding safety. In each DCE task, participants were asked to imagine making decisions in three scenarios: now; when trying to conceive; and when pregnant.
Analysis
Two mixed logit models were estimated, one to assess the statistical significance between scenarios and one in maximum acceptable risk space to allow comparison of the magnitudes of parameters between scenarios.
Sample
Women with RRMS who were considering having a child in the future, recruited from a UK MS patient register.
Results
Sixty respondents completed the survey. Participants preferred no treatment in 12.6% of choices in the ânowâ scenario, rising significantly to 37.6% in the âtrying to conceiveâ scenario and 60.3% in the âpregnantâ scenario (KruskalâWallis pâ<â0.001). This pattern corresponds with results from models that included a no-treatment alternative-specific constant (ASC) capturing differences between taking and not taking a DMT not specified by the attributes. The ASC was lower in the trying to conceive scenario than in the now scenario, and lower still in the pregnant scenario, indicating an intrinsic preference for no treatment. Participants also placed relatively less preference on reducing relapses and avoiding disease progression in the trying to conceive and pregnant scenarios compared with a lower risk of problems with pregnancy. In the trying to conceive scenario, participantsâ preference for treatments with shorter washout periods increased.
Conclusion
Women with RRMS considering having a child prefer DMTs with more favourable reproduction-related attributes, even when not trying to conceive. Reproductive issues also influenced preferences for DMT attributes not directly related to pregnancy, with preferences dependent on the life circumstances in which choices were made. The design of the DCE highlights the benefits of considering the scenario in which participants make choices, as they may change over time