{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T13:36:51Z","timestamp":1794490611218,"version":"4.9.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009487","name":"Stiftelsen Forska Utan Djurf\u00f6rs\u00f6k","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009487","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006285","name":"Magnus Bergvalls Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006285","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swedish Society for Medical Research, Lions research foundation and Swedish Research Council for Sport Science"},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2017-00644"],"award-info":[{"award-number":["2017-00644"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin induced tendinopathy. We studied association between statin use and different tendon injuries in two population-based Swedish cohorts by time-dependent Cox regression analysis. Additionally, we tested simvastatin in a 3D cell culture model with human tenocytes. Compared with never-users, current users of statins had a higher incidence of trigger finger with adjusted hazard ratios (aHRs) of 1.50 for men (95% confidence interval [CI] 1.21\u20131.85) and 1.21 (1.02\u20131.43) for women. We also found a higher incidence of shoulder tendinopathy in both men (aHR 1.43; 1.24\u20131.65) and women (aHR 1.41; 0.97\u20132.05). Former users did not confer a higher risk of tendinopathies.\n                    <jats:italic>In vitro<\/jats:italic>\n                    experiments revealed an increased release of matrix metalloproteinase (MMP)-1 and MMP-13 and a weaker, disrupted matrix after simvastatin exposure. Current statin use seems to increase the risk of trigger finger and shoulder tendinopathy, possibly through increased MMP release, and subsequently, a weakened tendon matrix which will be more prone to injuries.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-53238-7","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T06:03:10Z","timestamp":1575007390000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release \u2013 a cohort study design combined with an experimental study"],"prefix":"10.1038","volume":"9","author":[{"given":"Pernilla","family":"Eliasson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-8268","authenticated-orcid":false,"given":"Franciele","family":"Dietrich-Zagonel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Carin","family":"Lundin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Aspenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Wolk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Micha\u00eblsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,29]]},"reference":[{"key":"53238_CR1","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1016\/S0140-6736(14)61368-4","volume":"385","author":"C Cholesterol Treatment Trialists","year":"2015","unstructured":"Cholesterol Treatment Trialists, C. et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 385, 1397\u20131405, https:\/\/doi.org\/10.1016\/S0140-6736(14)61368-4 (2015).","journal-title":"Lancet"},{"key":"53238_CR2","doi-asserted-by":"publisher","unstructured":"Taylor, F. et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev, CD004816, https:\/\/doi.org\/10.1002\/14651858.CD004816.pub5 (2013).","DOI":"10.1002\/14651858.CD004816.pub5"},{"key":"53238_CR3","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1161\/CIRCRESAHA.118.312782","volume":"124","author":"NC Ward","year":"2019","unstructured":"Ward, N. C., Watts, G. F. & Eckel, R. H. Statin Toxicity. Circ Res 124, 328\u2013350, https:\/\/doi.org\/10.1161\/CIRCRESAHA.118.312782 (2019).","journal-title":"Circ Res"},{"key":"53238_CR4","doi-asserted-by":"publisher","first-page":"e42866","DOI":"10.1371\/journal.pone.0042866","volume":"7","author":"KB Hoffman","year":"2012","unstructured":"Hoffman, K. B., Kraus, C., Dimbil, M. & Golomb, B. A. A survey of the FDA\u2019s AERS database regarding muscle and tendon adverse events linked to the statin drug class. PLoS One 7, e42866, https:\/\/doi.org\/10.1371\/journal.pone.0042866 (2012).","journal-title":"PLoS One"},{"key":"53238_CR5","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.ptsp.2009.01.003","volume":"10","author":"MR Carmont","year":"2009","unstructured":"Carmont, M. R., Highland, A. M., Blundell, C. M. & Davies, M. B. Simultaneous bilateral Achilles tendon ruptures associated with statin medication despite regular rock climbing exercise. Phys Ther Sport 10, 150\u2013152, https:\/\/doi.org\/10.1016\/j.ptsp.2009.01.003 (2009).","journal-title":"Phys Ther Sport"},{"key":"53238_CR6","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/S1297-319X(01)00300-1","volume":"68","author":"P Chazerain","year":"2001","unstructured":"Chazerain, P., Hayem, G., Hamza, S., Best, C. & Ziza, J. M. Four cases of tendinopathy in patients on statin therapy. Joint Bone Spine 68, 430\u2013433 (2001).","journal-title":"Joint Bone Spine"},{"key":"53238_CR7","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1002\/art.23309","volume":"59","author":"I Marie","year":"2008","unstructured":"Marie, I. et al. Tendinous disorders attributed to statins: a study on ninety-six spontaneous reports in the period 1990\u20132005 and review of the literature. Arthritis Rheum 59, 367\u2013372, https:\/\/doi.org\/10.1002\/art.23309 (2008).","journal-title":"Arthritis Rheum"},{"key":"53238_CR8","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.amjcard.2007.02.068","volume":"100","author":"RC Pullatt","year":"2007","unstructured":"Pullatt, R. C., Gadarla, M. R., Karas, R. H., Alsheikh-Ali, A. A. & Thompson, P. D. Tendon rupture associated with simvastatin\/ezetimibe therapy. Am J Cardiol 100, 152\u2013153, https:\/\/doi.org\/10.1016\/j.amjcard.2007.02.068 (2007).","journal-title":"Am J Cardiol"},{"key":"53238_CR9","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1097\/FJC.0b013e3181a0ce8b","volume":"53","author":"A Beri","year":"2009","unstructured":"Beri, A., Dwamena, F. C. & Dwamena, B. A. Association between statin therapy and tendon rupture: a case-control study. J Cardiovasc Pharmacol 53, 401\u2013404, https:\/\/doi.org\/10.1097\/FJC.0b013e3181a0ce8b (2009).","journal-title":"J Cardiovasc Pharmacol"},{"key":"53238_CR10","doi-asserted-by":"publisher","unstructured":"Bakker, E. A. et al. Association Between Statin Use and Prevalence of Exercise-Related Injuries: A Cross-Sectional Survey of Amateur Runners in the Netherlands. Sports Med, https:\/\/doi.org\/10.1007\/s40279-017-0681-7 (2017).","DOI":"10.1007\/s40279-017-0681-7"},{"key":"53238_CR11","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1097\/MJT.0000000000000039","volume":"22","author":"T Contractor","year":"2015","unstructured":"Contractor, T., Beri, A., Gardiner, J. C., Tang, X. & Dwamena, F. C. Is Statin Use Associated With Tendon Rupture? A Population-Based Retrospective Cohort Analysis. Am J Ther 22, 377\u2013381, https:\/\/doi.org\/10.1097\/MJT.0000000000000039 (2015).","journal-title":"Am J Ther"},{"key":"53238_CR12","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1177\/0363546515588173","volume":"43","author":"TT Lin","year":"2015","unstructured":"Lin, T. T. et al. The effect of diabetes, hyperlipidemia, and statins on the development of rotator cuff disease: a nationwide, 11-year, longitudinal, population-based follow-up study. Am J Sports Med 43, 2126\u20132132, https:\/\/doi.org\/10.1177\/0363546515588173 (2015).","journal-title":"Am J Sports Med"},{"key":"53238_CR13","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1142\/S0218810412500153","volume":"17","author":"C Savvidou","year":"2012","unstructured":"Savvidou, C. & Moreno, R. Spontaneous distal biceps tendon ruptures: are they related to statin administration? Hand Surg 17, 167\u2013171, https:\/\/doi.org\/10.1142\/S0218810412500153 (2012).","journal-title":"Hand Surg"},{"key":"53238_CR14","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1007\/s40264-016-0462-5","volume":"39","author":"J Spoendlin","year":"2016","unstructured":"Spoendlin, J. et al. The Risk of Achilles or Biceps Tendon Rupture in New Statin Users: A Propensity Score-Matched Sequential Cohort Study. Drug Saf 39, 1229\u20131237, https:\/\/doi.org\/10.1007\/s40264-016-0462-5 (2016).","journal-title":"Drug Saf"},{"key":"53238_CR15","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/S0278-5919(03)00004-8","volume":"22","author":"N Maffulli","year":"2003","unstructured":"Maffulli, N., Wong, J. & Almekinders, L. C. Types and epidemiology of tendinopathy. Clin Sports Med 22, 675\u2013692 (2003).","journal-title":"Clin Sports Med"},{"key":"53238_CR16","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/j.1600-0838.2012.01514.x","volume":"24","author":"AC Lundin","year":"2014","unstructured":"Lundin, A. C., Aspenberg, P. & Eliasson, P. Trigger finger, tendinosis, and intratendinous gene expression. Scand J Med Sci Sports 24, 363\u2013368, https:\/\/doi.org\/10.1111\/j.1600-0838.2012.01514.x (2014).","journal-title":"Scand J Med Sci Sports"},{"key":"53238_CR17","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1177\/1753193411421853","volume":"37","author":"AC Lundin","year":"2012","unstructured":"Lundin, A. C., Eliasson, P. & Aspenberg, P. Trigger finger and tendinosis. J Hand Surg Eur Vol 37, 233\u2013236, https:\/\/doi.org\/10.1177\/1753193411421853 (2012).","journal-title":"J Hand Surg Eur Vol"},{"key":"53238_CR18","doi-asserted-by":"publisher","first-page":"e0172797","DOI":"10.1371\/journal.pone.0172797","volume":"12","author":"P Eliasson","year":"2017","unstructured":"Eliasson, P. et al. Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern. PLoS One 12, e0172797, https:\/\/doi.org\/10.1371\/journal.pone.0172797 (2017).","journal-title":"PLoS One"},{"key":"53238_CR19","doi-asserted-by":"publisher","unstructured":"Beri, A. & Khattri, S. Tendon rupture and statin therapy: is there a link? Comment on the article by Marie et al. Arthritis Rheum 59, 1202; author reply 1202, https:\/\/doi.org\/10.1002\/art.23917 (2008).","DOI":"10.1002\/art.23917"},{"key":"53238_CR20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1136\/ard.52.1.44","volume":"52","author":"P Klemp","year":"1993","unstructured":"Klemp, P., Halland, A. M., Majoos, F. L. & Steyn, K. Musculoskeletal manifestations in hyperlipidaemia: a controlled study. Ann Rheum Dis 52, 44\u201348 (1993).","journal-title":"Ann Rheum Dis"},{"key":"53238_CR21","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.csm.2012.07.001","volume":"31","author":"RZ Tashjian","year":"2012","unstructured":"Tashjian, R. Z. Epidemiology, natural history, and indications for treatment of rotator cuff tears. Clin Sports Med 31, 589\u2013604, https:\/\/doi.org\/10.1016\/j.csm.2012.07.001 (2012).","journal-title":"Clin Sports Med"},{"key":"53238_CR22","doi-asserted-by":"publisher","unstructured":"Tilley, B. J., Cook, J. L., Docking, S. I. & Gaida, J. E. Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review. Br J Sports Med, https:\/\/doi.org\/10.1136\/bjsports-2015-095100 (2015).","DOI":"10.1136\/bjsports-2015-095100"},{"key":"53238_CR23","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.cardiores.2005.12.002","volume":"69","author":"H Nagase","year":"2006","unstructured":"Nagase, H., Visse, R. & Murphy, G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69, 562\u2013573, https:\/\/doi.org\/10.1016\/j.cardiores.2005.12.002 (2006).","journal-title":"Cardiovasc Res"},{"key":"53238_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-271","volume":"11","author":"S Lakemeier","year":"2010","unstructured":"Lakemeier, S. et al. Expression of matrix metalloproteinases 1, 3, and 9 in degenerated long head biceps tendon in the presence of rotator cuff tears: an immunohistological study. BMC Musculoskelet Disord 11, 271, https:\/\/doi.org\/10.1186\/1471-2474-11-271 (2010).","journal-title":"BMC Musculoskelet Disord"},{"key":"53238_CR25","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1177\/0363546503262200","volume":"32","author":"IK Lo","year":"2004","unstructured":"Lo, I. K., Marchuk, L. L., Hollinshead, R., Hart, D. A. & Frank, C. B. Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med 32, 1223\u20131229, https:\/\/doi.org\/10.1177\/0363546503262200 (2004).","journal-title":"Am J Sports Med"},{"key":"53238_CR26","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.jse.2011.02.015","volume":"20","author":"MK Shindle","year":"2011","unstructured":"Shindle, M. K. et al. Full-thickness supraspinatus tears are associated with more synovial inflammation and tissue degeneration than partial-thickness tears. J Shoulder Elbow Surg 20, 917\u2013927, https:\/\/doi.org\/10.1016\/j.jse.2011.02.015 (2011).","journal-title":"J Shoulder Elbow Surg"},{"key":"53238_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-11-450","volume":"11","author":"JF Ludvigsson","year":"2011","unstructured":"Ludvigsson, J. F. et al. External review and validation of the Swedish national inpatient register. BMC Public Health 11, 450, https:\/\/doi.org\/10.1186\/1471-2458-11-450 (2011).","journal-title":"BMC Public Health"},{"key":"53238_CR28","doi-asserted-by":"publisher","unstructured":"The DIPART (vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 340, b5463, https:\/\/doi.org\/10.1136\/bmj.b5463 (2010).","DOI":"10.1136\/bmj.b5463"},{"key":"53238_CR29","doi-asserted-by":"publisher","first-page":"b5087","DOI":"10.1136\/bmj.b5087","volume":"340","author":"LE Levesque","year":"2010","unstructured":"Levesque, L. E., Hanley, J. A., Kezouh, A. & Suissa, S. Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ 340, b5087, https:\/\/doi.org\/10.1136\/bmj.b5087 (2010).","journal-title":"BMJ"},{"key":"53238_CR30","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.2522\/ptj.20130135","volume":"94","author":"BM Huisstede","year":"2014","unstructured":"Huisstede, B. M., Hoogvliet, P., Coert, J. H., Friden, J. & European, H. G. Multidisciplinary consensus guideline for managing trigger finger: results from the European HANDGUIDE Study. Phys Ther 94, 1421\u20131433, https:\/\/doi.org\/10.2522\/ptj.20130135 (2014).","journal-title":"Phys Ther"},{"key":"53238_CR31","doi-asserted-by":"publisher","first-page":"f228","DOI":"10.1136\/bmj.f228","volume":"346","author":"K Michaelsson","year":"2013","unstructured":"Michaelsson, K. et al. Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study BMJ 346, f\u2009228, https:\/\/doi.org\/10.1136\/bmj.f228 (2013).","journal-title":"BMJ"},{"key":"53238_CR32","doi-asserted-by":"publisher","first-page":"g6015","DOI":"10.1136\/bmj.g6015","volume":"349","author":"K Michaelsson","year":"2014","unstructured":"Michaelsson, K. et al. Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ 349, g6015, https:\/\/doi.org\/10.1136\/bmj.g6015 (2014).","journal-title":"BMJ"},{"key":"53238_CR33","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1097\/EDE.0b013e3181810e29","volume":"19","author":"TJ VanderWeele","year":"2008","unstructured":"VanderWeele, T. J., Hernan, M. A. & Robins, J. M. Causal directed acyclic graphs and the direction of unmeasured confounding bias. Epidemiology 19, 720\u2013728, https:\/\/doi.org\/10.1097\/EDE.0b013e3181810e29 (2008).","journal-title":"Epidemiology"},{"key":"53238_CR34","doi-asserted-by":"publisher","unstructured":"Michaelsson, K., Wolk, A., Melhus, H. & Byberg, L. Milk, Fruit and Vegetable, and Total Antioxidant Intakes in Relation to Mortality Rates: Cohort Studies in Women and Men. Am J Epidemiol, 1\u201317, https:\/\/doi.org\/10.1093\/aje\/kww124 (2017).","DOI":"10.1093\/aje\/kww124"},{"key":"53238_CR35","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1007\/s10654-008-9273-z","volume":"23","author":"N Orsini","year":"2008","unstructured":"Orsini, N. et al. Validity of self-reported total physical activity questionnaire among older women. Eur J Epidemiol 23, 661\u2013667, https:\/\/doi.org\/10.1007\/s10654-008-9273-z (2008).","journal-title":"Eur J Epidemiol"},{"key":"53238_CR36","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1016\/j.ejca.2006.04.015","volume":"42","author":"SC Larsson","year":"2006","unstructured":"Larsson, S. C., Rutegard, J., Bergkvist, L. & Wolk, A. Physical activity, obesity, and risk of colon and rectal cancer in a cohort of Swedish men. Eur J Cancer 42, 2590\u20132597, https:\/\/doi.org\/10.1016\/j.ejca.2006.04.015 (2006).","journal-title":"Eur J Cancer"},{"key":"53238_CR37","doi-asserted-by":"crossref","unstructured":"Willett, W. C., Howe, G. R. & Kushi, L. H. Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65, 1220S\u20131228S; discussion 1229S-1231S (1997).","DOI":"10.1093\/ajcn\/65.4.1220S"},{"key":"53238_CR38","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","volume":"40","author":"ME Charlson","year":"1987","unstructured":"Charlson, M. E., Pompei, P., Ales, K. L. & MacKenzie, C. R. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. Journal of Chronic Diseases 40, 373\u2013383 (1987).","journal-title":"Journal of Chronic Diseases"},{"key":"53238_CR39","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1097\/01.mlr.0000182534.19832.83","volume":"43","author":"H Quan","year":"2005","unstructured":"Quan, H. et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Medical Care 43, 1130\u20131139 (2005).","journal-title":"Medical Care"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53238-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53238-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53238-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T11:39:00Z","timestamp":1671277140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-53238-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,29]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["53238"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-53238-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,29]]},"assertion":[{"value":"19 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17958"}}