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Background. Recently, there has been a notable rise in requests for research ethics training from institutions across the Southern African Developing Community (SADC) region. This surge prompted the Southern African Research and Innovation Research Management Association (SARIMA) to seek input from all stakeholders to guide their efforts. SARIMA aims to enhance the professionalisation of research management and administration throughout SADC, thereby complementing the portfolio of skills for research administrators and managers who support Research Ethics Committees (RECs). Objective. To gauge the needs and requirements for research ethics training within the SADC region and to determine the themes and topics that require attention and in-depth focus to support and facilitate ethical research development. Methods. This quantitative study surveyed SARIMA members. In total, 84 professionals working in research ethics and integrity responded to the survey. The geographical scope was Southern Africa, encompassing 16 member states of the SADC region. Results. Most respondents indicated strong institutional support or a positive attitude from institutional leadership toward RECs and related matters. Institutions were recognised for their responsibility in providing training in ethics and research conduct across the research ecosystem, including postgraduate students, researchers, managers and administrators. There are Communities of Practice in Research Ethics and Integrity in the SADC region under the auspices of SARIMA with the required knowledge and expertise to deliver such training upon request. Conclusion. Providing training in ethics and research conduct for all involved in the research ecosystem is a collective responsibility shared by institutions and researchers. Research management and administration professionals play a vital role in ensuring training initiatives in research ethics and integrity are available to their research community. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis is a chronic immune-mediated disease of the central nervous system affecting nearly 3 million people worldwide. Although much progress has been made in the understanding and treatment of MS, cures remain elusive., Objectives: To accelerate the development of cures for MS by updating the Pathways to Cures Research Roadmap based on a contemporary understanding of disease. The refined Roadmap will help to promote research in scientific areas with great potential to reveal insights leading to cures and inspire greater coordination of global resources., Methods: Refinements to the Roadmap were achieved during a Global Summit that included close to 200 academic and industry scientists, health care providers, policy makers, funders, and people with MS from 15 countries., Results: The refined Roadmap describes three pathways that target opportunities for generating scientific insights leading to cures. Recommendations for accelerating research progress include, lowering barriers for global data sharing, enhancing collaboration and coordination among research supporters, committing to sustained funding, considering implications for implementation, engaging PwMS and committing to diversity, equity, and inclusion in the global MS movement., Conclusion: The refined roadmap provides a strategic framework for tackling the complexities of MS and advancing prevention strategies, effective treatments, and cures., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BFB has as no relevant conflicts. BLB serves as a consultant to Novartis, UCB, Roche, and Sanofi for work unrelated to the present manuscript. BLB receives funding for research grants from the NIH and National MS Society. CCW has no relevant conflicts. TC has received travel support from Sanofi. UD has no relevant conflicts. PLD has received research support from Biogen and Merck Serono. AKP has no relevant conflicts. VWY is funded by research grants from MS Canada, the Canadian Institutes of Health Research, USA Department of Defense Multiple Sclerosis Research Program, Genentech and Novartis. He has received speaker honoraria from Biogen, EMD Serono, Novartis, Roche, Sanofi-Genzyme and Teva Canada. He is the recipient of unrestricted educational grants from Biogen, EMD Serono, Novartis, Roche, Sanofi-Genzyme and Teva Canada to support educational activities of the Alberta MS Network, which he directs. ENB has no relevant conflicts. AJT is Co-Chair, UCL-Eisai Steering Committee drug discovery collaboration (paid to institution), Member, National MS Society (USA) Scientific Advisory Committee (receive support for travel), Clinical Trials Committee, Progressive MS Alliance (receive support for travel), Board member, European Charcot Foundation (receive support for travel), Editor in Chief, Multiple Sclerosis Journal (receiving honorarium from SAGE Publishers), Editorial Board Member, The Lancet Neurology (receiving free subscription).

Introduction: Multiple sclerosis (MS) is an immune-mediated central nervous system disorder and a growing global health challenge affecting nearly 3 million people worldwide. Incidence and prevalence continue to increase with no known cause or cure. Globally governments and non-profit organizations fund research toward better understanding of and treatments for multiple sclerosis., Methods: This study identified MS research projects funded between 2021 and 2023 by government and non-profit organization sources. Projects were described by type of scientific approach, Pathways to Cure research category (i.e. Stop, Restore, End), and other key characteristics., Results: Over 2,300 MS research projects were identified through 16 non-profit MS organizations and 18 government databases. The overall global portfolio of these projects is valued at nearly one and a half billion Euros. The majority of projects were classified in the Stop category (60%). Research collaboration occurs in many forms among the research community; around 272 projects were reported to be co-funded., Conclusion: Global MS research collaboration will accelerate progress toward increased knowledge, effective treatments, improved health outcomes, and ultimately cures for MS. This landscape analysis highlights the current distribution of MS research investment between topics and begins to suggest where the MS community should focus to increase potential impact for current and future endeavors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Significant advancements have been achieved in delineating the progress of the Global PROMS (PROMS) Initiative. The PROMS Initiative, a collaborative endeavor by the European Charcot Foundation and the Multiple Sclerosis International Federation, strives to amplify the influence of patient input on MS care and establish a cohesive perspective on Patient-Reported Outcomes (PROs) for diverse stakeholders. This initiative has established an expansive, participatory governance framework launching four dedicated working groups that have made substantive contributions to research, clinical management, eHealth, and healthcare system reform. The initiative prioritizes the global integration of patient (For the purposes of the Global PROMS Initiative, the term "patient" refers to the people with the disease (aka People with Multiple Sclerosis - pwMS): any individual with lived experience of the disease. People affected by the disease/Multiple Sclerosis: any individual or group that is affected by the disease: E.g., family members, caregivers will be also engaged as the other stakeholders in the initiative). insights into the management of MS care. It merges subjective PROs with objective clinical metrics, thereby addressing the complex variability of disease presentation and progression. Following the completion of its second phase, the initiative aims to help increasing the uptake of eHealth tools and passive PROs within research and clinical settings, affirming its unwavering dedication to the progressive refinement of MS care. Looking forward, the initiative is poised to continue enhancing global surveys, rethinking to the relevant statistical approaches in clinical trials, and cultivating a unified stance among 'industry', regulatory bodies and health policy making regarding the application of PROs in MS healthcare strategies., Competing Interests: LuC was employed by Hoffmann-La Roche. LoC was employed by Ad Scientiam. PK was employed by Merck KGaA. ACV has received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen Colombia, Genzyme Colombia, Merck Colombia, Roche Colombia, Novartis Colombia. CB has received travel support and/or research grants and/or lecture fees and/or advisory services by Novartis, Merck, Genesis, Sanofi, Teva, Roche, Biogen, Mylan, Tikun Europe ECC has received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen Argentina and LATAM, Genzyme Argentina, Merck Argentina and LATAM, Roche Argentina and LATAM, Raffo, Novartis Argentina, AstraZeneca Argentina, Horizon therapeutics, LACTRIMS, Harvard Medical School MP has received reimbursement for developing educational presentations from Biogen and Merck. SG has received reimbursement for developing educational presentations, research grants, consultation fees, and/or travel stipends from Roche, Merck and the Sumaira Foundation. VC received a grant from the European Charcot Foundation, received support for scientific meetings from Biogen, Janssen, Novartis, BMS, Roche and speaking honoraria from Novartis and Alexion. VR reports fees for traveling from Novartis, Merck, Biogen and Roche, speaker’s honoraria from Novartis, Sandoz, Merck, Biogen, consulting fees from Biogen, Merck, Novartis, Janssen, M3 Global Research and Atheneum Partners, all outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. H-PH declared that he was an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zaratin, Samadzadeh, Seferoğlu, Ricigliano, dos Santos Silva, Tunc, Brichetto, Coetzee, Helme, Khan, McBurney, Peryer, Weiland, Baneke, Battaglia, Block, Capezzuto, Carment, Cortesi, Cutter, Leocani, Hartung, Hillert, Hobart, Immonen, Kamudoni, Middleton, Moghames, Montalban, Peeters, Sormani, van Tonder, White, Comi and Vermersch.)

Background and Objectives: The current clinical course descriptors of multiple sclerosis (MS) include a combination of clinical and magnetic resonance imaging (MRI) features. Recently there has been a growing call to base these descriptors more firmly on biological mechanisms. We investigated the implications of proposing a new mechanism-driven framework for describing MS., Methods: In a web-based survey, multiple stakeholders rated the need to change current MS clinical course descriptors, the definitions of disease course and their value in clinical practice and related topics., Results: We received 502 responses across 49 countries. In all, 77% of the survey respondents supported changing the current MS clinical course descriptors. They preferred a framework that informs treatment decisions, aids the design and conduct of clinical trials, allows patients to understand their disease, and links disease mechanisms and clinical expression of disease. Clinical validation before dissemination and ease of communication to patients were rated as the most important aspects to consider when developing any new framework for describing MS., Conclusion: A majority of MS stakeholders agreed that the current MS clinical course descriptors need to change. Any change process will need to engage a wide range of affected stakeholders and be guided by foundational principles., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Judicious multiple sclerosis (MS) diagnosis and early start of disease modifying therapy significantly improves long-term disability outcomes in persons with MS (pwMS). Retrospective analysis based on 25-year New York State MS Consortium (NYSMSC) data determined the effect of changes in the respective diagnostic criteria in shortening the time between symptom onset to MS diagnosis. Based on 9378 current and historical MS cases, there was a significant decrease in time to diagnosis in pwMS from 1982-2001 to >2017 periods (average 4.2 vs. 1.1 years, p < 0.001). Additional improvements and better implementation of the MS diagnostic criteria can further decrease the diagnosis lag.

Background:  Many caregivers from low-middle income (LMI) households consider that preschool children are too young for shared book reading. Thus, many caregivers are unaware of their potentially powerful role in their children's emergent literacy and communication., Objectives:  To describe (1) caregivers' perceptions of shared reading, (2) caregivers' perceptions of barriers to shared reading and (3) changes in these perceptions following a short intervention., Method:  A qualitative methodology was used to understand the perceptions of 40 caregivers from a semi-rural South African township. Two semi-structured interviews were conducted before and after intervention. The intervention was a short training video about shared reading., Results:  Caregivers described the unfamiliar reading culture and viewed reading as an educational activity that they knew little about. Barriers to shared reading included lack of time, few reading materials and low levels of literacy or lack of exposure to this type of activity. Following the intervention, they acknowledged the importance of shared reading, described growing confidence in their shared reading abilities and closer relationships with their children., Conclusion:  Speech-language therapists (SLTs) have a pivotal role to play in caregiver training of emergent literacy skills and can make a marked impact in guiding caregivers' shared reading. A short video-based intervention can alter caregiver perceptions and practices, which may be the first step in changing behaviours.Contribution: The study provides an example of a simple and cost-effective intervention that changed caregiver perception and caregivers' reported shared reading practice.

Traditionally, multiple sclerosis has been categorised by distinct clinical descriptors-relapsing-remitting, secondary progressive, and primary progressive-for patient care, research, and regulatory approval of medications. Accumulating evidence suggests that the clinical course of multiple sclerosis is better considered as a continuum, with contributions from concurrent pathophysiological processes that vary across individuals and over time. The apparent evolution to a progressive course reflects a partial shift from predominantly localised acute injury to widespread inflammation and neurodegeneration, coupled with failure of compensatory mechanisms, such as neuroplasticity and remyelination. Ageing increases neural susceptibility to injury and decreases resilience. These observations encourage a new consideration of the course of multiple sclerosis as a spectrum defined by the relative contributions of overlapping pathological and reparative or compensatory processes. New understanding of key mechanisms underlying progression and measures to quantify progressive pathology will potentially have important and beneficial implications for clinical care, treatment targets, and regulatory decision-making., Competing Interests: Declaration of interests TK received research funding from the German Research Foundation, Interdisciplinary Centre for Clinical Studies (IZKF) Münster, National Multiple Sclerosis Society (USA), European Leukodystrophy Association, Progressive MS Alliance, European Commission (H2020-MSCA-ITN-2018), and Novartis; and received compensation for serving on a scientific advisory board (Novartis) and speaker honoraria from Novartis and Roche. MM has received research grants from MAGNIMS-ECTRIMS, Multiple Sclerosis Society UK, and Merck; consulting fees from Ipsen, BMS Celgene, Biogen, Sanofi-Genzyme, Roche, and Merck; honoraria for lectures from Merck, Roche, and Sanofi-Genzyme; and support for attending meetings from Merck, Biogen, and Sanofi-Genzyme. TC is an employee of the National Multiple Sclerosis Society (USA), which is one of the sponsors of the International Advisory Committee on Clinical Trials in Multiple Sclerosis. JAC has received personal compensation for consulting for Biogen, Bristol-Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; for speaking for H3 Communications; and for serving as an editor of the Multiple Sclerosis Journal. JC has received grants or contracts from Biogen, Merck and UC San Francisco; and has received payments or honoraria for lectures, speaker bureaus, or presentations from Biogen, Merck, Sanofi Genzyme, Novartis, Bristol-Myers, and Roche; participation on Data Safety Monitoring Boards or Advisory Boards from Novartis, Merck, Sanofi Genzyme, and Biogen. JG has received grant and contract research support from the National Multiple Sclerosis Society (USA), Biogen, and Octave Biosciences; serves on a steering committee for a trial supported by Novartis; has received speaker fees from Alexion and BMS; and served on an advisory board for Genentech. XM received speaking honoraria and travel expenses for participation in scientific meetings; has been a steering committee member of clinical trials or participated in advisory boards of clinical trials with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Sandoz, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics, Excemed, Multiple Sclerosis International Federation, and National Multiple Sclerosis Society (USA). RAM receives research funding from Biogen Idec and Roche; and is the chair of the Medical Advisory Committee of the Multiple Sclerosis Society of Canada. VWY is funded by research grants from the Multiple Sclerosis Society of Canada, the Canadian Institutes of Health Research, Canadian Cancer Society, and Genentech; has received speaker honoraria from Biogen, EMD Serono, Novartis, Roche, and Sanofi-Genzyme; and is the recipient of unrestricted educational grants from Biogen, EMD Serono, Novartis, Roche, Sanofi-Genzyme, and Teva Canada to support educational activities of the Alberta MS Network, which he directs. AJT reports personal fees as an editorial board member for The Lancet Neurology receiving a free subscription; is Editor-in-Chief for the Multiple Sclerosis Journal receiving an honorarium from SAGE Publications; receives support from the UCLH NIHR Biomedical Research Centre; and receives support for travel as Chair of the Scientific Advisory Committee and International Progressive MS Alliance from the National MS Society (USA) as member, National Multiple Sclerosis Society (USA) Research Programs Advisory Committee, and as a Board member of the European Charcot Foundation; has received payment in the past 36 months (paid to the UCL) from Eisai and from the German Aerospace Centre, Health Research (ERA-NET NEURON); has received fees or support for travel from Hoffman La Roche, Novartis, and CanProCo SAB; had received honoraria or support for travel from EXCEMED and Almirall; has received support for travel to PACTRIMS and has received support for travel to the Multiple Sclerosis Society of Canada; unpaid roles include as a Guarantor of BRAIN, Trustee of the National Brain Appeal (National Hospital for Neurology and Neurosurgery), and as Chair of the Scientific Ambassadors, ‘STOP MS’ Appeal Board (Multiple Sclerosis Society UK). DSR reports personal fees from Bounds Law Group LLC, grants from Vertex, grants from Sanofi-Genzyme, grants from Abata Therapeutics, outside the submitted work; has a patent system and method of automatically detecting tissue abnormalities (US Patent 9,607,392) issued, a patent method of analysing multisequence MRI data for analysing brain abnormalities in a subject (US Patent 9,888,876) issued, a patent Automatic identification of subjects at risk of multiple sclerosis (US Patent application 16/254,710) issued, and a patent high-resolution cerebrospinal fluid-suppressed T2*-weighted magnetic resonance imaging of cortical lesions (US Patent application 62/838,578) pending., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The COVID-19 pandemic has reinforced the importance of research for the health of our society and highlighted the need for stakeholders of the health research and care continuum to form a collaborative and interdependent ecosystem., Objective: With the world still reeling from waves of the COVID-19 pandemic and adapting to the vaccine rollout at widely different rates, the International Progressive MS Alliance (hereafter Alliance) organized a meeting (April 2021) to consider how the Covid-19 pandemic impacts the health and well-being of people with progressive Multiple Sclerosis (MS)., Methods: We invited the Alliance stakeholders and experts to present what they have learned about SARS-CoV-2 infection and progressive MS and to define future scientific priorities., Results: The meeting highlighted three priorities for additional focus: (1) the impact of Disease Modifying Therapies (DMTs) on the risk of COVID-19 and on the efficacy of COVID-19 vaccines in people with progressive MS; (2) the long-term impact of COVID-19 and COVID-19 vaccines on the biology of progressive MS; and (3) the impact on well-being of people with progressive MS., Conclusion: This paper's calls to action could represent a path toward a shared research agenda. Multi-stakeholder and long-term investigations will be required to drive and evolve such an agenda., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B Banwell serves as an advisor to Novartis, Roche, UCB, UTSW and Sanofi, and has received grant funding from Canadian MS Society, NMSS and NIH. T Coetzee is an employee of the National Multiple Sclerosis Society, a managing member of the International Progressive MS Alliance and has no conflict of interest. G Comi has received compensation for consulting services for Bristol Myers Squibb, Janssen, Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Excemed, Roche, Almirall, Chugai, Receptos, and Forward Pharma and compensation for speaking activities for Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Excemed, and Roche. A Feinstein is on an Advisory Board for Akili Interactive and reports grants from the MS Society of Canada, book royalties from Johns Hopkins University Press, Cambridge University Press and Amadeus Press and speaker’s honoraria from Novartis, Biogen, Roche, and Sanofi-Genzyme. R. Hyde is an employee of Biogen and co-chair of the International Progressive MS Alliance Industry Forum. M. Salvetti reports speaking honoraria and research support from Merck, Sanofi, Novartis, Biogen, Roche, Bristol Myers Squibb. K Smith receives consulting fees for project work from the International Progressive MS Alliance, and travel support from the Alliance as a member of the Scientific Steering Committee and the National MS Society as a member of their Scientific Advisory Committee. P Zaratin is an employee of the Italian Multiple Sclerosis Society, a managing member of the International Progressive MS Alliance and has no conflict of interest., (© The Author(s), 2022.)

On 12 September 2019, the global Patient Reported Outcome for Multiple Sclerosis (PROMS) Initiative was launched at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The multi-stakeholder PROMS Initiative is jointly led by the European Charcot Foundation (ECF) and the Multiple Sclerosis International Federation (MSIF), with the Italian Multiple Sclerosis Society (AISM) acting as the lead agency for and on behalf of the global MSIF movement. The initiative has the ambitious mission to (i) maximize the impact of science with and of patient input on the life of people affected by MS, and (ii) to represent a unified view on Patient-Reported Outcomes for MS to people affected by MS, healthcare providers, regulatory agencies and Health Technologies Assessments agencies. Equipped with an innovative participatory governance of an international and interdisciplinary network of different stakeholders, PROMS has the potential to guide future breakthroughs in MS patient-focused research and care. In this paper we present the progresses of the global PROMS Initiative and discuss the open questions that we aim to address., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Multiple Sclerosis (MS) is a growing global health challenge affecting nearly 3 million people. Progress has been made in the understanding and treatment of MS over the last several decades, but cures remain elusive. The National MS Society is focused on achieving cures for MS., Objectives: Cures for MS will be hastened by having a roadmap that describes knowledge gaps, milestones, and research priorities. In this report, we share the Pathways to Cures Research Roadmap and recommendations for strategies to accelerate the development of MS cures., Methods: The Roadmap was developed through engagement of scientific thought leaders and people affected by MS from North America and the United Kingdom. It also included the perspectives of over 300 people living with MS and was endorsed by many leading MS organizations., Results: The Roadmap consist of three distinct but overlapping cure pathways: (1) stopping the MS disease process, (2) restoring lost function by reversing damage and symptoms, and (3) ending MS through prevention. Better alignment and focus of global resources on high priority research questions are also recommended., Conclusions: We hope the Roadmap will inspire greater collaboration and alignment of global resources that accelerate scientific breakthroughs leading to cures for MS.

Background: Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term 'active' secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management., Objective: This paper reviews recent progress, highlights continued knowledge and proposes, on behalf of the International Progressive MS Alliance, a global research strategy for progressive MS., Methods: Literature searches of PubMed between 2015 and May, 2021 were conducted using the search terms "progressive multiple sclerosis", "primary progressive multiple sclerosis", "secondary progressive MS". Proposed strategies were developed through a series of in-person and virtual meetings of the International Progressive MS Alliance Scientific Steering Committee., Results: Sustaining and accelerating progress will require greater understanding of underlying mechanisms, identification of potential therapeutic targets, biomarker discovery and validation, and conduct of clinical trials with improved trial design. Encouraging developments in symptomatic and rehabilitative interventions are starting to address ongoing challenges experienced by people with progressive MS., Conclusion: We need to manage these challenges and realise the opportunities in the context of a global research strategy, which will improve quality of life for people with progressive MS.

Sharing clinical trial data can provide value to research participants and communities by accelerating the development of new knowledge and therapies as investigators merge data sets to conduct new analyses, reproduce published findings to raise standards for original research, and learn from the work of others to generate new research questions. Nonprofit funders, including disease advocacy and patient-focused organizations, play a pivotal role in the promotion and implementation of data sharing policies. Funders are uniquely positioned to promote and support a culture of data sharing by serving as trusted liaisons between potential research participants and investigators who wish to access these participants' networks for clinical trial recruitment. In short, nonprofit funders can drive policies and influence research culture. The purpose of this paper is to detail a set of aspirational goals and forward thinking, collaborative data sharing solutions for nonprofit funders to fold into existing funding policies. The goals of this paper convey the complexity of the opportunities and challenges facing nonprofit funders and the appropriate prioritization of data sharing within their organizations and may serve as a starting point for a data sharing toolkit for nonprofit funders of clinical trials to provide the clarity of mission and mechanisms to enforce the data sharing practices their communities already expect are happening., (©Timothy Coetzee, Mad Price Ball, Marc Boutin, Abby Bronson, David T Dexter, Rebecca A English, Patricia Furlong, Andrew D Goodman, Cynthia Grossman, Adrian F Hernandez, Jennifer E Hinners, Lynn Hudson, Annie Kennedy, Mary Jane Marchisotto, Elizabeth Myers, W Benjamin Nowell, Brian A Nosek, Todd Sherer, Carolyn Shore, Ida Sim, Luba Smolensky, Christopher Williams, Julie Wood, Sharon F Terry, Lynn Matrisian. Originally published in Journal of Participatory Medicine (http://jopm.jmir.org), 29.03.2021.)

Therapies for infiltrative inflammation in multiple sclerosis (MS) have advanced greatly, but neurodegeneration and compartmentalized inflammation remain virtually untargeted as in other diseases of the nervous system. Consequently, many therapies are available for the relapsing-remitting form of MS, but the progressive forms remain essentially untreated. The objective of the International Progressive MS Alliance is to expedite the development of effective therapies for progressive MS through new initiatives that foster innovative thinking and concrete advancements. Based on these principles, the Alliance is developing a new funding programme that will focus on experimental medicine trials. Here, we discuss the reasons behind the focus on experimental medicine trials, the strengths and weaknesses of these approaches and of the programme, and why we hope to advance therapies while improving the understanding of progression in MS. We are soliciting public and academic feedback, which will help shape the programme and future strategies of the Alliance.

Introduction: Cryptosporidium, Giardia and rotaviruses are amongst the leading causes of acute gastroenteritis in children ≤5 years worldwide. The purpose of this study was to determine the occurrence of Cryptosporidium parvum, Giardia intestinalis and molecular characteristics of rotaviruses after Rotarix® introduction in Botswana., Methods: in this case study, 200 diarrheic stool specimens and 100 control samples from children under five years old were collected between March and November, 2017. Samples were analyzed by modified Ziehl Neelsen staining technique for cryptosporidium, wet mount procedure for Giardia and negative samples were confirmed by immunochromatographic assay. Specimens were analyzed for rotavirus by ELISA, PAGE, RT-PCR, sequencing of VP7 and VP4 antigen followed by phylogenetic analysis., Results: prevalence rates of 20.5%, 16.5% and 11.0% in diarrhea cases were observed for Cryptosporidium parvum, Giardia intestinalis and rotavirus, respectively. Four percent of diarrheic specimens had multiple infections. The predominant rotavirus genotype was GIP[8] (7/15) followed by G2P[4] (2/15) and G3P[8] (1/15). Twenty percent of specimens were non-typeable. One mixed strain, G1+G2P[4,8] (2/15), was detected. Phylogenetic analysis of VP4 and VP7 sequences clustered Botswana rotavirus strains within G1 lineages 1 and 2, G3 lineage 1, P[8] lineage 3 and P[4] lineage 5 together with Southern African strains., Conclusion: this study provides important information on occurrence and demographic risk groups for Cryptosporidium parvum, Giardia intestinalis and rotavirus in young children as well as genetic diversity of rotaviruses after vaccine introduction in Botswana. Constant monitoring of circulating rotavirus strains is essential in assessing effectiveness of current vaccines in Botswana., Competing Interests: The authors declare no competing interests., (Copyright: Lineage Kurenzvi et al.)

The clinical courses of multiple sclerosis were defined in 1996 and refined in 2013 to provide a time-based assessment of the current status of the individual. These definitions have been successfully used by clinicians, clinical trialists, and regulatory authorities. Recent regulatory decisions produced variations and discrepancies in the use of the clinical course descriptions. We provide here a clarification of the concepts underlying these descriptions and restate the principles used in their development. Importantly, we highlight the critical importance of time framing the disease course modifiers activity and progression and clarify the difference between the terms worsening and progressing., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The purpose of this study is to examine measurement invariance of scoring of teaching behavior, as perceived by students, across six cultural contexts (Netherlands, Spain, Turkey, South Africa, South Korea, and Indonesia). It also aims to compare perceived teaching behavior across the six countries based on a uniform student measure. Results from multi-group confirmatory factor analyses (MGCFA) showed perceived teaching behavior in the six countries to be adequately invariant. Perceived teaching behavior was the highest in South Korea and the lowest in Indonesia. The findings provide new insights into the relevance and differences of teaching behavior across cultural contexts., (Copyright © 2020 André, Maulana, Helms-Lorenz, Telli, Chun, Fernández-García, de Jager, Irnidayanti, Inda-Caro, Lee, Safrina, Coetzee and Jeon.)

'Active' and 'non-active' secondary progressive MS (SPMS) have distinct pathophysiological mechanisms and clinical characteristics, but there is still no consensus regarding the frequency of these MS forms in the real-world setting. We aimed to evaluate the frequency of 'active' and 'non-active' SPMS in a large cohort of Italian MS patients and the differences in terms of clinical and MRI characteristics and disease progression. This multicenter study collected data about MS patients who have transitioned to the SP form in the period between 1st January 2014 and 31st December 2019 and followed by the MS centers contributing to the Italian MS Registry. Patients were divided into 'active SPMS' and 'non-active SPMS', based on both reported MRI data and relapse activity in the year before conversion to SPMS. Out of 68,621, 8,316 (12.1%) patients were diagnosed with SPMS. Out of them, 872 (10.5%) were classified into patients with either 'active' or 'non-active' SPMS. A total of 237 were classified into patients with 'active SPMS' (27.2%) and 635 as 'non-active SPMS' (72.8%). 'Non-active SPMS' patients were older, with a longer disease duration compared to those with 'active SPMS'. The percentages of patients showing progression independent of relapse activity (PIRA) at 24 months were similar between 'active' and 'non-active' SPMS patients (67 [27.4%] vs 188 [29.6%]; p = 0.60). In the 'active' group, 36 (15.2%) patients showed relapse-associated worsening (RAW). Comparison of the survival curves to EDSS 6 and 7 according to disease activity did not show significant differences (p = 0.68 and p = 0.71). 'Active' and 'non-active' SPMS patients had a similar risk of achieving disability milestones, suggesting that progression is primarily attributed to PIRA and only to a small extent to disease activity., (© 2024. The Author(s).)

The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Glycosphingolipids and cholesterol form lateral assemblies, or lipid ‘rafts’, within biological membranes. Lipid rafts are routinely studied biochemically as low-density, detergent-insoluble complexes (in non-ionic detergents at 4°C; DIGs, detergent-insoluble glycosphingolipid/cholesterol microdomains). Recent discrepancies recommended a re-evaluation of the conditions used for the biochemical analysis of lipid rafts. We have investigated the detergent insolubility of several known proteins present in the glycosphingolipid/cholesterol-rich myelin membrane, using four detergents representing different chemical classes (TX-100, CHAPS, Brij 96 and TX-102), under four conditions: detergent extraction of myelin either at (i) 4°C or (ii) 37°C, or at 4°C after pre-extraction with (iii) saponin or (iv) methyl-β-cyclodextrin (MβCD). Each detergent was different in its ability to solubilize myelin proteins and in the density of the DIGs produced. Brij 96 DIGs floated to a lower density than other detergents tested, possibly representing a subpopulation of DIGs in myelin. DIGs pre-extracted with saponin were denser than DIGs pre-extracted with MβCD. Furthermore, pre-extraction with MβCD solubilized proteolipid protein (known to associate with cholesterol), whereas pre-extraction with saponin did not, suggesting that saponin is less effective as a cholesterol-perturbing agent than is MβCD. These results demonstrate that DIGs isolated by different detergents are not necessarily comparable, and that these detergent-specific DIGs may represent distinct biochemical, and possibly physiological, entities based on the solubilities of specific lipids/proteins in each type of detergent. [ABSTRACT FROM AUTHOR]