Adherence to subcutaneous interferon beta-1a treatment using an electronic injection device:a prospective open-label Scandinavian noninterventional study (the ScanSmart study)

Background: Disease modifying drugs help control the course of relapsing remitting multiple sclerosis (RRMS); however, good adherence is needed for long-term outcomes. Objective: To evaluate patient adherence to treatment with subcutaneous interferon beta-1a using RebiSmart® and assess injection-site reactions and treatment satisfaction. Methods: This prospective, single-arm, open-label, noninterventional multicenter Phase IV trial included disease modifying drug-experienced mobile patients with RRMS. Adherence was measured over 12 weeks. Items 13–23, 35, 37, and 38 of the Multiple Sclerosis Treatment Concerns Questionnaire (injection-site reactions and treatment satisfaction) were recorded at 12 weeks. Results: Sixty patients were recruited (mean age 43.7 [±SD 7.9] years; 83% female; mean years since multiple sclerosis diagnosis 6.7 [SD 4.5]). Adherence data were obtained in 54 patients only due to technical problems with six devices. Over 12 weeks, 89% (n=48) of patients had ≥90% adherence to treatment. Most patients experienced mild influenza-like symptoms and injection-site reactions, and global side effects were minimal. Most patients (78%) rated the convenience as the most important aspect of the device, and most experienced no or mild pain. Conclusion: RRMS patients treated with subcutaneous interferon beta-1a, administered with RebiSmart, demonstrated generally good adherence, and the treatment was generally well tolerated

SVM recursive feature elimination analyses of structural brain MRI predicts near-term relapses in patients with clinically isolated syndromes suggestive of multiple sclerosis

Esclerosi múltiple; Classificació d'aprenentatge automàtic; Selecció de funcionsEsclerosis múltiple; Clasificación de aprendizaje automático; Selección de característicasMultiple sclerosis; Machine learning classification; Feature selectionMachine learning classification is an attractive approach to automatically differentiate patients from healthy subjects, and to predict future disease outcomes. A clinically isolated syndrome (CIS) is often the first presentation of multiple sclerosis (MS), but it is difficult at onset to predict who will have a second relapse and hence convert to clinically definite MS. In this study, we thus aimed to distinguish CIS converters from non-converters at onset of a CIS, using recursive feature elimination and weight averaging with support vector machines. We also sought to assess the influence of cohort size and cross-validation methods on the accuracy estimate of the classification. We retrospectively collected 400 patients with CIS from six European MAGNIMS MS centres. Patients underwent brain MRI at onset of a CIS according to local standard-of-care protocols. The diagnosis of clinically definite MS at one-year follow-up was the standard against which the accuracy of the model was tested. For each patient, we derived MRI-based features, such as grey matter probability, white matter lesion load, cortical thickness, and volume of specific cortical and white matter regions. Features with little contribution to the classification model were removed iteratively through an interleaved sample bootstrapping and feature averaging approach. Classification of CIS outcome at one-year follow-up was performed with 2-fold, 5-fold, 10-fold and leave-one-out cross-validation for each centre cohort independently and in all patients together. The estimated classification accuracy across centres ranged from 64.9% to 88.1% using 2-fold cross-validation and from 73% to 92.9% using leave-one-out cross-validation. The classification accuracy estimate was higher in single-centre, smaller data sets than in combinations of data sets, being the lowest when all patients were merged together. Regional MRI features such as WM lesions, grey matter probability in the thalamus and the precuneus or cortical thickness in the cuneus and inferior temporal gyrus predicted the occurrence of a second relapse in patients at onset of a CIS using support vector machines. The increased accuracy estimate of the classification achieved with smaller and single-centre samples may indicate a model bias (overfitting) when data points were limited, but also more homogeneous. We provide an overview of classifier performance from a range of cross-validation schemes to give insight into the variability across schemes. The proposed recursive feature elimination approach with weight averaging can be used both in single- and multi-centre data sets in order to bridge the gap between group-level comparisons and making predictions for individual patients.This project received funding from the European Union's Horizon2020 Research and Innovation Program EuroPOND under grant agreement number 666992, and it was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. We thank all participating partners of the MAGNIMS study group for sharing their data with us

Тактика ведения пациентов при синдроме Мэллори-Вейсса

МЭЛЛОРИ-ВЕЙСА СИНДРОМ /диагн /терПИЩЕВОДА ПЕРФОРАЦИЯ /диагн /терЖЕЛУДОЧНО-КИШЕЧНОЕ КРОВОТЕЧЕНИЕГЕМОСТАЗ ЭНДОСКОПИЧЕСКИ

The Etiology of Multiple Sclerosis: Genetic Evidence for the Involvement of the Human Endogenous Retrovirus HERV-Fc1

We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Clinical Perspectives on Using Remote Measurement Technology in Assessing Epilepsy, Multiple Sclerosis, and Depression: Delphi Study

Background: Multiple sclerosis (MS), epilepsy, and depression are chronic central nervous system conditions in which remote measurement technology (RMT) may offer benefits compared with usual assessment. We previously worked with clinicians, patients, and researchers to develop 13 use cases for RMT: 5 in epilepsy (seizure alert, seizure counting, risk scoring, triage support, and trend analysis), 3 in MS (detecting silent progression, detecting depression in MS, and donating data to a biobank), and 5 in depression (detecting trends, reviewing treatment, self-management, comorbid monitoring, and carer alert). Objective: In this study, we aimed to evaluate the use cases and related implementation issues with an expert panel of clinicians external to our project consortium. Methods: We used a Delphi exercise to validate the use cases and suggest a prioritization among them and to ascertain the importance of a variety of implementation issues related to RMT. The expert panel included clinicians from across Europe who were external to the project consortium. The study had 2 survey rounds (n=23 and n=17) and a follow-up interview round (n=9). Data were analyzed for consensus between participants and for stability between survey rounds. The interviews explored the reasons for answers given in the survey. Results: The findings showed high stability between rounds on questions related to specific use cases but lower stability on questions relating to wider issues around the implementation of RMT. Overall, questions on wider issues also had less consensus. All 5 use cases for epilepsy (seizure alert, seizure counting, risk scoring, triage support, and trend analysis) were considered beneficial, with consensus among participants above the a priori threshold for most questions, although use case 3 (risk scoring) was considered less likely to facilitate or catalyze care. There was very little consensus on the benefits of the use cases in MS, although this may have resulted from a higher dropout rate of MS clinicians (50%). Participants agreed that there would be benefits for all 5 of the depression use cases, although fewer questions on use case 4 (triage support) reached consensus agreement than for depression use cases 1 (detecting trends), 2 (reviewing treatment), 3 (self-management), and 5 (carer alert). The qualitative analysis revealed further insights into each use case and generated 8 themes on practical issues related to implementation. Conclusions: Overall, these findings inform the prioritization of use cases for RMT that could be developed in future work, which may include clinical trials, cost-effectiveness studies, and the commercial development of RMT products and services. Priorities for further development include the use of RMT to provide more accurate records of symptoms and treatment response than is currently possible and to provide data that could help inform patient triage and generate timely alerts for patients and carers

The socioeconomic consequences of optic neuritis with and without multiple sclerosis: a controlled national study

Optic neuritis (ON) often precedes multiple sclerosis (MS). MS is associated with a significant socioeconomic burden. However, the burden of ON with and without MS before and after its diagnosis has never been calculated