{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:51:48Z","timestamp":1792169508263,"version":"4.4.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteoarthritis (OA) is a common degenerative musculoskeletal disease highly prevalent in aging societies worldwide. Traditionally, knee OA is diagnosed using conventional radiography. However, structural changes of articular cartilage or menisci cannot be directly evaluated using this method. On the other hand, ultrasound is a promising tool able to provide direct information on soft tissue degeneration. The aim of our study was to systematically determine the site-specific diagnostic performance of semi-quantitative ultrasound grading of knee femoral articular cartilage, osteophytes and meniscal extrusion, and of radiographic assessment of joint space narrowing and osteophytes, using MRI as a reference standard. Eighty asymptomatic and 79 symptomatic subjects with mean age of 57.7 years were included in the study. Ultrasound performed best in the assessment of femoral medial and lateral osteophytes, and medial meniscal extrusion. In comparison to radiography, ultrasound performed better or at least equally well in identification of tibio-femoral osteophytes, medial meniscal extrusion and medial femoral cartilage morphological degeneration. Ultrasound provides relevant additional diagnostic information on tissue-specific morphological changes not depicted by conventional radiography. Consequently, the use of ultrasound as a complementary imaging tool along with radiography may enable more accurate and cost-effective diagnostics of knee osteoarthritis at the primary healthcare level.<\/jats:p>","DOI":"10.1038\/srep22365","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T11:46:32Z","timestamp":1456832792000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Comparison of Diagnostic Performance of Semi-Quantitative Knee Ultrasound and Knee Radiography with MRI: Oulu Knee Osteoarthritis Study"],"prefix":"10.1038","volume":"6","author":[{"given":"Jana","family":"Podlipsk\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Guermazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petri","family":"Lehenkari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Niinim\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Roemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari P.","family":"Arokoski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"Kaukinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esa","family":"Liukkonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveliina","family":"Lammentausta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miika T.","family":"Nieminen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osmo","family":"Tervonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhani M.","family":"Koski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simo","family":"Saarakkala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"BFsrep22365_CR1","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1136\/annrheumdis-2013-204763","volume":"73","author":"M Cross","year":"2014","unstructured":"Cross, M. et al. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Annals of the Rheumatic Diseases 73, 1323\u20131330 (2014).","journal-title":"Annals of the Rheumatic Diseases"},{"key":"BFsrep22365_CR2","doi-asserted-by":"crossref","unstructured":"Wick, M. C., Kastlunger, M. & Weiss, R. J. Clinical Imaging Assessments of Knee Osteoarthritis in the Elderly: A Mini-Review. Gerontology (2014).","DOI":"10.1159\/000357756"},{"key":"BFsrep22365_CR3","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.joca.2011.02.003","volume":"19","author":"D Hayashi","year":"2011","unstructured":"Hayashi, D., Guermazi, a. & Hunter, D. J. Osteoarthritis year 2010 in review: imaging. Osteoarthr. Cartil. 19, 354\u201360 (2011).","journal-title":"Osteoarthr. Cartil."},{"key":"BFsrep22365_CR4","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.berh.2014.02.002","volume":"28","author":"FW Roemer","year":"2014","unstructured":"Roemer, F. W., Eckstein, F., Hayashi, D. & Guermazi, A. The role of imaging in osteoarthritis. Best Pract. Res. Clin. Rheumatol. 28, 31\u201360 (2014).","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"BFsrep22365_CR5","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1136\/ard.16.4.494","volume":"16","author":"JH Kellgren","year":"1957","unstructured":"Kellgren, J. H. & Lawrence, J. S. Radiological assessment of osteo-arthrosis. Ann. Rheum. Dis. 16, 494\u2013502 (1957).","journal-title":"Ann. Rheum. Dis."},{"key":"BFsrep22365_CR6","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.rdc.2012.10.003","volume":"39","author":"A Guermazi","year":"2013","unstructured":"Guermazi, A. et al. Imaging of osteoarthritis. Rheum. Dis. Clin. North Am. 39, 67\u2013105 (2013).","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"BFsrep22365_CR7","doi-asserted-by":"publisher","first-page":"A1","DOI":"10.1016\/j.joca.2006.11.009","volume":"15","author":"RD Altman","year":"2007","unstructured":"Altman, R. D. & Gold, G. E. Atlas of individual radiographic features in osteoarthritis, revised. Osteoarthritis Cartilage 15 Suppl A, A1\u201356 (2007).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep22365_CR8","doi-asserted-by":"publisher","first-page":"3152","DOI":"10.1002\/art.21296","volume":"52","author":"S Amin","year":"2005","unstructured":"Amin, S. et al. The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis. Arthritis Rheum 52, 3152\u20139 (2005 Oct).","journal-title":"Arthritis Rheum"},{"key":"BFsrep22365_CR9","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1053\/joca.1999.0256","volume":"7","author":"DR Gale","year":"1999","unstructured":"Gale, D. R. et al. Meniscal subluxation: association with osteoarthritis and joint space narrowing. Osteoarthritis Cartilage 7, 526\u2013532 (1999).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep22365_CR10","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/S0009-9260(99)90846-2","volume":"54","author":"JG Adams","year":"1999","unstructured":"Adams, J. G., McaLindon, T., Dimasi, M., Carey, J. & Eustace, S. Contribution of meniscal extrusion and cartilage loss to joint space narrowing in osteoarthritis. Clin. Radiol. 54, 502\u2013506 (1999).","journal-title":"Clin. Radiol."},{"key":"BFsrep22365_CR11","doi-asserted-by":"publisher","first-page":"2488","DOI":"10.1002\/art.22016","volume":"54","author":"DJ Hunter","year":"2006","unstructured":"Hunter, D. J. et al. Change in joint space width: hyaline articular cartilage loss or alteration in meniscus? Arthritis Rheum. 54, 2488\u20132495 (2006).","journal-title":"Arthritis Rheum."},{"key":"BFsrep22365_CR12","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1016\/j.joca.2011.05.004","volume":"19","author":"DJ Hunter","year":"2011","unstructured":"Hunter, D. J. et al. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthritis Cartilage 19, 990\u20131002 (2011).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep22365_CR13","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1016\/j.joca.2014.06.020","volume":"22","author":"BF Riecke","year":"2014","unstructured":"Riecke, B. F. et al. An ultrasound score for knee osteoarthritis: a cross-sectional validation study. Osteoarthritis Cartilage 22, 1675\u20131691 (2014).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep22365_CR14","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.joca.2012.01.016","volume":"20","author":"S Saarakkala","year":"2012","unstructured":"Saarakkala, S. et al. Diagnostic performance of knee ultrasonography for detecting degenerative changes of articular cartilage. Osteoarthritis Cartilage 20, 376\u2013381 (2012).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep22365_CR15","unstructured":"Koski, J. M. et al. Atlas-based knee osteophyte assessment with ultrasonography and radiography. Relation to arthroscopic degeneration of articular cartilage. Scand J Rheumatol, 1\u20137 (2015)."},{"key":"BFsrep22365_CR16","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1093\/rheumatology\/ket110","volume":"52","author":"C Acebes","year":"2013","unstructured":"Acebes, C., Romero, F. I., Contreras, M. A., Mahillo, I. & Herrero-Beaumont, G. Dynamic ultrasound assessment of medial meniscal subluxation in knee osteoarthritis. Rheumatology (Oxford) 52, 1443\u20131447 (2013).","journal-title":"Rheumatology (Oxford)"},{"key":"BFsrep22365_CR17","doi-asserted-by":"publisher","first-page":"584","DOI":"10.2214\/AJR.14.12522","volume":"204","author":"MH Nogueira-Barbosa","year":"2015","unstructured":"Nogueira-Barbosa, M. H. et al. Ultrasound assessment of medial meniscal extrusion: a validation study using MRI as reference standard. AJR Am. J. Roentgenol. 204, 584\u2013588 (2015).","journal-title":"AJR Am. J. Roentgenol."},{"key":"BFsrep22365_CR18","doi-asserted-by":"crossref","unstructured":"Bruyn, G. A. et al. An OMERACT reliability exercise of inflammatory and structural abnormalities in patients with knee osteoarthritis using ultrasound assessment. Ann. Rheum. Dis (2015).","DOI":"10.1136\/annrheumdis-2014-206774"},{"key":"BFsrep22365_CR19","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/art.33319","volume":"64","author":"K Kawaguchi","year":"2012","unstructured":"Kawaguchi, K., Enokida, M., Otsuki, R. & Teshima, R. Ultrasonographic evaluation of medial radial displacement of the medial meniscus in knee osteoarthritis. Arthritis & Rheumatism 64, 173\u2013180 (2012).","journal-title":"Arthritis & Rheumatism"},{"key":"BFsrep22365_CR20","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/s00776-013-0524-9","volume":"19","author":"S Yanagisawa","year":"2014","unstructured":"Yanagisawa, S. et al. Morphological evaluation and diagnosis of medial type osteoarthritis of the knee using ultrasound. J. Orthop. Sci. 19, 270\u2013274 (2014).","journal-title":"J. Orthop. Sci."},{"key":"BFsrep22365_CR21","doi-asserted-by":"publisher","first-page":"e92901","DOI":"10.1371\/journal.pone.0092901","volume":"9","author":"KK Chan","year":"2014","unstructured":"Chan, K. K., Sit, R. W., Wu, R. W. & Ngai, A. H. Clinical, radiological and ultrasonographic findings related to knee pain in osteoarthritis. PLoS One 9, e92901 (2014).","journal-title":"PLoS One"},{"key":"BFsrep22365_CR22","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/1756-185X.12190","volume":"17","author":"F\u00dc Malas","year":"2014","unstructured":"Malas, F. \u00dc., Kara, M., Kaymak, B., Akinci, A. & \u00d6z\u00e7akar, L. Ultrasonographic evaluation in symptomatic knee osteoarthritis: clinical and radiological correlation. International Journal of Rheumatic Diseases 17, 536\u2013540 (2014).","journal-title":"International Journal of Rheumatic Diseases"},{"key":"BFsrep22365_CR23","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s10067-002-0694-x","volume":"22","author":"S Tarhan","year":"2003","unstructured":"Tarhan, S. & Unlu, Z. Magnetic resonance imaging and ultrasonographic evaluation of the patients with knee osteoarthritis: a comparative study. Clin. Rheumatol. 22, 181\u2013188 (2003).","journal-title":"Clin. Rheumatol."},{"key":"BFsrep22365_CR24","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.joca.2007.07.013","volume":"16","author":"CL Lee","year":"2008","unstructured":"Lee, C. L. et al. The validity of in vivo ultrasonographic grading of osteoarthritic femoral condylar cartilage: a comparison with in vitro ultrasonographic and histologic gradings. Osteoarthritis Cartilage 16, 352\u2013358 (2008).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep22365_CR25","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1007\/s10067-008-0956-3","volume":"27","author":"CH Yoon","year":"2008","unstructured":"Yoon, C. H. et al. Validity of the sonographic longitudinal sagittal image for assessment of the cartilage thickness in the knee osteoarthritis. Clin. Rheumatol. 27, 1507\u20131516 (2008).","journal-title":"Clin. Rheumatol."},{"key":"BFsrep22365_CR26","doi-asserted-by":"crossref","unstructured":"Abraham, A. M., Goff, I., Pearce, M. S., Francis, R. M. & Birrell, F. Reliability and validity of ultrasound imaging of features of knee osteoarthritis in the community. BMC Musculoskelet. Disord. 12, 70-2474-12-70 (2011).","DOI":"10.1186\/1471-2474-12-70"},{"key":"BFsrep22365_CR27","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.joca.2005.02.008","volume":"13","author":"E Naredo","year":"2005","unstructured":"Naredo, E. et al. Ultrasonographic findings in knee osteoarthritis: A comparative study with clinical and radiographic assessment. Osteoarthritis Cartilage 13, 568\u2013574 (2005).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep22365_CR28","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1148\/radiology.153.3.6387794","volume":"153","author":"AM Aisen","year":"1984","unstructured":"Aisen, A. M. et al. Sonographic evaluation of the cartilage of the knee. Radiology 153, 781\u2013784 (1984).","journal-title":"Radiology"},{"key":"BFsrep22365_CR29","first-page":"230","volume":"254","author":"WJ McCune","year":"1990","unstructured":"McCune, W. J., Dedrick, D. K., Aisen, A. M. & MacGuire, A. Sonographic evaluation of osteoarthritic femoral condylar cartilage. Correlation with operative findings. Clin. Orthop. Relat. Res. 254, 230\u2013235 (1990).","journal-title":"Clin. Orthop. Relat. Res"},{"key":"BFsrep22365_CR30","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3109\/03009749209099222","volume":"21","author":"A Iagnocco","year":"1992","unstructured":"Iagnocco, A., Coari, G. & Zoppini, A. Sonographic Evaluation of Femoral Condylar Cartilage in Osteoarthritis and Rheumatoid Arthritis. Scand. J. Rheumatol. 21, 201\u2013203 (1992).","journal-title":"Scand. J. Rheumatol."},{"key":"BFsrep22365_CR31","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/ar2531","volume":"11","author":"DT Felson","year":"2009","unstructured":"Felson, D. T. Developments in the clinical understanding of osteoarthritis. Arthritis Research & Therapy 11, 203\u2013203 (2009).","journal-title":"Arthritis Research & Therapy"},{"key":"BFsrep22365_CR32","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.joca.2012.10.017","volume":"21","author":"W Wirth","year":"2012","unstructured":"Wirth, W. et al. Direct Comparison of Fixed Flexion Radiography and MRI in Knee Osteoarthritis: Responsiveness Data from the Osteoarthritis Initiative. Osteoarthr. Cartil. 21, 117\u2013125 (2012).","journal-title":"Osteoarthr. Cartil."},{"key":"BFsrep22365_CR33","doi-asserted-by":"publisher","first-page":"837","DOI":"10.2307\/2531595","volume":"44","author":"ER DeLong","year":"1988","unstructured":"DeLong, E. R., DeLong, D. M. & Clarke-Pearson, D. L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44, 837\u2013845 (1988).","journal-title":"Biometrics"},{"key":"BFsrep22365_CR34","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/art.1780340402","volume":"34","author":"RS Fife","year":"1991","unstructured":"Fife, R. S. et al. Relationship between arthroscopic evidence of cartilage damage and radiographic evidence of joint space narrowing in early osteoarthritis of the knee. Arthritis Rheum. 34, 377\u2013382 (1991).","journal-title":"Arthritis Rheum."},{"key":"BFsrep22365_CR35","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.bone.2011.11.019","volume":"51","author":"HJ Braun","year":"2012","unstructured":"Braun, H. J. & Gold, G. E. Diagnosis of osteoarthritis: imaging. Bone 51, 278\u2013288 (2012).","journal-title":"Bone"},{"key":"BFsrep22365_CR36","doi-asserted-by":"publisher","first-page":"2116","DOI":"10.1136\/annrheumdis-2013-203620","volume":"73","author":"HJ Kerkhof","year":"2014","unstructured":"Kerkhof, H. J. et al. Prediction model for knee osteoarthritis incidence, including clinical, genetic and biochemical risk factors. Ann. Rheum. Dis. 73, 2116\u20132121 (2014).","journal-title":"Ann. Rheum. Dis."},{"key":"BFsrep22365_CR37","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1136\/ard.60.10.977","volume":"60","author":"FM Cicuttini","year":"2001","unstructured":"Cicuttini, F. M., Wluka, A. E. & Stuckey, S. L. Tibial and femoral cartilage changes in knee osteoarthritis. Annals of the Rheumatic Diseases 60, 977\u2013980 (2001).","journal-title":"Annals of the Rheumatic Diseases"},{"key":"BFsrep22365_CR38","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/art.11483","volume":"50","author":"FM Cicuttini","year":"2004","unstructured":"Cicuttini, F. M., Wluka, A. E., Wang, Y. & Stuckey, S. L. Longitudinal study of changes in tibial and femoral cartilage in knee osteoarthritis. Arthritis Rheum. 50, 94\u201397 (2004).","journal-title":"Arthritis Rheum."}],"updated-by":[{"DOI":"10.1038\/srep33109","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T00:00:00Z","timestamp":1473984000000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep22365.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep22365","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep22365.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T18:12:34Z","timestamp":1718388754000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep22365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,1]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,3,21]]}},"alternative-id":["BFsrep22365"],"URL":"https:\/\/doi.org\/10.1038\/srep22365","relation":{"erratum":[{"id-type":"doi","id":"10.1038\/srep33109","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,1]]},"assertion":[{"value":"3 December 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2016","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.P., P.L., J.N., P.K., E.L., M.T.N., O.T., S.S., declares no competing financial interests. A.G. reports activities not related to the present article: received personal fees from MerckSerono, Genzyme, TissueGene, AstraZeneca, and Orthotrophix; is a shareholder in Boston Imaging Core Lab. (BICL), LLC, a company providing image assessment services to academia and the pharmaceutical industry. F.W.R. reports activities not related to the present article: is CMO and shareholder in Boston Imaging Core Lab. (BICL), LLC, a company providing image assessment services to academia and the pharmaceutical industry. J.P.A. reports activities not related to the present article: personal fees from MSD Finland Oy, personal fees from Pfizer Oy, personal fees from Mundipharma Oy, personal fees from Eli Lilly Finland Oy. J.M.K. reports activities not related to the present article: personal fees from Abbott, personal fees from AbbVie, personal fees from MSD, personal fees from Pfizer, personal fees from Roche, personal fees from Bristol-Myers Squibb, personal fees from Orion, personal fees from UCB, personal fees from GE.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22365"}}