| 1. |
- Kappos, Ludwig, et al.
(författare)
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Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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| 2. |
- Ferreira, Marisa Borges, et al.
(författare)
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Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients
- 2018
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Ingår i: PeerJ. - : PeerJ, Inc. - 2167-8359. ; 6, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Stroop test is frequently used to assess deficits in inhibitory control in people with multiple sclerosis (MS). This test has limitations and antisaccade eye movements, that also measure inhibitory control, may be an alternative to Stroop.ObjectivesThe aim of this study was twofold: (i) to investigate if the performance in the antisaccade task is altered in patients with MS and (ii) to investigate the correlation between performances in neuropsychological tests, the Stroop test and the antisaccade task.MethodsWe measured antisaccades (AS) parameters with an infrared eye tracker (SMIRED 250 Hz) using a standard AS paradigm. A total of 38 subjects diagnosed with MS and 38 age and gender matched controls participated in this study. Neuropsychological measures were obtained from the MS group.ResultsPatients with MS have higher error rates and prolonged latency than controls in the antisaccade task. There was a consistent association between the Stroop performance and AS latency. Stroop performance but not AS latency was associated with other neuropsychological measures in which the MS group showed deficits.ConclusionsOur findings suggest that AS may be a selective and independent measure to investigate inhibitory control in patients with MS. More studies are necessary to confirm our results and to describe brain correlates associated with impaired performance in the antisaccade task in people diagnosed with MS.
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| 3. |
- Gaspar-Cunha, Antonio, et al.
(författare)
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e-xtruder.net-Concepção e desenvolvimento de um sistema automático de modelação e optimização de extrusoras
- 2004
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Ingår i: softEXTRUSION 2004 - Modelação da Extrusão de Polímeros. - Portugal : -. - 9729060843 ; , s. 27-46
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Apresenta-se um software para o processo de extrusão monofuso que congrega um tutorial, a monitorização, a modelação e a optimização do processo. O programa foi desenvolvido por um consórcio nacional e pretende constituir-se como uma ferramenta de apoio à actividade industrial de extrusão. A modelação permite prever o comportamento da extrusora ao processar um determinado material em determinadas condições operatórias. O módulo de optimização estima, de forma automática, as condições operatórias e/ou a geometria do sistema mais adequadas a uma aplicação específica. O tutorial, de natureza interactiva, pode ser utilizado na formação dos quadros das empresas. Finalmente, o módulo de monitorização complementa as capacidades do equipamento disponível e proporciona o controlo estatístico do processo.
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| 4. |
- Macedo, António Filipe, et al.
(författare)
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Anti-saccades in early stages of multiple sclerosis
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Eye movements disability is common finding in multiple sclerosis (MS) but the exact stage at which changes are visible is not clear. The aim of study was to assess if anti-saccade (AS) planning and execution are altered at early stages of the disease.Methods: A total of 48 participants with MS selected by a neurologist (JJC) at Hospital de Braga and 52 controls participated in this study. Inclusion criteria: relapsing-remitting course, EDSS≤3, 1 month or more without MS crisis, and normal or corrected visual acuity. Exclusion criteria (MS and Control): cognitive impairment, traumatic brain injury or stroke. The mean age in the MS group was 37y and 33y in the control group. Eye movements were monitored using a binocular infrared eyetracker running at 250Hz(RED250, SMI Gmb Germany), precision <0.4deg, stimuli were presented in a 22 monitor (Dell P2210). Code for running the experiment and data analysis was written using the Matlab (Mathworks Inc). Participants were seated in a room dim light at 74cm from the monitor and head movements were minimized by a headband. The task was to fixate, after a variable period between steady fixation and the stimulus of 1250ms or 1600ms, participants looked as quickly as possible for the opposite direction where the target (a 30x30mm cross) was presented (anti-saccade movement). Each subject performed 40 trails.Results: The main results were the proportion of the directional errors (wherein the participant voluntarily looked for the wrong side), and latencies for: i) anti-saccades, ii) pro-saccades (movement in the same direction of the stimulus) and iii) correction (reaction time that the participant takes from the error fixation until to start the movement). The mean number of errors was 28%(SD=19) in MS group and 16%(SD=11) in the control group, mean difference 12%, t(74)=3.83, p<.001. Anti-saccades latency was 330msec (SD=61) in the MS group and 294ms(SD=59) in the control group, mean difference 36ms, F(1,98)=10.99, p<.05. The mean of the correction latency value was 178ms(SD=111) in the MS group and 129ms(SD=107) in the control group with a mean difference of 49ms, F(1,98)=6, p<.05. No statistically significant differences were found in accuracy and pro-saccade latency between groups.Conclusions: This study shows that anti-saccades latency and errors are increased at early stages of multiple sclerosis. Anti-saccades might be a sensitive tool to assess functional status in people with this condition.
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| 5. |
- Marisa, Ferreira, 1992-, et al.
(författare)
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Using endogenous saccades to characterize fatigue in multiple sclerosis
- 2017
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 14, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- PurposeMultiple Sclerosis (MS) is likely to cause dysfunction of neural circuits between brain regions increasing brain working load or a subjective overestimation of such working load leading to fatigue symptoms. The aim of this study was to investigate if saccades can reveal the effect of fatigue in patients with MS.MethodsPatients diagnosed with MS (EDSS<=3) and age matched controls were recruited. Eye movements were monitored using an infrared eyetracker. Each participant performed 40 trials in an endogenous generated saccade paradigm (valid and invalid trials). The fatigue severity scale (FSS) was used to assess the severity of fatigue. FSS scores were used to define two subgroups, the MS fatigue group (score above normal range) and the MS non-fatigue. Differences between groups were tested using linear mixed models.ResultsThirty-one MS patients and equal number of controls participated in this study. FSS scores were above the normal range in 11 patients. Differences in saccade latency were found according to group (p<0.001) and trial validity (p=0.023). Differences were 16.9 ms, between MS fatigue and MS non-fatigue, 15.5 ms between MS fatigue and control. The mean difference between valid and invalid trials was 7.5 ms. Differences in saccade peak velocity were found according to group (p<0.001), the difference between MS fatigue and control was 22.3°/s and between MS fatigue and non-fatigue was 12.3°/s. Group was a statistically significant predictor for amplitude (p<0.001). FSS scores were correlated with peak velocity (p=0.028) and amplitude (p=0.019).ConclusionConsistent with the initial hypothesis, our study revealed altered saccade latency, peak velocity and amplitude in patients with fatigue symptoms. Eye movement testing can complement the standard inventories when investigating fatigue because they do not share similar limitations. Our findings contribute to the understanding of functional changes induced by MS and might be useful for clinical trials and treatment decisions.
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