{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T18:49:26Z","timestamp":1774032566139,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100014382","name":"Ipsen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014382","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Calcif Tissue Int"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder that leads to heterotopic ossification (HO), resulting in progressive restriction of physical function. In this study, low-dose, whole-body computed tomography (WBCT) and dual energy X-ray absorptiometry (DXA) were evaluated to determine the preferred method for assessing total body burden of HO in patients with FOP. This was a non-interventional, two-part natural history study in patients with FOP (NCT02322255; date of registration: December 2014). In Part A (described here), WBCT and DXA scans were individually assessed for HO presence and severity across 15 anatomical regions. All images were independently reviewed by an expert imaging panel. Ten adult patients were enrolled across four sites. The sensitivity to HO presence and severity varied considerably between the two imaging modalities, with WBCT demonstrating HO in more body regions than DXA (76\/138 [55%] versus 47\/113 [42%]) evaluable regions). Inability to evaluate HO presence, due to overlapping body regions (positional ambiguity), occurred less frequently by WBCT than by DXA (mean number of non-evaluable regions per scan 1.2 [standard deviation: 1.5] versus 2.4 [1.4]). Based on the increased sensitivity and decreased positional ambiguity of low-dose WBCT versus DXA in measuring HO in patients with FOP, low-dose WBCT was chosen as the preferred imaging for measuring HO. Therefore, low-dose WBCT was carried forward to Part B of the natural history study, which evaluated disease progression over 36\u00a0months in a larger population of patients with FOP.<\/jats:p>","DOI":"10.1007\/s00223-021-00877-6","type":"journal-article","created":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T08:02:56Z","timestamp":1627718576000},"page":"615-625","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Whole-body Computed Tomography Versus Dual Energy X\u2011ray Absorptiometry for Assessing Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva"],"prefix":"10.1007","volume":"109","author":[{"given":"Sarah E.","family":"Warner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick S.","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Pignolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacy E.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward C.","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"De Cunto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Di Rocco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Harnett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Grogan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry K.","family":"Genant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"877_CR1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1385\/BMM:3:3-4:201","volume":"3","author":"EM Shore","year":"2005","unstructured":"Shore EM, Feldman GJ, Xu M, Kaplan FS (2005) The genetics of fibrodysplasia ossificans progressiva. Clin Rev Bone Miner Metab 3:201\u2013204","journal-title":"Clin Rev Bone Miner Metab"},{"key":"877_CR2","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13023-017-0674-5","volume":"12","author":"G Baujat","year":"2017","unstructured":"Baujat G, Choquet R, Bou\u00e9e S, Jeanbat V, Courouve L, Ruel A, Michot C, Le Quan Sang KH, Lapidus D, Messiaen C, Landais P, Cormier-Daire V (2017) Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: an estimate based on a record linkage of two national databases. Orphanet J Rare Dis 12:123","journal-title":"Orphanet J Rare Dis"},{"key":"877_CR3","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.cytogfr.2009.10.006","volume":"20","author":"FS Kaplan","year":"2009","unstructured":"Kaplan FS, Pignolo RJ, Shore EM (2009) The FOP metamorphogene encodes a novel type I receptor that dysregulates BMP signaling. Cytokine Growth Factor Rev 20:399\u2013407","journal-title":"Cytokine Growth Factor Rev"},{"key":"877_CR4","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1002\/humu.20868","volume":"30","author":"FS Kaplan","year":"2009","unstructured":"Kaplan FS, Xu M, Seemann P, Connor M, Glaser DL, Carroll L, Delai P, Fastnacht-Urban E, Forman SJ, Gillessen-Kaesbach G, Hoover-Fong J, K\u00f6ster B, Pauli RM, Reardon W, Zaidi SA, Zasloff M, Morhart R, Mundlos S, Groppe J, Shore EM (2009) Classic and atypical FOP phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat 30:379\u2013390","journal-title":"Hum Mutat"},{"key":"877_CR5","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/ng1783","volume":"38","author":"EM Shore","year":"2006","unstructured":"Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS (2006) A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38:525\u2013527","journal-title":"Nat Genet"},{"key":"877_CR6","doi-asserted-by":"publisher","first-page":"e10172","DOI":"10.1002\/jbm4.10172","volume":"3","author":"C Meyers","year":"2019","unstructured":"Meyers C, Lisiecki J, Miller S, Levin A, Fayad L, Ding C, Sono T, McCarthy E, Levi B, James AW (2019) Heterotopic ossification: a comprehensive review. JBMR Plus 3:e10172","journal-title":"JBMR Plus"},{"key":"877_CR7","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s11832-015-0704-6","volume":"9","author":"F Ortiz-Agapito","year":"2015","unstructured":"Ortiz-Agapito F, Colmenares-Bonilla D (2015) Quality of life of patients with fibrodysplasia ossificans progressiva. J Child Orthop 9:489\u2013493","journal-title":"J Child Orthop"},{"key":"877_CR8","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s13023-017-0659-4","volume":"12","author":"M Di Rocco","year":"2017","unstructured":"Di Rocco M, Baujat G, Bertamino M, Brown M, De Cunto CL, Delai PLR, Eekhoff EMW, Haga N, Hsiao E, Keen R, Morhart R, Pignolo RJ, Kaplan FS (2017) International physician survey on management of FOP: a modified Delphi study. Orphanet J Rare Dis 12:110","journal-title":"Orphanet J Rare Dis"},{"key":"877_CR9","first-page":"865","volume-title":"Primer on the metabolic bone diseases and disorders of mineral metabolism","author":"FS Kaplan","year":"2019","unstructured":"Kaplan FS, Pignolo RJ, Al Mukaddam M, Shore EM (2019) Genetic disorders of heterotopic ossification: fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. In: Bilezikian JP (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 9th edn. Wiley, Washington, D.C., pp 865\u2013870","edition":"9"},{"key":"877_CR10","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1080\/21678707.2017.1304211","volume":"5","author":"FS Kaplan","year":"2017","unstructured":"Kaplan FS, Pignolo RJ, Al Mukaddam MM, Shore EM (2017) Hard targets for a second skeleton: therapeutic horizons for fibrodysplasia ossificans progressiva (FOP). Expert Opin Orphan Drugs 5:291\u2013294","journal-title":"Expert Opin Orphan Drugs"},{"issue":"Suppl 2","key":"877_CR11","first-page":"437","volume":"10","author":"RJ Pignolo","year":"2013","unstructured":"Pignolo RJ, Shore EM, Kaplan FS (2013) Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic horizons. Pediatr Endocrinol Rev 10(Suppl 2):437\u2013448","journal-title":"Pediatr Endocrinol Rev"},{"key":"877_CR12","unstructured":"Kaplan FS, Al Mukaddam M, Baujat G, Brown M, Cali A, Cho T-J, Crowe C, De Cunto C, Delai P, Diecidue R, Di Rocco M, Eekhoff EMW, Friedman C, Grunwald Z, Haga N, Hsiao E, Keen R, Kitterman J, Levy C, Morhart R, Netelenbos C, Scott C, Shore EM, Zasloff M, Zhang K, Pignolo RJ (2019) The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. IFOPA https:\/\/www.ifopa.org\/updated_fop_treatment_guidelines_released. Accessed 5 Nov 2020"},{"key":"877_CR13","unstructured":"ClinicalTrials.gov (2014) Identifier: NCT02322255 A natural history study of fibrodysplasia ossificans progressiva (FOP). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02322255. Accessed 5 Nov 2020"},{"key":"877_CR14","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.bone.2017.08.011","volume":"109","author":"M Al Mukaddam","year":"2018","unstructured":"Al Mukaddam M, Rajapakse CS, Pignolo RJ, Kaplan FS, Smith SE (2018) Imaging assessment of fibrodysplasia ossificans progressiva: qualitative, quantitative and questionable. Bone 109:147\u2013152","journal-title":"Bone"},{"key":"877_CR15","doi-asserted-by":"publisher","first-page":"113","DOI":"10.5812\/kmp.iranjradiol.17351065.3392","volume":"8","author":"J Hashemi","year":"2011","unstructured":"Hashemi J, Shahfarhat A, Beheshtian A (2011) Fibrodysplasia ossificans progressiva: report of a case and review of articles. Iran J Radiol 8:113\u2013117","journal-title":"Iran J Radiol"},{"key":"877_CR16","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.bone.2013.09.002","volume":"57","author":"W Zhang","year":"2013","unstructured":"Zhang W, Zhang K, Song L, Pang J, Ma H, Shore EM, Kaplan FS, Wang P (2013) The phenotype and genotype of fibrodysplasia ossificans progressiva in China: a report of 72 cases. Bone 57:386\u2013391","journal-title":"Bone"},{"key":"877_CR17","doi-asserted-by":"crossref","unstructured":"Kaplan FS, Strear CM, Zasloff MA (1994) Radiographic and scintigraphic features of modeling and remodeling in the heterotopic skeleton of patients who have fibrodysplasia ossificans progressiva. Clin Orthop Relat Res (304):238\u2013247","DOI":"10.1097\/00003086-199407000-00037"},{"key":"877_CR18","first-page":"454","volume":"6","author":"O Rogoveanu","year":"2013","unstructured":"Rogoveanu O, Traistaru R, Streba CT, Stoica Z, Popescu R (2013) Clinical, evolution and therapeutical considerations upon a case of fibrodysplasia ossificans progressiva (FOP). J Med Life 6:454\u2013458","journal-title":"J Med Life"},{"key":"877_CR19","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1007\/s00247-009-1281-y","volume":"39","author":"R Kulwin","year":"2009","unstructured":"Kulwin R, Binkovitz LA (2009) PET\/CT of fibrodysplasia ossificans progressiva. Pediatr Radiol 39:991\u2013994","journal-title":"Pediatr Radiol"},{"key":"877_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bone.2019.03.009","volume":"124","author":"E Botman","year":"2019","unstructured":"Botman E, Raijmakers PGHM, Yaqub M, Teunissen B, Netelenbos C, Lubbers W, Schwarte LA, Micha D, Bravenboer N, Schoenmaker T, de Vries TJ, Pals G, Smit JM, Koolwijk P, Trotter DG, Lammertsma AA, Eekhoff EMW (2019) Evolution of heterotopic bone in fibrodysplasia ossificans progressiva: an [18F]NaF PET\/CT study. Bone 124:1\u20136","journal-title":"Bone"},{"key":"877_CR21","unstructured":"ALARA Principle (2008) In: Baert AL (ed) Encyclopedia of diagnostic imaging. Springer, Berlin, Heidelberg"},{"key":"877_CR22","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.bone.2017.04.015","volume":"101","author":"FS Kaplan","year":"2017","unstructured":"Kaplan FS, Al Mukaddam M, Pignolo RJ (2017) A cumulative analogue joint involvement scale (CAJIS) for fibrodysplasia ossificans progressiva (FOP). Bone 101:123\u2013128","journal-title":"Bone"},{"key":"877_CR23","doi-asserted-by":"publisher","first-page":"215","DOI":"10.2106\/00004623-199302000-00008","volume":"75","author":"RB Cohen","year":"1993","unstructured":"Cohen RB, Hahn GV, Tabas JA, Peeper J, Levitz CL, Sando A, Sando N, Zasloff M, Kaplan FS (1993) The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg Am 75:215\u2013219","journal-title":"J Bone Joint Surg Am"},{"key":"877_CR24","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1002\/jbmr.2728","volume":"31","author":"RJ Pignolo","year":"2016","unstructured":"Pignolo RJ, Bedford-Gay C, Liljesthr\u00f6m M, Durbin-Johnson BP, Shore EM, Rocke DM, Kaplan FS (2016) The natural history of flare-ups in fibrodysplasia ossificans progressiva (FOP): a comprehensive global assessment. J Bone Miner Res 31:650\u2013656","journal-title":"J Bone Miner Res"},{"key":"877_CR25","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.bone.2017.06.009","volume":"109","author":"RJ Pignolo","year":"2018","unstructured":"Pignolo RJ, Durbin-Johnson BP, Rocke DM, Kaplan FS (2018) Joint-specific risk of impaired function in fibrodysplasia ossificans progressiva (FOP). Bone 109:124\u2013133","journal-title":"Bone"},{"key":"877_CR26","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1111\/bcp.13777","volume":"85","author":"EC Hsiao","year":"2019","unstructured":"Hsiao EC, Di Rocco M, Cali A, Zasloff M, Al Mukaddam M, Pignolo RJ, Grunwald Z, Netelenbos C, Keen R, Baujat G, Brown MA, Cho TJ, De Cunto C, Delai P, Haga N, Morhart R, Scott C, Zhang K, Diecidue RJ, Friedman CS, Kaplan FS, Eekhoff EMW (2019) Special considerations for clinical trials in fibrodysplasia ossificans progressiva (FOP). Br J Clin Pharmacol 85:1199\u20131207","journal-title":"Br J Clin Pharmacol"},{"key":"877_CR27","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s00247-006-0153-y","volume":"37","author":"LA Binkovitz","year":"2007","unstructured":"Binkovitz LA, Henwood MJ (2007) Pediatric DXA: technique and interpretation. Pediatr Radiol 37:21\u201331","journal-title":"Pediatr Radiol"},{"key":"877_CR28","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.bone.2017.06.010","volume":"104","author":"J Shepherd","year":"2017","unstructured":"Shepherd J, Ng B, Sommer M, Heymsfield SB (2017) Body composition by DXA. Bone 104:101\u2013105","journal-title":"Bone"},{"key":"877_CR29","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/1750-1172-6-80","volume":"6","author":"RJ Pignolo","year":"2011","unstructured":"Pignolo RJ, Shore EM, Kaplan FS (2011) Fibrodysplasia ossificans progressiva: clinical and genetic aspects. Orphanet J Rare Dis 6:80","journal-title":"Orphanet J Rare Dis"},{"key":"877_CR30","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.2967\/jnumed.109.065912","volume":"50","author":"AM Alessio","year":"2009","unstructured":"Alessio AM, Kinahan PE, Manchanda V, Ghioni V, Aldape L, Parisi MT (2009) Weight-based, low-dose pediatric whole-body PET\/CT protocols. J Nucl Med 50:1570\u20131577","journal-title":"J Nucl Med"},{"key":"877_CR31","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ejrad.2004.04.015","volume":"54","author":"M Horger","year":"2005","unstructured":"Horger M, Claussen CD, Bross-Bach U, Vonthein R, Trabold T, Heuschmid M, Pfannenberg C (2005) Whole-body low-dose multidetector row-CT in the diagnosis of multiple myeloma: an alternative to conventional radiography. Eur J Radiol 54:289\u2013297","journal-title":"Eur J Radiol"},{"key":"877_CR32","unstructured":"United States Environmental Protection Agency (2019) Radiation sources and doses. https:\/\/www.epa.gov\/radiation\/radiation-sources-and-doses. Accessed 5 Nov 2020"},{"key":"877_CR33","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s13023-019-1068-7","volume":"14","author":"RJ Pignolo","year":"2019","unstructured":"Pignolo RJ, Baujat G, Brown MA, De Cunto C, Di Rocco M, Hsiao EC, Keen R, Al Mukaddam M, Sang KLQ, Wilson A, White B, Grogan DR, Kaplan FS (2019) Natural history of fibrodysplasia ossificans progressiva: cross-sectional analysis of annotated baseline phenotypes. Orphanet J Rare Dis 14:98","journal-title":"Orphanet J Rare Dis"}],"container-title":["Calcified Tissue International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-021-00877-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00223-021-00877-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-021-00877-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T13:05:38Z","timestamp":1634821538000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00223-021-00877-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,31]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["877"],"URL":"https:\/\/doi.org\/10.1007\/s00223-021-00877-6","relation":{},"ISSN":["0171-967X","1432-0827"],"issn-type":[{"value":"0171-967X","type":"print"},{"value":"1432-0827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,31]]},"assertion":[{"value":"26 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"SEW: Employee of PAREXEL International (dba Calyx); FSK: Research investigator: Ipsen, Regeneron; Advisory board: IFOPA Medical Advisory Board; Founder and Immediate Past-President of the International Clinical Council (ICC) on FOP; Chair of the Publications Committee of the ICC; RJP: Research investigator: Ipsen, Regeneron; Advisory board: President of the International Clinical Council on FOP; Chair of the Publications Committee for the IFOPA Registry Medical Advisory Board; SES: None declared; ECH: Advisory board (all voluntary): Fibrous Dysplasia Foundation, IFOPA Registry Medical Advisory Board, International Clinical Council on FOP; Research support: International FOP Association, Ipsen, National Institutes of Health, Radiant Hope Foundation; Prior research support: Regeneron, Neurocrine Biosciences Inc; Research investigator: Ipsen; CDC: Research investigator: Ipsen; MDR: Advisory board: Ipsen; Research investigator: Ipsen, Regeneron; HKG: Consultant for Agnovos, Amgen, AstraZeneca, Bioclinica, BioMarin, Ipsen, Medimmune, Medtronic, Radius and Regeneron; KH, DG: Employees of Ipsen.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Although not a clinical trial involving an investigational agent, this study was conducted in accordance with the principles that have their origin in the Declaration of Helsinki, inclusive of any subsequent amendment(s), and that are consistent with the International Council for Harmonization (ICH) Good Clinical Practice (GCP), European Union Directive 2001\/20\/EC, United States Food and Drug Administration (FDA) Code of Federal Regulations, and other applicable local regulatory requirement(s), whichever affords greater patient protection. The original protocol, all protocol amendments, and informed consent\/assent forms and updates were reviewed and approved by the corresponding Institutional Review Board (IRB) or Independent Ethics Committee (IEC) at each site in accordance with local regulatory requirements.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Prior to participation in the study, the Investigator and\/or delegate fully explained to the patients and\/or parents all aspects of the study that were relevant to the decision to participate. Informed consent was documented by means of a written, signed, and dated consent form, prior to study initiation.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Participants provided informed consent for the anonymized publication of the results of the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}]}}