{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T11:34:29Z","timestamp":1781264069192,"version":"3.54.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T00:00:00Z","timestamp":1579046400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T00:00:00Z","timestamp":1579046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Validated clinical prediction models to identify children with poor prognosis at the time of juvenile idiopathic arthritis (JIA) diagnosis would be very helpful for tailoring treatments, and avoiding under- or over-treatment. Our objective was to externally validate Nordic clinical prediction models in Canadian patients with JIA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used data from 513 subjects at the 3-year follow-up from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcomes were non-achievement of remission, severe disease course, and functional disability. The Nordic models were evaluated exactly as published and after fine-tuning the logistic regression coefficients using multiple data splits of the Canadian cohort. Missing data was handled with multiple imputation, and prediction ability was assessed with C-indices. C-index values &gt;\u20090.7 were deemed to reflect helpful prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 81% of evaluable patients did not achieve remission off medications, 15% experienced a severe disease course, and 38% reported disability (CHAQ score\u2009&gt;\u20090). The Nordic model for predicting non-achievement of remission had a C-index of 0.68 (95% CI 0.62\u20130.74), and 0.74 (0.67\u20130.80) after fine-tuning. For prediction of severe disease course, it had a C-index of 0.69 (0.61\u20130.78), and 0.79 (0.68\u20130.91) after fine-tuning. The fine-tuned Nordic model identified 85% of the cohort as low risk for a severe disease course (&lt;\u200920% chance) and 7% as high risk (&gt;\u200960% chance). The Nordic model to predict functional disability had a C-index of 0.57 (0.50\u20130.63), and 0.51 (0.39\u20130.63) after fine-tuning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fine-tuned Nordic models, combining active joint count, physician global assessment of disease activity, morning stiffness, and ankle involvement, predicted well non-achievement of remission and severe disease course in Canadian patients with JIA. The Nordic model for predicting disability could not predict functional disability in Canadian patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-019-2091-8","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T08:02:22Z","timestamp":1579075342000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Validation of prediction models of severe disease course and non-achievement of remission in juvenile idiopathic arthritis part 2: results of the Nordic model in the Canadian cohort"],"prefix":"10.1186","volume":"22","author":[{"name":"for the ReACCh-Out and NoSPeR Investigators","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Henrey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Rypdal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rypdal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Loughin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Nordal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Guzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"key":"2091_CR1","first-page":"390","volume":"31","author":"RE Petty","year":"2004","unstructured":"Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. JRheumatol. 2004;31:390\u20132.","journal-title":"JRheumatol"},{"key":"2091_CR2","doi-asserted-by":"publisher","first-page":"91G","DOI":"10.1016\/0002-9149(87)90165-2","volume":"59","author":"PW Wilson","year":"1987","unstructured":"Wilson PW, Castelli WP, Kannel WB. Coronary risk prediction in adults (the Framingham Heart Study). Am J Cardiol. 1987;59:91G\u20134G.","journal-title":"Am J Cardiol"},{"key":"2091_CR3","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1002\/jbmr.123","volume":"25","author":"WD Leslie","year":"2010","unstructured":"Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA, et al. Independent clinical validation of a Canadian FRAX model: fracture prediction and model calibration. J Bone Miner Res. 2010;25:2350\u20138.","journal-title":"J Bone Miner Res"},{"key":"2091_CR4","doi-asserted-by":"publisher","first-page":"W1","DOI":"10.7326\/M14-0698","volume":"162","author":"KG Moons","year":"2015","unstructured":"Moons KG, Altman DG, Reitsma JB, Ioannidis JP, Macaskill P, Steyerberg EW, et al. Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med. 2015;162:W1\u201373.","journal-title":"Ann Intern Med"},{"key":"2091_CR5","doi-asserted-by":"publisher","first-page":"55","DOI":"10.7326\/M14-0697","volume":"162","author":"GS Collins","year":"2015","unstructured":"Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): the TRIPOD statement. Ann Intern Med. 2015;162:55\u201363.","journal-title":"Ann Intern Med"},{"key":"2091_CR6","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1161\/CIRCULATIONAHA.109.849166","volume":"121","author":"DM Lloyd-Jones","year":"2010","unstructured":"Lloyd-Jones DM. Cardiovascular risk prediction: basic concepts, current status, and future directions. Circulation. 2010;121:1768\u201377.","journal-title":"Circulation"},{"key":"2091_CR7","doi-asserted-by":"publisher","first-page":"230","DOI":"10.3899\/jrheum.160197","volume":"44","author":"J Guzman","year":"2017","unstructured":"Guzman J, Henrey A, Loughin T, Berard RA, Shiff NJ, Jurencak R, et al. Predicting which children with juvenile idiopathic arthritis will have a severe disease course: results from the ReACCh-Out cohort. J Rheumatol. 2017;44:230\u201340.","journal-title":"J Rheumatol"},{"key":"2091_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13075-018-1571-6","volume":"20","author":"V Rypdal","year":"2018","unstructured":"Rypdal V, Arnstad ED, Aalto K, Berntson L, Ekelund M, Fasth A, et al. Predicting unfavorable long-term outcome in juvenile idiopathic arthritis: results from the Nordic cohort study. Arthritis Res Ther. 2018;20:91.","journal-title":"Arthritis Res Ther"},{"key":"2091_CR9","doi-asserted-by":"publisher","unstructured":"Rypdal V, Guzman J, Henrey A, Loughin T, Glerup M, Arnstad ED, Aalto K, Rygg M, Nielsen S, Herlin T, Fasth A, Berntson L, Rypdal M, Nordal E. ReACCh-Out and NoSPeR Investigators. Validation of prediction models of severe disease course and non-achievement of remission in juvenile idiopathic arthritis: part 1-results of the Canadian model in the Nordic cohort. Arthritis Res Ther. 2019;21(1):270. https:\/\/doi.org\/10.1186\/s13075-019-2060-2.","DOI":"10.1186\/s13075-019-2060-2"},{"key":"2091_CR10","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1002\/art.24539","volume":"61","author":"K Oen","year":"2009","unstructured":"Oen K, Tucker L, Huber AM, Miettunen P, Scuccimarri R, Campillo S, et al. Predictors of early inactive disease in a juvenile idiopathic arthritis cohort: results of a Canadian multicenter, prospective inception cohort study. Arthritis Rheum. 2009;61:1077\u201386.","journal-title":"Arthritis Rheum"},{"key":"2091_CR11","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1136\/annrheumdis-2014-205372","volume":"74","author":"J Guzman","year":"2015","unstructured":"Guzman J, Oen K, Tucker LB, Huber AM, Shiff N, Boire G, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis. 2015;74:1854\u201360.","journal-title":"Ann Rheum Dis"},{"key":"2091_CR12","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1002\/1529-0131(199707)40:7<1202::AID-ART3>3.0.CO;2-R","volume":"40","author":"EH Giannini","year":"1997","unstructured":"Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum. 1997;40:1202\u20139.","journal-title":"Arthritis Rheum"},{"key":"2091_CR13","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.1002\/art.30426","volume":"63","author":"E Nordal","year":"2011","unstructured":"Nordal E, Zak M, Aalto K, Berntson L, Fasth A, Herlin T, et al. Ongoing disease activity and changing categories in a long-term nordic cohort study of juvenile idiopathic arthritis. Arthritis Rheum. 2011;63:2809\u201318.","journal-title":"Arthritis Rheum"},{"key":"2091_CR14","first-page":"2290","volume":"31","author":"CA Wallace","year":"2004","unstructured":"Wallace CA, Ruperto N, Giannini E, Arthritis C, Alliance RR, Pediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol. 2004;31:2290\u20134.","journal-title":"J Rheumatol"},{"key":"2091_CR15","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1136\/annrheumdis-2014-207164","volume":"75","author":"J Guzman","year":"2016","unstructured":"Guzman J, Oen K, Huber AM, Watanabe Duffy K, Boire G, Shiff N, et al. The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort. Ann Rheum Dis. 2016;75:1092\u20138.","journal-title":"Ann Rheum Dis"},{"key":"2091_CR16","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1002\/acr.20497","volume":"63","author":"CA Wallace","year":"2011","unstructured":"Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N, Childhood Arthritis Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; Paediatric Rheumatology International Trials Organisation. American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2011;63:929\u201336.","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2091_CR17","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1002\/art.1780371209","volume":"37","author":"G Singh","year":"1994","unstructured":"Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of health status in children with juvenile rheumatoid arthritis. Arthritis Rheum. 1994;37:1761\u20139.","journal-title":"Arthritis Rheum"},{"key":"2091_CR18","volume-title":"The CHQ: a user\u2019s manual","author":"JM Landgraf","year":"1996","unstructured":"Landgraf JM, Abetz L, Ware JE Jr. The CHQ: a user\u2019s manual. 1st ed. Boston: The Health Institute, New England Medical Center; 1996.","edition":"1"},{"key":"2091_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v045.i03","volume":"45","author":"S van Buuren","year":"2011","unstructured":"van Buuren S, Groothuis-Oudshoorn K. MICE: multivariate imputation by chained equations in R. J Stat Softw. 2011;45:1\u201367.","journal-title":"J Stat Softw"},{"key":"2091_CR20","volume-title":"Multiple imputation for nonresponse in surveys","author":"DB Rubin","year":"2004","unstructured":"Rubin DB. Multiple imputation for nonresponse in surveys. New York: Wiley; 2004."},{"key":"2091_CR21","doi-asserted-by":"publisher","first-page":"Article8","DOI":"10.2202\/1544-6115.1322","volume":"7","author":"W Jiang","year":"2008","unstructured":"Jiang W, Varma S, Simon R. Calculating confidence intervals for prediction error in microarray classification using resampling. Stat Appl Genet Mol Biol. 2008;7:Article8. https:\/\/doi.org\/10.2202\/1544-6115.1322.","journal-title":"Stat Appl Genet Mol Biol"},{"key":"2091_CR22","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1136\/annrheumdis-2014-205265","volume":"74","author":"EH van Dijkhuizen","year":"2015","unstructured":"van Dijkhuizen EH, Wulffraat NM. Early predictors of prognosis in juvenile idiopathic arthritis: a systematic literature review. Ann Rheum Dis. 2015;74:1996\u20132005.","journal-title":"Ann Rheum Dis"},{"key":"2091_CR23","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1136\/annrheumdis-2011-200942","volume":"71","author":"M Bulatovic","year":"2012","unstructured":"Bulatovic M, Heijstek MW, Van Dijkhuizen EH, Wulffraat NM, Pluijm SM, de Jonge R. Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis. Ann Rheum Dis. 2012;71:1484\u20139.","journal-title":"Ann Rheum Dis"},{"key":"2091_CR24","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12969-015-0002-3","volume":"13","author":"EH van Dijkhuizen","year":"2015","unstructured":"van Dijkhuizen EH, Bulatovi\u0107 \u0106alasan M, Pluijm SM, de Rotte MC, Vastert SJ, Kamphuis S, de Jonge R, Wulffraat NM. Prediction of methotrexate intolerance in juvenile idiopathic arthritis: a prospective, observational cohort study. Pediatr Rheumatol Online J. 2015;13:5. https:\/\/doi.org\/10.1186\/s12969-015-0002-3.","journal-title":"Pediatr Rheumatol Online J"},{"key":"2091_CR25","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1093\/rheumatology\/key148","volume":"57","author":"EHP van Dijkhuizen","year":"2018","unstructured":"van Dijkhuizen EHP, Aidonopoulos O, Ter Haar NM, Pires Marafon D, Magni-Manzoni S, Ioannidis YE, et al. Prediction of inactive disease in juvenile idiopathic arthritis: a multicentre observational cohort study. Rheumatology (Oxford). 2018;57:1752\u201360.","journal-title":"Rheumatology (Oxford)"},{"key":"2091_CR26","doi-asserted-by":"publisher","first-page":"628","DOI":"10.3899\/jrheum.180456","volume":"46","author":"J Guzman","year":"2019","unstructured":"Guzman J, Henrey A, Loughin T, Berard RA, Shiff NJ, Jurencak R, et al. Predicting which children with juvenile idiopathic arthritis will not attain early remission with conventional treatment: results from the ReACCh-Out cohort. J Rheumatol. 2019;46:628\u201335.","journal-title":"J Rheumatol"},{"key":"2091_CR27","doi-asserted-by":"publisher","first-page":"3554","DOI":"10.1002\/art.21389","volume":"52","author":"CA Wallace","year":"2005","unstructured":"Wallace CA, Huang B, Bandeira M, Ravelli A, Giannini EH. Patterns of clinical remission in select categories of juvenile idiopathic arthritis. Arthritis Rheum. 2005;52:3554\u201362.","journal-title":"Arthritis Rheum"},{"key":"2091_CR28","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1093\/rheumatology\/kep144","volume":"48","author":"S Ringold","year":"2009","unstructured":"Ringold S, Seidel KD, Koepsell TD, Wallace CA. Inactive disease in polyarticular juvenile idiopathic arthritis: current patterns and associations. Rheumatology (Oxford). 2009;48:972\u20137.","journal-title":"Rheumatology (Oxford)"},{"key":"2091_CR29","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1002\/acr.22393","volume":"66","author":"A Consolaro","year":"2014","unstructured":"Consolaro A, Negro G, Chiara Gallo M, Bracciolini G, Ferrari C, Schiappapietra B, et al. Defining criteria for disease activity states in nonsystemic juvenile idiopathic arthritis based on a three-variable juvenile arthritis disease activity score. Arthritis Care Res (Hoboken). 2014;66:1703\u20139.","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2091_CR30","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1136\/annrheumdis-2016-210511","volume":"76","author":"SJW Shoop-Worrall","year":"2017","unstructured":"Shoop-Worrall SJW, Verstappen SMM, Baildam E, Chieng A, Davidson J, Foster H, et al. How common is clinically inactive disease in a prospective cohort of patients with juvenile idiopathic arthritis? The importance of definition. Ann Rheum Dis. 2017;76:1381\u20138.","journal-title":"Ann Rheum Dis"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-019-2091-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-019-2091-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-019-2091-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T19:10:23Z","timestamp":1610565023000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-019-2091-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,15]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2091"],"URL":"https:\/\/doi.org\/10.1186\/s13075-019-2091-8","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737223500.793582484","asserted-by":"object"}]},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,15]]},"assertion":[{"value":"26 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"ReACCh-Out was approved by Research Ethics Boards at all participating institutions and performed in accordance with the Declaration of Helsinki, including informed written consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10"}}