{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:33:10Z","timestamp":1767141190931,"version":"build-2238731810"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Novartis Pharma Portugal"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were na\u00efve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10072-020-04726-6","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T04:05:14Z","timestamp":1601438714000},"page":"1995-2003","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6081-6955","authenticated-orcid":false,"given":"S.","family":"Batista","sequence":"first","affiliation":[]},{"given":"C. C.","family":"Nunes","sequence":"additional","affiliation":[]},{"given":"J. J.","family":"Cerqueira","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Martins Silva","sequence":"additional","affiliation":[]},{"given":"J.","family":"Correia de S\u00e1","sequence":"additional","affiliation":[]},{"given":"J.","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"M. T.","family":"Mendon\u00e7a","sequence":"additional","affiliation":[]},{"given":"J.","family":"Pinheiro","sequence":"additional","affiliation":[]},{"given":"V.","family":"Salgado","sequence":"additional","affiliation":[]},{"given":"A. S.","family":"Correia","sequence":"additional","affiliation":[]},{"given":"J.","family":"Sequeira","sequence":"additional","affiliation":[]},{"given":"A.","family":"Costa","sequence":"additional","affiliation":[]},{"given":"L.","family":"Sousa","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"4726_CR1","first-page":"CD009371","volume":"4","author":"L La Mantia","year":"2016","unstructured":"La Mantia L, Tramacere I, Firwana B, Pacchetti I, Palumbo R, Filippini G (2016) Fingolimod for relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev 4:CD009371","journal-title":"Cochrane Database Syst Rev"},{"key":"4726_CR2","doi-asserted-by":"crossref","unstructured":"AlSharoqi IA, Aljumah M, Bohlega S, Boz C, Daif A, El-Koussa S, Inshasi J, Kurtuncu M, M\u00fcller T, Retief C, Sahraian MA, Shaygannejad V, Slassi I, Taha K, Zakaria M, S\u00f8rensen PS (2020) Immune reconstitution therapy or continuous immunosuppression for the management of active relapsing-remitting multiple sclerosis patients? A Narrative Review. Neurol Ther","DOI":"10.1007\/s40120-020-00187-3"},{"key":"4726_CR3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1097\/WNF.0b013e3181cbf825","volume":"33","author":"J Chun","year":"2010","unstructured":"Chun J, Hartung HP (2010) Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol 33:91\u2013101","journal-title":"Clin Neuropharmacol"},{"key":"4726_CR4","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s10072-017-3176-2","volume":"39","author":"G Dalla Costa","year":"2018","unstructured":"Dalla Costa G, Finardi A, Garzetti L, Carandini T, Comi G, Martinelli V, Furlan R (2018) Disease-modifying treatments modulate myeloid cells in multiple sclerosis patients. Neurol Sci 39:373\u2013376","journal-title":"Neurol Sci"},{"key":"4726_CR5","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1056\/NEJMoa0909494","volume":"362","author":"L Kappos","year":"2010","unstructured":"Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, Selmaj K, Agoropoulou C, Leyk M, Zhang-Auberson L, Burtin P (2010) A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362:387\u2013401","journal-title":"N Engl J Med"},{"key":"4726_CR6","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1056\/NEJMoa0907839","volume":"362","author":"JA Cohen","year":"2010","unstructured":"Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S, Aradhye S, Kappos L (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362:402\u2013415","journal-title":"N Engl J Med"},{"key":"4726_CR7","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S1474-4422(14)70049-3","volume":"13","author":"PA Calabresi","year":"2014","unstructured":"Calabresi PA, Radue EW, Goodin D, Jeffery D, Rammohan KW, Reder AT, Vollmer T, Agius MA, Kappos L, Stites T, Li B, Cappiello L, von Rosenstiel P, Lublin FD (2014) Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 13:545\u2013556","journal-title":"Lancet Neurol"},{"key":"4726_CR8","unstructured":"Fingolimod SPC. Approved by EMA. Updated 2017"},{"key":"4726_CR9","unstructured":"Direc\u00e7\u00e3o Geral de Sa\u00fade Portugal (2015) Norma de Orienta\u00e7\u00e3o Cl\u00ednica sobre Terap\u00eautica Modificadora da Esclerose M\u00faltipla em Idade Pedi\u00e1trica e no Adulto"},{"key":"4726_CR10","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1056\/NEJMoa1800149","volume":"379","author":"T Chitnis","year":"2018","unstructured":"Chitnis T, Arnold DL, Banwell B, Br\u00fcck W, Ghezzi A, Giovannoni G, Greenberg B, Krupp L, Rost\u00e1sy K, Tardieu M, Waubant E, Wolinsky JS, Bar-Or A, Stites T, Chen Y, Putzki N, Merschhemke M, G\u00e4rtner J (2018) Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. N Engl J Med 379:1017\u20131027","journal-title":"N Engl J Med"},{"key":"4726_CR11","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.msard.2016.01.003","volume":"6","author":"I Correia","year":"2016","unstructured":"Correia I, Batista S, Marques IB, Sousa M, Ferreira R, Nunes C, Macario MC, Sousa L (2016) The effectiveness of fingolimod in a Portuguese real-world population. Mult Scler Relat Disord 6:41\u201348","journal-title":"Mult Scler Relat Disord"},{"key":"4726_CR12","doi-asserted-by":"publisher","first-page":"e0176174","DOI":"10.1371\/journal.pone.0176174","volume":"12","author":"G Izquierdo","year":"2017","unstructured":"Izquierdo G, Damas F, Paramo MD, Ruiz-Pena JL, Navarro G (2017) The real-world effectiveness and safety of fingolimod in relapsing-remitting multiple sclerosis patients: an observational study. PLoS One 12:e0176174","journal-title":"PLoS One"},{"key":"4726_CR13","first-page":"205521731880163","volume":"4","author":"G Mazibrada","year":"2018","unstructured":"Mazibrada G, Sharples C, Perfect I (2018) Real-world experience of fingolimod in patients with multiple sclerosis (MS Fine): An observational study in the UK. Mult Scler J Exp Transl Clin 4:2055217318801638","journal-title":"Mult Scler J Exp Transl Clin"},{"key":"4726_CR14","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1111\/ene.13594","volume":"25","author":"C Zecca","year":"2018","unstructured":"Zecca C, Roth S, Findling O, Perriard G, Bachmann V, Pless ML, Baumann A, Kamm CP, Lalive PH, Czaplinski A (2018) Real-life long-term effectiveness of fingolimod in Swiss patients with relapsing-remitting multiple sclerosis. Eur J Neurol 25:762\u2013767","journal-title":"Eur J Neurol"},{"key":"4726_CR15","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s10072-016-2701-z","volume":"38","author":"A Laroni","year":"2017","unstructured":"Laroni A, Brogi D, Brescia Morra V, Guidi L, Pozzilli C, Comi G, Lugaresi A, Turrini R, Raimondi D, Uccelli A, Mancardi GL (2017) Safety and tolerability of fingolimod in patients with relapsing-remitting multiple sclerosis: results of an open-label clinical trial in Italy. Neurol Sci 38:53\u201359","journal-title":"Neurol Sci"},{"key":"4726_CR16","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/ana.22366","volume":"69","author":"CH Polman","year":"2011","unstructured":"Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292\u2013302","journal-title":"Ann Neurol"},{"key":"4726_CR17","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","volume":"33","author":"JF Kurtzke","year":"1983","unstructured":"Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 33:1444\u20131452","journal-title":"Neurology."},{"key":"4726_CR18","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1097\/WNF.0000000000000292","volume":"41","author":"AH Ribeiro de Barros","year":"2018","unstructured":"Ribeiro de Barros AH, Fiadeiro Sequeira JP, Lopes de Sousa AS, Chegancas Capela CM, Gomes Pedrosa RM, Dos Santos Manita MA (2018) Safety and Effectiveness of Fingolimod in Real-World Multiple Sclerosis Portuguese Patients. Clin Neuropharmacol 41:129\u2013135","journal-title":"Clin Neuropharmacol"},{"key":"4726_CR19","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s40261-016-0471-2","volume":"37","author":"V Ticha","year":"2017","unstructured":"Ticha V, Kodym R, Pocikova Z, Kadlecova P (2017) Real-World outcomes in fingolimod-treated patients with multiple sclerosis in the Czech Republic: results from the 12-month GOLEMS study. Clin Drug Investig 37:175\u2013186","journal-title":"Clin Drug Investig"},{"key":"4726_CR20","doi-asserted-by":"crossref","unstructured":"Mallada-Frechin J, Meca-Lallana V, Barrero F, Martinez-Gines ML, Marzo-Sola ME, Ricart J, Garcia E En Representacion de Los Investigadores Del Estudio Ms Next E (2018) [Efficacy and safety of fingolimod in routine clinical practice in patients with relapsing-remitting multiple sclerosis in Spain: an intermediate analysis of the MS NEXT study]. Rev Neurol 67:157\u2013167","DOI":"10.33588\/rn.6705.2017372"},{"key":"4726_CR21","doi-asserted-by":"crossref","unstructured":"Comi G, Pozzilli C, Morra VB, Bertolotto A, Sangalli F, Prosperini L, Carotenuto A, Iaffaldano P, Capobianco M, Colombo D, Nica M, Rizzoli S, Trojano M (2020) Effectiveness of fingolimod in real-world relapsing-remitting multiple sclerosis Italian patients: the GENIUS study. Neurol Sci","DOI":"10.1007\/s10072-020-04380-y"},{"key":"4726_CR22","doi-asserted-by":"crossref","unstructured":"Ziemssen T, Albrecht H, Haas J, Klotz L, Lang M, Lassek C, Schmidt S, Tackenberg B, Cornelissen C (2017) 5 years effectiveness of fingolimod in daily clinical practice: results of the non-interventional study PANGAEA documenting RRMS patients treated with fingolimod in Germany. Poster P6345 presented at the 69th American Academy of Neurology (AAN) annual meeting, April 22 \u2013 28, 2017, Boston","DOI":"10.1212\/WNL.88.16_supplement.P6.345"},{"key":"4726_CR23","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s12883-015-0342-0","volume":"15","author":"T Ziemssen","year":"2015","unstructured":"Ziemssen T, Kern R, Cornelissen C (2015) The PANGAEA study design - a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice. BMC Neurol 15:93","journal-title":"BMC Neurol"},{"key":"4726_CR24","doi-asserted-by":"crossref","unstructured":"Ziemssen T, Albrecht H, Haas J, Klotz L, Lang M, Lassek C, Schmidt S, Tackenberg B, Cornelissen C (2016) 4 years PANGAEA: long term data on effectiveness and safety from natalizumab patients switching to fingolimod in real world. Poster P6188 presented at the 68th American Academy of Neurology (AAN) annual meeting, April 15 \u2013 21, 2016, Vancouver","DOI":"10.1212\/WNL.86.16_supplement.P6.188"},{"key":"4726_CR25","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1007\/s40263-014-0185-z","volume":"28","author":"J Al-Hashel","year":"2014","unstructured":"Al-Hashel J, Ahmed SF, Behbehani R, Alroughani R (2014) Real-world use of fingolimod in patients with relapsing remitting multiple sclerosis: a retrospective study using the national multiple sclerosis registry in Kuwait. CNS Drugs 28:817\u2013824","journal-title":"CNS Drugs"},{"key":"4726_CR26","doi-asserted-by":"publisher","first-page":"129","DOI":"10.17712\/nsj.2018.2.20170434","volume":"23","author":"E Ouspid","year":"2018","unstructured":"Ouspid E, Razazian N, Moghadasi AN, Moradian N, Afshari D, Bostani A, Sariaslani P, Ansarian A (2018) Clinical effectiveness and safety of fingolimod in relapsing remitting multiple sclerosis in Western Iran. Neurosciences (Riyadh) 23:129\u2013134","journal-title":"Neurosciences (Riyadh)"},{"key":"4726_CR27","unstructured":"Ziemssen T, Albrecht H, Haas J, Klotz L, Lang M, Lassek C, Schmidt S, Tackenberg B, Cornelissen C (2016) 4 years PANGAEA: A 5-year non-interventional study of safety, effectiveness and pharmacoeconomic data for fingolimod patients in daily clinical practice \u2013 effectiveness update. Poster P3072 presented at the 68th American Academy of Neurology (AAN) annual meeting, April 15 \u2013 21, 2016, Vancouver"},{"key":"4726_CR28","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1212\/WNL.0000000000001462","volume":"84","author":"L Kappos","year":"2015","unstructured":"Kappos L, O'Connor P, Radue EW, Polman C, Hohlfeld R, Selmaj K, Ritter S, Schlosshauer R, von Rosenstiel P, Zhang-Auberson L, Francis G (2015) Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. Neurology. 84:1582\u20131591","journal-title":"Neurology."},{"key":"4726_CR29","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1002\/ana.25463","volume":"85","author":"BAC Cree","year":"2019","unstructured":"Cree BAC, Hollenbach JA, Bove R, Kirkish G, Sacco S, Caverzasi E, Bischof A, Gundel T, Zhu AH, Papinutto N, Stern WA, Bevan C, Romeo A, Goodin DS, Gelfand JM, Graves J, Green AJ, Wilson MR, Zamvil SS, Zhao C, Gomez R, Ragan NR, Rush GQ, Barba P, Santaniello A, Baranzini SE, Oksenberg JR, Henry RG, Hauser SL (2019) Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol 85:653\u2013666","journal-title":"Ann Neurol"},{"key":"4726_CR30","doi-asserted-by":"crossref","unstructured":"Ziemssen T, Albrecht H, Haas J, Klotz L, Lang M, Lassek C, Schmidt S, Tackenberg B, Cornelissen C (2017) 5 years safety of fingolimod in real world: First results from PANGAEA, a noninterventional study of RRMS patients treated with fingolimod, on safety and adherence after 5 years of fingolimod in daily clinical practice. Poster P5365 presented at the 69th American Academy of Neurology (AAN) annual meeting, April 22 \u2013 28, 2017, Boston","DOI":"10.1212\/WNL.88.16_supplement.P5.365"},{"key":"4726_CR31","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1001\/archneur.63.12.1686","volume":"63","author":"A Langer-Gould","year":"2006","unstructured":"Langer-Gould A, Popat RA, Huang SM, Cobb K, Fontoura P, Gould MK, Nelson LM (2006) Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review. Arch Neurol 63:1686\u20131691","journal-title":"Arch Neurol"}],"updated-by":[{"DOI":"10.1007\/s10072-020-04879-4","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T00:00:00Z","timestamp":1604880000000}}],"container-title":["Neurological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-020-04726-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10072-020-04726-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-020-04726-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:59:45Z","timestamp":1723683585000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10072-020-04726-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,30]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["4726"],"URL":"https:\/\/doi.org\/10.1007\/s10072-020-04726-6","relation":{},"ISSN":["1590-1874","1590-3478"],"issn-type":[{"value":"1590-1874","type":"print"},{"value":"1590-3478","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,30]]},"assertion":[{"value":"28 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2020","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s10072-020-04879-4","URL":"https:\/\/doi.org\/10.1007\/s10072-020-04879-4","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"S\u00f3nia Batista has received compensation as a speaker in meetings and for consulting and advisory board participation from Biogen, Bayer, Merck Serono,Novartis, Roche, and Sanofi-Genzyme.Ana Martins da Silva has received compensation as a speaker in meetings and for consulting, clinical trial research, and advisory board participation fromBiogen, Bayer, Merck Serono, Novartis, Roche, and Sanofi-Genzyme.L\u00edvia Sousa has received compensation as a speaker in meetings and for consulting, clinical trial research, and advisory board participation from Biogen,Bayer, Merck Serono, Novartis, Roche, and Sanofi-Genzyme.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The study protocol was approved by the local Ethics Committee. An informed consent was obtained from each participant and the research was conducted according to the principles of the Helsinki Declaration.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"An informed consent was obtained from each participant.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}