{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:58:46Z","timestamp":1793948326092,"version":"4.8.0"},"reference-count":45,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K006525\/1"],"award-info":[{"award-number":["MR\/K006525\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["NIWA1"],"award-info":[{"award-number":["NIWA1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2019,9,25]]},"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To describe the epidemiology of diagnosed hypermobility spectrum disorder (HSD) and Ehlers-Danlos syndromes (EDS) using linked electronic medical records. To examine whether these conditions remain rare and primarily affect the musculoskeletal system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Nationwide linked electronic cohort and nested case\u2013control study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Routinely collected data from primary care and hospital admissions in Wales, UK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>People within the primary care or hospital data systems with a coded diagnosis of EDS or joint hypermobility syndrome (JHS) between 1 July 1990 and 30 June 2017.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>Combined prevalence of JHS and EDS in Wales. Additional diagnosis and prescription data in those diagnosed with EDS or JHS compared with matched controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found 6021 individuals (men: 30%, women: 70%) with a diagnostic code of either EDS or JHS. This gives a diagnosed point prevalence of 194.2 per 100\u2009000 in 2016\/2017 or roughly 10 cases in a practice of 5000 patients. There was a pronounced gender difference of 8.5 years (95%\u2009CI: 7.70 to 9.22) in the mean age at diagnosis. EDS or JHS was not only associated with high odds for other musculoskeletal diagnoses and drug prescriptions but also with significantly higher odds of a diagnosis in other disease categories (eg, mental health, nervous and digestive systems) and higher odds of a prescription in most disease categories (eg, gastrointestinal and cardiovascular drugs) within the 12 months before and after the first recorded diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EDS and JHS (since March 2017 classified as EDS or HSD) have historically been considered rare diseases only affecting the musculoskeletal system and soft tissues. These data demonstrate that both these assertions should be reconsidered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-031365","type":"journal-article","created":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T01:26:10Z","timestamp":1572917170000},"page":"e031365","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":254,"title":["Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case\u2013control comparison"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-6271","authenticated-orcid":false,"given":"Joanne C","family":"Demmler","sequence":"first","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J","family":"Reinhold","sequence":"additional","affiliation":[{"name":"Royal College of General Practitioners, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Choy","sequence":"additional","affiliation":[{"name":"School of Medicine, Cardiff University, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-000X","authenticated-orcid":false,"given":"Ronan A","family":"Lyons","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinead T","family":"Brophy","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"2025120521004723000_9.11.e031365.1","unstructured":"Cecil RLF , Goldman L , Bennett JC . Cecil textbook of medicine: W. B. Saunders, 2000."},{"key":"2025120521004723000_9.11.e031365.2","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1002\/acr.21979","article-title":"Modest association of joint hypermobility with disabling and limiting musculoskeletal pain: results from a large-scale General population-based survey","volume":"65","author":"Mulvey","year":"2013","journal-title":"Arthritis Care Res"},{"key":"2025120521004723000_9.11.e031365.3","unstructured":"Commission of the European Communities . Commission of the European communities communication from the Commission to the European Parliament, the Council, the European economic and social Committee and the Committee of the regions on rare diseases: Europe's challenges. Brussels: Commission of the European Communities, 2008."},{"key":"2025120521004723000_9.11.e031365.4","doi-asserted-by":"crossref","first-page":"kew478","DOI":"10.1093\/rheumatology\/kew478","article-title":"Establishment and baseline characteristics of a nationwide Danish cohort of patients with Ehlers-Danlos syndrome","volume":"56","author":"Kulas S\u00f8borg","year":"2017","journal-title":"Rheumatology"},{"key":"2025120521004723000_9.11.e031365.5","doi-asserted-by":"crossref","unstructured":"Cederl\u00f6f M , Larsson H , Lichtenstein P , et al . Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers\u2013Danlos syndrome or hypermobility syndrome and their siblings. BMC Psychiatry 2016;16.doi:10.1186\/s12888-016-0922-6","DOI":"10.1186\/s12888-016-0922-6"},{"key":"2025120521004723000_9.11.e031365.6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1742-1241.2003.tb10455.x","article-title":"A simple questionnaire to detect hypermobility: an adjunct to the assessment of patients with diffuse musculoskeletal pain","volume":"57","author":"Hakim","year":"2003","journal-title":"Int J Clin Pract"},{"key":"2025120521004723000_9.11.e031365.7","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31538"},{"key":"2025120521004723000_9.11.e031365.8","doi-asserted-by":"crossref","unstructured":"Gazit Y , Jacob G , Grahame R . Ehlers-Danlos Syndrome-Hypermobility type: a much neglected multisystemic disorder. Rambam Maimonides Med J 2016;7. doi:doi:10.5041\/RMMJ.10261","DOI":"10.5041\/RMMJ.10261"},{"key":"2025120521004723000_9.11.e031365.9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2012.01858.x"},{"key":"2025120521004723000_9.11.e031365.10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/ajmg.c.31543","article-title":"Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome-Hypermobile type","volume":"175","author":"Hakim","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2025120521004723000_9.11.e031365.11","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/ajmg.c.31546","article-title":"Gastrointestinal involvement in the Ehlers-Danlos syndromes","volume":"175","author":"Fikree","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2025120521004723000_9.11.e031365.12","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/ajmg.c.31544","article-title":"Psychiatric and psychological aspects in the Ehlers-Danlos syndromes","volume":"175","author":"Bulbena","year":"2017","journal-title":"Am. J. Med. Genet."},{"key":"2025120521004723000_9.11.e031365.13","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/ajmg.c.31542","article-title":"Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type","volume":"175","author":"Hakim","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2025120521004723000_9.11.e031365.14","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/ajmg.c.31554","article-title":"Pain management in the Ehlers-Danlos syndromes","volume":"175","author":"Chopra","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2025120521004723000_9.11.e031365.15","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1007\/s00192-015-2896-1","article-title":"Association between joint hypermobility and pelvic organ prolapse in women: a systematic review and meta-analysis","volume":"27","author":"Veit-Rubin","year":"2016","journal-title":"Int Urogynecol J"},{"key":"2025120521004723000_9.11.e031365.16","doi-asserted-by":"crossref","unstructured":"Hugon-Rodin J , Leb\u00e8gue G , Becourt S , et al . Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type Ehlers-Danlos syndrome: a cohort study. Orphanet J Rare Dis 2016;11.doi:10.1186\/s13023-016-0511-2","DOI":"10.1186\/s13023-016-0511-2"},{"key":"2025120521004723000_9.11.e031365.17","doi-asserted-by":"crossref","first-page":"217","DOI":"10.12968\/bjom.2018.26.4.217","article-title":"Hypermobile Ehlers-Danlos syndrome during pregnancy, birth and beyond","volume":"26","author":"Pezaro","year":"2018","journal-title":"Br J Midwifery"},{"key":"2025120521004723000_9.11.e031365.18","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/ajmg.c.31555","article-title":"Mast cell disorders in Ehlers-Danlos syndrome","volume":"175","author":"Seneviratne","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2025120521004723000_9.11.e031365.19","doi-asserted-by":"crossref","unstructured":"Cheung I , Vadas P . A New Disease Cluster: Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, and Ehlers-Danlos Syndrome. Journal of Allergy and Clinical Immunology 2015;135.doi:10.1016\/j.jaci.2014.12.1146","DOI":"10.1016\/j.jaci.2014.12.1146"},{"key":"2025120521004723000_9.11.e031365.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2004.07.023"},{"key":"2025120521004723000_9.11.e031365.21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/ajmg.c.31431","article-title":"Gastrointestinal and nutritional issues in joint hypermobility syndrome\/ehlers-danlos syndrome, hypermobility type","volume":"169","author":"Castori","year":"2015","journal-title":"Am J Med Genet"},{"key":"2025120521004723000_9.11.e031365.22","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/cmv026"},{"key":"2025120521004723000_9.11.e031365.23","unstructured":"EURORDIS AKFF . The voice of 12,000 patients. experiences and expectations of rare disease patients on diagnosis and care in Europe. Eurordis, 2009."},{"key":"2025120521004723000_9.11.e031365.24","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1071\/AH080766","article-title":"A decade of data linkage in Western Australia: strategic design, applications and benefits of the WA data linkage system","volume":"32","author":"Holman","year":"2008","journal-title":"Australian Health Review"},{"key":"2025120521004723000_9.11.e031365.25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0126105","article-title":"The cost of ankylosing spondylitis in the UK using linked routine and patient-reported survey data","volume":"10","author":"Cooksey","year":"2015","journal-title":"PLoS One"},{"key":"2025120521004723000_9.11.e031365.26","doi-asserted-by":"crossref","unstructured":"Lyons RA , Jones KH , John G , et al . The Sail databank: linking multiple health and social care datasets. BMC Med Inform Decis Mak 2009;9.doi:10.1186\/1472-6947-9-3","DOI":"10.1186\/1472-6947-9-3"},{"key":"2025120521004723000_9.11.e031365.27","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.300.6732.1092"},{"key":"2025120521004723000_9.11.e031365.28","unstructured":"World Health Organization . Icd-10: international statistical classification of diseases and related health problems. World Health Organization, 2016."},{"key":"2025120521004723000_9.11.e031365.29","unstructured":"R Foundation for Statistical Computing . R: A Language and Environment for Statistical Computing [program]. Vienna, Austria R Foundation for Statistical Computing; 2017."},{"key":"2025120521004723000_9.11.e031365.30","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh557"},{"key":"2025120521004723000_9.11.e031365.31","first-page":"263","article-title":"Joint hypermobility syndrome is highly prevalent in general rheumatology clinics, its occurrence and clinical presentation being gender, age and race-related","volume":"65","author":"Grahame","year":"2006","journal-title":"Annals of the Rheumatic Diseases"},{"key":"2025120521004723000_9.11.e031365.32","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1002\/ajmg.a.37733","article-title":"Ehlers-Danlos syndrome(s) mimicking child abuse: Is there an impact on clinical practice?","volume":"170","author":"Castori","year":"2016","journal-title":"Am J Med Genet A"},{"key":"2025120521004723000_9.11.e031365.33","unstructured":"Association for Improvements in Maternity Services (AIMS) . The child protection system in England: written evidence submitted by the association for improvements in the maternity services (aims), 2011. Available: http:\/\/www.publications.parliament.uk\/pa\/cm201012\/cmselect\/cmeduc\/writev\/1514\/cp29.htm [Accessed 14 Feb 2019]."},{"key":"2025120521004723000_9.11.e031365.34","doi-asserted-by":"publisher","DOI":"10.3109\/09638280903178407"},{"key":"2025120521004723000_9.11.e031365.35","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1093\/rheumatology\/kex148","article-title":"The natural history of children with joint hypermobility syndrome and Ehlers\u2013Danlos hypermobility type: a longitudinal cohort study","volume":"56","author":"Scheper","year":"2017","journal-title":"Rheumatology"},{"key":"2025120521004723000_9.11.e031365.36","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/ajmg.c.31545","article-title":"The evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome\/hypermobile Ehlers Danlos syndrome","volume":"175","author":"Engelbert","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2025120521004723000_9.11.e031365.37","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/ajmg.c.31551","article-title":"Orthopaedic management of the Ehlers-Danlos syndromes","volume":"175","author":"Ericson","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2025120521004723000_9.11.e031365.38","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000449106","article-title":"Increased need for gastrointestinal surgery and increased risk of surgery-related complications in patients with Ehlers-Danlos syndrome: a systematic review","volume":"34","author":"Kulas S\u00f8borg","year":"2017","journal-title":"Dig Surg"},{"key":"2025120521004723000_9.11.e031365.39","doi-asserted-by":"crossref","unstructured":"Rodgers KR , Gui J , Dinulos MBP , et al . Ehlers-Danlos syndrome hypermobility type is associated with rheumatic diseases. Sci Rep 2017;7.doi:10.1038\/srep39636","DOI":"10.1038\/srep39636"},{"key":"2025120521004723000_9.11.e031365.40","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2013-304822"},{"key":"2025120521004723000_9.11.e031365.41","first-page":"1777","article-title":"The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS)","volume":"27","author":"Grahame","year":"2000","journal-title":"Journal of Rheumatology"},{"key":"2025120521004723000_9.11.e031365.42","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O"},{"key":"2025120521004723000_9.11.e031365.43","doi-asserted-by":"publisher","DOI":"10.1136\/adc.80.2.188"},{"key":"2025120521004723000_9.11.e031365.44","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"key":"2025120521004723000_9.11.e031365.45","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/ajmg.c.31425","article-title":"Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome\/Ehlers-Danlos syndrome, hypermobility type","volume":"169","author":"Castori","year":"2015","journal-title":"Am J Med Genet"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2019-031365","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T05:00:56Z","timestamp":1764997256000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2019-031365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11,4]]},"published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1136\/bmjopen-2019-031365"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2019-031365","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11]]}}}