{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T01:40:24Z","timestamp":1745458824950,"version":"3.37.3"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"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":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypalbuminemia is associated with numerous postoperative complications, so a perioperative albumin substitution is often considered. The objective of SuperAdd is to investigate whether substitution of human albumin, aiming to maintain a serum concentration &gt;\u200930\u2009g\/l, can reduce postoperative complications in normovolemic surgical patients in comparison with standard care.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods\/design<\/jats:title><jats:p>SuperAdd is a single-center, prospective, randomized, outcome-assessor blinded, patient blinded controlled trial. The primary outcome is the frequency of postoperative complications identified using the Postoperative Morbidity Survey graded \u2265\u20092 according to the Clavien-Dindo Score. Adult patients at risk to develop hypalbuminemia, i.e., ASA III or IV or high-risk surgery, are recruited after written informed consent was obtained. The albumin concentration is assessed before the induction of anesthesia and every 3\u00a0h until admission to the postanesthesia care unit. If albumin concentrations drop below 30\u2009g\/l, patients are randomly allocated to the control or the treatment group. The study intervention is a goal-directed human albumin substitution aimed at a concentration &gt;\u200930\u2009g\/l during surgery and postanesthesia care unit stay. The patients in the control group are treated according to standard clinical care. Postoperative visits are to be performed on days 1, 3, 5, 8, and 15, as well as by telephone 6\u2009months after surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>SuperAdd is the first clinical trial in a surgical population investigating the effect of a goal-directed albumin substitution aiming at a serum level &gt;\u200930\u2009g\/l. The nonrestrictive selection of patients guarantees that the patients without albumin screening will most likely not develop hypalbuminemia, thus ensuring generalizability of the study results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>EudraCT 2016-001313-24. Registered on 5 September 2016. Clinical Trials NCT03167645. Registered on 18 October 2016 and has the Universal Trial Number (UTN) U1111-1181-2625.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13063-020-04626-2","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T11:02:57Z","timestamp":1597748577000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Substitution of perioperative albumin deficiency disorders (SuperAdd) in adults undergoing vascular, abdominal, trauma, or orthopedic surgery: protocol for a randomized controlled trial"],"prefix":"10.1186","volume":"21","author":[{"given":"Stefan J.","family":"Schaller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Fuest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard","family":"Ulm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherina","family":"Bubb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00fcdiger","family":"von Eisenhart-Rothe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Friess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chlodwig","family":"Kirchhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Stadlbauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Luppa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0370-5247","authenticated-orcid":false,"given":"Manfred","family":"Blobner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Jungwirth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"issue":"10170","key":"4626_CR1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/S0140-6736(18)33139-8","volume":"393","author":"D Nepogodiev","year":"2019","unstructured":"Nepogodiev D, Martin J, Biccard B, Makupe A, Bhangu A, National Institute for Health Research Global Health Research Unit on Global S. Global burden of postoperative death. Lancet. 2019;393(10170):401..","journal-title":"Lancet"},{"issue":"10","key":"4626_CR2","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1007\/s00134-010-1928-z","volume":"36","author":"CJ Wiedermann","year":"2010","unstructured":"Wiedermann CJ, Wiedermann W, Joannidis M. Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies. Intensive Care Med. 2010;36(10):1657\u201365.","journal-title":"Intensive Care Med"},{"issue":"3","key":"4626_CR3","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.ygyno.2015.07.005","volume":"138","author":"B Ataseven","year":"2015","unstructured":"Ataseven B, du Bois A, Reinthaller A, Traut A, Heitz F, Aust S, Prader S, Polterauer S, Harter P, Grimm C. Pre-operative serum albumin is associated with post-operative complication rate and overall survival in patients with epithelial ovarian cancer undergoing cytoreductive surgery. Gynecol Oncol. 2015;138(3):560\u20135.","journal-title":"Gynecol Oncol"},{"issue":"11","key":"4626_CR4","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1001\/archsurg.142.11.1072","volume":"142","author":"S Ganai","year":"2007","unstructured":"Ganai S, Lee KF, Merrill A, Lee MH, Bellantonio S, Brennan M, Lindenauer P. Adverse outcomes of geriatric patients undergoing abdominal surgery who are at high risk for delirium. Arch Surg. 2007;142(11):1072\u20138.","journal-title":"Arch Surg"},{"issue":"5","key":"4626_CR5","doi-asserted-by":"publisher","first-page":"359","DOI":"10.5468\/ogs.2015.58.5.359","volume":"58","author":"J Kim","year":"2015","unstructured":"Kim J, Shim SH, Oh IK, Yoon SH, Lee SJ, Kim SN, Kang SB. Preoperative hypoalbuminemia is a risk factor for 30-day morbidity after gynecological malignancy surgery. Obstet Gynecol Sci. 2015;58(5):359\u201367.","journal-title":"Obstet Gynecol Sci"},{"issue":"1","key":"4626_CR6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13054-016-1283-8","volume":"20","author":"A Norberg","year":"2016","unstructured":"Norberg A, Rooyackers O, Segersvard R, Wernerman J. Leakage of albumin in major abdominal surgery. Crit Care. 2016;20(1):113.","journal-title":"Crit Care"},{"issue":"2","key":"4626_CR7","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1093\/bja\/aet348","volume":"112","author":"K Skhirtladze","year":"2014","unstructured":"Skhirtladze K, Base EM, Lassnigg A, Kaider A, Linke S, Dworschak M, Hiesmayr MJ. Comparison of the effects of albumin 5%, hydroxyethyl starch 130\/0.4 6%, and Ringer\u2019s lactate on blood loss and coagulation after cardiac surgery. Br J Anaesth. 2014;112(2):255\u201364.","journal-title":"Br J Anaesth"},{"issue":"2","key":"4626_CR8","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1111\/j.1399-6576.1981.tb01623.x","volume":"25","author":"H Zetterstrom","year":"1981","unstructured":"Zetterstrom H. Albumin treatment following major surgery. II. Effects on postoperative lung function and circulatory adaptation. Acta Anaesthesiol Scand. 1981;25(2):133\u201341.","journal-title":"Acta Anaesthesiol Scand"},{"issue":"3","key":"4626_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151005","volume":"11","author":"E Damiani","year":"2016","unstructured":"Damiani E, Ince C, Orlando F, Pierpaoli E, Cirioni O, Giacometti A, Mocchegiani F, Pelaia P, Provinciali M, Donati A. Effects of the infusion of 4% or 20% human serum albumin on the skeletal muscle microcirculation in endotoxemic rats. PLoS One. 2016;11(3):e0151005.","journal-title":"PLoS One"},{"issue":"2","key":"4626_CR10","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1097\/00003246-199702000-00009","volume":"25","author":"H Rubin","year":"1997","unstructured":"Rubin H, Carlson S, DeMeo M, Ganger D, Craig RM. Randomized, double-blind study of intravenous human albumin in hypoalbuminemic patients receiving total parenteral nutrition. Crit Care Med. 1997;25(2):249\u201352.","journal-title":"Crit Care Med"},{"issue":"15","key":"4626_CR11","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1056\/NEJMoa1305727","volume":"370","author":"P Caironi","year":"2014","unstructured":"Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370(15):1412\u201321.","journal-title":"N Engl J Med"},{"issue":"22","key":"4626_CR12","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1056\/NEJMoa040232","volume":"350","author":"S Finfer","year":"2004","unstructured":"Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R, Investigators SS. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22):2247\u201356.","journal-title":"N Engl J Med"},{"issue":"1","key":"4626_CR13","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jclinane.2010.06.007","volume":"23","author":"K Mahkovic-Hergouth","year":"2011","unstructured":"Mahkovic-Hergouth K, Kompan L. Is replacement of albumin in major abdominal surgery useful? J Clin Anesth. 2011;23(1):42\u20136.","journal-title":"J Clin Anesth"},{"issue":"5","key":"4626_CR14","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1097\/ALN.0000000000001051","volume":"124","author":"EH Lee","year":"2016","unstructured":"Lee EH, Kim WJ, Kim JY, Chin JH, Choi DK, Sim JY, Choo SJ, Chung CH, Lee JW, Choi IC. Effect of exogenous albumin on the incidence of postoperative acute kidney injury in patients undergoing off-pump coronary artery bypass surgery with a preoperative albumin level of less than 4.0 g\/dl. Anesthesiology. 2016;124(5):1001\u201311.","journal-title":"Anesthesiology"},{"issue":"5","key":"4626_CR15","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.amjsurg.2007.10.030","volume":"196","author":"XY Yuan","year":"2008","unstructured":"Yuan XY, Zhang CH, He YL, Yuan YX, Cai SR, Luo NX, Zhan WH, Cui J. Is albumin administration beneficial in early stage of postoperative hypoalbuminemia following gastrointestinal surgery?: a prospective randomized controlled trial. Am J Surg. 2008;196(5):751\u20135.","journal-title":"Am J Surg"},{"key":"4626_CR16","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e7586","volume":"346","author":"AW Chan","year":"2013","unstructured":"Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hrobjartsson A, Schulz KF, Parulekar WR, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.","journal-title":"BMJ"},{"issue":"9","key":"4626_CR17","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/j.jclinepi.2006.12.003","volume":"60","author":"MP Grocott","year":"2007","unstructured":"Grocott MP, Browne JP, Van der Meulen J, Matejowsky C, Mutch M, Hamilton MA, Levett DZ, Emberton M, Haddad FS, Mythen MG. The Postoperative Morbidity Survey was validated and used to describe morbidity after major surgery. J Clin Epidemiol. 2007;60(9):919\u201328.","journal-title":"J Clin Epidemiol"},{"issue":"2","key":"4626_CR18","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","volume":"240","author":"D Dindo","year":"2004","unstructured":"Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205\u201313.","journal-title":"Ann Surg"},{"key":"4626_CR19","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13054-016-1237-1","volume":"20","author":"S Schmid","year":"2016","unstructured":"Schmid S, Kapfer B, Heim M, Bogdanski R, Anetsberger A, Blobner M, Jungwirth B. Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial. Crit Care. 2016;20:50.","journal-title":"Crit Care"},{"key":"4626_CR20","first-page":"671","volume":"55","author":"G Marx","year":"2014","unstructured":"Marx G. Deutsche Gesellschaft f\u00fcr An\u00e4sthesiologie und Intensivmedizin: Intravasale Volumentherapie beim Erwachsenen - S3 Leitlinie. An\u00e4sth Intensivmed. 2014;55:671\u20138.","journal-title":"An\u00e4sth Intensivmed"},{"key":"4626_CR21","volume-title":"Querschnitts-Leitlinien (B\u00c4K) zur Therapie mit Blutkomponenten und Plasmaderivaten, 4 edn","author":"Bundes\u00e4rztekammer","year":"2014","unstructured":"Bundes\u00e4rztekammer. Querschnitts-Leitlinien (B\u00c4K) zur Therapie mit Blutkomponenten und Plasmaderivaten, 4 edn. Deutschland: Deutscher \u00c4rzte-Verlag; 2014."},{"issue":"1","key":"4626_CR22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1213\/00000539-199901000-00016","volume":"88","author":"PS Myles","year":"1999","unstructured":"Myles PS, Hunt JO, Nightingale CE, Fletcher H, Beh T, Tanil D, Nagy A, Rubinstein A, Ponsford JL. Development and psychometric testing of a quality of recovery score after general anesthesia and surgery in adults. Anesth Analg. 1999;88(1):83\u201390.","journal-title":"Anesth Analg"},{"issue":"6","key":"4626_CR23","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00101-002-0322-9","volume":"51","author":"LH Eberhart","year":"2002","unstructured":"Eberhart LH, Greiner S, Geldner G, Wulf H. Patient evaluation of postoperative recovery. An evaluation of the QoR scores in 577 patients. Anaesthesist. 2002;51(6):463\u20136.","journal-title":"Anaesthesist"},{"issue":"11","key":"4626_CR24","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1515\/cclm-2013-0252","volume":"51","author":"L Meintker","year":"2013","unstructured":"Meintker L, Haimerl M, Ringwald J, Krause SW. Measurement of immature platelets with Abbott CD-Sapphire and Sysmex XE-5000 in haematology and oncology patients. Clin Chem Lab Med. 2013;51(11):2125\u201331.","journal-title":"Clin Chem Lab Med"},{"issue":"17","key":"4626_CR25","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.1002\/sim.6122","volume":"33","author":"B Klingenberg","year":"2014","unstructured":"Klingenberg B. A new and improved confidence interval for the Mantel-Haenszel risk difference. Stat Med. 2014;33(17):2968\u201383.","journal-title":"Stat Med"},{"issue":"10","key":"4626_CR26","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1160\/TH16-10-0804","volume":"117","author":"A Anetsberger","year":"2017","unstructured":"Anetsberger A, Blobner M, Haller B, Schmid S, Umgelter K, Hager T, Langgartner C, Kochs EF, Laugwitz KL, Jungwirth B, et al. Immature platelets as a novel biomarker for adverse cardiovascular events in patients after non-cardiac surgery. Thromb Haemost. 2017;117(10):1887\u201395.","journal-title":"Thromb Haemost"},{"issue":"16","key":"4626_CR27","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1001\/jama.2017.4360","volume":"317","author":"PJ Devereaux","year":"2017","unstructured":"Devereaux PJ, Biccard BM, Sigamani A, Xavier D, Chan MTV, Srinathan SK, Walsh M, Abraham V, Pearse R, Wang CY, et al. Association of postoperative high-sensitivity troponin levels with myocardial injury and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2017;317(16):1642.","journal-title":"JAMA"},{"issue":"7","key":"4626_CR28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133871","volume":"10","author":"A Anetsberger","year":"2015","unstructured":"Anetsberger A, Blobner M, Krautheim V, Umgelter K, Schmid S, Jungwirth B. Self-reported, structured measures of recovery to detect postoperative morbidity. PLoS One. 2015;10(7):e0133871.","journal-title":"PLoS One"},{"issue":"10","key":"4626_CR29","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1097\/00003643-200310000-00003","volume":"20","author":"GR Haynes","year":"2003","unstructured":"Haynes GR, Navickis RJ, Wilkes MM. Albumin administration--what is the evidence of clinical benefit? A systematic review of randomized controlled trials. Eur J Anaesthesiol. 2003;20(10):771\u201393.","journal-title":"Eur J Anaesthesiol"},{"issue":"5","key":"4626_CR30","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1093\/bja\/aew066","volume":"116","author":"PS Myles","year":"2016","unstructured":"Myles PS, Grocott MP, Boney O, Moonesinghe SR, Group CO-S. Standardizing end points in perioperative trials: towards a core and extended outcome set. Br J Anaesth. 2016;116(5):586\u20139.","journal-title":"Br J Anaesth"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04626-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-020-04626-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-020-04626-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T20:47:13Z","timestamp":1667854033000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-020-04626-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,18]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["4626"],"URL":"https:\/\/doi.org\/10.1186\/s13063-020-04626-2","relation":{},"ISSN":["1745-6215"],"issn-type":[{"type":"electronic","value":"1745-6215"}],"subject":[],"published":{"date-parts":[[2020,8,18]]},"assertion":[{"value":"19 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study is approved by the ethics committee of the School of Medicine of the Technical University of Munich (approval number 359\/16) and the competent national authority in Germany (Paul-Ehrlich Institut, Langen, Germany, approval number 2880\/01). The study is registered in EudraCT (2016-001313-24) in ClinicalTrials (NCT03167645) and has the Universal Trial Number (UTN) U1111-1181-2625. The current study protocol is version 4.1 (08.08.2018). The trial will be conducted in agreement with the principles of the Declaration of Helsinki and the German Pharmaceuticals Act. All participants will be informed about the purpose of the trial, the risks, and the potential benefits. There is no anticipated harm and compensation for trial participation. Written informed consent will be obtained by the local study physician from each participant including the hospital\u2019s policy of collection and storage of biological specimens. The Department of Anesthesiology and Intensive Care of the School of Medicine, Technical University of Munich, will coordinate the study. The original study protocol (in German) and the statistical analysis plan including amendments are publicly available at.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The study report will be submitted for publication to a peer-reviewed medical journal. In addition, it will be made available via the department\u2019s website. Furthermore, a study report will be submitted to the related authorities.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SJS reports grants from MSD (Haar, Germany); non-financial support from Fresenius, Germany, from the Technical University of Munich, Germany, and from national (e.g., DGAI) and international (e.g., ESICM) medical societies or their congress organizers in the field of anesthesiology and intensive care; and personal fees and non-financial support from Bavarian Medical Association, all outside the submitted work; he holds stocks from Alphabet Inc., Rhoen-Klinikum, Bayer AG, and Siemens AG; these holdings have not affected any decisions regarding his research or this study. TS has received research funding grants from Bayer Pharm (Berlin, Germany) and is a lecturer for Bayer Pharm (Berlin, Germany), Bristol-Myers Squibb (Munich, Germany), Pfizer (Berlin, Germany), and Daiichi Sankyo (Munich, Germany). MB received research support from MSD (Haar, Germany) not related to this manuscript and received honoraria for giving lectures from GE Healthcare (Helsinki, Finland) and Gr\u00fcnenthal (Aachen, Germany). BJ received honoraria for giving lectures from Pulsion Medical Systems SE (Feldkirchen, Germany). The other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"726"}}