16 research outputs found

    Spatial and temporal characteristics of gait as outcome measures in multiple sclerosis (EDSS 0 to 6.5)

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    Background: Gait impairment represents one of the most common and disabling symptom of multiple sclerosis. Quantification of the gait is an important aspect of clinical trials. In order to identify which temporal or spatial parameters of gait could be used as outcome measures in interventional studies of patients with different levels of disability, we evaluated characteristics of these parameters in MS patients across the whole spectrum of mobility from EDSS 0 to 6.5. Methods: This is a cross-sectional study of spatial and temporal parameters of gait at self selected speed and at fast speed of walking in 284 patients with multiple sclerosis (108 men, mean age 38 years ± SD 10.8 years, range 18–64) divided into seven levels of disability (EDSS 0 to 1.5, EDSS 2.0 to 2.5, EDSS 3.0 to 3.5, EDSS 4.0 to 4.5, EDSS 5.0 to 5.5, EDSS 6.0, EDSS 6.5). Results: The velocity of gait decreases with increasing EDSS levels. Hovewer, the spatio-temporal parameters of gait that are involved in this process differ across the EDSS levels. The step length is decreased at higher EDSS levels up to the EDSS 6.0, but was not different between EDSS 6.0 and 6.5. The step time is significantly longer at EDSS 6.0 and 6.5, while the step length remains the same at those levels. The increase in percentage of double support time becomes statistically significant at EDSS 3.0-3.5 and continues to increase until EDSS 6.5. Variability of step time, step length or step width did not show significant difference between studied EDSS levels. Conclusions: There is no single spatio-temporal parameter of gait (other than velocity of gait) that would show significant differences among all levels of EDSS. The step length reflects shortening of steps at lower EDSS levels (2.0 to 6.0), and percentage of double support time better reflects changes at higher EDSS levels 3.0 – 6.5. Gait variability is not associated with disability in MS and therefore would not be a suitable outcome measure. T

    Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study

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    © The Author(s), 2018. Background: Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5. Objective: Evaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis. Methods: In the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.5 or 1 mg) or placebo. After 24 weeks, participants could enter a 2-year, dose-blinded extension. Ozanimod-treated participants continued their assigned dose; placebo participants were re-randomized (1:1) to ozanimod hydrochloride 0.5 or 1 mg (equivalent to ozanimod 0.46 and 0.92 mg). Results: A total of 223 (89.6%) of the 249 participants completed the blinded extension. At 2 years of the extension, the percentage of participants who were gadolinium-enhancing lesion-free ranged from 86.5% to 94.6%. Unadjusted annualized relapse rate during the blinded extension (week 24—end of treatment) was 0.32 for ozanimod hydrochloride 0.5 mg → ozanimod hydrochloride 0.5 mg, 0.18 for ozanimod hydrochloride 1 mg → ozanimod hydrochloride 1 mg, 0.30 for placebo → ozanimod hydrochloride 0.5 mg, and 0.18 for placebo → ozanimod hydrochloride 1 mg. No second-degree or higher atrioventricular block or serious opportunistic infection was reported. Conclusion: Ozanimod demonstrated sustained efficacy in participants continuing treatment up to 2 years and reached similar efficacy in participants who switched from placebo; no unexpected safety signals emerged

    Efficacy and safety of ozanimod in multiple sclerosis : Dose-blinded extension of a randomized phase II study

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    Altres ajuts: The study was sponsored by Celgene Corporation.Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5. Evaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis. In the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.5 or 1 mg) or placebo. After 24 weeks, participants could enter a 2-year, dose-blinded extension. Ozanimod-treated participants continued their assigned dose; placebo participants were re-randomized (1:1) to ozanimod hydrochloride 0.5 or 1 mg (equivalent to ozanimod 0.46 and 0.92 mg). A total of 223 (89.6%) of the 249 participants completed the blinded extension. At 2 years of the extension, the percentage of participants who were gadolinium-enhancing lesion-free ranged from 86.5% to 94.6%. Unadjusted annualized relapse rate during the blinded extension (week 24-end of treatment) was 0.32 for ozanimod hydrochloride 0.5 mg → ozanimod hydrochloride 0.5 mg, 0.18 for ozanimod hydrochloride 1 mg → ozanimod hydrochloride 1 mg, 0.30 for placebo → ozanimod hydrochloride 0.5 mg, and 0.18 for placebo → ozanimod hydrochloride 1 mg. No second-degree or higher atrioventricular block or serious opportunistic infection was reported. Ozanimod demonstrated sustained efficacy in participants continuing treatment up to 2 years and reached similar efficacy in participants who switched from placebo; no unexpected safety signals emerged

    The viability of a breeding programme for ash in the British Isles in the face of ash dieback

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    To evaluate the viability and feasibility of a future breeding programme to produce trees resistant to an emerging pest or pathogen, it is helpful to ask the following questions: How much variation in resistance exists in tree populations? To what extent is this resistance heritable? How many genetic loci are involved? What level of resistance is found in other species of the same genus? Here, we survey current knowledge of these issues in relation to the degree of resistance of European ash (Fraxinus excelsior) to H. fraxineus, the fungus causing ash dieback (ADB). Several studies have found a low frequency of heritable resistance in F. excelsior populations, which seems to be determined by many genetic loci. This suggests that a breeding programme is viable and that natural selection may also increase the mean resistance of populations over time. More research is needed on the genetic basis of resistance to ADB to understand how quickly natural selection can operate in woodlands and what acceleration may be possible in breeding programmes, including via use of genetic markers. Hybrid breeding programmes may also be a possibility, as some ash species appear to be more resistant to ADB than is F. excelsior, but more research is needed on this issue. We do not yet know if it will be possible to breed F. excelsior to have resistance to both ADB and the emerging threat of emerald ash borer. We recommend short‐term mitigation measures for the ADB epidemic and future research directions

    MSJ789884_CONSORT_checklist – Supplemental material for Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study

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    <p>Supplemental material, MSJ789884_CONSORT_checklist for Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study by Jeffrey A Cohen, Giancarlo Comi, Douglas L Arnold, Amit Bar-Or, Krzysztof W Selmaj, Lawrence Steinman, Eva K Havrdová, Bruce AC Cree, Xavier Montalbán, Hans-Peter Hartung, Vivian Huang, Paul Frohna, Brett E Skolnick and Ludwig Kappos in Multiple Sclerosis Journal</p

    MSJ789884_data_supplement – Supplemental material for Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study

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    <p>Supplemental material, MSJ789884_data_supplement for Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study by Jeffrey A Cohen, Giancarlo Comi, Douglas L Arnold, Amit Bar-Or, Krzysztof W Selmaj, Lawrence Steinman, Eva K Havrdová, Bruce AC Cree, Xavier Montalbán, Hans-Peter Hartung, Vivian Huang, Paul Frohna, Brett E Skolnick and Ludwig Kappos in Multiple Sclerosis Journal</p

    MSJ789884_supplementary_appendix – Supplemental material for Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study

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    <p>Supplemental material, MSJ789884_supplementary_appendix for Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study by Jeffrey A Cohen, Giancarlo Comi, Douglas L Arnold, Amit Bar-Or, Krzysztof W Selmaj, Lawrence Steinman, Eva K Havrdová, Bruce AC Cree, Xavier Montalbán, Hans-Peter Hartung, Vivian Huang, Paul Frohna, Brett E Skolnick and Ludwig Kappos in Multiple Sclerosis Journal</p
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