Primary Literature

Bronchodilators

• Kirkland SW, Vandenberghe C, Voaklander B, Nikel T, Campbell S, Rowe BH. Combined inhaled beta-agonist and anticholinergic agents for emergency management in adults with asthma. Cochrane Database Syst Rev. 2017 Jan 11;1(1):CD001284. doi: 10.1002/14651858.CD001284.pub2. PMID: 28076656; PMCID: PMC6465060.
• Vézina K, Chauhan BF, Ducharme FM. Inhaled anticholinergics and short-acting beta(2)-agonists versus short-acting beta2-agonists alone for children with acute asthma in hospital. Cochrane Database Syst Rev. 2014 Jul 31;(7):CD010283. doi: 10.1002/14651858.CD010283.pub2. PMID: 25080126.
• Goggin N., Macarthur C., Parkin P.C.: Randomized trial of the addition of ipratropium bromide to albuterol and corticosteroid therapy in children hospitalized because of an acute asthma exacerbation. Arch Pediatr Adolesc Med 2001; 155: pp. 1329-1334
• Nowak R, Emerman C, Hanrahan JP, Parsey MV, Hanania NA, Claus R, Schaefer K, Baumgartner RA; XOPENEX Acute Severe Asthma Study Group. A comparison of levalbuterol with racemic albuterol in the treatment of acute severe asthma exacerbations in adults. Am J Emerg Med. 2006 May;24(3):259-67. doi: 10.1016/j.ajem.2006.01.027. PMID: 16635694.
• Garrett JE, Town GI, Rodwell P, Kelly AM. Nebulized salbutamol with and without ipratropium bromide in the treatment of acute asthma. J Allergy Clin Immunol. 1997 Aug;100(2):165-70. doi: 10.1016/s0091-6749(97)70219-7. PMID: 9275135.
• Karpel JP, Schacter EN, Fanta C, Levey D, Spiro P, Aldrich T, Menjoge SS, Witek TJ. A comparison of ipratropium and albuterol vs albuterol alone for the treatment of acute asthma. Chest. 1996 Sep;110(3):611-6. doi: 10.1378/chest.110.3.611. PMID: 8797400.
• Salo D, Tuel M, Lavery RF, Reischel U, Lebowitz J, Moore T. A randomized, clinical trial comparing the efficacy of continuous nebulized albuterol (15 mg) versus continuous nebulized albuterol (15 mg) plus ipratropium bromide (2 mg) for the treatment of acute asthma. J Emerg Med. 2006 Nov;31(4):371-6. doi: 10.1016/j.jemermed.2006.05.025. PMID: 17046476.
• Rodrigo GJ, Rodrigo C. First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department. Am J Respir Crit Care Med. 2000 Jun;161(6):1862-8. doi: 10.1164/ajrccm.161.6.9908115. PMID: 10852758.
• Newman KB, Milne S, Hamilton C, Hall K. A comparison of albuterol administered by metered-dose inhaler and spacer with albuterol by nebulizer in adults presenting to an urban emergency department with acute asthma. Chest. 2002 Apr;121(4):1036-41. doi: 10.1378/chest.121.4.1036. PMID: 11948030.
• Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013 Sep 13;2013(9):CD000052. doi: 10.1002/14651858.CD000052.pub3. PMID: 24037768; PMCID: PMC7032675.
• Plotnick LH, Ducharme FM. Should inhaled anticholinergics be added to beta2 agonists for treating acute childhood and adolescent asthma? A systematic review. BMJ. 1998 Oct 10;317(7164):971-7. doi: 10.1136/bmj.317.7164.971. PMID: 9765164; PMCID: PMC28680.
• Rossing TH, Fanta CH, Goldstein DH, Snapper JR, McFadden ER Jr. Emergency therapy of asthma: comparison of the acute effects of parenteral and inhaled sympathomimetics and infused aminophylline. Am Rev Respir Dis. 1980 Sep;122(3):365-71. doi: 10.1164/arrd.1980.122.3.365. PMID: 7416612.
• Stoodley RG, Aaron SD, Dales RE. The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials. Ann Emerg Med. 1999 Jul;34(1):8-18. doi: 10.1016/s0196-0644(99)70266-0. PMID: 10381989.
• Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005 Sep;60(9):740-6. doi: 10.1136/thx.2005.040444. Epub 2005 Jul 29. Erratum in: Thorax. 2006 Mar;61(3):274. Erratum in: Thorax. 2006 May;61(5):458. Erratum in: Thorax. 2008 Nov;63(11):1029. Erratum in: Thorax. 2010 Dec;65(12):1118. PMID: 16055613; PMCID: PMC1747524.
• Castle W., Fuller R., Hall J., et. al.: Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ 1993; 306: pp. 1034-1037.
• Nelson H.S., Weiss S.T., Bleecker E.R., et. al.: The salmeterol multicenter asthma research trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006; 129: pp. 15-26.
• Mann M, Chowdhury B, Sullivan E, Nicklas R, Anthracite R, Meyer RJ. Serious asthma exacerbations in asthmatics treated with high-dose formoterol. Chest. 2003 Jul;124(1):70-4. doi: 10.1378/chest.124.1.70. PMID: 12853504.
• Mendes ES, Cadet L, Arana J, Wanner A. Acute effect of an inhaled glucocorticosteroid on albuterol-induced bronchodilation in patients with moderately severe asthma. Chest. 2015 Apr;147(4):1037-1042. doi: 10.1378/chest.14-1742. PMID: 25611803.

Steroids

• Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A Randomized Controlled Noninferiority Trial of Single Dose of Oral Dexamethasone Versus 5 Days of Oral Prednisone in Acute Adult Asthma. Ann Emerg Med. 2016 Nov;68(5):608-613. doi: 10.1016/j.annemergmed.2016.03.017. Epub 2016 Apr 22. PMID: 27117874.
• Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001;(1):CD002178. doi: 10.1002/14651858.CD002178. PMID: 11279756.
• Fanta CH, Rossing TH, McFadden ER Jr. Glucocorticoids in acute asthma. A critical controlled trial. Am J Med. 1983 May;74(5):845-51. doi: 10.1016/0002-9343(83)91076-8. PMID: 6340496.
• Rodrigo GJ. Comparison of inhaled fluticasone with intravenous hydrocortisone in the treatment of adult acute asthma. Am J Respir Crit Care Med. 2005 Jun 1;171(11):1231-6. doi: 10.1164/rccm.200410-1415OC. Epub 2005 Mar 11. PMID: 15764724.
• FitzGerald JM, Shragge D, Haddon J, Jennings B, Lee J, Bai T, Pare P, Kassen D, Grunfeld A. A randomized, controlled trial of high dose, inhaled budesonide versus oral prednisone in patients discharged from the emergency department following an acute asthma exacerbation. Can Respir J. 2000 Jan-Feb;7(1):61-7. doi: 10.1155/2000/587957. PMID: 10700672.
• Cronin JJ, McCoy S, Kennedy U, et al. A randomized trial of single-dose oral dexamethasone versus multidose prednisolone for acute exacerbations of asthma in children who attend the emergency department. Ann Emerg Med 2016; 67:593–601
• Edmonds ML, Camargo CA Jr, Brenner BE, Rowe BH. Replacement of oral corticosteroids with inhaled corticosteroids in the treatment of acute asthma following emergency department discharge: a meta-analysis. Chest. 2002 Jun;121(6):1798-805. doi: 10.1378/chest.121.6.1798. PMID: 12065341.
• Edmonds ML, Milan SJ, Camargo CA Jr, Pollack CV, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD002308. doi: 10.1002/14651858.CD002308.pub2. PMID: 23235589; PMCID: PMC6513646.
• Bateman ED, Fairall L, Lombardi DM, English R. Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol. Respir Res. 2006 Jan 24;7(1):13. doi: 10.1186/1465-9921-7-13. PMID: 16433920; PMCID: PMC1386666.
• Belda J, Margarit G, Martínez C, Bellido-Casado J, Casan P, Torrejón M, Brufal M, Rodríguez-Jerez F, Sanchis J. Anti-inflammatory effects of high-dose inhaled fluticasone versus oral prednisone in asthma exacerbations. Eur Respir J. 2007 Dec;30(6):1143-9. doi: 10.1183/09031936.00050306. Epub 2007 Aug 9. PMID: 17690122.
• Estrada-Reyes E, Del Río-Navarro BE, Rosas-Vargas MA, Nava-Ocampo AA. Co-administration of salbutamol and fluticasone for emergency treatment of children with moderate acute asthma. Pediatr Allergy Immunol. 2005 Nov;16(7):609-14. doi: 10.1111/j.1399-3038.2005.00317.x. PMID: 16238587.
• Pansegrouw DF. Acute resistant asthma caused by excessive beta-2-adrenoceptor agonist inhalation and reversed by inhalation of beclomethasone. S Afr Med J. 1992 Sep;82(3):179-82. PMID: 1355618.
• Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000195. doi: 10.1002/14651858.CD000195.pub2. PMID: 17636617.

Magnesium

• Hossein S, Pegah A, Davood F, Said A, Babak M, Mani M, Mahdi R, Peyman H. The effect of nebulized magnesium sulfate in the treatment of moderate to severe asthma attacks: a randomized clinical trial. Am J Emerg Med. 2016 May;34(5):883-6. doi: 10.1016/j.ajem.2016.01.024. Epub 2016 Jan 21. PMID: 26964827.
• Ling ZG, Wu YB, Kong JL, Tang ZM, Liu W, Chen YQ. Lack of efficacy of nebulized magnesium sulfate in treating adult asthma: A meta-analysis of randomized controlled trials. Pulm Pharmacol Ther. 2016 Dec;41:40-47. doi: 10.1016/j.pupt.2016.09.008. Epub 2016 Sep 17. PMID: 27651324.
• Levy Z, Slesinger TL. Does intravenous magnesium reduce the need for hospital admission among adult patients with acute asthma exacerbations? Ann Emerg Med. 2015 Jun;65(6):702-3. doi: 10.1016/j.annemergmed.2014.07.019. Epub 2014 Aug 13. PMID: 25128007.
• Skobeloff EM, Spivey WH, McNamara RM, Greenspon L. Intravenous magnesium sulfate for the treatment of acute asthma in the emergency department. JAMA. 1989 Sep 1;262(9):1210-3. PMID: 2761061.
• Kew KM, Kirtchuk L, Michell CI. Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. Cochrane Database Syst Rev. 2014 May 28;(5):CD010909. doi: 10.1002/14651858.CD010909.pub2. PMID: 24865567.
• Griffiths B, Kew KM. Intravenous magnesium sulfate for treating children with acute asthma in the emergency department. Cochrane Database Syst Rev. 2016;(4):CD011050.
• Goodacre S, Cohen J, Bradburn M, Stevens J, Gray A, Benger J, Coats T; 3Mg Research Team. The 3Mg trial: a randomised controlled trial of intravenous or nebulised magnesium sulphate versus placebo in adults with acute severe asthma. Health Technol Assess. 2014 Apr;18(22):1-168. doi: 10.3310/hta18220. PMID: 24731521; PMCID: PMC4781576.
• Knightly R, Milan SJ, Hughes R, Knopp-Sihota JA, Rowe BH, Normansell R, Powell C. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2017 Nov 28;11(11):CD003898. doi: 10.1002/14651858.CD003898.pub6. PMID: 29182799; PMCID: PMC6485984.
• Bijani KH, Moghadamnia AA, Islami Khalili E. Intravenous magnesium sulfate as an adjunct in the treatment of severe asthmatic patients non‐responding to conventional therapy. Acta Medica Iranica 2001;39(4):219‐21.
• Bloch H, Silverman R, Mancherje N, Grant S, Jagminas L, Scharf SM. Intravenous magnesium sulfate as an adjunct in the treatment of acute asthma. Chest 1995;107(6):1576‐81.
• Bradshaw TA, Matusiewicz SP, Crompton GK, Alastair Innes J, Greening AP. Intravenous magnesium sulphate provides no additive benefit to standard management in acute asthma. Respiratory Medicine 2008;102(1):143‐9.
• Singh AK, Gaur S, Kumar R. A randomized controlled trial of intravenous magnesium sulphate as an adjunct to standard therapy in acute severe asthma. Iranian Journal of Allergy, Asthma, and Immunology 2008;7(4):221‐9.
• Griffiths B, Kew KM, Normansell R. Intravenous magnesium sulfate for treating children with acute asthma in the emergency department. Paediatr Respir Rev 2016; 20:45–47

Ketamine

• Tiwari A, Guglani V, Jat KR. Ketamine versus aminophylline for acute asthma in children: A randomized, controlled trial. Ann Thorac Med. 2016 Oct-Dec;11(4):283-288. doi: 10.4103/1817-1737.191874. PMID: 27803755; PMCID: PMC5070438.
• Jat KR, Chawla D. Ketamine for management of acute exacerbations of asthma in children. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD009293. doi: 10.1002/14651858.CD009293.pub2. PMID: 23152273; PMCID: PMC6483733.
• Strube PJ, Hallam PL. Ketamine by continuous infusion in status asthmaticus. Anaesthesia. 1986 Oct;41(10):1017-9. doi: 10.1111/j.1365-2044.1986.tb12744.x. PMID: 3789345.
• Rock MJ, Reyes de la Rocha S, L’Hommedieu CS, Truemper E. Use of ketamine in asthmatic children to treat respiratory failure refractory to conventional therapy. Crit Care Med. 1986 May;14(5):514-6. doi: 10.1097/00003246-198605000-00019. PMID: 3698618.
• Hemming A, MacKenzie I, Finfer S. Response to ketamine in status asthmaticus resistant to maximal medical treatment. Thorax. 1994 Jan;49(1):90-1. doi: 10.1136/thx.49.1.90. PMID: 8153950; PMCID: PMC474120.
• Denmark TK, Crane HA, Brown L. Ketamine to avoid mechanical ventilation in severe pediatric asthma. J Emerg Med. 2006 Feb;30(2):163-6. doi: 10.1016/j.jemermed.2005.09.003. PMID: 16567251.
• Shlamovitz GZ, Hawthorne T. Intravenous ketamine in a dissociating dose as a temporizing measure to avoid mechanical ventilation in adult patient with severe asthma exacerbation. J Emerg Med. 2011 Nov;41(5):492-4. doi: 10.1016/j.jemermed.2008.03.035. Epub 2008 Oct 15. PMID: 18922662.
• Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Ann Emerg Med. 2005 Jul;46(1):43-50. doi: 10.1016/j.annemergmed.2005.02.024. PMID: 15988425.
• Elkoundi A, Bentalha A, El Koraichi A, El Kettani SE. Nebulized ketamine to avoid mechanical ventilation in a pediatric patient with severe asthma exacerbation. Am J Emerg Med. 2018 Apr;36(4):734.e3-734.e4. doi: 10.1016/j.ajem.2018.01.027. Epub 2018 Jan 6. PMID: 29321114.
• Petrillo TM, Fortenberry JD, Linzer JF, Simon HK. Emergency department use of ketamine in pediatric status asthmaticus. J Asthma. 2001;38:657–64. 
• Howton JC, Rose J, Duffy S, Zoltanski T, Levitt MA. Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. Ann Emerg Med. 1996;27:170–5
• Heshmati F, Zeinali MB, Noroozinia H, Abbacivash R, Mahoori A. Use of ketamine in severe status asthmaticus in intensive care unit. Iran J Allergy Asthma Immunol. 2003 Dec;2(4):175-80. PMID: 17301376.
• Shlamovitz GZ, Hawthorne T. Intravenous ketamine in a dissociating dose as a temporizing measure to avoid mechanical ventilation in adult patient with severe asthma exacerbation. J Emerg Med. 2011 Nov;41(5):492-4. doi: 10.1016/j.jemermed.2008.03.035. Epub 2008 Oct 15. PMID: 18922662.
• Hemmingsen C, Nielsen PK, Odorico J. Ketamine in the treatment of bronchospasm during mechanical ventilation. Am J Emerg Med. 1994 Jul;12(4):417-20. doi: 10.1016/0735-6757(94)90051-5. PMID: 8031424.
• Youssef-Ahmed MZ, Silver P, Nimkoff L, Sagy M. Continuous infusion of ketamine in mechanically ventilated children with refractory bronchospasm. Intensive Care Med. 1996;22:972–6.
• Howton JC, Rose J, Duffy S, Zoltanski T, Levitt MA. Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. Ann Emerg Med. 1996 Feb;27(2):170-5. doi: 10.1016/s0196-0644(96)70319-0. PMID: 8629747.

Other Therapies

• Doymaz S, Schneider J. Safety of terbutaline for treatment of acute severe pediatric asthma. Pediatr Emerg Care 2016;
• Adair E, Dibaba D, Fowke JH, Snider M. The Impact of Terbutaline as Adjuvant Therapy in the Treatment of Severe Asthma in the Pediatric Emergency Department. Pediatr Emerg Care. 2020 Oct 29. doi: 10.1097/PEC.0000000000002269. Epub ahead of print. PMID: 33136831.
• Travers AH, Milan SJ, Jones AP, Camargo CA Jr, Rowe BH. Addition of intravenous beta(2)-agonists to inhaled beta(2)-agonists for acute asthma. Cochrane Database Syst Rev. 2012 Dec 12;12:CD010179. doi: 10.1002/14651858.CD010179. PMID: 23235685.
• Needleman JP, Kaifer MC, Nold JT, Shuster PE, Redding MM, Gladstein J. Theophylline does not shorten hospital stay for children admitted for asthma. Arch Pediatr Adolesc Med. 1995 Feb;149(2):206-9. doi: 10.1001/archpedi.1995.02170140088016. PMID: 7849886.
• D’Avila RS, Piva JP, Marostica PJ, Amantea SL. Early administration of two intravenous bolus of aminophylline added to the standard treatment of children with acute asthma. Respir Med. 2008 Jan;102(1):156-61. doi: 10.1016/j.rmed.2007.07.030. Epub 2007 Sep 14. PMID: 17869497.
• DiGiulio GA, Kercsmar CM, Krug SE, Alpert SE, Marx CM. Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid. J Pediatr. 1993 Mar;122(3):464-9. doi: 10.1016/s0022-3476(05)83442-0. PMID: 8441107.
• Ream RS, Loftis LL, Albers GM, Becker BA, Lynch RE, Mink RB. Efficacy of IV theophylline in children with severe status asthmaticus. Chest. 2001 May;119(5):1480-8. doi: 10.1378/chest.119.5.1480. PMID: 11348957.
• Spiteri MA, Millar AB, Pavia D, Clarke SW. Subcutaneous adrenaline versus terbutaline in the treatment of acute severe asthma. Thorax. 1988 Jan;43(1):19-23. doi: 10.1136/thx.43.1.19. PMID: 3281307; PMCID: PMC461081.
• Bag R., Bandi V., Fromm R.E., et. al.: The effect of heliox-driven bronchodilator aerosol therapy on pulmonary function tests in patients with asthma. J Asthma 2002; 39: pp. 659-665.
• El-Khatib MF, Jamaleddine G, Kanj N, Zeineddine S, Chami H, Bou-Akl I, Husari A, Alawieh M, Bou-Khalil P. Effect of heliox- and air-driven nebulized bronchodilator therapy on lung function in patients with asthma. Lung. 2014 Jun;192(3):377-83. doi: 10.1007/s00408-014-9570-0. Epub 2014 Mar 19. PMID: 24643901.
• Rodrigo GJ, Castro-Rodriguez JA. Heliox-driven β2-agonists nebulization for children and adults with acute asthma: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2014 Jan;112(1):29-34. doi: 10.1016/j.anai.2013.09.024. Epub 2013 Oct 23. PMID: 24331390.
• Watts K, Chavasse RJ. Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children. Cochrane Database Syst Rev. 2012 May 16;2012(5):CD006100. doi: 10.1002/14651858.CD006100.pub2. PMID: 22592708; PMCID: PMC7387678.
• Camargo CA Jr, Gurner DM, Smithline HA, Chapela R, Fabbri LM, Green SA, Malice MP, Legrand C, Dass SB, Knorr BA, Reiss TF. A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma. J Allergy Clin Immunol. 2010 Feb;125(2):374-80. doi: 10.1016/j.jaci.2009.11.015. PMID: 20159247.
• Harmanci K, Bakirtas A, Turktas I, Degim T. Oral montelukast treatment of preschool-aged children with acute asthma. Ann Allergy Asthma Immunol. 2006 May;96(5):731-5. doi: 10.1016/S1081-1206(10)61073-3. PMID: 16729788.
• Morris CR, Becker AB, Piñieiro A, Massaad R, Green SA, Smugar SS, Gurner DM. A randomized, placebo-controlled study of intravenous montelukast in children with acute asthma. Ann Allergy Asthma Immunol. 2010 Feb;104(2):161-71. doi: 10.1016/j.anai.2009.11.065. PMID: 20306820.
• Nelson KA, Smith SR, Trinkaus K, Jaffe DM. Pilot study of oral montelukast added to standard therapy for acute asthma exacerbations in children aged 6 to 14 years. Pediatr Emerg Care. 2008 Jan;24(1):21-7. doi: 10.1097/pec.0b013e31815f3968. PMID: 18165796.
• Todi VK, Lodha R, Kabra SK. Effect of addition of single dose of oral montelukast to standard treatment in acute moderate to severe asthma in children between 5 and 15 years of age: a randomised, double-blind, placebo controlled trial. Arch Dis Child. 2010 Jul;95(7):540-3. doi: 10.1136/adc.2009.168567. Epub 2010 Jun 3. PMID: 20522464.
• Camargo CA Jr, Smithline HA, Malice MP, Green SA, Reiss TF. A randomized controlled trial of intravenous montelukast in acute asthma. Am J Respir Crit Care Med. 2003 Feb 15;167(4):528-33. doi: 10.1164/rccm.200208-802OC. Epub 2002 Nov 27. PMID: 12456380.
• Okubo Y, Horimukai K, Michihata N, Morita K, Matsui H, Fushimi K, Yasunaga H. Association between early antibiotic treatment and clinical outcomes in children hospitalized for asthma exacerbation. J Allergy Clin Immunol. 2021 Jan;147(1):114-122.e14. doi: 10.1016/j.jaci.2020.05.030. Epub 2020 Jun 3. PMID: 32504615.
• Graham V, Lasserson T, Rowe BH. Antibiotics for acute asthma. Cochrane Database Syst Rev. 2001;(3):CD002741. doi: 10.1002/14651858.CD002741. Update in: Cochrane Database Syst Rev. 2018 Jun 25;6:CD002741. PMID: 11687022.

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