•Enhanced effective connectivity between OFC and VS is associated with the likehood of taking medications.•Enhanced effective connectivity between OFC, insula and amygdala is associated with the ...likehood of refusing treatment.•Participants demonstrated increased skin conductance response prior to making riskier treatment decisions.•Neural and physiological results mirrored behavioral data and fit within a behavioral economic theoretical framework.
Great progress has been made in understanding how people make financial decisions. However, there is little research on how people make health and treatment choices. Our study aimed to examine how participants weigh benefits (reduction in disease progression) and probability of risk (medications' side effects) when making hypothetical treatment decisions, and to identify the neural networks implicated in this process.
Fourteen healthy participants were recruited to perform a treatment decision probability discounting task using MRI. Behavioral responses and skin conductance responses (SCRs) were measured. A whole brain analysis were performed to compare activity changes between "mild" and "severe" medications' side effects conditions. Then, orbitofrontal cortex (OFC), ventral striatum (VS), amygdala and insula were chosen for effective connectivity analysis.
Behavioral data showed that participants are more likely to refuse medication when side effects are high and efficacy is low. SCRs values were significantly higher when people made medication decisions in the severe compared to mild condition. Functionally, OFC and VS were activated in the mild condition and were associated with increased likehood of choosing to take medication (higher area under the curve "AUC" side effects/efficacy). These regions also demonstrated an increased effective connectivity when participants valued treatment benefits. By contrast, the OFC, insula and amygdala were activated in the severe condition and were associated with and increased likelihood to refuse treatment. These regions showed enhanced effective connectivity when participants were confronted with increased side effects severity. This is the first study to examine the behavioral and neural bases of medical decision making.
Objectives: The objective of this study is to investigate the efficacy of psychological Interventions – Mindfulness or Implementation Intention – associated with a Physical Activity program, ...delivered via internet, in reducing Multiple Sclerosis symptoms. Method: Thirty-five adults were randomly assigned to one of the three groups: a Mindfulness-Based Intervention group ( N = 12), Implementation Intention group ( N = 11), and a Control Group ( N = 12). All the groups received the same Physical Activity program. The Mindfulness condition group received daily training in the form of pre-recorded sessions while the Implementation group elaborated their specific plans once a week. Mobility, fatigue, and the impact of the disease on the patient’s life were measured. Two measurement times are carried out in pre-post intervention, at baseline and after eight weeks. Results: Overall, after 8 weeks intervention, results show that there was a significant increase in Walking distance in the three groups. In addition, the within-group analysis showed a statistically significant improvement between pre and post intervention on the physical component of the Disease Impact scale in the Implementation Intention group ( p = 0.023) with large effect size, in the Mindfulness-Based Intervention group ( p = 0.008) with a medium effect size and in the control group ( p = 0.028) with small effect size. In the Implementation Intention group, all physical, psychosocial and cognitive Fatigue Impact subscales scores decreased significantly ( p = 0.022, p = 0.023, and p = 0.012, respectively) and the physical component was statistically and negatively correlated ( r = −0.745; p = 0.008 ) when Implementation Intention group practice a mild to moderate physical activity. In the Mindfulness-Based Intervention group, the physical component (MFIS) showed a statistically significant improvement ( p = 0.028) but no correlation with moderate-to-vigorous physical activity (MVPA); the control group outcomes did not reveal any significant change. Conclusion: The results of this study are very encouraging and show the feasibility of Mindfulness interventions associated with physical activity to improve the health of people with MS. Further study should assess Mindfulness interventions tailored to MS condition and using both hedonic and eudemonic measures of happiness.
L’objectif de cette étude est d’évaluer l’impact de l’hypothermie sur la valeur pronostique de l’EEG standard de longue durée au cours de l’encéphalopathie anoxo-ischémique 1 . À travers une étude ...rétrospective déroulée au centre hospitalier de Poissy durant la de janvier 2013 à mars 2017, 17 nouveau-nés à terme présentant une EAI modéré à sévère ont été colligés dans le cadre d’un protocole hypothermie contrôlée avec réalisation d’EEG longue durée durant la procédure. Les tracés ont été réinterprétés d’une façon aveugle et classés selon la classification française 2 . L’étude de la valeur pronostique de l’EEG a été réalisée en calculant la sensibilité et la spécificité. La corrélation entre les variables a été étudiée au moyen du test Chi2 avec un p significatif < 0,5. Un tracé de fond type 4 au cours des premières 24 h était prédictif de survenue de décès ou la persistance de séquelles majeures (sensibilité : 100 %, spécificité : 83 %). La persistance d’un tracé de type discontinu avant réchauffement était prédictif d’une mauvaise évolution (sensibilité : 71,4 %, spécificité : 80 %). Par contre, un tracé de type 1 ou 2 prédit une bonne évolution neurologique (sensibilité : 80 %, spécificité : 85,9 %). La normalisation du tracé à j7 de vie était peu prédictif d’une bonne évolution (sensibilité : 30 %, spécificité : 66,67 %). L’évolution à moyen terme était corrélée à l’enregistrement de crise au cours du premier EEG ( p = 0,36) et la persistance d’anomalies paroxystiques à j3 ( p = 0,43). En conclusion, l’EEG à j1 de l’hypothermie et avant réchauffement sont un bon indicateur pronostique.
In patients with multiple sclerosis (MS), factors associated with severe COVID-19 include anti-CD20 therapies and neurologic disability, but it is still unclear whether these 2 variables are ...independently associated with severe COVID-19 or whether the association depends on MS clinical course.
To assess the association between anti-CD20 therapies and COVID-19 severity in patients with relapsing-remitting MS (RRMS) and progressive MS (PMS).
This multicenter, retrospective cohort study used data from the COVISEP study, which included patients with MS and COVID-19 from February 1, 2020, to June 30, 2022, at 46 French MS expert centers, general hospitals, and private neurology practices. Eligible patients with RRMS were those treated with high-efficacy MS therapy (ie, anti-CD20, fingolimod, or natalizumab), and eligible patients with PMS were those younger than 70 years with an Expanded Disability Status Scale (EDSS) score of 8 or lower. Patients were monitored from COVID-19 symptom onset until recovery or death.
Current anti-CD20 therapy (ocrelizumab or rituximab).
The main outcome was severe COVID-19 (ie, hospitalization with any mode of oxygenation or death). All analyses were conducted separately in patients with RRMS and PMS using propensity score-weighted logistic regression. Subgroup analyses were performed according to COVID-19 vaccine status, sex, EDSS score, and age.
A total of 1400 patients, 971 with RRMS (median age, 39.14 years IQR, 31.38-46.80 years; 737 76.1% female) and 429 with PMS (median age, 54.21 years IQR, 48.42-60.14 years; 250 58.3% female) were included in the study. A total of 418 patients with RRMS (43.0%) and 226 with PMS (52.7%) were treated with anti-CD20 therapies. In weighted analysis, 13.4% and 2.9% of patients with RRMS treated and not treated with anti-CD20 had severe COVID-19, respectively, and anti-CD20 treatment was associated with increased risk of severe COVID-19 (odds ratio OR, 5.20; 95% CI, 2.78-9.71); this association persisted among vaccinated patients (7.0% vs 0.9%; OR, 8.85; 95% CI, 1.26-62.12). Among patients with PMS, 19.0% and 15.5% of patients treated and not treated with anti-CD20 had severe COVID-19, respectively, and there was no association between anti-CD20 treatment and severe COVID-19 (OR, 1.28; 95% CI, 0.76-2.16). In PMS subgroup analysis, anti-CD20 exposure interacted negatively with EDSS score (P = .009 for interaction) and age (P = .03 for interaction); anti-CD20 therapies were associated with risk of severe COVID-19 only in patients with less neurologic disability and younger patients with PMS.
In this cohort study, risk of severe COVID-19 was higher in patients with PMS than in those with RRMS. Use of anti-CD20 therapies was associated with an increased risk of severe COVID-19 among patients with RRMS. In patients with PMS, there was no association between anti-CD20 therapies and risk of severe COVID-19.
Abstract Memantine, an uncompetitive antagonist of N-methyl- d -aspartate (NMDA)-type glutamate receptors that was approved for the treatment of moderate to severe Alzheimer's disease, has been ...negatively evaluated for the treatment of cognitive disorders of multiple sclerosis, but these studies were conducted only during short-term administration and on a heterogeneous group of patients with different forms of the disease. In addition, many adverse reactions were observed in these patients. Aims The purpose of the “EMERITE” (NCT01074619) study was to examine the efficacy and safety of the long-term administration of memantine as a symptomatic treatment for cognitive disorders in patients with relapsing-remitting multiple sclerosis (RR-MS). Methods The study was supported by the French Ministry of Health and received additional support from Lundbeck. In this double-blind, placebo-controlled, parallel group, randomized trial, the participants were assigned to receive memantine (20 mg/day) or a placebo for 52 weeks. The participants included males and females, 18–60 years of age, with a diagnosis of RR-MS and presenting with a cognitive complaint and/or demonstrating moderate cognitive impairment. The data were collected in the Department of Neurology in 19 French centers. The primary outcome was the Paced Auditory Serial Addition Test (PASAT) score at week 52. Secondary measurements included additional neuropsychological tests and the annualized relapse rate. The scores were adjusted according to the baseline scores in the analysis. The safety was assessed by the number of adverse events. The random sequence was generated using the Excel software. At each center, only the pharmacist had access to the allocation sequence and could be asked to unblind the trial. Results Fifty patients were allocated to the memantine group, and 43 to the placebo group. The intent-to-treat (ITT) population included 31 patients in each group. After adjusting for the PASAT scores at baseline, the PASAT scores at the end point did not differ between the memantine and the placebo groups (p = 0.88). Adjusted mean score difference (memantine minus placebo), was − 0.40 (95% confidence interval: -5.5; + 4.7). No significant differences were observed for the secondary outcomes (short term memory and attention scores, EDSS, and relapse rate). The findings remained unchanged after multiple imputation of the missing values. Neurological and psychiatric adverse events were significantly higher in the memantine group than in the placebo group, and these parameters were higher than those reported in the product literature of memantine. Conclusions No differences between the placebo and memantine groups were observed. Nevertheless, the tolerability of memantine was significantly worse than expected.
The development of oral treatments for relapsing-remitting multiple sclerosis (RRMS) may alter patient satisfaction and quality of life (QoL). The aim of this survey was to evaluate treatment ...satisfaction and QoL in patients treated with fingolimod in everyday clinical practice in France.
Neurologists treating MS in France were invited to participate in the survey by telephone. Each physician was expected to recruit up to six patients with RRMS currently being treated with fingolimod. Enrolled patients were asked to complete the Treatment Satisfaction Questionnaire for Medication (TSQM), the 3-level 5-dimension EuroQoL instrument, as well as specific questions on change in QoL since starting fingolimod. Factors associated with the TSQM score were evaluated using multiple logistic regression analysis.
Two hundred and fourteen patients were recruited by 54 neurologists. The mean age of the patients was 41.6±10.0 years, and 73.4% of them were women. During the hospitalization for initiation of fingolimod treatment, 70.1% of patients had received information on MS, 76.6% had received information on fingolimod, and 20.7% had participated in a therapeutic education program. The two variables with the strongest associations with high TSQM scores (≥75) were a positive perception of initial hospitalization (hazard ratio: 10.27) and receiving information on MS during hospitalization (hazard ratio: 5.70). The mean EQ-visual analog scale score was 71.6±16.8. The mean EQ-visual analog scale score was significantly higher in patients satisfied with their treatment (75.8±15.2) compared to those unsatisfied with treatment (66.6±17.2). The proportion of patients who reported an improvement in their capacity to plan for the future was higher in satisfied (72.6%) than in unsatisfied patients (49.5%).
The majority of patients treated with fingolimod are satisfied with their treatment. Treatment satisfaction is associated with better self-rated QoL and an improvement of QoL since starting treatment.
Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate ...(GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3–6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 95 % confidence interval (CI) 0.81–0.91 before the change to 0.32 (95 % CI 0.26–0.40;
p
< 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (
p
< 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.
De nombreuses études montrent les bénéfices de la pratique de l’activité physique (AP) chez les patients atteints de sclérose en plaques (SEP). Mais l’adhésion des patients à l’AP est difficile à ...obtenir, et surtout, à maintenir. L’objectif de cette étude est d’évaluer deux types de soutiens visant à aider le patient à initier et à pérenniser sa pratique.
Quarante-cinq patients seront répartis aléatoirement dans 3 groupes : une intervention basée sur l’implémentation d’intention 1, une intervention basée sur la pleine conscience 2 et un groupe contrôle. Ces deux 1ers groupes bénéficient d’un soutien internet et d’un soutien téléphonique hebdomadaire. Les participants bénéficient du même programme d’AP, de 2 heures par semaines sur 2 mois. Des mesures d’actimétries sont effectuées avant et après le programme sur une durée de 7 jours, puis, à 3 et à 6 mois après le programme. Des questionnaires mesurant les changements de comportement au regard de la motivation à l’AP et des questionnaires mesurant l’impact des interventions complémentaires, permettront de déterminer l’efficacité des soutiens proposés. Enfin, des scores d’évaluations moteurs et psychologiques seront effectués.
Douze patients ont terminé le programme à 3 mois. Ces résultats ne permettent actuellement pas de constater de différences significatives entre les groupes pour l’actimétrie, mais montrent une amélioration significative (p<0,05) des tests moteurs après le programme d’AP pour les 3 groupes.
Ces résultats préliminaires confirment l’efficacité de la pratique de l’AP sur les tests moteurs. Ils devront être complétés par un nombre de patients plus important pour observer des résultats sur l’actimétrie et sur l’impact des interventions sur la pratique de l’AP chez les patients.
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