https://doi.org/10.4081/ejtm.2022.10833
Optimal dosing interval of intravenous Colistin monotherapy versus combination therapy: A systematic review and meta-analysis
Submitted: 3 September 2022
Accepted: 9 September 2022
Published: 27 October 2022
Accepted: 9 September 2022
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Supplementary Materials: 94
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
We aimed to maximize the clinical response and effectiveness of colistin antibiotics in patients with multi-drug (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, there is an increasing interest in colistin combination therapy with other antibiotics and extended interval dosing regimens. This systematic review and meta-analysis aim is to evaluate if the combination therapy is superior to monotherapy with colistin regarding increased survival and also which dose interval is the most effective to utilize. English language, peer-reviewed journal publications from the first date available to 25 January 2022 were identified by searching the PubMed and Web of Science databases. Forest plots for overall and subgroups and funnel plots were graphed. 42 studies were included in the study. Among them, 38 studies were on combination therapy, and four on dose interval. The overall pooled odds ratio is 0.77 (CI: 0.62; 0.95) (p value < 0.017). The I^2 value was 43% (p value < 0.01). The Begg correlation test of funnel plot asymmetry showed no significant publication bias (0.064). The overall pooled odds ratio for Carbapenem is 0.74 (CI: 0.48; 1.13). A prospective randomized controlled trials (RCT) on 40 adults intensive care unit (ICU) patients with ventilator-associated pneumonia (VAP), comparing the mortality and ICU length of stay of 8- or 24- hour intervals regimens, showed that the ICU length of stay and ICU mortality were; 31.31, 35.3 days, and 32.06, 22.2% in groups 24-h interval and 8- hour interval (p value: 0.39, 0.87), respectively. It seems that combination therapy is associated with drug synergism and increased survival. The extended interval colistin administration may result in higher peak concentration and bacterial eradication. In both cases, we face a dearth of literature.
Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, Paterson DL. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis. 2006 Sep;6(9):589-601.
DOI: https://doi.org/10.1016/S1473-3099(06)70580-1
Brink AJ, Richards GA, Colombo G, Bortolotti F, Colombo P, Jehl F. Multicomponent antibiotic substances produced by fermentation: implications for regulatory authorities, critically ill patients and generics. Int J Antimicrob Agents. 2014 Jan;43(1):1-6. Epub 2013 Aug 3.
DOI: https://doi.org/10.1016/j.ijantimicag.2013.06.013
Nation RL, Li J, Cars O, Couet W, Dudley MN, Kaye KS, Mouton JW, Paterson DL, Tam VH, Theuretzbacher U, Tsuji BT, Turnidge JD. Framework for optimisation of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus. Lancet Infect Dis. 2015 Feb;15(2):225-34. Epub 2014 Oct 21.
DOI: https://doi.org/10.1016/S1473-3099(14)70850-3
Petrosillo N, Ioannidou E, Falagas ME. Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies. Clin Microbiol Infect. 2008 Sep;14(9):816-27.
DOI: https://doi.org/10.1111/j.1469-0691.2008.02061.x
Bergen PJ, Li J, Nation RL, Turnidge JD, Coulthard K, Milne RW. Comparison of once-, twice- and thrice-daily dosing of colistin on antibacterial effect and emergence of resistance: studies with Pseudomonas aeruginosa in an in vitro pharmacodynamic model. J Antimicrob Chemother. 2008 Mar;61(3):636-42. Epub 2008 Jan 28.
DOI: https://doi.org/10.1093/jac/dkm511
Mohamed AF, Cars O, Friberg LE. A pharmacokinetic/pharmacodynamic model developed for the effect of colistin on Pseudomonas aeruginosa in vitro with evaluation of population pharmacokinetic variability on simulated bacterial killing. J Antimicrob Chemother. 2014 May;69(5):1350-61. Epub 2014 Jan 27.
DOI: https://doi.org/10.1093/jac/dkt520
Ghazaeian M, Mokhtari M, Kouchek M, Miri M, Goharani R, Ghodssi-Ghassemabadi R, Sistanizad M. Once Versus Thrice Daily Colistin in Critically Ill Ptients with Multi-Drug Resistant Infections. Iran J Pharm Res. 2017 Summer;16(3):1247-1253.
Luque S, Grau S, Valle M, Sorlí L, Horcajada JP, Segura C, Alvarez-Lerma F. Differences in pharmacokinetics and pharmacodynamics of colistimethate sodium (CMS) and colistin between three different CMS dosage regimens in a critically ill patient infected by a multidrug-resistant Acinetobacter baumannii. Int J Antimicrob Agents. 2013 Aug;42(2):178-81. Epub 2013 Jun 14.
DOI: https://doi.org/10.1016/j.ijantimicag.2013.04.018
Daikos GL, Skiada A, Pavleas J, Vafiadi C, Salatas K, Tofas P, Tzanetou K, Markogiannakis A, Thomopoulos G, Vafiadi I, Petrikkos G. Serum bactericidal activity of three different dosing regimens of colistin with implications for optimum clinical use. J Chemother. 2010 Jun;22(3):175-8.
DOI: https://doi.org/10.1179/joc.2010.22.3.175
Abdelsalam MFA, Abdalla MS, El-Abhar HSE. Prospective, comparative clinical study between high-dose colistin monotherapy and colistin-meropenem combination therapy for treatment of hospital-acquired pneumonia and ventilator-associated pneumonia caused by multidrug-resistant Klebsiella pneumoniae. J Glob Antimicrob Resist. 2018 Dec;15:127-135. Epub 2018 Oct 11.
DOI: https://doi.org/10.1016/j.jgar.2018.07.003
Aydemir H, Akduman D, Piskin N, Comert F, Horuz E, Terzi A, Kokturk F, Ornek T, Celebi G. Colistin vs. the combination of colistin and rifampicin for the treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia. Epidemiol Infect. 2013 Jun;141(6):1214-22. Epub 2012 Sep 7.
DOI: https://doi.org/10.1017/S095026881200194X
Batirel A, Balkan II, Karabay O, Agalar C, Akalin S, Alici O, Alp E, Altay FA, Altin N, Arslan F, Aslan T, Bekiroglu N, Cesur S, Celik AD, Dogan M, Durdu B, Duygu F, Engin A, Engin DO, Gonen I, Guclu E, Guven T, Hatipoglu CA, Hosoglu S, Karahocagil MK, Kilic AU, Ormen B, Ozdemir D, Ozer S, Oztoprak N, Sezak N, Turhan V, Turker N, Yilmaz H. Comparison of colistin-carbapenem, colistin-sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections. Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1311-22. Epub 2014 Feb 15. PMID: 24532009.
DOI: https://doi.org/10.1007/s10096-014-2070-6
Capone A, Giannella M, Fortini D, Giordano A, Meledandri M, Ballardini M, Venditti M, Bordi E, Capozzi D, Balice MP, Tarasi A, Parisi G, Lappa A, Carattoli A, Petrosillo N. High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality. Clin Microbiol Infect. 2013 Jan;19(1):E23-E30. doi: 10.1111/1469-0691.12070. Epub 2012 Nov 9.
DOI: https://doi.org/10.1111/1469-0691.12070
Daikos GL, Petrikkos P, Psichogiou M, Kosmidis C, Vryonis E, Skoutelis A, Georgousi K, Tzouvelekis LS, Tassios PT, Bamia C, Petrikkos G. Prospective observational study of the impact of VIM-1 metallo-beta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother. 2009 May;53(5):1868-73. Epub 2009 Feb 17.
DOI: https://doi.org/10.1128/AAC.00782-08
Daikos GL, Tsaousi S, Tzouvelekis LS, Anyfantis I, Psichogiou M, Argyropoulou A, Stefanou I, Sypsa V, Miriagou V, Nepka M, Georgiadou S, Markogiannakis A, Goukos D, Skoutelis A. Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems. Antimicrob Agents Chemother. 2014;58(4):2322-8. Epub 2014 Feb 10.
DOI: https://doi.org/10.1128/AAC.02166-13
Durante-Mangoni E, Signoriello G, Andini R, Mattei A, De Cristoforo M, Murino P, Bassetti M, Malacarne P, Petrosillo N, Galdieri N, Mocavero P, Corcione A, Viscoli C, Zarrilli R, Gallo C, Utili R. Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial. Clin Infect Dis. 2013 Aug;57(3):349-58. Epub 2013 Apr 24.
DOI: https://doi.org/10.1093/cid/cit253
Falagas ME, Rafailidis PI, Matthaiou DK, Virtzili S, Nikita D, Michalopoulos A. Pandrug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii infections: characteristics and outcome in a series of 28 patients. Int J Antimicrob Agents. 2008 Nov;32(5):450-4. Epub 2008 Sep 2.
DOI: https://doi.org/10.1016/j.ijantimicag.2008.05.016
Garnacho-Montero J, Amaya-Villar R, Gutiérrez-Pizarraya A, Espejo-Gutiérrez de Tena E, Artero-González ML, Corcia-Palomo Y, Bautista-Paloma J. Clinical efficacy and safety of the combination of colistin plus vancomycin for the treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii. Chemotherapy. 2013;59(3):225-31. Epub 2013 Dec 13.
DOI: https://doi.org/10.1159/000356004
Hernández-Torres A, García-Vázquez E, Gómez J, Canteras M, Ruiz J, Yagüe G. Multidrug and carbapenem-resistant Acinetobacter baumannii infections: Factors associated with mortality. Med Clin (Barc). 2012 May 26;138(15):650-5. Epub 2011 Nov 16.
DOI: https://doi.org/10.1016/j.medcli.2011.06.024
Kalin G, Alp E, Akin A, Coskun R, Doganay M. Comparison of colistin and colistin/sulbactam for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia. Infection. 2014 Feb;42(1):37-42. Epub 2013 Jul 5.
DOI: https://doi.org/10.1007/s15010-013-0495-y
Katip W, Oberdorfer P. Clinical Efficacy and Nephrotoxicity of Colistin Alone versus Colistin Plus Vancomycin in Critically Ill Patients Infected with Carbapenem-Resistant Acinetobacter baumannii: A Propensity Score-Matched Analysis. Pharmaceutics. 2021 Jan 26;13(2):162. doi: 10.3390/pharmaceutics13020162.
DOI: https://doi.org/10.3390/pharmaceutics13020162
Katip W, Uitrakul S, Oberdorfer P. The effectiveness and nephrotoxicity of loading dose colistin combined with or without meropenem for the treatment of carbapenem-resistant A. baumannii. Int J Infect Dis. 2020 Aug;97:391-395. Epub 2020 Jun 2.
DOI: https://doi.org/10.1016/j.ijid.2020.05.100
Katip W, Uitrakul S, Oberdorfer P. A Comparison of Colistin versus Colistin Plus Meropenem for the Treatment of Carbapenem-Resistant Acinetobacter baumannii in Critically Ill Patients: A Propensity Score-Matched Analysis. Antibiotics (Basel). 2020 Sep 28;9(10):647.
DOI: https://doi.org/10.3390/antibiotics9100647
Kontopidou F, Giamarellou H, Katerelos P, Maragos A, Kioumis I, Trikka-Graphakos E, Valakis C, Maltezou HC; Group for the Study of KPC-producing Klebsiella pneumoniae infections in intensive care units. Infections caused by carbapenem-resistant Klebsiella pneumoniae among patients in intensive care units in Greece: a multi-centre study on clinical outcome and therapeutic options. Clin Microbiol Infect. 2014 Feb;20(2):O117-23. Epub 2013 Aug 30. PMID: 23992130.
DOI: https://doi.org/10.1111/1469-0691.12341
Ku K, Pogue JM, Moshos J, Bheemreddy S, Wang Y, Bhargava A, Campbell M, Khandker N, Lephart PR, Chopra T, Hayakawa K, Martin ET, Abreu-Lanfranco O, Dhar S, Kaye KS, Marchaim D. Retrospective evaluation of colistin versus tigecycline for the treatment of Acinetobacter baumannii and/or carbapenem-resistant Enterobacteriaceae infections. Am J Infect Control. 2012 Dec;40(10):983-7. Epub 2012 Mar 21.
DOI: https://doi.org/10.1016/j.ajic.2011.12.014
López-Cortés LE, Cisneros JM, Fernández-Cuenca F, Bou G, Tomás M, Garnacho-Montero J, Pascual A, Martínez-Martínez L, Vila J, Pachón J, Rodríguez Baño J; GEIH/REIPI-Ab2010 Group. Monotherapy versus combination therapy for sepsis due to multidrug-resistant Acinetobacter baumannii: analysis of a multicentre prospective cohort. J Antimicrob Chemother. 2014 Nov;69(11):3119-26. Epub 2014 Jun 25.
Makris D, Petinaki E, Tsolaki V, Manoulakas E, Mantzarlis K, Apostolopoulou O, Sfyras D, Zakynthinos E. Colistin versus Colistin Combined with Ampicillin-Sulbactam for Multiresistant Acinetobacter baumannii Ventilator-associated Pneumonia Treatment: An Open-label Prospective Study. Indian J Crit Care Med. 2018 Feb;22(2):67-77.
DOI: https://doi.org/10.4103/ijccm.IJCCM_302_17
Mouloudi E, Protonotariou E, Zagorianou A, Iosifidis E, Karapanagiotou A, Giasnetsova T, Tsioka A, Roilides E, Sofianou D, Gritsi-Gerogianni N. Bloodstream infections caused by metallo-β-lactamase/Klebsiella pneumoniae carbapenemase-producing K. pneumoniae among intensive care unit patients in Greece: risk factors for infection and impact of type of resistance on outcomes. Infect Control Hosp Epidemiol. 2010 Dec;31(12):1250-6. Epub 2010 Oct 25.
DOI: https://doi.org/10.1086/657135
Navarro-San Francisco C, Mora-Rillo M, Romero-Gómez MP, Moreno-Ramos F, Rico-Nieto A, Ruiz-Carrascoso G, Gómez-Gil R, Arribas-López JR, Mingorance J, Paño-Pardo JR. Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge. Clin Microbiol Infect. 2013 Feb;19(2):E72-9. Epub 2012 Dec 12.
DOI: https://doi.org/10.1111/1469-0691.12091
Nutman A, Carmeli Y. Re: 'Colistin plus meropenem for carbapenem-resistant gram-negative infections: in vitro synergism is not associated with better clinical outcomes'-Author's reply. Clin Microbiol Infect. 2020 Sep;26(9):1275. Epub 2020 May 25.
DOI: https://doi.org/10.1016/j.cmi.2020.05.010
Özvatan T, Akalın H, Sınırtaş M, Ocakoğlu G, Yılmaz E, Heper Y, Kelebek N, İşçimen R, Kahveci F. Nosocomial Acinetobacter pneumonia: Treatment and prognostic factors in 356 cases. Respirology. 2016 Feb;21(2):363-9. Epub 2015 Dec 3.
DOI: https://doi.org/10.1111/resp.12698
Papadimitriou-Olivgeris M, Marangos M, Christofidou M, Fligou F, Bartzavali C, Panteli ES, Vamvakopoulou S, Filos KS, Anastassiou ED. Risk factors for infection and predictors of mortality among patients with KPC-producing Klebsiella pneumoniae bloodstream infections in the intensive care unit. Scand J Infect Dis. 2014 Sep;46(9):642-8. Epub 2014 Jul 14.
DOI: https://doi.org/10.3109/00365548.2014.923106
Parchem NL, Bauer KA, Cook CH, Mangino JE, Jones CD, Porter K, Murphy CV. Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia. Eur J Clin Microbiol Infect Dis. 2016 Sep;35(9):1433-9. Epub 2016 May 26.
DOI: https://doi.org/10.1007/s10096-016-2681-1
Park HJ, Cho JH, Kim HJ, Han SH, Jeong SH, Byun MK. Colistin monotherapy versus colistin/rifampicin combination therapy in pneumonia caused by colistin-resistant Acinetobacter baumannii: A randomised controlled trial. J Glob Antimicrob Resist. 2019 Jun;17:66-71. Epub 2018 Nov 23.
DOI: https://doi.org/10.1016/j.jgar.2018.11.016
Park JJ, Seo YB, Lee J, Choi YK, Jeon J. Colistin monotherapy versus colistin-based combination therapy for treatment of bacteremia in burn patients due to carbapenem-resistant gram negative bacteria. Burns. 2020 Dec;46(8):1848-1856. Epub 2020 Jun 21.
DOI: https://doi.org/10.1016/j.burns.2020.06.014
Park SY, Si HJ, Eom JS, Lee JS. Survival of carbapenem-resistant Acinetobacter baumannii bacteremia: colistin monotherapy versus colistin plus meropenem. J Int Med Res. 2019 Dec;47(12):5977-5985. Epub 2019 Oct 15.
DOI: https://doi.org/10.1177/0300060519879336
Paul M, Daikos GL, Durante-Mangoni E, Yahav D, Carmeli Y, Benattar YD, Skiada A, Andini R, Eliakim-Raz N, Nutman A, Zusman O, Antoniadou A, Pafundi PC, Adler A, Dickstein Y, Pavleas I, Zampino R, Daitch V, Bitterman R, Zayyad H, Koppel F, Levi I, Babich T, Friberg LE, Mouton JW, Theuretzbacher U, Leibovici L. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis. 2018 Apr;18(4):391-400. Epub 2018 Feb 16.
DOI: https://doi.org/10.1016/S1473-3099(18)30099-9
Petrosillo N, Giannella M, Antonelli M, Antonini M, Barsic B, Belancic L, Inkaya A C, De Pascale G, Grilli E, Tumbarello M, Akova M. Clinical experience of colistin-glycopeptide combination in critically ill patients infected with Gram-negative bacteria. Antimicrob Agents Chemother. 2014;58(2):851-8. Epub 2013 Nov 25.
DOI: https://doi.org/10.1128/AAC.00871-13
Pintado V, San Miguel LG, Grill F, Mejía B, Cobo J, Fortún J, Martín-Dávila P, Moreno S. Intravenous colistin sulphomethate sodium for therapy of infections due to multidrug-resistant gram-negative bacteria. J Infect. 2008 Mar;56(3):185-90. Epub 2008 Feb 15.
DOI: https://doi.org/10.1016/j.jinf.2008.01.003
Porwal R, Gopalakrishnan R, Rajesh NJ, Ramasubramanian V. Carbapenem resistant Gram-negative bacteremia in an Indian intensive care unit: A review of the clinical profile and treatment outcome of 50 patients. Indian J Crit Care Med. 2014 Nov;18(11):750-3.
DOI: https://doi.org/10.4103/0972-5229.144021
Shi H, Lee JS, Park SY, Ko Y, Eom JS. Colistin Plus Carbapenem versus Colistin Monotherapy in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Pneumonia. Infect Drug Resist. 2019 Dec 23;12:3925-3934.
DOI: https://doi.org/10.2147/IDR.S234211
Simsek F, Gedik H, Yildirmak MT, Iris NE, Türkmen A, Ersoy A, Ersöz M, Gücüyener A. Colistin against colistin-only-susceptible Acinetobacter baumannii-related infections: Monotherapy or combination therapy? Indian J Med Microbiol. 2012 Oct-Dec;30(4):448-52.
DOI: https://doi.org/10.4103/0255-0857.103767
Sirijatuphat R, Thamlikitkul V. Preliminary study of colistin versus colistin plus fosfomycin for treatment of carbapenem-resistant Acinetobacter baumannii infections. Antimicrob Agents Chemother. 2014 Sep;58(9):5598-601. Epub 2014 Jun 30.
DOI: https://doi.org/10.1128/AAC.02435-13
Souli M, Kontopidou FV, Papadomichelakis E, Galani I, Armaganidis A, Giamarellou H. Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-beta-lactamase in a Greek University Hospital. Clin Infect Dis. 2008 Mar 15;46(6):847-54.
DOI: https://doi.org/10.1086/528719
Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, Spanu T, Ambretti S, Ginocchio F, Cristini F, Losito AR, Tedeschi S, Cauda R, Bassetti M. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012 Oct;55(7):943-50. Epub 2012 Jul 2.
DOI: https://doi.org/10.1093/cid/cis588
Yilmaz GR, Guven T, Guner R, Kocak Tufan Z, Izdes S, Tasyaran MA, Acikgoz ZC. Colistin alone or combined with sulbactam or carbapenem against A. baumannii in ventilator-associated pneumonia. J Infect Dev Ctries. 2015 May 18;9(5):476-85.
DOI: https://doi.org/10.3855/jidc.6195
Zarkotou O, Pournaras S, Tselioti P, Dragoumanos V, Pitiriga V, Ranellou K, Prekates A, Themeli-Digalaki K, Tsakris A. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin Microbiol Infect. 2011 Dec;17(12):1798-803. Epub 2011 May 20.
DOI: https://doi.org/10.1111/j.1469-0691.2011.03514.x
Zusman O, Altunin S, Koppel F, Dishon Benattar Y, Gedik H, Paul M. Polymyxin monotherapy or in combination against carbapenem-resistant bacteria: systematic review and meta-analysis. J Antimicrob Chemother. 2017 Jan;72(1):29-39. Epub 2016 Sep 13.
DOI: https://doi.org/10.1093/jac/dkw377
Yaghoubi S, Zekiy AO, Krutova M, Gholami M, Kouhsari E, Sholeh M, Ghafouri Z, Maleki F. Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review. Eur J Clin Microbiol Infect Dis. 2022 Jul;41(7):1003-1022.
DOI: https://doi.org/10.1007/s10096-020-04121-1
Sato Y, Ubagai T, Tansho-Nagakawa S, Yoshino Y, Ono Y. Effects of colistin and tigecycline on multidrug-resistant Acinetobacter baumannii biofilms: advantages and disadvantages of their combination. Sci Rep. 2021 Jun 3;11(1):11700.
DOI: https://doi.org/10.1038/s41598-021-90732-3
How to Cite
Ahmadpour, F., Shaseb, E., Izadpanah, M., Rakhshan, A., & Hematian, F. (2022). Optimal dosing interval of intravenous Colistin monotherapy versus combination therapy: A systematic review and meta-analysis. European Journal of Translational Myology, 32(4). https://doi.org/10.4081/ejtm.2022.10833
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