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Abstract Background Medical students face a demanding workload, stressful situations, and irregular sleep patterns, which can lead to elevated sleep disturbances and high fatigue levels. These difficulties may be further associated with a major decline in well-being, quality of life, performance, and health. Thus, these struggles must be addressed to reduce these students’ sleep disturbances and fatigue during their curriculum. Methods The PROMESS-Sleep clinical trial aims to support future healthcare professionals by enhancing their abilities to manage their sleep. The support will be provided through a three-session sleep management program. Each session will include an individual meeting between a PROMESS-Sleep expert and a medical student, during which self-care education, advice, and personalized goals will be established. The present protocol is designed to assess the influence of this program on 45 undergraduate medical students (fourth- and fifth-year) of the Lyon-Est Faculty of Medicine (Claude Bernard University Lyon 1, France). Assessments of sleep and fatigue will be conducted before and during the intervention using self-reported questionnaires and actigraphy. At the end of the third session, the student’s satisfaction levels regarding the program will be assessed. The primary outcome will be changes in scores on the Pittsburgh Sleep Quality Index (PSQI) during the program. Secondary outcomes will provide a detailed characterization of changes in various aspects of sleep disturbances, fatigue, sleep habits, and sleep-wake rhythms. Exploratory outcomes will provide information regarding the students’ satisfaction levels and will determine the moderators of the program’s efficacy. Data will be analyzed according to the intention-to-treat principle and presented in accordance with the CONSORT Guidelines. Ethical approval has been obtained by the Institutional Review Board (IRB: 2023-07-04-03), and all procedures will be performed in adherence to the Helsinki Declaration. The results from this study will be presented at scientific conferences and in peer-reviewed scientific journals. Discussion The results will provide valuable insights into the program’s efficacy in reducing sleep disturbances and fatigue. If its efficacy is proven, PROMESS-Sleep could become an integral and sustainable part of medical education due to fostering a healthier and more resilient future for healthcare professionals. This manuscript follows the SPIRIT guidelines (Additional files 1 & 8). Trial registration ClinicalTrials.gov: NCT06297330; retrospectively registered.

IntroductionMyeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes.MethodsCombination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing.ResultsMyeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis. Notably, this patients’ subgroup exhibited a more aggressive disease phenotype two years post-diagnosis. This monocytic population, detected in both the CSF and blood, was characterized by CD206, CD209, CCR5 and CCR2 expression, and was found to be more frequent in MS patients carrying the HLA-DRB1*15:01 allele. Furthermore, pathways analysis predicted that these cells had antigen presentation capabilities coupled with pro-inflammatory phenotype.DiscussionAltogether, these results point toward the amplification of a specific and pathogenic myeloid cell subset in MS patients with genetic susceptibilities.

Le bien-être des chevaux figure parmi les préoccupations de leurs détenteurs et utilisateurs. Optimiser le bien-être nécessite au préalable de pouvoir évaluer de façon objective l’état physique et mental des animaux à l’aide de protocoles validés, afin de pouvoir adapter les pratiques mises en œuvre. Cet article présente les trois principaux protocoles d’évaluation disponibles. Le premier (SEBWAT) est adapté aux animaux des pays à revenu faible ou intermédiaire, dont le niveau global de bien-être est plutôt faible. Il ne comporte que des indicateurs observés sur les animaux, dont peu d’indicateurs d’état mental et ne peut être réalisé que par des évaluateurs formés et entraînés. Les deux autres (AWIN Horse et Cheval Bien-être) sont plus adaptés aux chevaux des pays à revenu élevé et sont destinés à tous les détenteurs. Ils comportent des indicateurs observés sur les animaux et dans leur environnement. Le plus récent, le protocole Cheval Bien-être est en français et a intégré de nouveaux indicateurs d’état mental négatif. Ces deux protocoles pourraient être améliorés en adaptant certains des indicateurs et en intégrant des indicateurs d’état mental positif.

Societal concerns for animal welfare extend to all domestic species, including high-level sport horses. The welfare of these horses, notably highlighted during the recent Olympics, has garnered significant public interest, prompting inquiries into their living conditions. Animal welfare studies have emphasised three key needs crucial to equine welfare: unlimited access to forage, freedom of movement, and social interactions with peers, commonly referred to as the “3Fs”—access to Forage, Freedom of movement, and interactions with Friend conspecifics. However, the feasibility and benefits of satisfying these needs specifically for sport horses remain unexplored. Indeed, they may face unique challenges such as high physical workload, extensive travel, limited time in their home stables, weight management, and high economic value necessitating careful handling. Consequently, restrictions on feeding, freedom of movement, and social contact are often deemed necessary. This field study aims to assess the actual level of implementation of welfare in high-level sport horses by evaluating body condition, injury risk, and behavioural welfare indicators in their home stable. To achieve this objective, the welfare of 56 high-level sport horses competing internationally was assessed using behavioural indicators of welfare through scan sampling (abnormal behaviours, i.e., stereotypies, aggression towards humans, withdrawn behaviour, and alert behaviours; positions of the ears in a backward position while foraging, watching behaviours, and through other Animal Welfare Indicators (AWIN) protocol measures). This study shows that there exists a large variability among horses regarding their access to the 3Fs, with some of them having a lot of restrictions and others not, meaning it is possible to respect them while competing at a high level. Second, we observed that the fewer restrictions the horses experience regarding the 3Fs while in their home stables, the better their welfare, as demonstrated by the indicators we assessed. These results undeniably support the fact that unrestricted access to forage, the ability to move freely outdoors, and the opportunity to interact socially with conspecifics are fundamental needs of horses that could be provided to horses, also to high-performance ones. It is therefore essential that solutions are put in place to ensure that these conditions are met.

BackgroundSmartphones and wearables are revolutionizing the assessment of cognitive and motor function in neurological disorders, allowing for objective, frequent, and remote data collection. However, these assessments typically provide a plethora of sensor-derived measures (SDMs), and selecting the most suitable measure for a given context of use is a challenging, often overlooked problem. ObjectiveThis analysis aims to develop and apply an SDM selection framework, including automated data quality checks and the evaluation of statistical properties, to identify robust SDMs that describe the cognitive and motor function of people with multiple sclerosis (MS). MethodsThe proposed framework was applied to data from a cross-sectional study involving 85 people with MS and 68 healthy participants who underwent in-clinic supervised and remote unsupervised smartphone-based assessments. The assessment provided high-quality recordings from cognitive, manual dexterity, and mobility tests, from which 47 SDMs, based on established literature, were extracted using previously developed and publicly available algorithms. These SDMs were first separately and then jointly screened for bias and normality by 2 expert assessors. Selected SDMs were then analyzed to establish their reliability, using an intraclass correlation coefficient and minimal detectable change at 95% CI. The convergence of selected SDMs with in-clinic MS functional measures and patient-reported outcomes was also evaluated. ResultsA total of 16 (34%) of the 47 SDMs passed the selection framework. All selected SDMs demonstrated moderate-to-good reliability in remote settings (intraclass correlation coefficient 0.5-0.85; minimal detectable change at 95% CI 19%-35%). Selected SDMs extracted from the smartphone-based cognitive test demonstrated good-to-excellent correlation (Spearman correlation coefficient, |ρ|>0.75) with the in-clinic Symbol Digit Modalities Test and fair correlation with Expanded Disability Status Scale (EDSS) scores (0.25≤|ρ|0.75) for mobility test SDMs. Overall, correlations were similar when smartphone-based tests were performed in a clinic or remotely. ConclusionsReported results highlight that smartphone-based assessments are suitable tools to remotely obtain high-quality SDMs of cognitive and motor function in people with MS. The presented SDM selection framework promises to increase the interpretability and standardization of smartphone-based SDMs in people with MS, paving the way for their future use in interventional trials.

Abstract Introduction Neurosarcoidosis (NS) is a systemic inflammatory granulomatous disease affecting of patients with sarcoidosis. Its diagnosis is difficult as there is no specific test for it. Because of its rarity, the management of NS has so far only been described in case series and short retrospective cohorts. The objective of this study is description of the clinical, paraclinical presentation and the therapeutic management of central nervous system (CNS) involvement in NS patients in France. Methods This multicenter, retrospective, observational study involved patients hospitalized between 2010 and 2019 with a diagnosis of sarcoidosis and CNS involvement. Results We included 118 patients (38 with isolated NS, 80 with NS associated with systemic sarcoidosis). NS was the initial presentation in 78% of patients, with cranial nerve involvement (36%), medullary symptoms (23%), and seizures (21%). Twenty‐one percent of the patients had already been diagnosed with systemic sarcoidosis. The most frequent biological abnormality was lymphopenia (62.5%), while angiotensin‐converting enzyme was increased in 21%. Meningitis was present in 45% and hyperproteinorachia in 69.5% of cases. MRI mainly revealed white matter abnormalities and leptomeningeal enhancement (34%). Corticosteroids were the most useful treatment, and immunosuppressive agents were used in steroid‐resistant patients and to limit side effects. Methotrexate, cyclophosphamide, and anti‐TNFα were also used, exhibiting good efficacy. Conclusions This cohort contributes to a better understanding of the clinical phenotype and associated imaging and biological abnormalities. Sharing of clinical, biological, and imaging data, as well as the therapeutic responses, of patients with NS helps to better understand and manage this disease that affects a small number of patients per center. A database project could be implemented in the future to enable this.

In France, sickle cell disease newborn screening (SCD NBS) has been targeted to at-risk regions since 1984, but generalization to the whole population will be implemented from November 2024. Although tandem mass spectrometry (MS/MS) is already used for the NBS of several inherited metabolic diseases, its application for SCD NBS has not been widely adopted worldwide. The aim of this study was to evaluate a dedicated MS/MS kit (Targeted MS/MS Hemo, ZenTech, LaCAR Company, Liege, Belgium) for SCD NBS and to compare the results obtained with those from an NBS reference center using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and cation-exchange high-performance liquid chromatography (CE-HPLC, Variant NBS, Biorad Laboratories, Inc., Hercules, CA, USA) as confirmatory method. The MS/MS Hemo kit was used according to the manufacturer’s instructions and performed on a Waters Xevo TQ-D (Waters Corporation, USA). The software provided by the manufacturer was used for the calculation and analysis of peptide signal ratios. Among the 1333 samples, the results of 1324 samples were consistent with the HPLC and/or MALDI-TOF results (1263 FA, 50 FAS, 7 FAC, 1 FAO-Arab, and 3 FS). All the discordant results (one FAS on MS/MS vs. FA in CE-HPLC, one FA on MS/MS vs. FAS in CE-HPLC, seven FS on MS/MS vs. FAS in CE-HPLC) were corrected after modifying the peptide signal ratios thresholds, allowing the MS/MS Hemo kit to achieve near-100% sensitivity and specificity for SCD NBS. In conclusion, the MS/MS Hemo kit appears to be an effective method for SCD NBS, particularly for laboratories already equipped with MS/MS technology. However, these results should be confirmed in a larger cohort including a greater number of positive samples for SCD.

Objective Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs).Methods Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis.Results Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5–10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3–6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown.Conclusion EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.

In stabled horses, several behaviours are considered to be important indicators of the state of welfare at the individual level: stereotypies, aggressive behaviours towards humans and the “withdrawn”, alert, sternal, lateral and observation postures. Until now, these behaviours have been extensively studied in relation to different horse management practices. However, little is known about their changes or consistency over time. This study aimed to investigate differences in the expression of these behaviours assessed on 44 stabled horses during an initial 3-month period and then again on the same individuals 2 years later. Out of the six behaviours studied, two showed significant differences between the 2 years with medium effect sizes: the levels of aggressiveness towards humans increased (Wilcoxon signed-rank test: V = 65, P = 0.005) and those of recumbent rest during the day decreased (V = 416, P

ObjectiveAs phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta-analysis compares the efficacy of first-line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still widely used.MethodsStudies identified by the systematic review of Huang et al. (2019) were selected if they considered at least two first-line immunosuppressants among RTX, MMF, and AZA. We updated this review. The Medline, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials databases were queried between November 2018 and April 2020. To be included, the hazard ratio (HR) [95% CI] for the time to first relapse after first-line immunosuppression had to be available, calculable, or provided by the authors.ResultsWe gathered data from 919 NMO patients (232 RTX-, 294 MMF-, and 393 AZA-treated patients). The risk of first relapse after first-line immunosuppression was 1.55 [1.04, 2.31] (p = 0.03) for MMF compared with RTX, 1.42 [0.87, 2.30] (p = 0.16) for AZA compared with RTX, and 0.94 [0.58, 1.54] (p = 0.08) for MMF compared with AZA.InterpretationThe findings suggest that RTX is more efficient than MMF as a first-line therapy. Even if the results of our meta-analysis cannot conclude that RTX has a better efficacy in delaying the first relapse than AZA, the observed effect difference between both treatments combined with the results of previous studies using as outcome the annualized relapse rate may be in favor of RTX.

The improvement of horse welfare through housing conditions has become a real issue in recent years and have highlighted the detrimental effect of individual housing of horses on their health and behaviour. In this new study, we analysed the blood transcriptome of 45 sport horses housed individually that were previously examined for their behaviour and gut microbiota. We performed differential and regression analyses of gene expression, followed by downstream bioinformatic analyses, to unveil the molecular pathways related to the behavioural changes associated with welfare impairment in these sport horses. We found that aggressiveness towards humans was the behavioural indicator the most correlated to blood gene expression and that the pathways involved belonged mainly to systemic inflammation. In contrast, the correlations between genes, alert postures and unresponsiveness towards the environment were weak. When blood gene expression profiling was combined with faecal microbiota of a sub-population of horses, stereotypies came out as the most correlated to blood gene expression. This study shows that aggressiveness towards humans and stereotypies are behavioural indicators that covary with physiological alterations. Further studies are needed regarding the biological correlates of unresponsiveness to the environment and alert postures.

Background: Medical students face a demanding workload, stressful situations, and irregular sleep patterns, which can lead to elevated sleep disturbances and high fatigue levels. These difficulties may be further associated with a major decline in well-being, quality of life, performance, and health. Thus, these struggles must be addressed to reduce these students' sleep disturbances and fatigue during their curriculum. Methods: The PROMESS-Sleep clinical trial aims to support future healthcare professionals by enhancing their abilities to manage their sleep. The support will be provided through a three-session sleep management program. Each session will include an individual meeting between a PROMESS-Sleep expert and a medical student, during which self-care education, advice, and personalized goals will be established. The present protocol is designed to assess the influence of this program on 45 undergraduate medical students (fourth- and fifth-year) of the Lyon-Est Faculty of Medicine (Claude Bernard University Lyon 1, France). Assessments of sleep and fatigue will be conducted before and during the intervention using self-reported questionnaires and actigraphy. At the end of the third session, the student's satisfaction levels regarding the program will be assessed. The primary outcome will be changes in scores on the Pittsburgh Sleep Quality Index (PSQI) during the program. Secondary outcomes will provide a detailed characterization of changes in various aspects of sleep disturbances, fatigue, sleep habits, and sleep-wake rhythms. Exploratory outcomes will provide information regarding the students' satisfaction levels and will determine the moderators of the program's efficacy. Data will be analyzed according to the intention-to-treat principle and presented in accordance with the CONSORT Guidelines. Ethical approval has been obtained by the Institutional Review Board (IRB: 2023-07-04-03), and all procedures will be performed in adherence to the Helsinki Declaration. The results from this study will be presented at scientific conferences and in peer-reviewed scientific journals. Discussion: The results will provide valuable insights into the program's efficacy in reducing sleep disturbances and fatigue. If its efficacy is proven, PROMESS-Sleep could become an integral and sustainable part of medical education due to fostering a healthier and more resilient future for healthcare professionals. This manuscript follows the SPIRIT guidelines (Additional files 1 & 8). Trial registration: ClinicalTrials.gov: NCT06297330; retrospectively registered. [ABSTRACT FROM AUTHOR]

Introduction: Myeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes. Methods: Combination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing. Results: Myeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis. Notably, this patients' subgroup exhibited a more aggressive disease phenotype two years post-diagnosis. This monocytic population, detected in both the CSF and blood, was characterized by CD206, CD209, CCR5 and CCR2 expression, and was found to be more frequent in MS patients carrying the HLA-DRB1*15:01 allele. Furthermore, pathways analysis predicted that these cells had antigen presentation capabilities coupled with pro-inflammatory phenotype. Discussion: Altogether, these results point toward the amplification of a specific and pathogenic myeloid cell subset in MS patients with genetic susceptibilities. Multiple sclerosis patients were included at diagnosis, for mass cytometry or single-cell RNA sequencing studies (scRNA-seq). Differential abundance analysis on cytof data indicated the exclusive blood enrichment in circulating myeloid cells co-expressing CD14, CCR5, CD206, and CD209 in a group of MS patients. Characterization of these patients demonstrated a significantly higher proportion of HLA-DRB1*15-01 patients allotype and a worsen outcome after 2 years follow up compared to other patients. scRNA-seq analysis confirmed the pathogenic potential of this monocyte subset through their definition as antigen presenting pro-inflammatory cells. [ABSTRACT FROM AUTHOR]

Background: Studies have reported an association between socioeconomic status and disability progression in multiple sclerosis (MS), but findings using the pre-MS individual socioeconomic status are missing. Objective: The objective was to investigate the association between education level and disability progression. Methods: All Observatoire Français de la Sclérose en Plaques (OFSEP) patients with MS clinical onset over 1960–2014, and aged ⩾25 years at MS onset were included. Education level was classified into four categories from low (primary/secondary school) to very high (master/doctoral degree). Time from MS onset to EDSS 4.0 was studied using flexible parametric survival models adjusted for age, period, and center, and stratified by phenotype (relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS)) and sex. Results: A total of 11,586 patients were included (women/men ratio = 2.5; age = 36.7 ± 8.6 years; follow-up duration 16.7 ± 9.3 years; 86.4% RMS). For women with RMS, the risk of reaching the outcome at 5 years was inversely associated with the education level (Hazard Ratio medium: 0.74 (0.63–0.87), high: 0.51 (0.43–0.62), very high: 0.39 (0.30–0.50) vs low). Results were similar for men. In PPMS, the risk was significantly different between the extreme groups (very high vs low) for women (0.45 (0.28–0.75)) and men (0.54 (0.32–0.91)), but no gradient was evident. Conclusion: Our study showed a strong association between education level and disability progression, regardless of sex and phenotype. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that differences in access to disease-modifying treatments (DMTs) could explain the association between socioeconomic status and disability progression in multiple sclerosis (MS). Objective: This study aimed to analyze the association between education level and DMT use in France. Methods: All patients from OFSEP network with MS onset over 1996–2014 and aged ⩾ 25 years at onset were included. Three time-to-event outcomes were investigated using flexible parametric survival regression models: time from MS onset to first DMT (any) and to platform therapy, and time from platform therapy to switch to high-efficacy therapy. Results: Overall, 7563 patients were included (mean follow-up 12.6 ± 5.9 years). The percentages of patients aged less than 40 years at MS onset and who initiated treatment before the age of 40 years were significantly higher in the groups with a higher education level. The time-to-event outcomes showed no major difference in DMT practices according to education level, except for women who had a significantly shorter time to DMT initiation in medium to very high education level groups versus low, at 5 years from MS clinical onset. Conclusion: Our results suggest that the association between education level and MS disability progression does not solely reflect different therapeutic practices, particularly in men. [ABSTRACT FROM AUTHOR]

Abstract Background Natalizumab and fingolimod are used as high-efficacy treatments in relapsing–remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. Methods Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. Results Overall, 5,148 relapsing–remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. Conclusions This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Abstract Objective As phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta‐analysis compares the efficacy of first‐line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still widely used. Methods Studies identified by the systematic review of Huang et al. (2019) were selected if they considered at least two first‐line immunosuppressants among RTX, MMF, and AZA. We updated this review. The Medline, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials databases were queried between November 2018 and April 2020. To be included, the hazard ratio (HR) [95% CI] for the time to first relapse after first‐line immunosuppression had to be available, calculable, or provided by the authors. Results We gathered data from 919 NMO patients (232 RTX‐, 294 MMF‐, and 393 AZA‐treated patients). The risk of first relapse after first‐line immunosuppression was 1.55 [1.04, 2.31] (p = 0.03) for MMF compared with RTX, 1.42 [0.87, 2.30] (p = 0.16) for AZA compared with RTX, and 0.94 [0.58, 1.54] (p = 0.08) for MMF compared with AZA. Interpretation The findings suggest that RTX is more efficient than MMF as a first‐line therapy. Even if the results of our meta‐analysis cannot conclude that RTX has a better efficacy in delaying the first relapse than AZA, the observed effect difference between both treatments combined with the results of previous studies using as outcome the annualized relapse rate may be in favor of RTX.