{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:39:21Z","timestamp":1788485961462,"version":"build-2803163510"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      We conducted a 3-month, prospective study in a population of patients with Myasthenia Gravis (MG), utilizing a fully decentralized approach for recruitment and monitoring (\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      Identifier: NCT04590716). The study objectives were to assess the feasibility of collecting real-world data through a smartphone-based research platform, in order to characterize symptom involvement during MG exacerbations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary data collection included daily electronically recorded patient-reported outcomes (ePROs) on the presence of MG symptoms, the level of symptom severity (using the MG-Activities of Daily Living assessment, MG-ADL), and exacerbation status. Participants were also given the option to contribute data on their physical activity levels from their own wearable devices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study enrolled and onboarded 113 participants across 37 US states, and 73% (N= 82) completed the study. The mean age of participants was 53.6 years, 60% were female. Participants were representative of a moderate to severe MG phenotype, with frequent exacerbations, high symptom burden and multiple comorbidities. 55% of participants (N=45) reported MG exacerbations during the study, with an average of 6.3 exacerbation days per participant. Median average MG-ADL scores for participants during self-reported exacerbation and non-exacerbation periods were 7 (interquartile range 4-9, range 1-19) and 0.3 (interquartile range 0-0.8, range 0-9), respectively. Analyses examining relationships between patient-reported and patient-generated health data streams and exacerbation status demonstrated concordance between self-reported MG-ADL scores and exacerbation status, and identified features that may be used to understand and predict the onset of MG symptom exacerbations, including: 1.) dynamic changes in day-to-day symptom reporting and severity 2.) daily step counts as a measure of physical activity and 3.) clinical characteristics of the patient, including the amount of time since their initial diagnosis and their active medications related to MG treatment. Finally, application of unsupervised machine learning methods identified unique clusters of exacerbation subtypes, each with their own specific representation of symptoms and symptom severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>While these symptom signatures require further study and validation, our results suggest that digital phenotyping, characterized by increased multidimensionality and frequency of the data collection, holds promise for furthering our understanding of clinically significant exacerbations and reimagining the approach to treating MG as a heterogeneous condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2023.1144183","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T03:17:05Z","timestamp":1690859825000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["A decentralized, prospective, observational study to collect real-world data from patients with myasthenia gravis using smartphones"],"prefix":"10.3389","volume":"14","author":[{"given":"Sandra","family":"Steyaert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meelis","family":"Lootus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chethan","family":"Sarabu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeenia","family":"Framroze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Dickinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Steels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Rinaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"ref1","first-page":"91","article-title":"Clinical presentation of myasthenia gravis","author":"Catalin","year":"2020","journal-title":"Thymus"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/1750-1172-2-44","article-title":"Myasthenia gravis","volume":"2","author":"Juel","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"985","DOI":"10.4103\/0301-4738.145987","article-title":"Ocular myasthenia gravis: a review","volume":"62","author":"Nair","year":"2014","journal-title":"Indian J Ophthalmol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/mus.20950","article-title":"Lifetime course of myasthenia gravis","volume":"37","author":"Grob","year":"2008","journal-title":"Muscle Nerve"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1097\/CND.0000000000000257","article-title":"Impact of refractory myasthenia gravis on health-related quality of life","volume":"20","author":"Boscoe","year":"2019","journal-title":"J Clin Neuromuscul Dis"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1177\/1941875210382918","article-title":"Myasthenic crisis","volume":"1","author":"Wendell","year":"2011","journal-title":"Neurohospitalist"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"E10","DOI":"10.1055\/s-0043-118441","article-title":"Myasthenia gravis \u2013 exacerbation and crisis","volume":"2","author":"Schroeter","year":"2018","journal-title":"Neurol Int Open"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1212\/WNL.0000000000011124","article-title":"International consensus guidance for Management of Myasthenia Gravis: 2020 update","volume":"96","author":"Narayanaswami","year":"2021","journal-title":"Neurol Int"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"505.3","DOI":"10.1212\/WNL.0000000000003570","article-title":"Author response: international consensus guidance for management of myasthenia gravis: executive summary","volume":"88","author":"Sanders","year":"2017","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1186\/s13023-022-02388-5","article-title":"What role can decentralized trial designs play to improve rare disease studies?","volume":"17","author":"Moore","year":"2022","journal-title":"Orphanet J Rare Dis"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/S1474-4422(15)00145-3","article-title":"Myasthenia gravis: subgroup classification and therapeutic strategies","volume":"14","author":"Gilhus","year":"2015","journal-title":"Lancet Neurol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"573","DOI":"10.7326\/0003-4819-147-8-200710160-00010","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"147","author":"von Elm","year":"2007","journal-title":"Ann Intern Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1002\/mus.27476","article-title":"Utilization of MG-ADL in myasthenia gravis clinical research and care","volume":"65","author":"Muppidi","year":"2022","journal-title":"Muscle Nerve"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1001\/archneur.60.2.243","article-title":"Development of generalized disease at 2 years in patients with ocular myasthenia gravis","volume":"60","author":"Kupersmith","year":"2003","journal-title":"Arch Neurol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/wics.101","article-title":"Principal component analysis","volume":"2","author":"Abdi","year":"2010","journal-title":"Wiley Interdiscip Rev Comput Stat"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ins.2018.01.007","article-title":"Unsupervised learning by cluster quality optimization","author":"L\u00f3pez-Rubio","year":"2018","journal-title":"Inf Sci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1007\/s00415-020-09770-y","article-title":"\u201cMinimal symptom expression\u201d in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab","volume":"267","author":"Vissing","year":"2020","journal-title":"J Neurol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e1617","DOI":"10.1212\/WNL.0000000000010574","article-title":"Patient-acceptable symptom states in myasthenia gravis","volume":"95","author":"Mendoza","year":"2020","journal-title":"Neurology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1136\/jnnp.2003.020180","article-title":"Quantified measurement of activity provides insight into motor function and recovery in neurological disease","volume":"75","author":"Busse","year":"2004","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e1426","DOI":"10.1212\/WNL.0000000000010209","article-title":"Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis","volume":"95","author":"Tomschik","year":"2020","journal-title":"Neurology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.coi.2017.07.006","article-title":"Pathophysiology and immunological profile of myasthenia gravis and its subgroups","volume":"49","author":"Romi","year":"2017","journal-title":"Curr Opin Immunol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1007\/s10072-021-05823-w","article-title":"Myasthenia gravis exacerbation and myasthenic crisis associated with COVID-19: case series and literature review","volume":"43","author":"Rodrigues","year":"2022","journal-title":"Neurol Sci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.1111\/ene.15158","article-title":"Predictive factors for a severe course of COVID-19 infection in myasthenia gravis patients with an overall impact on myasthenic outcome status and survival","volume":"29","author":"Jakubikova","year":"2022","journal-title":"Eur J Neurol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/mus.27324","article-title":"COVID-19 in patients with myasthenia gravis: epidemiology and disease course","volume":"64","author":"Businaro","year":"2021","journal-title":"Muscle Nerve"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1144183\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T03:17:09Z","timestamp":1690859829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1144183\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,1]]},"references-count":24,"alternative-id":["10.3389\/fneur.2023.1144183"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1144183","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,1]]},"article-number":"1144183"}}