{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:25:04Z","timestamp":1785410704508,"version":"3.56.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Clinical research has offered many definitions and fragmented perspectives of joint morbidity in haemophilia. As joint damage, pain and mobility impairment can be present without clinical record of persistent bleeding, a person-centric joint morbidity characterisation remained a priority for the haemophilia community, giving rise to the \u2018problem joint\u2019 concept.<\/jats:p>\n            <jats:p>As diagnosing and managing joint morbidity is critical, the aim of this study was to analyse the holistic burden of problem joints in people with moderate or severe haemophilia A (HA).<\/jats:p>\n            <jats:p>Data from the \u2018Cost of Haemophilia in Europe: a Socioeconomic Survey\u2019 (CHESS) cross-sectional studies were used. CHESS-Paediatrics included male paediatric patients (\u2264\u200917\u00a0years) with congenital moderate or severe haemophilia, while CHESS II included adult males (\u2265\u200918\u00a0years) of any severity. Both studies sought to collect detailed information on the clinical, economic and humanistic burden of haemophilia.<\/jats:p>\n            <jats:p>Demographics, clinical outcomes, treatment regimen, adherence, physical activity, healthcare resource use and number of problem joints were evaluated and described by HA severity and number of problem joints (none, 1,\u2009\u2265\u20092).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In total, 1171 people with non-inhibitor moderate or severe HA from CHESS-Paediatrics (<jats:italic>n<\/jats:italic>\u2009=\u2009703) and CHESS II (<jats:italic>n<\/jats:italic>\u2009=\u2009468) were included in this analysis.<\/jats:p>\n            <jats:p>Presence of problem joints was more prevalent among CHESS II participants (44%) than in CHESS-Paediatrics (14%). Around two-thirds (67%) of CHESS-Paediatrics and 39% of CHESS II participants received prophylactic factor VIII replacement therapy. The presence of chronic pain was greater in severe HA with \u2018\u2009\u2265\u20092\u2019 problem joints in both cohorts. Clinical symptoms and bleed-related hospitalizations were more prevalent in the presence of problem joints regardless of HA severity in both cohorts.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This analysis of the CHESS population studies has expanded on previous work by examining the relevance of the problem joint measure of haemophilic morbidity and its associated burden. Adverse clinical symptoms and increased bleed-related hospitalizations were observed in the presence of problem joints in both children\/adolescents and adults across HA severities. Use of person-centric characterizations of joint morbidity may improve analysis of long-term outcomes and lead to improvements in future haemophilia care.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-024-03514-1","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T09:43:47Z","timestamp":1736761427000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An assessment of burden associated with problem joints in children and adults with moderate or severe haemophilia A: analysis of the CHESS-Paediatrics and CHESS II cross-sectional studies"],"prefix":"10.1186","volume":"20","author":[{"given":"Paul","family":"McLaughlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hortensia","family":"De la Corte-Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6768-1670","authenticated-orcid":false,"given":"Tom","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Nissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martynas","family":"Aizenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katya","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"O\u2019Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"3514_CR1","doi-asserted-by":"publisher","first-page":"540","DOI":"10.7326\/M19-1208","volume":"171","author":"A Iorio","year":"2019","unstructured":"Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C, et al. Establishing the prevalence and prevalence at birth of hemophilia in males: a meta-analytic approach using national registries. Ann Intern Med. 2019;171:540\u20136.","journal-title":"Ann Intern Med"},{"key":"3514_CR2","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1111\/jth.12672","volume":"12","author":"VS Blanchette","year":"2014","unstructured":"Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A. Definitions in hemophilia: Communication from the SSC of the ISTH. J Thromb Haemost. 2014;12:1935\u20139.","journal-title":"J Thromb Haemost"},{"key":"3514_CR3","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s11420-009-9140-9","volume":"6","author":"EC Rodriguez-Merchan","year":"2010","unstructured":"Rodriguez-Merchan EC. Musculoskeletal complications of hemophilia. HSS J. 2010;6:37\u201342.","journal-title":"HSS J"},{"key":"3514_CR4","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.2147\/PPA.S212723","volume":"13","author":"ML Witkop","year":"2019","unstructured":"Witkop ML, Lambing A, Nichols CD, Munn JE, Anderson TL, Tortella BJ. Interrelationship between depression, anxiety, pain, and treatment adherence in hemophilia: Results from a US cross-sectional survey. Patient Prefer Adherence. 2019;13:1577\u201387.","journal-title":"Patient Prefer Adherence"},{"key":"3514_CR5","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1111\/hae.13214","volume":"23","author":"M Witkop","year":"2017","unstructured":"Witkop M, Neff A, Buckner TW, Wang M, Batt K, Kessler CM, et al. Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study. Haemophilia. 2017;23:556\u201365.","journal-title":"Haemophilia"},{"key":"3514_CR6","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12955-018-0908-9","volume":"16","author":"J O\u2019Hara","year":"2018","unstructured":"O\u2019Hara J, Walsh S, Camp C, Mazza G, Carroll L, Hoxer C, et al. The impact of severe haemophilia and the presence of target joints on health-related quality-of-life. Health Qual Life Outcomes. 2018;16:84.","journal-title":"Health Qual Life Outcomes"},{"key":"3514_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13561-018-0185-7","volume":"8","author":"J O\u2019Hara","year":"2018","unstructured":"O\u2019Hara J, Walsh S, Camp C, Mazza G, Carroll L, Hoxer C, et al. The relationship between target joints and direct resource use in severe haemophilia. Heal Econ Rev. 2018;8:1\u20137.","journal-title":"Heal Econ Rev"},{"issue":"Suppl 4","key":"3514_CR8","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1111\/j.1365-2516.2004.00976.x","volume":"10","author":"K Mulder","year":"2004","unstructured":"Mulder K, Llin\u00e1s A. The target joint. Haemophilia. 2004;10(Suppl 4):152\u20136.","journal-title":"Haemophilia"},{"key":"3514_CR9","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1046\/j.1365-2516.2000.00439.x","volume":"6","author":"MJ Manco-Johnson","year":"2000","unstructured":"Manco-Johnson MJ, Nuss R, Funk S, Murphy J. Joint evaluation instruments for children and adults with haemophilia. Haemophilia. 2000;6:649\u201357.","journal-title":"Haemophilia"},{"key":"3514_CR10","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1111\/j.1365-2516.2006.01202.x","volume":"12","author":"S Donadel-Claeyssens","year":"2006","unstructured":"Donadel-Claeyssens S. European Paediatric Network for Haemophilia Management. Current co-ordinated activities of the PEDNET (European Paediatric Network for Haemophilia Management). Haemophilia. 2006;12:124\u20137.","journal-title":"Haemophilia"},{"key":"3514_CR11","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1365-2516.2006.01409.x","volume":"13","author":"S Ota","year":"2007","unstructured":"Ota S, Mclimont M, Carcao MD, Blanchette VS, Graham N, Paradis E, et al. Definitions for haemophilia prophylaxis and its outcomes: the Canadian consensus study. Haemophilia. 2007;13:12\u201320.","journal-title":"Haemophilia"},{"key":"3514_CR12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/hae.13666","volume":"25","author":"J O\u2019Hara","year":"2019","unstructured":"O\u2019Hara J, Khair K, McLaughlin P, O\u2019Mahony B, Laffan M, Pasi KJ, et al. \u201cProblem Joint\u201d a more patient relevant definition for joint morbidity in haemophilia (P154) - Poster presentations. Haemophilia. 2019;25:35\u2013188.","journal-title":"Haemophilia"},{"key":"3514_CR13","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1111\/hae.14731","volume":"29","author":"T Burke","year":"2023","unstructured":"Burke T, Rodriguez-Santana I, Chowdary P, Curtis R, Khair K, Laffan M, et al. Humanistic burden of problem joints for children and adults with haemophilia. Haemophilia. 2023;29:608\u201318.","journal-title":"Haemophilia"},{"key":"3514_CR14","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1182\/bloodadvances.2019001311","volume":"4","author":"BB Warren","year":"2020","unstructured":"Warren BB, Thornhill D, Stein J, Fadell M, Ingram JD, Funk S, et al. Young adult outcomes of childhood prophylaxis for severe hemophilia A: Results of the joint outcome continuation study. Blood Adv. 2020;4:2451\u20139.","journal-title":"Blood Adv"},{"key":"3514_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/hae.14046","volume":"26","author":"A Srivastava","year":"2020","unstructured":"Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al. WFH Guidelines for the Management of Hemophilia 3rd edition. Haemophilia. 2020;26:1\u2013158.","journal-title":"Haemophilia"},{"key":"3514_CR16","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1182\/blood.V99.7.2337","volume":"99","author":"K Fischer","year":"2002","unstructured":"Fischer K, van der Bom JG, Mauser-Bunschoten EP, Roosendaal G, Prejs R, de Kleijn P, et al. The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia. Blood. 2002;99:2337\u201341.","journal-title":"Blood"},{"key":"3514_CR17","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1055\/s-0031-1300954","volume":"38","author":"A Coppola","year":"2012","unstructured":"Coppola A, Tagliaferri A, Di Capua M, Franchini M. Prophylaxis in children with hemophilia: evidence-based achievements, old and new challenges. Semin Thromb Hemost. 2012;38:79\u201394.","journal-title":"Semin Thromb Hemost"},{"key":"3514_CR18","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/hae.14236","volume":"27","author":"P Chowdary","year":"2021","unstructured":"Chowdary P, Hermans C, Asghar S, Burke T, Nissen F, Aizenas M, et al. Evaluating the economic burden associated with problem joints, across moderate and severe haemophilia A, in children and adults: CHESS Paediatrics and CHESS II. Haemophilia. 2021;27:18\u2013181.","journal-title":"Haemophilia"},{"key":"3514_CR19","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1111\/hae.14766","volume":"29","author":"P Chowdary","year":"2023","unstructured":"Chowdary P, Nissen F, Burke T, Aizenas M, Czirok T, Dhillon H, et al. The humanistic and economic burden of problem joints for children and adults with moderate or severe haemophilia A: Analysis of the CHESS population studies. Haemophilia. 2023;29:753\u201360.","journal-title":"Haemophilia"},{"key":"3514_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-022-02300-1","volume":"17","author":"I Rodriguez-Santana","year":"2022","unstructured":"Rodriguez-Santana I, DasMahapatra P, Burke T, Hakimi Z, Bartelt-Hofer J, Nazir J, et al. Differential humanistic and economic burden of mild, moderate and severe haemophilia in european adults: a regression analysis of the CHESS II study. Orphanet J Rare Dis. 2022;17:1\u201310.","journal-title":"Orphanet J Rare Dis"},{"key":"3514_CR21","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1111\/hae.13777","volume":"25","author":"F Peyvandi","year":"2019","unstructured":"Peyvandi F, Tavakkoli F, Frame D, Quinn J, Kim B, Lawal A, et al. Burden of mild haemophilia A: systematic literature review. Haemophilia: Official J World Federat Hemophilia. 2019;25:755\u201363.","journal-title":"Haemophilia: Official J World Federat Hemophilia"},{"key":"3514_CR22","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1111\/hae.15116","volume":"30","author":"C Ay","year":"2024","unstructured":"Ay C, Mancuso ME, Matino D, Strike K, Pasta G. The haemophilia joint health score for the assessment of joint health in patients with haemophilia. Haemophilia. 2024;30:1265.","journal-title":"Haemophilia"},{"key":"3514_CR23","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1111\/hae.14734","volume":"29","author":"ME Mancuso","year":"2023","unstructured":"Mancuso ME, Holstein K, O\u2019Donnell JS, Lobet S, Klamroth R. FVIII Think Tank Study Group. Synovitis and joint health in patients with haemophilia: Statements from a European e-Delphi consensus study. Haemophilia. 2023;29:619\u201328.","journal-title":"Haemophilia"},{"key":"3514_CR24","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s13023-017-0660-y","volume":"12","author":"J O\u2019Hara","year":"2017","unstructured":"O\u2019Hara J, Hughes D, Camp C, Burke T, Carroll L, Diego DAG. The cost of severe haemophilia in Europe: the CHESS study. Orphanet J Rare Dis. 2017;12:106.","journal-title":"Orphanet J Rare Dis"},{"key":"3514_CR25","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1182\/blood-2020-134658","volume":"136","author":"K Khair","year":"2020","unstructured":"Khair K, Nissen F, Silkey M, Burke T, Shang A, Aizenas M, et al. Effect of moderate and severe hemophilia a on daily life in children and their caregivers: A CHESS paediatrics study analysis. Blood. 2020;136:43\u20135.","journal-title":"Blood"},{"key":"3514_CR26","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1182\/blood-2020-140950","volume":"136","author":"T Burke","year":"2020","unstructured":"Burke T, Rodriguez Santana I, Chowdary P, Curtis R, Khair K, Laffan M, et al. Examination and validation of a patient-centric joint metric: \u201cproblem joint\u201d; empirical evidence from the CHESS US dataset. Blood. 2020;136:25\u20136.","journal-title":"Blood"},{"key":"3514_CR27","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1111\/hae.14302","volume":"27","author":"J O\u2019Hara","year":"2021","unstructured":"O\u2019Hara J, Noone D, Jain M, Pedra G, Landis S, Hawes C, et al. Clinical attributes and treatment characteristics are associated with work productivity and activity impairment in people with severe haemophilia A. Haemophilia. 2021;27:938\u201346.","journal-title":"Haemophilia"},{"key":"3514_CR28","doi-asserted-by":"publisher","first-page":"505","DOI":"10.2147\/JBM.S363028","volume":"13","author":"E Ferri Grazzi","year":"2022","unstructured":"Ferri Grazzi E, Sun SX, Burke T, O\u2019Hara J. The impact of pharmacokinetic-guided prophylaxis on clinical outcomes and healthcare resource utilization in hemophilia a patients: real-world evidence from the CHESS II study. JBM. 2022;13:505\u201316.","journal-title":"JBM"},{"key":"3514_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-022-02301-0","volume":"17","author":"I Rodriguez-Santana","year":"2022","unstructured":"Rodriguez-Santana I, DasMahapatra P, Burke T, Hakimi Z, Bartelt-Hofer J, Nazir J, et al. Health-related quality of life, direct medical and societal costs among children with moderate or severe haemophilia in Europe: multivariable models of the CHESS-PAEDs study. Orphanet J Rare Dis. 2022;17:1\u20139.","journal-title":"Orphanet J Rare Dis"},{"key":"3514_CR30","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14731","author":"T Burke","year":"2022","unstructured":"Burke T, Rodriguez-Santana I, Chowdary P, Curtis R, Khair K, Laffan M, et al. Humanistic burden of problem joints for children and adults with haemophilia. Haemophilia. 2022. https:\/\/doi.org\/10.1111\/hae.14731.","journal-title":"Haemophilia"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03514-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03514-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03514-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T21:41:38Z","timestamp":1736804498000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03514-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,13]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3514"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03514-1","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,13]]},"assertion":[{"value":"5 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The CHESS II and CHESS Paediatrics studies were approved by the Research Ethics Sub Committee of the Faculty of Health and Social care within the University of Chester and conducted in correspondence with regional and relevant guidelines, and were conducted in collaboration with the UK Haemophilia Society and governed by a steering committees chaired by Mr. Brian O\u2019Mahony (CHESS II) and Dr. Kate Khair (CHESS Paediatrics). Patient consent was obtained via tick box selection for the patient-reported element of the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"TB and JOH are employees of HCD Economics which received research funding for this study from F. Hoffmann-La Roche Ltd. FN, MK and AN are employees of F. Hoffmann-La Roche Ltd. PM and HCR have no relevant relationships or financial interests related to this work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18"}}