{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:03:41Z","timestamp":1787317421053,"version":"build-2736575974"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Tisento Therapeutics","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Patient Rep Outcomes"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare genetic syndrome mostly associated with pathogenic variants in mitochondrial DNA. As there is limited research on the life experience of patients with MELAS, this study aimed to develop an understanding of the patient experience of MELAS through qualitative interviews to identify, describe, and substantiate important and relevant signs, symptoms, and health-related quality-of-life (HRQoL) impact (S\/S\/I) concepts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinician and patient interviews were conducted virtually using semi-structured interview guides. During 60-minute interviews with five experts in the United States, clinicians were asked for their perspective on S\/S\/I of patients with MELAS, patient experience of fatigue and cognitive impairment, and whether patients would be able to accurately report and rate their symptoms and complete a 90-minute patient experience interview. During a 45-minute interview conducted with 16 adults with confirmed pathogenic variant and clinical diagnosis of MELAS, patients were asked about S\/S\/I. Interviews were recorded, transcribed, anonymized, coded, and analyzed for saturation and concept frequency and clarification (e.g., severity, frequency, duration).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Experts reported 44 distinct S\/S and 36 HRQoL impact concepts. All five experts confirmed that cognitive impairment would not inhibit a typical patient\u2019s ability to report on their own experiences; three reported that patients with MELAS would not be able to complete a 90-minute interview. Sixteen patient interviews (mean age: 42.3 [11.1],\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910 women) were conducted. Interviews with patients with MELAS achieved saturation of concept and yielded 35\u00a0S\/S concepts and 68 HRQoL impacts across 15 domains. The most frequently reported S\/S concepts were physical fatigue (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200915, 93.8%), hearing loss (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913, 81.3%), mental fatigue (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912, 75.0%), and exercise intolerance and memory problems (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911, 68.8% each). The most frequently reported impact domains were adaptive behaviors and work impacts (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914, 87.5% each) and emotional function (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913, 81.3%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Patients with MELAS can self-report on S\/S\/I. Results from both patient and clinician interviews demonstrate that symptoms related to fatigue and cognitive impairment are frequent, bothersome, and important to improve. Assessments of fatigue and cognitive function should therefore be considered key outcome measures in clinical trials enrolling patients with MELAS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41687-025-00962-6","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T14:28:14Z","timestamp":1761575294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Signs, symptoms, and health-related quality of life in MELAS: measuring what\u2019s important from the patient and clinician perspectives"],"prefix":"10.1186","volume":"9","author":[{"given":"Paolo","family":"Medrano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Banderas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Brimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Settel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Shields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Karaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Larson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Parikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Scaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karra Danyelle","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris James","family":"Edgar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Ventola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Webster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Chickering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Gwaltney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phebe","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Glasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"962_CR1","doi-asserted-by":"publisher","first-page":"1298569","DOI":"10.3389\/fneur.2023.1298569","volume":"14","author":"BC Cox","year":"2023","unstructured":"Cox BC, Pearson JY, Mandrekar J, Gavrilova RH (2023) The clinical spectrum of MELAS and associated disorders across ages: a retrospective cohort study. 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No IRB approval was required or sought for the clinician advice meetings. Materials for the conduct of interviews with patients received approval from Sterling IRB on 18 October 2023. All patient interviews were conducted with written and verbal consent, and all clinician advice meetings were conducted with verbal consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/A.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"J Chickering, P Wilson, M Webster, and C Glasser are employed by and hold stock\/stock options in Tisento Therapeutics, Inc. B Banderas, S Berger, P Medrano, L Settel, M Brimmer are or were employed by Adelphi Values, an outcomes consultancy, and A Shields are employed by Adelphi Values, an outcomes consultancy that received payment from Tisento Therapeutics, Inc. to support the research activities presented in this manuscript. C Gwaltney is employed by Gwaltney Consulting, an outcomes consultancy that also received payment from Tisento Therapeutics, Inc. to support the research activities presented in this manuscript. A Goldstein is employed by the Children\u2019s Hospital of Philadelphia A Karaa is a consultant for Tisento and is a Principal Investigator of the Tisento-sponsored Phase 2 MELAS clinical trial. A Larson is a consultant for Tisento, Mirum, and UCB. He performs contracted research with Tisento, Stealth, Astellas, Neuren, and Sentanyl and serves on the scientific advisory board for the United Mitochondrial Foundation. S Parikh serves on the SMAB for the CHAMP Foundation, is a speaker for the UMDF, serves on the DSMB for Tisento, receives clinical research support from the CHAMP Foundation and is employed by the Cleveland Clinic. F Scaglia received research grants from PTC Therapeutics, Astellas Pharma, Saol Therapeutics, FDA, and the NIH (U54 NS078059 and U54 NS115198). He has received consulting payments from Acer Therapeutics, Precision BioSciences, Tisento Therapeutics, and UCB. He has received research support from the Mervar Foundation and the Courage for a Cure Foundation. KD Harrington is a full-time employee of Cogstate Ltd. P Ventola is a full-time employee of Cogstate Ltd. CJ Edgar is a consultant to Cogstate and a shareholder. He has also received consulting payments from Vanqua Bio.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"127"}}