Digital Endpoints: Definition, Benefits, and Current Barriers in Accelerating Development and Adoption DOI Creative Commons

Matthew Landers,

Ray Dorsey,

Suchi Saria

et al.

Digital Biomarkers, Journal Year: 2021, Volume and Issue: 5(3), P. 216 - 223

Published: Sept. 13, 2021

The assessment of health and disease requires a set criteria to define status progression. These measures are referred as “endpoints.” A “digital endpoint” is defined by its use sensor-generated data often collected outside clinical setting such in patient’s free-living environment. Applicable sensors exist an array devices can be applied diverse contexts. For example, smartphone’s microphone might used diagnose or predict mild cognitive impairment due Alzheimer’s wrist-worn activity monitor (such those found smartwatches) may measure drug’s effect on the nocturnal patients with sickle cell disease. Digital endpoints generating considerable excitement because they permit more authentic experience, reveal formerly untold realities burden, cut drug discovery costs half. However, before these benefits realized, effort must not only technical creation digital but also environment that allows for their development application. future rests meaningful interdisciplinary collaboration, sufficient evidence realize promise, ecosystem which vast quantities generate analyzed. fundamental nature care changing. With coronavirus 2019 serving catalyst, there has been rapid expansion home models, telehealth, remote patient monitoring. increasing adoption health-care innovations will expedite requirement characterization current tools rely upon direct interaction thus fit purpose administered remotely. ubiquity relatively inexpensive sensors, positioned drive this consequential change. It therefore surprising regulators, physicians, researchers, consultants have each offered novel tools. we further describe later, broad require cooperative effort. In article, present analysis state endpoints. We attempt unify perspectives parties involved deployment conclude interdependent list challenges collaboratively addressed widely adopted.

Language: Английский

Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course DOI Creative Commons

Rosalind Kalb,

Theodore R. Brown,

Susan Coote

et al.

Multiple Sclerosis Journal, Journal Year: 2020, Volume and Issue: 26(12), P. 1459 - 1469

Published: April 23, 2020

Objectives: To provide clinicians who treat multiple sclerosis (MS) patients with evidence-based or expert opinion–based recommendations for promoting exercise and lifestyle physical activity across disability levels. Methods: The National MS Society (“Society”) convened clinical research experts in the fields of MS, exercise, rehabilitation, to (1) reach consensus on optimal individuals at levels 0–9.0 Expanded Disability Status Scale (EDSS) (2) identify address barriers/facilitators participation. Recommendations: Based current evidence opinion, makes following recommendations, endorsed by Consortium Multiple Sclerosis Centers: Healthcare providers should endorse promote benefits/safety every person MS. Early evaluation a occupational therapist sport scientist, experienced (hereafter referred as “specialists”), is recommended establish an individualized and/or plan. Taking into account comorbidities symptom fluctuations, healthcare encourage ⩾150 min/week activity. Progress toward these targets be gradual, based person’s abilities, preferences, safety. If increases exercise/physical becomes more challenging, referrals specialists are essential ensure safe appropriate prescriptions. When mobility very limited, facilitated trained assistant.

Language: Английский

Citations

238
Molecular biomarkers in multiple sclerosis DOI Creative Commons
Tjalf Ziemssen, Katja Akgün, Wolfgang Brück

et al.

Journal of Neuroinflammation, Journal Year: 2019, Volume and Issue: 16(1)

Published: Dec. 1, 2019

Abstract Multiple sclerosis (MS) is an inflammatory-neurodegenerative disease of the central nervous system presenting with significant inter- and intraindividual heterogeneity. However, application clinical imaging biomarkers currently not able to allow individual characterization prediction. Complementary, molecular which are easily quantifiable come from areas immunology neurobiology due causal pathomechanisms can excellently complement other characteristics. Only a few have so far been routinely used in practice as their validation transfer take long time. This review describes characteristics that ideal MS biomarker should challenges establishing new biomarkers. In addition, clinically relevant promising blood cerebrospinal fluid presented useful for diagnosis prognosis well assessment therapy response side effects.

Language: Английский

Citations

212
Neurodegeneration in multiple sclerosis DOI Creative Commons
Gabrielle M. Mey, Kedar Mahajan, Tara M. DeSilva

et al.

WIREs Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 15(1)

Published: Aug. 10, 2022

Abstract Axonal loss in multiple sclerosis (MS) is a key component of disease progression and permanent neurologic disability. MS heterogeneous demyelinating neurodegenerative the central nervous system (CNS) with varying presentation, courses, prognosis. Immunomodulatory therapies reduce frequency severity inflammatory events that are hallmark MS, but there minimal therapy to treat progressive no cure. Data from patients post‐mortem histological analysis, animal models have elucidated patterns pathogenesis underlying mechanisms neurodegeneration. MRI molecular biomarkers been proposed identify predictors neurodegeneration risk factors for progression. Early signs axonal dysfunction come light including impaired mitochondrial trafficking, structural changes, synaptic alterations. With sustained inflammation as well remyelination, axons succumb degeneration contributing CNS atrophy worsening disease. These studies highlight role chronic demyelination perpetuating loss, difficulty promoting remyelination repair amidst persistent insult. Regenerative neuroprotective strategies essential overcome this barrier, early intervention being critical rescue integrity function. The clinical basic research discussed review set stage identifying propagators leading way therapeutic development. This article categorized under: Immune System Diseases > Molecular Cellular Physiology Neurological

Language: Английский

Citations

94
Clinical outcome measures in multiple sclerosis: A review DOI
Hernán Inojosa, Dirk Schriefer, Tjalf Ziemssen

et al.

Autoimmunity Reviews, Journal Year: 2020, Volume and Issue: 19(5), P. 102512 - 102512

Published: March 12, 2020

Language: Английский

Citations

138
Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study DOI Open Access
Bruce D. Trapp, Megan Vignos,

Jessica Dudman

et al.

The Lancet Neurology, Journal Year: 2018, Volume and Issue: 17(10), P. 870 - 884

Published: Aug. 22, 2018

Language: Английский

Citations

132
Review: Patient-reported outcomes in multiple sclerosis care DOI
Emanuele D’Amico, Rocco Haase, Tjalf Ziemssen

et al.

Multiple Sclerosis and Related Disorders, Journal Year: 2019, Volume and Issue: 33, P. 61 - 66

Published: May 28, 2019

Language: Английский

Citations

106
Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis DOI
John J. Moore, Jennifer Massey,

Carole Ford

et al.

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2018, Volume and Issue: 90(5), P. 514 - 521

Published: Dec. 11, 2018

Background Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present outcomes, safety immune reconstitution (IR) patients active, treatment refractory MS. Methods This study was single-centre, phase II trial AHSCT for active relapsing remitting (RRMS) secondary progressive MS (SPMS). Patients underwent using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin regimen. Outcomes The primary outcome event-free survival (EFS); defined no or radiological relapses disability progression. Multiparameter flow cytometry performed evaluation post-transplant IR both lymphoma receiving same chemotherapy Results Thirty-five (20 RRMS, 15 SPMS) completed AHSCT, median follow-up 36 months (range 12–66). Expanded Disability Status Scores (EDSS) 6 (2–7) had failed 4 modifying therapies. 66% natalizumab. EFS at 3 years 60%, (70% RRMS). Sustained improvement EDSS seen (44%) patients. There treatment-related mortality. A sustained rise CD39 + T regulatory cells, immunosuppressive CD56 hi natural killer cells ablation proinflammatory mucosal-associated invariant 12 following These did not occur AHSCT. Conclusions our cohort is significantly greater than other high-efficacy therapies similar to studies despite more heavily pretreated cohort. Trial registration number ACTRN12613000339752.

Language: Английский

Citations

84
Complement: Bridging the innate and adaptive immune systems in sterile inflammation DOI

Martin W. Lo,

Trent M. Woodruff

Journal of Leukocyte Biology, Journal Year: 2020, Volume and Issue: 108(1), P. 339 - 351

Published: March 17, 2020

The complement system is a collection of soluble and membrane-bound proteins that together act as powerful amplifier the innate adaptive immune systems. Although its role in infection well established, becoming increasingly recognized key contributor to sterile inflammation, chronic inflammatory process often associated with noncommunicable diseases. In this context, damaged tissues release danger signals trigger complement, which acts on range leukocytes augment bridge Given detrimental effect therefore placed an anti-inflammatory drug target. review, we provide general outline activators, effectors, targets series examples (i.e., hypertension, cancer, allograft transplant rejection, neuroinflammation) highlight complement's ability 2 arms system.

Language: Английский

Citations

84
Digital Biomarkers in Multiple Sclerosis DOI Creative Commons

Anja Dillenseger,

Marie Luise Weidemann,

Katrin Trentzsch

et al.

Brain Sciences, Journal Year: 2021, Volume and Issue: 11(11), P. 1519 - 1519

Published: Nov. 16, 2021

For incurable diseases, such as multiple sclerosis (MS), the prevention of progression and preservation quality life play a crucial role over entire therapy period. In MS, patients tend to become ill at younger age are so variable in terms their disease course that there is no standard therapy. Therefore, it necessary enable personalized possible respond promptly any changes, whether with noticeable symptoms or symptomless. Here, measurable parameters biological processes can be used, which provide good information regard prognostic diagnostic aspects, activity response therapy, so-called biomarkers Increasing digitalization availability easy-to-use devices technology also healthcare professionals use new class digital biomarkers-digital health technologies-to explain, influence and/or predict health-related outcomes. The from these stem quite broad, range wearables collect patients' during digitalized functional tests (e.g., Multiple Sclerosis Performance Test, dual-tasking performance speech) procedures optical coherence tomography) software-supported magnetic resonance imaging evaluation. These technologies offer timesaving way valuable data on regular basis long period time, not only once twice year routine visit clinic. they lead real-life acquisition, closer patient monitoring thus dataset useful for precision medicine. Despite great benefit increasing digitalization, now, path implementing widely unknown inconsistent. Challenges around validation, infrastructure, evidence generation, consistent collection analysis still persist. this narrative review, we explore existing future opportunities capture clinical care people may twin patient. To do this, searched published papers different systems context gathered perspectives under development already research approach.

Language: Английский

Citations

79
Fitness, physical activity, and exercise in multiple sclerosis: a systematic review on current evidence for interactions with disease activity and progression DOI Creative Commons
Sebastian Proschinger,

Puya Kuhwand,

Annette Rademacher

et al.

Journal of Neurology, Journal Year: 2022, Volume and Issue: 269(6), P. 2922 - 2940

Published: Jan. 27, 2022

Abstract Background A moderate to high level of physical activity, including regular exercise, represents an established behavioral and rehabilitative approach for persons with multiple sclerosis (pwMS). Although being increasingly proposed limit disease activity progression, high-quality evidence is lacking. Objective The objective the study provide valuable information MS clinicians researchers by systematically evaluating current state (i) whether exercise interventions affect clinical measures progression in pwMS (i.e., EDSS, relapse rate, lesion load, brain volume, MSFC) (ii) how fitness interact these measures. Methods Literature search was conducted MEDLINE, EMBASE, CINAHL, SPORTDiscus. Evaluation quality done based on standards published American Academy Neurology. Results It likely that improves MSFC score, whereas EDSS volume are remain unchanged over intervention period. possible decreases rate. from cross-sectional studies indicate beneficial effects a or which, however, not corroborated quality. Conclusions (supportive) disease-modifying effect cannot be concluded. rather low existing RCTs underlines need conduct more well-designed assessing different as primary end points. major limitation short duration which limits meaningful exercise-induced most disability Findings difficult contextualize regarding importance due their solely associative character PROSPERO registration number CRD42020188774.

Language: Английский

Citations

53