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1.
JMIR Med Inform ; 10(11): e37945, 2022 Nov 10.
Article in English | MEDLINE | ID: covidwho-2198071

ABSTRACT

BACKGROUND: The increasing availability of "real-world" data in the form of written text holds promise for deepening our understanding of societal and health-related challenges. Textual data constitute a rich source of information, allowing the capture of lived experiences through a broad range of different sources of information (eg, content and emotional tone). Interviews are the "gold standard" for gaining qualitative insights into individual experiences and perspectives. However, conducting interviews on a large scale is not always feasible, and standardized quantitative assessment suitable for large-scale application may miss important information. Surveys that include open-text assessments can combine the advantages of both methods and are well suited for the application of natural language processing (NLP) methods. While innovations in NLP have made large-scale text analysis more accessible, the analysis of real-world textual data is still complex and requires several consecutive steps. OBJECTIVE: We developed and subsequently examined the utility and scientific value of an NLP pipeline for extracting real-world experiences from textual data to provide guidance for applied researchers. METHODS: We applied the NLP pipeline to large-scale textual data collected by the Swiss Multiple Sclerosis (MS) registry. Such textual data constitute an ideal use case for the study of real-world text data. Specifically, we examined 639 text reports on the experienced impact of the first COVID-19 lockdown from the perspectives of persons with MS. The pipeline has been implemented in Python and complemented by analyses of the "Linguistic Inquiry and Word Count" software. It consists of the following 5 interconnected analysis steps: (1) text preprocessing; (2) sentiment analysis; (3) descriptive text analysis; (4) unsupervised learning-topic modeling; and (5) results interpretation and validation. RESULTS: A topic modeling analysis identified the following 4 distinct groups based on the topics participants were mainly concerned with: "contacts/communication;" "social environment;" "work;" and "errands/daily routines." Notably, the sentiment analysis revealed that the "contacts/communication" group was characterized by a pronounced negative emotional tone underlying the text reports. This observed heterogeneity in emotional tonality underlying the reported experiences of the first COVID-19-related lockdown is likely to reflect differences in emotional burden, individual circumstances, and ways of coping with the pandemic, which is in line with previous research on this matter. CONCLUSIONS: This study illustrates the timely and efficient applicability of an NLP pipeline and thereby serves as a precedent for applied researchers. Our study thereby contributes to both the dissemination of NLP techniques in applied health sciences and the identification of previously unknown experiences and burdens of persons with MS during the pandemic, which may be relevant for future treatment.

2.
Mult Scler Relat Disord ; 68: 104109, 2022 Aug 13.
Article in English | MEDLINE | ID: covidwho-2181740

ABSTRACT

BACKGROUND: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has been approved in Europe for the treatment of adult patients with active relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), on the basis of previous phase III studies. However, limited data were available on ocrelizumab efficacy in RMS according to the Lublin definition of activity (clinical and/or imaging features) used in the current drug label. The PRO-MSACTIVE study was thus designed to provide additional data on ocrelizumab efficacy according to this definition, and also on safety and patient reported outcomes (PROs). METHODS: PRO-MSACTIVE is a national, multicenter, open-label, single-arm phase IV French study, conducted in patients with active RMS (relapsing-remitting multiple sclerosis, RRMS, or secondary progressive multiple sclerosis, SPMS). The primary endpoint, which was assessed at week (W) 48, was defined as the proportion of patients free of disease activity (defined by no relapses and no T1 gadolinium-enhancing nor new and/or enlarging T2 lesions using brain MRI). Disease activity, disability and PROs using 6 questionnaires for disease severity, quality of life, impact on work productivity, and treatment satisfaction were described at W24 and W48. Adverse events were described until W72. RESULTS: Among the 422 analyzed patients (RRMS: 376, SPMS: 46), 63.3% (95% CI [58.5%; 67.9%]) were free of disease activity at W48 (RRMS: 62.2% [57.1%; 67.2%], SPMS: 71.7% [56.5%; 84.0%]). A total of 358 patients (84.8%; RRMS: 84.6%, SPMS: 87.0%) were relapse-free up to W48, and the overall adjusted annualized relapse rate was 0.14 (RRMS: 0.15, SPMS: 0.09). Overall, 67.8% of patients (RRMS: 66.8%, SPMS: 76.1%) had no evidence of MRI activity (no T1 gadolinium-enhancing lesions [83.4%] and no new/enlarging T2 lesions [75.1%]); 58.5% of patients (RRMS: 57.7%, SPMS: 65.2%) achieved No Evidence of Disease Activity (NEDA: no relapses, no confirmed disability progression, and no MRI activity) at W48. All PRO scores were stable between the first dose of ocrelizumab and W48 and better outcomes were seen for patients having an EDSS score ≥4. Overall, 89.3% of patients reported adverse events, 62.3% adverse events assessed as related to ocrelizumab, and 8.5% serious adverse events. No serious infusion-related reactions, opportunistic infections, progressive multifocal leukoencephalopathy, nor deaths were reported. No new safety signal was identified. CONCLUSION: These data confirm the efficacy of ocrelizumab in a pragmatic setting and its favorable benefit-risk profile in patients with RMS. (ClinicalTrials.gov identifier: NCT03589105; EudraCT identifier: 2018-000780-91).

3.
Mult Scler Relat Disord ; 63: 103921, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2181738

ABSTRACT

BACKGROUND: Infections in people with multiple sclerosis (PwMS) may have a detrimental effect on disease progression, risk of hospitalization, and healthcare resource utilization (HRU). The infection risk and HRU costs may vary between disease-modifying therapies (DMTs); however, the individual risks and differences associated with DMTs are not well characterized. Some DMTs may increase the risk for infections in PwMS; however, previous studies have reported an intact humoral immune response in dimethyl fumarate (DMF)-treated patients. The objective was to compare infection-related HRU and healthcare costs (HCCs) between PwMS treated with DMF or ocrelizumab (OCR). METHODS: Eligible patients were identified from the Optum US claims database between April 2017 and September 2020 (DMF n = 1429; OCR n = 3170). Patients were followed from index date to first occurrence of: (1) end of study, (2) end of insurance eligibility, (3) discontinuation of index DMT, or (4) switch from index DMT to another DMT. Outcomes were annualized rate of infection encounters (defined as infection encounters [n] during follow-up window / days followed [n] × 365); annualized infection-related HCCs (defined as aggregated costs of infection encounters during follow-up window / days followed [n] × 365); location-specific infections, and overall infection-related events. Propensity score matching (PSM) 1:1 method was used; PS was calculated via logistic regression for probability of DMF treatment conditional on demographics and comorbidities. Mean differences (MD) were reported for infection encounter measures. RESULTS: After PSM, DMF and OCR cohorts (n = 1094 in each cohort) were balanced based on baseline characteristics (standardized MD of adjusted baseline characteristics <0.1). Mean (standard deviation) follow-up was 296 (244) days for DMF patients and 297 (243) for OCR patients. DMF patients experienced lower annualized rates of overall infection encounters vs OCR patients (MD -0.51 [95% confidence interval (CI): -0.92 to -0.11], p = 0.01). When stratified by type of infection encounter, DMF patients experienced significantly lower annualized rates of outpatient (MD [95% CI]: -0.44 [-0.80 to -0.08], p = 0.02) and inpatient/hospitalization infection encounters (-0.08 [-0.14 to -0.02], p<0.01) vs OCR patients. A trend towards a shorter duration of infection-related hospitalization in the DMF vs the OCR group was observed (MD [95% CI]: -2.20 [-4.73 to 0.26] days, p = 0.08). The most common infection types in both DMT groups were urinary tract infections, sepsis, and pneumonia. DMF patients experienced lower annualized infection-related HCCs (MD [95% CI]: -$3642 [-$6380 to -$904], p < 0.01) vs OCR patients, which were driven largely by infection-related hospitalization costs (-$3639 [-$6019 to -$1259], p < 0.01). CONCLUSION: DMF-treated patients PS-matched with OCR patients experienced lower annualized rates of infection encounters and lower infection-related HCCs.


Subject(s)
Dimethyl Fumarate , Multiple Sclerosis , Antibodies, Monoclonal, Humanized/adverse effects , Dimethyl Fumarate/therapeutic use , Health Care Costs , Humans , Multiple Sclerosis/chemically induced , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Retrospective Studies
4.
Healthcare ; 11(1):84, 2023.
Article in English | ProQuest Central | ID: covidwho-2199991

ABSTRACT

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that leads to a great deterioration in the quality of life. Objective: We aimed to assess the effectiveness of two individual programs, one based on transcranial direct current stimulation (tDCS) and another based on the effect of physical exercise on fatigue and quality of life in patients with MS. Methods: A total of 12 patients with relapsing–remitting and progressive secondary MS participated. Fatigue and quality of life were assessed before and after intervention. The exercise program and tDCS were carried out over a 4-week period, with a washout period of 5 months. Results: The results show significant improvements in the different quality of life subscales after the application of tDCS, activities of daily living (r = 0.625;p = 0.037) (g = 0.465), psychological well-being (r = 0.856;p = 0.004) (g = 0.727) and coping (r = 0.904;p = 0.18) (g = 0.376), and in those after the application of exercise, activities of daily living (r = 0.853;p = 0.003) (g = 0.570) and psychological well-being (r = 0.693;p = 0.041) (g = 0.417). After the application of both therapies, more than 50% of the subjects did not have a positive fatigue score on the MFIS scale. Conclusion: The major findings suggest that the application of both therapies produces a beneficial effect with significant improvements in the quality of life of this sample.

5.
Frontiers in Public Health ; 10, 2022.
Article in English | Web of Science | ID: covidwho-2199514

ABSTRACT

BackgroundFalls and resulting injury are a significant concern for individuals living with multiple sclerosis (MS) that use a wheelchair and/or scooter to support mobility. Effective fall prevention efforts are vital to support the health, wellbeing, and participation for these individuals. AimsThis study reports the findings from the process evaluation conducted in association with a pilot study evaluating the efficacy of Individualized Reduction of FaLLs-Online (iROLL-O), an online, group fall prevention, and management program specifically designed for community-based people living with multiple sclerosis (pwMS) who are full-time wheelchair or scooter users. MethodsA mixed-methods process evaluation was conducted, with specific attention to the impact of online delivery on intervention implementation, participant satisfaction, and mechanisms of change (MOC). Multiple data sources were utilized, including post-session and post-intervention participant and trainer feedback forms and participant qualitative interview data. Descriptive analysis was conducted using Microsoft Excel. Close-ended questions were analyzed by examining five-point Likert scale responses. Qualitative interview data was explored using thematic analysis. ResultsTwelve participants and three trainers (one occupational therapist and two physical therapists) contributed to the study. Online delivery did not compromise session fidelity, which averaged 95%. No significant adaptations to the intervention were made during delivery. Participant satisfaction was high at 4.6/5.0. Post-course Trainer Feedback Forms indicate trainer satisfaction with the group dynamic, ability to address unique group needs, and program content. Reach improved with online delivery as transportation barriers were removed and recruitment from a broader geographic area was enabled. Three themes reflecting key MOC emerged from the analysis: group context, motivation for participant engagement, and the multifaceted nature of the program. The COVID-19 pandemic was identified as a contextual factor impacting community participation. Both participants and trainers identified the group dynamic as a strength. The trainers valued the program's flexibility in allowing them to address individual and/or group-specific fall prevention needs. ConclusionFeedback from key stakeholders was essential to a meaningful process evaluation. Online delivery supported program implementation, including reach, and resulted in high levels of satisfaction among participants and trainers. Future iterations should aim to uphold the positive group context, recruit, and train skilled interventionists who are licensed as occupational or physical therapists and continue to provide the program's diverse approach to fall prevention and management.

6.
Drugs of Today ; 58(12):605-620, 2022.
Article in English | Web of Science | ID: covidwho-2196790

ABSTRACT

The SARS-COV-2 pandemic has been a global pub -lic health problem since 2019, with over 400 million reported cases, 6 million deaths, and significant economic and social damage. Overlapping SARS-CoV-2 infection in patients with chronic diseases, such as multiple sclerosis (MS), causes manage-ment problems, especially in patients treated with disease-modifying therapies. Studies investigating COVID-19 vaccination effectiveness have shown vari-ability in postvaccination immune response that depends on the patient's background treatment, and special attention is required for anti-CD20 therapies.Existing data on the efficacy of COVID-19 vaccination in patients with MS undergoing disease-modifying treatment are summarized and critically evaluated in this article.

7.
Neurology ; 10(2), 2023.
Article in English | EMBASE | ID: covidwho-2196712

ABSTRACT

BACKGROUND AND OBJECTIVES: Prospective, deeply phenotyped research cohorts monitoring individuals with chronic neurologic conditions, such as multiple sclerosis (MS), depend on continued participant engagement. The COVID-19 pandemic restricted in-clinic research activities, threatening this longitudinal engagement, but also forced adoption of televideo-enabled care. This offered a natural experiment in which to analyze key dimensions of remote research: (1) comparison of remote vs in-clinic visit costs from multiple perspectives and (2) comparison of the remote with in-clinic measures in cross-sectional and longitudinal disability evaluations. METHOD(S): Between March 2020 and December 2021, 207 MS cohort participants underwent hybrid in-clinic and virtual research visits;96 contributed 100 "matched visits," that is, in-clinic (Neurostatus-Expanded Disability Status Scale [NS-EDSS]) and remote (televideo-enabled EDSS [tele-EDSS];electronic patient-reported EDSS [ePR-EDSS]) evaluations. Clinical, demographic, and socioeconomic characteristics of participants were collected. RESULT(S): The costs of remote visits were lower than in-clinic visits for research investigators (facilities, personnel, parking, participant compensation) but also for participants (travel, caregiver time) and carbon footprint (p < 0.05 for each). Median cohort EDSS was similar between the 3 modalities (NS-EDSS: 2, tele-EDSS: 1.5, ePR-EDSS: 2, range 0.6.5);the remote evaluations were each noninferior to the NS-EDSS within +/-0.5 EDSS point (TOST for noninferiority, p < 0.01 for each). Furthermore, year to year, the % of participants with worsening/stable/improved EDSS scores was similar, whether each annual evaluation used NS-EDSS or whether it switched from NS-EDSS to tele-EDSS. DISCUSSION: Altogether, the current findings suggest that remote evaluations can reduce the costs of research participation for patients, while providing a reasonable evaluation of disability trajectory longitudinally. This could inform the design of remote research that is more inclusive of diverse participants. Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

8.
Bmc Neurology ; 22(1), 2022.
Article in English | Web of Science | ID: covidwho-2196098

ABSTRACT

Background and aimHealth-promoting lifestyle behaviors (HPLBs) have a significant impact on disease management among people with multiple sclerosis (MS). However, the coronavirus disease 2019 (COVID-19) pandemic has significantly affected lifestyle of all individuals, particularly patients with chronic diseases. The present study aimed to explore the barriers and facilitators to HPLBs among people with MS during the COVID-19 pandemic. MethodsThis qualitative study was conducted in Iran. Participants were sixteen people with MS purposively selected from the central MS clinic of a referral specialty neuroscience hospital in Tehran, Iran. Data were collected via in-depth semi-structured face-to-face interviews and concurrently analyzed through conventional content analysis. Findings: The mean of participants' age was 37.93 years and most participants were female (81.25%). The major barriers to HPLBs were lack of knowledge, limited access to resources, and poor health status, while the major facilitators were attention to inner abilities and social support. ConclusionMany different factors such as lack of knowledge, limited access to resources, poor health status, awareness, and social support can influence engagement in HPLBs among people with MS. Healthcare authorities and policymakers need to use quality educational and supportive interventions to improve knowledge, health literacy, perceived support, self-efficacy, and self-care ability among people with MS during the COVID-19 pandemic.

9.
Advances in Gerontology ; 12(4):386-395, 2022.
Article in English | Web of Science | ID: covidwho-2193602

ABSTRACT

The role of neuronal inflammation developing during the formation of amyloid plaques and Lewy bodies is investigated. The influence of various exogenous and endogenous factors on the development of neuroinflammation is established, but the role of various infectious agents in the development of this process is much less studied. Today, the existence of a universal trigger mechanism of the neurodegenerative process is obvious: a specific pathogen of a bacterial or viral nature (including long-term persistent in nervous tissue in a latent state), reactivating, penetrates into certain cerebral structures, where it is influenced by either A beta or resident macrophages of the central nervous system, which, in turn, are activated and induce the release of proinflammatory cytokines, leading to the development of neuronal inflammation, autophagy and neurodegeneration. The reactivation of latent infection, such as herpes, in APOE4 carriers significantly increases the risk of development of Alzheimer's disease. Class-II genes of the HLA locus (HLA II) may be related to the progression of neurodegenerative diseases. An increase in iron levels in the glia is induced by inflammation, which leads to neurodegeneration. Disruption of the homeostasis of redox-active metals, iron and copper, is an integral part of the pathogenesis of Alzheimer's disease and Parkinson's disease. The developing neuroinflammation leads to intensification of the processes of peroxidation, oxidation of metals and the development of ferroptosis.

10.
Hematology (United Kingdom) ; 28(1), 2023.
Article in English | Scopus | ID: covidwho-2187569

ABSTRACT

The severe adult respiratory syndrome virus type 2 (SARS-CoV-2) related acute respiratory distress syndrome (ARDS) has a strong immunological and inflammatory component;accordingly investigators are employing monoclonal antibodies to ameliorate the virus-induced cytokine storm such as antibodies against interleukin 6 (IL-6), tumor necrosis factors alpha (TNF-alpha) and CC chemokine receptor 5 (CCR5) (1). Cyclophosphamide (Cy) has proven its role in various settings including autoimmune diseases, and in the post-haploidentical stem cell transplant setting;Cy depletes cytotoxic and effector T cell populations while relatively sparing the regulatory T cells (Tregs) and could tip the balance away from the overtly pro-inflammatory setting (1). We present here the cases of three persons who were infected by the SARS-CoV-2 virus during the Cy-induced pancytopenia of an autologous hematopoietic stem cell transplantation (HSCT), aimed to down-regulate the immune response in multiple sclerosis (MS) (2). The surprisingly benign course of the COVID-19 in the three cases suggest that the Cy could have had a role in abrogating the inflammatory response in these persons. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

11.
Clinical Science ; 136(24):1809-1829, 2022.
Article in English | Web of Science | ID: covidwho-2186168

ABSTRACT

Inflammatory disease is often associated with an increased incidence of venous throm-boembolism in affected patients, although in most instances, the mechanistic basis for this increased thrombogenicity remains poorly understood. Acute infection, as exemplified by sepsis, malaria and most recently, COVID-19, drives 'immunothrombosis', where the im-mune defence response to capture and neutralise invading pathogens causes concurrent activation of deleterious prothrombotic cellular and biological responses. Moreover, dysreg-ulated innate and adaptive immune responses in patients with chronic inflammatory con-ditions, such as inflammatory bowel disease, allergies, and neurodegenerative disorders, are now recognised to occur in parallel with activation of coagulation. In this review, we describe the detailed cellular and biochemical mechanisms that cause inflammation-driven haemostatic dysregulation, including aberrant contact pathway activation, increased tis-sue factor activity and release, innate immune cell activation and programmed cell death, and T cell-mediated changes in thrombus resolution. In addition, we consider how lifestyle changes increasingly associated with modern life, such as circadian rhythm disruption, chronic stress and old age, are increasingly implicated in unbalancing haemostasis. Finally, we describe the emergence of potential therapies with broad-ranging immunothrombotic functions, and how drug development in this area is challenged by our nascent understand-ing of the key molecular and cellular parameters that control the shared nodes of proinflam-matory and procoagulant pathways. Despite the increasing recognition and understanding of the prothrombotic nature of inflammatory disease, significant challenges remain in ef-fectively managing affected patients, and new therapeutic approaches to curtail the key pathogenic steps in immune response-driven thrombosis are urgently required.

12.
Neuron ; 2023.
Article in English | ScienceDirect | ID: covidwho-2181845

ABSTRACT

Summary With recent findings connecting the Epstein-Barr virus to an increased risk of multiple sclerosis and growing concerns regarding the neurological impact of the coronavirus pandemic, we examined potential links between viral exposures and neurodegenerative disease risk. Using time series data from FinnGen for discovery and cross-sectional data from the UK Biobank for replication, we identified 45 viral exposures significantly associated with increased risk of neurodegenerative disease and replicated 22 of these associations. The largest effect association was between viral encephalitis exposure and Alzheimer's disease. Influenza with pneumonia was significantly associated with five of the six neurodegenerative diseases studied. We also replicated the Epstein-Barr/multiple sclerosis association. Some of these exposures were associated with an increased risk of neurodegeneration up to 15 years after infection. As vaccines are currently available for some of the associated viruses, vaccination may be a way to reduce some risk of neurodegenerative disease.

13.
Rev Neurol (Paris) ; 2023.
Article in English | PubMed | ID: covidwho-2181838

ABSTRACT

BACKGROUND: The global COVID-19 pandemic began in March 2019, and given the number of casualties and adverse effects on the economy, society, and all aspects of the health system, efforts have been made to develop vaccines from the beginning of the pandemic. Numerous vaccines against COVID-19 infection have been developed in several technologies and have spread rapidly. There have been reported multiple complications of the COVID-19 vaccines as with other vaccines. A number of studies have reported multiple sclerosis (MS ) and neuromyelitis optica spectrum disorder (NMOSD) as complications of COVID-19 vaccines. METHODS: First, we found 954 studies from 4 databases (PubMed, Embase, Scopus, and Web of Science) from inception to March 1(st), 2022. Next, duplicate articles were eliminated, and 476 studies remained. Then 412 studies were removed according to inclusion and exclusion criteria. After obtaining the full text of 64 articles, 12 studies were selected finally. RESULTS: The data were extracted from included studies in a table. Our data includes demographic data, comorbidities, vaccines information and side effects, NMOSD and MS symptoms, laboratory and cerebrospinal fluid (CSF) findings, magnetic resonance imaging (MRI) results, treatment, and outcome of all cases. CONCLUSION: MS and NMOSD are two neuroinflammatory disorders that arise in the CNS. Cases of MS and NMOSD have been reported following COVID-19 vaccination. Nevertheless, more studies with more subjects are needed to assess any possible relationship between the COVID-19 vaccine and central nervous system demyelination.

14.
Multiple Sclerosis and Related Disorders ; : 104512, 2023.
Article in English | ScienceDirect | ID: covidwho-2181745

ABSTRACT

Introduction During the COVID-19 pandemic, electronic health record (EHR) data has been used to investigate disease severity and risk factors for severe COVID-19 in people with multiple sclerosis (pwMS). Methodological challenges including sampling bias, and residual confounding should be considered when conducting EHR-based studies. We aimed to address these limitations related to the use of EHR data in order to identify risk factors, including the use of disease modifying therapies (DMTs), associated with hospitalization for COVID-19 amongst pwMS. Methods We performed a retrospective cohort study including a sample of 47,051 pwMS using a large US-based EHR and claims linked database. Follow-up started at the beginning of the pandemic, February 20th 2020, and continued until September 30th 2020. COVID-19 diagnosis was determined by the presence of ICD-10 diagnostic code for COVID-19, or a positive diagnostic laboratory test, or an ICD-10 diagnostic code for coronaviruses. We used Cox regression modelling to assess the impact of baseline demographics, MS disease history and pre-existing comorbidities on the risk of hospitalization for COVID-19. Then, we identified 5,169 pwMS using ocrelizumab (OCR) and 3,351 pwMS using dimethyl fumarate (DMF) at baseline, and evaluated the distribution of the identified COVID-19 risk factors between the two groups. Finally, we used Cox regression models, adjusted for the identified confounders, to estimate the risk of hospitalization for COVID-19 in pwMS treated with OCR compared to DMF. Results Among the pwMS cohort, we identified 799 COVID-19 cases (1.7%) which resulted in 182 hospitalizations for COVID-19 (0.4%). Population differences between the pwMS and COVID-19 cohorts were observed. Statistical modelling identified older age, male gender, African-American race, walking with assistance, non-ambulatory status, severe relapse requiring hospitalization in year prior to baseline, and specific comorbidities to be associated with a higher risk of COVID-19 related-hospitalization. Comparing the COVID-19 risk factors between OCR users and DMF users, MS characteristics including ambulatory status and MS subtype were highly imbalanced, likely arising from key differences in the labelled indications for these therapies. Compared to DMF use, in unadjusted (HR 1.58, 95% CI 0.73 - 3.44), adjusted (HR 1.28, 95% CI 0.58 - 2.83), propensity score weighted (HR 1.25, 95% CI 0.56 - 2.80), and doubly robust models (HR 1.29, 95% CI 0.57 - 2.89), no significantly increased risk of hospitalization for COVID-19 was associated with OCR use. Conclusion We observed significant population differences when comparing all pwMS to COVID-19 cases, as well as significant differences in key confounders between OCR and DMF treated patients. In unadjusted analyses we did not observe a statistically significant higher risk of COVID-19 hospitalization in pwMS treated with OCR compared to DMF, with further attenuation of risk when adjusting for the key confounders. This study re-emphasises the importance to appropriately consider both sampling and confounding bias in EHR-based MS research.

15.
Neurological Sciences ; 43(Supplement 1):S516-S517, 2022.
Article in English | EMBASE | ID: covidwho-2174387

ABSTRACT

Objectives: SARS-CoV-2 mRNA vaccines are a key factor fighting the COVID-19 pandemic across the globe. However, data are lacking on the efficacy of vaccination in patients with secondary progressive multiple sclerosis (SPMS) on disease-modifying therapies (DMTs) both over time and after a booster vaccination. We are aiming to understand the longitudinal cellular and humoral immune responses to SARS-CoV-2 mRNA vaccines depending on the timing of vaccination and SPMS treatment. Materials: AMA-VACC is an open-label, three-cohort, prospective study in Germany with 41 multiple sclerosis patients currently treated with siponimod, any first-line DMT or without treatment at all in clinical routine. Cohort 1 receives SARS-CoV-2 mRNA vaccination while continuing their current siponimod treatment, cohort 2 interrupts siponimod treatment for the purpose of a full vaccination cycle and cohort 3 receives vaccination during continuous treatment with first-line DMTs (glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine. Method(s): Primary endpoint is the rate of patients achieving seroconversion assessed by detection of serum neutralizing antibodies one week after SARS-CoV-2 mRNA vaccination. Furthermore, development and maintenance of SARS-CoV-2 specific T-cells is evaluated in all patients. Both parameters are analyzed in week one and month one and six after initial vaccination cycle and one month after a potential booster vaccination. Result(s): After a positive first interim analysis showing both SARSCoV- 2 neutralizing antibodies and T-cell responses one week after complete vaccination in siponimod patients data will be available in early 2022 for all patients at week one and later time points including first booster vaccinations. If possible, AMA- VACC results will be compared to findings from other clinical SARS-CoV-2 vaccination studies in patients with MS. Conclusion(s): This analysis will provide first longitudinal data on the immune response after SARS-CoV-2 mRNA vaccination in siponimod treated SPMS patients and enable physicians and patients to make an informed decision on the coordination of SARS-CoV-2 mRNA vaccination and SPMS treatment.

16.
Neurological Sciences ; 43(Supplement 1):S513, 2022.
Article in English | EMBASE | ID: covidwho-2174378

ABSTRACT

Background: The recent global health crisis - due to COVID-19 pandemic - has led to the death of millions, in particular among fragile individuals. Accordingly, people affected by chronic diseases are at increased risk for higher mortality fromCOVID-19. In this complicated context, the introduction of effective vaccines was a crucial moment for the management of SARS-CoV2 infection. However, the immunization campaign has been hampered by some hesitancy, especially by some subgroup of people who questioned the safety of new vaccines. This led to a general sense of distrust. In this literature review, our aim was to investigate the main evidence about the safety and side effects, immunogenicity, efficacy, and willingness of the COVID-19 vaccine in patients with Multiple Sclerosis (pwMS). Method(s): We considered articles published from 2020 to 2022, searching electronically on PubMed and Google Scholar databases. We used a combination of the following keywords/terms: COVID-19, SARSCoV- 2, Multiple Sclerosis, Vaccine, Safety, Efficacy, Acceptability, Willingness, Immunogenicity, Side effects, Disease-modifying therapies, Humoral response, Cellular response. Result(s): Due to massive information campaigns, the acceptability of SARS-CoV-2 vaccines has significantly increased in the last year, although a relevant cluster of pwMS is still doubtful about the safety of vaccination. Available evidence confirms the safety and effectiveness of the COVID-19 vaccination among vulnerable people. Nevertheless, lower-grade immunization has been recorded among MS patients undergoing specific pharmacological treatments, such as anti-CD20 therapies or sphingosine l-phosphate receptor modulators. Discussion(s): A strong recommendation for COVID-19 immunization should be promoted in patients with MS. Regarding people treated with anti-CD20 therapies and sphingosine l-phosphate receptor modulators, a tailored approach should be realized to identify the appropriate timing for vaccine administration. Further studies are needed to understand the role of cellular immunity in COVID-19 vaccination and the possible usefulness of further booster jabs.

17.
Neurological Sciences ; 43(Supplement 1):S506-S507, 2022.
Article in English | EMBASE | ID: covidwho-2174366

ABSTRACT

Aim: Describing safety and timing-proposal in vaccinating patients with multiple sclerosis (pw-MS) to orient a proper vaccinations' schedule. Material(s) and Method(s): Vaccination schedules were costumed according to national recommendations, clinical-/serological data, ongoing disease modifying drugs (DMDs) or therapy-start urgency. Disease-activity within 3 months stated the need of an accelerated cycle. Two different vaccines could be administered together and between the different administrations a 15-days-interval was recommended. Minimum 2 weeks from last inactivatedvaccine- administration to new therapy-start were required, 4-6 if live-attenuated. The essential immunization program's core included 4 vaccines (meningococcal-B, pneumococcal-conjugated, Haemophilus-influenzae-B and meningococcal-ACWY vaccines). Adverse events (AEs) were monitored during the vaccinationcycle;clinical relapses or magnetic resonance imaging (MRI)-activity were monitored at 3-/6-months after cycle-ending. Result(s): One-hundred-ninety-five patients across 2017-2021 were enrolled. One-hundred-twenty-four patients (63.6%) were addressed to vaccination before a therapy-start/-switch and 108 of them (87.1%) effectively started the protocol before DMDs start without any significant deferral. The remaining 71 (36.4%) underwent vaccination during an ongoing-therapy. Regarding AEs during the cycle, 2 (1.0%) patients presented clinical-relapses while 1 (0.5%) MRI-activity. Both patients having clinical-relapse were clinically active within 3-months before immunization. Three and 6 months after the completion of the program, 2 patients (1, 0.5%, and 1, 0.5%, respectively;1.0% globally) presented a relapse and 8 (4, 2.05%, and 4, 2.05%, respectively;4.10% globally) had MRI-activity;6 out of these last 8 patients (75.0%) with MRI-activity were already active 3-months before immunizationstart. The median (95% confidence interval) time for therapyswitch was 65 (32) days. The core vaccination-cycles had a duration of 40.5 (42) days. Thanks to the growing expertise, we observed a progressive reduction in the time to vaccination-completion, reaching a median of 27 (22) in 2020. Discussion(s): Despite the fundamental role of vaccines in preventing serious infections in at-risk patients [1], solid data regarding the achievement of a complete immunization in pw-MS are missing [2]. Moreover, real-life data regarding vaccinations' planning in pw-MS receiving DMDs is missing, especially in terms of starting a new therapy because of disease-activity. This might represent a challenging issue in the context of massive vaccination protocols as those linked to severe acute respiratory syndrome coronavirus [2]. Our real-world study prompts confidence in individualized vaccination-schedule increasing awareness in vaccinating pw-MS within a DMDs-switch. Conclusion(s): Our study confirmed the optimal tolerance-safety profile of vaccination in pw-MS. A vaccination-cycle of 27 days might be considerate adequate in order to vaccinate pw-MS without interfering with DMDs-start.

18.
Neurological Sciences ; 43(Supplement 1):S500, 2022.
Article in English | EMBASE | ID: covidwho-2174361

ABSTRACT

Background and aims: Multiple Sclerosis (MS) Centers experienced a significant disruption of their clinical activities during the first waves of COVID-19 pandemic. As part of a national multicenter survey (COVId Ms Patients SATisfaction survey - COVIMPSAT), we collected i) the opinion on quality of care (QoC) received by people with MS (pwMS) from MS Centers (MSC), and ii) data on therapeutic adherence and discontinuation, during the lockdown period (March-May 2020) in Italy. Material(s) and Method(s): In April-May 2021, 16 ItalianMSC compiled and sent a digital (35-item) survey to their patients. Statistical analyses were performed with SPSS, version 25. Result(s): 1670 pwMS (67.3% women) completed the survey. Most of them (89.9%) were on disease-modifying therapies (DMTs). The most used DMTs were dimethyl fumarate (18.6%), ocrelizumab (14.4%) and natalizumab (13.9%). During the lockdown period, 88% did not modify their DMT regimen, while 11% reported a change in DMT intake, with a reduction in 7.8% and a drug discontinuation in only 4.2% cases. Almost 9 out of 10 pwMS (89.1%) were able to get in contact with their MSC without difficulties. Thirty-six percent of pwMS contacted their MSC for getting information about COVID-19, while 30% were directly contacted from the MSC personnel to provide information on MS and COVID-19 and preventive behaviours. More than half of the patients (63.5%) performed their check-up visits at the MSC with the same schedule as the pre-pandemic period,while 36.5%of pwMS voluntary skipped follow-up visits mainly because of fear of getting COVID-19 infection (46%) and the sensation of feeling well without an absolute/urgent need of a checkup visit (16.8%). Interestingly, although only 1.3% of pwMSunderwent a teleneurology follow-up visit, 80%of patients suggested to investmore in telemedicine programs in order to expand contact channels with MSC. The overall opinion of pwMS on MSC during the pandemic period in Italy was more than positive, with 32% of pwMS declaring a significant increase in trust in their MSC. Discussion and Conclusion(s): Italian pwMS judged globally well the activity, accessibility and information received by their MSC during the first wave of COVID-19 pandemic. Only 1 out of 10 pwMS underwent a change in their DMT regimen, showing a high drug adherence. Our data also demonstrate that implementing telemedicine programs would further improve the QoC of patients, particularly those with higher disability or living far from the MSC.

19.
Neurological Sciences ; 43(Supplement 1):S382-S383, 2022.
Article in English | EMBASE | ID: covidwho-2174360

ABSTRACT

Background: The SARS-CoV-2 pandemic has led to COVID-19 vaccines development and campaign at an unprecedented magnitude and speed, providing the most effective tool to exit from global emergency. It is now well established that COVID-19 vaccines are unequivocally safe in the general population. However, data are now being collected for Rare Adverse Events, negligible from a statistical viewpoint but potentially relevant to single out specific risk factors and to gain insight about CNS disease pathophysiology. With respect to CNS Inflammatory Demyelinating Events (CIDEs) various cases have been described following COVID-19 vaccines. Although observational studies are showing that these events are rare and vaccines' benefits highly overcome the risks, collecting and characterizing post-COVID-19 vaccines may, at some point, disclose disease-relevant mechanisms. Method(s): Here we describe 6 CIDEs (2 Acute TransverseMyelitis (ATM), 3 Multiple Sclerosis (MS) and 1 Neuromyelitis Optica Spectrum Disorder (NMOSD)) occurring within 35 days from COVID-19 vaccines and perform a systematic search of post-COVID-19 vaccine CIDEs -including ATM, ADEM, MS and NMOSD/MOGAD- published worldwide from 1st December 2020 to 31st December 2021. Demographic/clinical/MRI/CSF/serum characteristics were extracted from reviewed studies and summarized. Result(s): Forty-nine studies were included in the systematic review, reporting a total number of 85 CIDEs. Considering our additional 6 cases, a total of 91 CIDEs were summarized, including 24 ATM, 11 ADEM, 47 MS (15 new diagnosis and 32 relapses), 8 NMOSD (7 new diagnosis and 1 relapse), and 1 newly diagnosed MOGAD. CIDEs occurred after both mRNA-based (n=46), adenoviral-vectored (n=37) and inactivated vaccines (n=8). Adenoviral-vectored vaccines accounted for the greatest number of ADEM and NMOSD/MOGAD, suggesting their possible higher tendency to trigger antibody-mediated diseases. Age was heterogeneous (19-88 years old) and female sex was prevalent. Time from vaccine to symptoms onset was highly various: interestingly 73% of very early onset CIDEs (within 3 days from vaccine) followed an mRNA-based vaccine and post-mRNA-vaccine ATMs occurred on average earlier compared to those following other vaccines (3 vs. 8 median days), with the same trend observed in MS relapses. Recovery was complete/almost complete in the majority ofMS and ADEM, while ATM and NMOSD/MOGAD reached good outcome in 44% of cases. Conclusion(s): While epidemiological studies have assessed the safety of COVID-19 vaccines, detailed clinical descriptions and systematic reviews of sporadic cases may be valuable for a better understanding of the pathophysiology of CNS inflammatory demyelinating events.

20.
Neurological Sciences ; 43(Supplement 1):S494, 2022.
Article in English | EMBASE | ID: covidwho-2174355

ABSTRACT

Objectives: Ocrelizumab (OCR), acting by depletion of the CD20+ B cells, is shown to be a highly effectiveness drug on disease inflammatory activity and progression for both relapsing-remitting (RR), active progressive and primary progressive multiple sclerosis (MS) patients [1]. The present study aimed to evaluate in the real world setting the trend in OCR use over the last 5 years, including the two-year period of the pandemic, also exploring possible predictors of therapeutic response according the NEDA 3 criteria (No Evidence of Disease Activity) [2]. Method(s): Demographic and clinical features of progressive (P) and relapsing remitting (RR) patients exposed to OCR, categorized as naive or switchers from Idegree and IIdegree line DMTs, were analysed. NEDA-3 status at 24 months was evaluated for RR patients by the three assessment components (no clinical relapses, no Expanded Disability Status Scale progression, no radiological activity). Determinants of therapeutic response were also explored by using regression analysis. Result(s): The sample included 285 MS patients, of which 260 (91.2%) were RR and 25 PMS (8.8%). RR patients were categorized as naive (34;13.1%) and switchers from Idegree (140;53.8%) and IIdegree line (86;33,1%) disease modifying treatment (DMTs). An increase of OCR use boh in PP and RR patients from 2017 were observed, included in the last two years, despite the SARSCov 2 pandemic. NEDA-3 status was calculated for 83 RR patients after 24 months of OCR treatment and achieved in 68 (83,1%) of these. Analyzing the predictors of response to OCR, a lower baseline age both in naive (p=0.01) and switchers (p=0,03), and in switchers a lower MS duration (p=0.016) with lower latency to start OCR (p=0.05) were associated with achievement of the NEDA-3. Conclusion(s): Our real-world experience confirms Ocrelizumab as highly effectiveness drug for naive, vertical and horizontal switchers. Age and MS duration were confirmed as factors influencing treatment response, in line with current literature data indicating that "early is better than late treatment, but late is better than never" [3].

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