{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:02:09Z","timestamp":1785542529704,"version":"3.56.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"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":["Pharmacol. Rep"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Introducing the principles of multimodal analgesic therapy is necessary to provide appropriate comfort for the patient after surgery. The main objective of the study was evaluating the influence of perioperative intravenous (i.v.) lidocaine infusion on postoperative morphine requirements during the first 48\u00a0h postoperatively in children undergoing major spine surgery.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>Prospective, randomized, double-blind study: 41 children, qualified to multilevel spine surgery, were randomly divided into two treatment groups: lidocaine and placebo (control). The lidocaine group received lidocaine as a bolus of 1.5 mg\/kg over 30 minutes, followed by a continuous infusion at 1 mg\/kg\/h to 6 hours after surgery. The protocol of perioperative management was identical for all patients. Measurements: morphine demand, intensity of postoperative pain (the Numerical Rating Scale), oral feeding initiation time, first attempts at assuming erect position, postoperative quality of life (the Acute Short-form \/SF-12\/ health survey).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Patient data did not differ demographically. Compared to the control group, lidocaine treatment reduced the demand for morphine during the first 24h [95% CI 0.13 (0.11-0.28) mg\/kg,<jats:italic> p<\/jats:italic> = 0.0122], 48h [95% CI 0.46 (0.22-0.52) mg\/kg,<jats:italic> p<\/jats:italic> = 0.0299] after surgery and entire hospitalization [95% CI 0.58 (0.19-0.78) mg\/kg,<jats:italic> p<\/jats:italic> = 0.04]; postoperative pain intensity; nutritional withdrawal period [introduction of liquid diet (<jats:italic>p<\/jats:italic> = 0.024) and solid diet (<jats:italic>p<\/jats:italic> = 0.012)], and accelerated the adoption of an upright position [sitting (<jats:italic>p<\/jats:italic> = 0.048); walking (<jats:italic>p<\/jats:italic> = 0.049)]. The SF-12 generic health survey did not differ between groups before operation, 2 months and 4 years after surgery.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Perioperative lidocaine administration, as a part of the applied analgesic therapy regimen, may decrease postoperative opioid demand and accelerates convalescence of children undergoing major surgery.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s43440-020-00100-7","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T13:03:42Z","timestamp":1586955822000},"page":"744-755","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Lidocaine as an element of multimodal analgesic therapy in major spine surgical procedures in children: a prospective, randomized, double-blind study"],"prefix":"10.1007","volume":"72","author":[{"given":"Ilona","family":"Batko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Ko\u015bcielniak-Merak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142aw J.","family":"Tomasik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Kobylarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Wordliczek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"100_CR1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1097\/00008480-200102000-00006","volume":"13","author":"G Shapiro","year":"2001","unstructured":"Shapiro G, Green DW, Fatica NS, Boachie-Adjei O. Medical complications in scoliosis surgery. Curr Opin Pediatr. 2001;13:36\u201341.","journal-title":"Curr Opin Pediatr"},{"issue":"5","key":"100_CR2","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1213\/ANE.0b013e3181d41dc2","volume":"110","author":"LM Rusy","year":"2010","unstructured":"Rusy LM, Hainsworth KR, Nelson TJ, Czarnecki ML, Tassone JC, Thometz JG, et al. Gabapentin use in pediatric spinal fusion patients: a randomized, double-blind, controlled trial. Anesth Analg. 2010;110(5):1393\u20138. https:\/\/doi.org\/10.1213\/ANE.0b013e3181d41dc2.","journal-title":"Anesth Analg"},{"issue":"4","key":"100_CR3","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1097\/ALN.0b013e318297d4a5","volume":"119","author":"E Farag","year":"2013","unstructured":"Farag E, Ghobrial M, Sessler DI, Dalton JE, Liu J, Lee JH, et al. Effect of perioperative intravenous lidocaine administration on pain, opioid consumption, and quality of life after complex spine surgery. Anesthesiology. 2013;119(4):932\u201340. https:\/\/doi.org\/10.1097\/ALN.0b013e318297d4a5.","journal-title":"Anesthesiology"},{"issue":"4 Suppl 2","key":"100_CR4","doi-asserted-by":"publisher","first-page":"85S","DOI":"10.1097\/PRS.0000000000000671","volume":"134","author":"EB Rosero","year":"2014","unstructured":"Rosero EB, Joshi GP. Preemptive, preventive, multimodal analgesia: what do they really mean? Plast Reconstr Surg. 2014;134(4 Suppl 2):85S\u201393S. https:\/\/doi.org\/10.1097\/PRS.0000000000000671.","journal-title":"Plast Reconstr Surg"},{"issue":"1","key":"100_CR5","first-page":"1","volume":"66","author":"M Mergeay","year":"2015","unstructured":"Mergeay M, Verster A, Van Aken D, Vercauteren M. Regional versus general anesthesia for spine surgery. A comprehensive review. Acta Anaesthesiol Belg. 2015;66(1):1\u20139.","journal-title":"Acta Anaesthesiol Belg"},{"key":"100_CR6","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0000000000000989","author":"DK Choudhry","year":"2017","unstructured":"Choudhry DK, Brenn BR, Sacks K, Shah S. Evaluation of gabapentin and clonidine use in children following spinal fusion surgery for idiopathic scoliosis: A retrospective review. J Pediatr Orthop. 2017. https:\/\/doi.org\/10.1097\/BPO.0000000000000989","journal-title":"J Pediatr Orthop."},{"issue":"5","key":"100_CR7","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1111\/aas.12304","volume":"58","author":"HJ Jabbour","year":"2014","unstructured":"Jabbour HJ, Naccache NM, Jawish RJ, Abou Zeid HA, Jabbour KB, Rabbaa-Khabbaz LG, et al. Ketamine and magnesium association reduces morphine consumption after scoliosis surgery: prospective randomised double-blind study. Acta Anaesthesiol Scand. 2014;58(5):572\u20139. https:\/\/doi.org\/10.1111\/aas.12304.","journal-title":"Acta Anaesthesiol Scand"},{"issue":"1","key":"100_CR8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1097\/AJP.0b013e318246d1a9","volume":"29","author":"YS Choi","year":"2013","unstructured":"Choi YS, Shim JK, Song JW, Kim JC, Yoo YC, Kwak YL. Combination of pregabalin and dexamethasone for postoperative pain and functional outcome in patients undergoing lumbar spinal surgery: a randomized placebo-controlled trial. Clin J Pain. 2013;29(1):9\u201314. https:\/\/doi.org\/10.1097\/AJP.0b013e318246d1a9.","journal-title":"Clin J Pain"},{"key":"100_CR9","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jclinane.2015.07.007","volume":"28","author":"JS Khan","year":"2016","unstructured":"Khan JS, Yousuf M, Victor JC, Sharma A, Siddiqui N. An estimation for an appropriate end time for an intraoperative intravenous lidocaine infusion in bowel surgery: a comparative meta-analysis. J Clin Anesth. 2016;28:95\u2013104. https:\/\/doi.org\/10.1016\/j.jclinane.2015.07.007.","journal-title":"J Clin Anesth"},{"key":"100_CR10","doi-asserted-by":"publisher","first-page":"177","DOI":"10.4103\/1658-354X.203027","volume":"11","author":"A Jendoubi","year":"2017","unstructured":"Jendoubi A, Naceur IB, Bouzouita A, Trifa M, Ghedira S, Chebil M, et al. A comparison between intravenous lidocaine and ketamine on acute and chronic pain after open nephrectomy: a prospective, double-blind, randomized, placebo-controlled study. Saudi J Anaesth. 2017;11:177\u201384.","journal-title":"Saudi J Anaesth"},{"issue":"6","key":"100_CR11","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1093\/bja\/aew101","volume":"116","author":"S Weibel","year":"2016","unstructured":"Weibel S, Jokinen J, Pace NL, Schnabel A, Hollmann MW, Hahnenkamp K, et al. Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis. Br J Anaesth. 2016;116(6):770\u201383. https:\/\/doi.org\/10.1093\/bja\/aew101.","journal-title":"Br J Anaesth"},{"issue":"9","key":"100_CR12","doi-asserted-by":"publisher","first-page":"e7121","DOI":"10.5867\/medwave.2017.09.7121","volume":"17","author":"MM Gonz\u00e1lez","year":"2017","unstructured":"Gonz\u00e1lez MM, Altermatt F. Is intravenous lidocaine effective for decreasing pain and speeding up recovery after surgery? Medwave. 2017;17(9):e7121. https:\/\/doi.org\/10.5867\/medwave.2017.09.7121.","journal-title":"Medwave"},{"issue":"3","key":"100_CR13","doi-asserted-by":"publisher","first-page":"e44732","DOI":"10.5812\/aapm.44732","volume":"7","author":"F Yousefshahi","year":"2017","unstructured":"Yousefshahi F, Predescu O, Francisco AJ. The efficacy of systemic lidocaine in the management of chronic pain: a literature review. Anesth Pain Med. 2017;7(3):e44732. https:\/\/doi.org\/10.5812\/aapm.44732.","journal-title":"Anesth Pain Med"},{"issue":"3","key":"100_CR14","doi-asserted-by":"publisher","first-page":"366","DOI":"10.4103\/0970-9185.137269","volume":"30","author":"P Tauzin-Fin","year":"2014","unstructured":"Tauzin-Fin P, Bernard O, Sesay M, Biais M, Richebe P, Quinart A, et al. Benefits of intravenous lidocaine on post-operative pain and acute rehabilitation after laparoscopic nephrectomy. J Anaesthesiol Clin Pharmacol. 2014;30(3):366\u201372. https:\/\/doi.org\/10.4103\/0970-9185.137269.","journal-title":"J Anaesthesiol Clin Pharmacol"},{"issue":"2","key":"100_CR15","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1213\/ANE.0b013e318257a380","volume":"115","author":"GS De Oliveira","year":"2012","unstructured":"De Oliveira GS, Fitzgerald P, Streicher LF, Marcus RJ, McCarthy RJ. Systemic lidocaine to improve postoperative quality of recovery after ambulatory laparoscopic surgery. Anesth Analg. 2012;115(2):262\u20137. https:\/\/doi.org\/10.1213\/ANE.0b013e318257a380.","journal-title":"Anesth Analg."},{"issue":"13","key":"100_CR16","doi-asserted-by":"publisher","first-page":"e0229","DOI":"10.1097\/MD.0000000000010229","volume":"97","author":"A Ibrahim","year":"2018","unstructured":"Ibrahim A, Aly M, Farrag W. Effect of intravenous lidocaine infusion on long-term postoperative pain after spinal fusion surgery. Medicine (Baltimore). 2018;97(13):e0229. https:\/\/doi.org\/10.1097\/MD.0000000000010229.","journal-title":"Medicine (Baltimore)"},{"key":"100_CR17","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD009642.pub2","author":"P Kranke","year":"2015","unstructured":"Kranke P, Jokinen J, Pace NL, Schnabel A, Hollmann MW, Hahnenkamp K, et al. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. Cochrane Database Syst Rev. 2015. https:\/\/doi.org\/10.1002\/14651858.CD009642.pub2.","journal-title":"Cochrane Database Syst Rev."},{"issue":"11","key":"100_CR18","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1016\/S0895-4356(98)00109-7","volume":"51","author":"B Gandek","year":"1998","unstructured":"Gandek B, Ware JE, Aaronson NK, Apolone G, Bjorner JB, Brazier JE, et al. Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: Results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol. 1998;51(11):1171\u20138.","journal-title":"J Clin Epidemiol."},{"issue":"2","key":"100_CR19","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1097\/ALN.0b013e31823c1030","volume":"116","author":"American Society of Anesthesiologists Task Force on Acute Pain Management","year":"2012","unstructured":"American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248\u201373. https:\/\/doi.org\/10.1097\/ALN.0b013e31823c1030.","journal-title":"Anesthesiology"},{"issue":"8","key":"100_CR20","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1097\/00001756-199404000-00005","volume":"5","author":"ML Sotgiu","year":"1994","unstructured":"Sotgiu ML, Biella G, Castagna A, Lacerenza M, Marchettini P. Different time-courses of i.v. lidocaine effect on ganglionic and spinal units in neuropathic rats. NeuroReport. 1994;5(8):873\u20136.","journal-title":"NeuroReport"},{"issue":"5","key":"100_CR21","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1002\/ejp.794","volume":"20","author":"SE van der Wal","year":"2016","unstructured":"van der Wal SE, van den Heuvel SA, Radema SA, van Berkum BF, Vaneker M, Steegers MA, et al. The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain. Eur J Pain. 2016;20(5):655\u201374. https:\/\/doi.org\/10.1002\/ejp.794.","journal-title":"Eur J Pain"},{"issue":"4","key":"100_CR22","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1097\/00002508-200207000-00002","volume":"18","author":"MS Cepeda","year":"2002","unstructured":"Cepeda MS, Lau J, Carr DB. Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: a narrative and systematic review. Clin J Pain. 2002;18(4):216\u201333.","journal-title":"Clin J Pain"},{"issue":"5","key":"100_CR23","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1097\/00000542-199105000-00020","volume":"74","author":"DL Tanelian","year":"1991","unstructured":"Tanelian DL, MacIver MB. Analgesic concentrations of lidocaine suppress tonic A-delta and C fiber discharges produced by acute injury. Anesthesiology. 1991;74(5):934\u20136.","journal-title":"Anesthesiology"},{"issue":"2","key":"100_CR24","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1046\/j.1365-2249.2002.01747.x","volume":"127","author":"M Lahav","year":"2002","unstructured":"Lahav M, Levite M, Bassani L, Lang A, Fidder H, Tal R, et al. Lidocaine inhibits secretion of IL-8 and IL-1beta and stimulates secretion of IL-1 receptor antagonist by epithelial cells. Clin Exp Immunol. 2002;127(2):226\u201333.","journal-title":"Clin Exp Immunol"},{"issue":"9","key":"100_CR25","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1016\/j.pain.2013.04.030","volume":"154","author":"RJ Docherty","year":"2013","unstructured":"Docherty RJ, Ginsberg L, Jadoon S, Orrell RW, Bhattacharjee A. TRPA1 insensitivity of human sural nerve axons after exposure to lidocaine. Pain. 2013;154(9):1569\u201377.","journal-title":"Pain"},{"issue":"1","key":"100_CR26","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ejphar.2011.10.035","volume":"674","author":"C Gronwald","year":"2012","unstructured":"Gronwald C, Vegh V, Hollmann MW, Hahnenkamp A, Garaj V, Hahnenkamp K. The inhibitory potency of local anesthetics on NMDA receptor signalling depends on their structural features. Eur J Pharmacol. 2012;674(1):13\u20139.","journal-title":"Eur J Pharmacol"},{"issue":"6","key":"100_CR27","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1097\/ALN.0b013e31825c47e2","volume":"116","author":"R Werdehausen","year":"2012","unstructured":"Werdehausen R, Kremer D, Brandenburger T, Schl\u00f6sser L, Jadasz J, K\u00fcry P, et al. Lidocaine metabolites inhibit glycine transporter 1: a novel mechanism for the analgesic action of systemic lidocaine? Anesthesiology. 2012;116(6):1404 (Erratum).","journal-title":"Anesthesiology"},{"key":"100_CR28","doi-asserted-by":"publisher","DOI":"10.23736\/S0375-9393.19.13703-0","author":"B Ko\u015bcielniak-Merak","year":"2019","unstructured":"Ko\u015bcielniak-Merak B, Batko I, Fleszar M, Kocot-K\u0119pska M, Gamian A, Kobylarz K, et al. Effect of intravenous, perioperative-administrated lidocaine on serum levels of endocannabinoids and related N-acylethanolamines in children. Miner Anestesiol. 2019. https:\/\/doi.org\/10.23736\/S0375-9393.19.13703-0.","journal-title":"Miner Anestesiol"},{"issue":"30","key":"100_CR29","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.2174\/1381612825666190718153209","volume":"25","author":"B Ko\u015bcielniak-Merak","year":"2019","unstructured":"Ko\u015bcielniak-Merak B, Batko I, Kobylarz K, Sztefko K, Kocot-K\u0119pska M, Tomasik PJ. Impact of intravenous, perioperative-administrated lidocaine on postoperative serum levels of endogenous opioids in children. Curr Pharm Des. 2019;25(30):3209\u201315. https:\/\/doi.org\/10.2174\/1381612825666190718153209.","journal-title":"Curr Pharm Des"},{"issue":"1","key":"100_CR30","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s12630-010-9407-0","volume":"58","author":"L Vigneault","year":"2011","unstructured":"Vigneault L, Turgeon AF, C\u00f4t\u00e9 D, Lauzier F, Zarychanski R, Moore L, et al. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011;58(1):22\u201337. https:\/\/doi.org\/10.1007\/s12630-010-9407-0.","journal-title":"Can J Anaesth"},{"issue":"4","key":"100_CR31","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1093\/bja\/aex038","volume":"118","author":"G Dewinter","year":"2017","unstructured":"Dewinter G, Moens P, Fieuws S, Vanaudenaerde B, Van de Velde M, Rex S. Systemic lidocaine fails to improve postoperative morphine consumption, postoperative recovery and quality of life in patients undergoing posterior spinal arthrodesis. A double-blind, randomized, placebo-controlled trial. Br J Anaesth. 2017;118(4):576\u201385. https:\/\/doi.org\/10.1093\/bja\/aex038.","journal-title":"Br J Anaesth."},{"issue":"8","key":"100_CR32","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1016\/j.spinee.2013.09.031","volume":"14","author":"KT Kim","year":"2014","unstructured":"Kim KT, Cho DC, Sung JK, Kim YB, Kang H, Song KS, et al. Intraoperative systemic infusion of lidocaine reduces postoperative pain after lumbar surgery: a double-blinded, randomized, placebo-controlled clinical trial. Spine J. 2014;14(8):1559\u2013666. https:\/\/doi.org\/10.1016\/j.spinee.2013.09.031.","journal-title":"Spine J"}],"container-title":["Pharmacological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-020-00100-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43440-020-00100-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-020-00100-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T07:39:44Z","timestamp":1618472384000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43440-020-00100-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["100"],"URL":"https:\/\/doi.org\/10.1007\/s43440-020-00100-7","relation":{},"ISSN":["1734-1140","2299-5684"],"issn-type":[{"value":"1734-1140","type":"print"},{"value":"2299-5684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,15]]},"assertion":[{"value":"12 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}