Canadian Anaphylaxis Network-Predicting Recurrence after Emergency Presentation for Allergic REaction (CAN-PREPARE): a prospective, cohort study protocol

Waleed Alqurashi, Marcus Shaker, George A Wells, Gary Stephen Collins, Matthew Greenhawt, Janet A Curran, Roger Zemek, Suzanne Schuh, Anne Ellis, Jennifer Gerdts, Cheryl Kreviazuk, Andrew Dixon, Mohamed Eltorki, Stephen B Freedman, Jocelyn Gravel, Naveen Poonai, Margitta Worm, Amy C Plint, Waleed Alqurashi, Marcus Shaker, George A Wells, Gary Stephen Collins, Matthew Greenhawt, Janet A Curran, Roger Zemek, Suzanne Schuh, Anne Ellis, Jennifer Gerdts, Cheryl Kreviazuk, Andrew Dixon, Mohamed Eltorki, Stephen B Freedman, Jocelyn Gravel, Naveen Poonai, Margitta Worm, Amy C Plint

Abstract

Introduction: Anaphylaxis is a severe, potentially fatal multiorgan system manifestation of an allergic reaction. The highest incidence of anaphylaxis is in children and adolescents. Biphasic anaphylaxis (BA) is defined as the recurrence of allergic symptoms after resolution of an initial reaction. It has been reported to occur in 10%-20% of cases within 1-48 hours from the onset of the initial reaction. The dilemma for physicians is determining which patients with resolved anaphylaxis should be observed for BA and for how long. Guidelines for duration of postanaphylaxis monitoring vary, are based on limited evidence and can have unintended negative impacts on patient safety, quality of life and healthcare resources. The objectives of this study are to derive a prognostic model for BA and to develop a risk-scoring system that informs disposition decisions of children who present to emergency departments (ED) with anaphylaxis.

Methods and analysis: This prospective multicentre cohort study will enrol 1682 patients from seven paediatric EDs that are members of the Paediatric Emergency Research Canada network. We will enrol patients younger than 18 years of age with an allergic reaction meeting anaphylaxis diagnostic criteria. Trained ED research assistants will screen, obtain consent and prospectively collect study data. Research assistants will follow patients during their ED visit and ascertain, in conjunction with the medical team, if the patient develops BA. A standardised follow-up survey conducted following study enrolment will determine if a biphasic reaction occurred after ED disposition. Model development will conform to the broad principles of the PROGRESS (Prognosis Research Strategy) framework and reporting will follow the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis Statement.

Ethics and dissemination: Ethics approval has been received from all participating centres. Our dissemination plan focuses on informing clinicians, policy makers and parents of the results through publication in peer-reviewed journals and broadcasting on multiple media platforms.

Trial registration number: NCT05135377.

Keywords: EPIDEMIOLOGY; PAEDIATRICS; Paediatric A&E and ambulatory care.

Conflict of interest statement

Competing interests: All authors have read and understood BMJ policy on declaration of interests and have no relevant interest to declare. ACP is supported by a Tier I University of Ottawa Research Chair. SF is supported by the Alberta Children’s Hospital Professorship in Child Health and Wellness.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Simons FER, Ardusso LRF, Bilò MB, et al. . World allergy organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J 2011;4:13–37. 10.1097/WOX.0b013e318211496c
    1. Castells M. Diagnosis and management of anaphylaxis in precision medicine. J Allergy Clin Immunol 2017;140:321–33. 10.1016/j.jaci.2017.06.012
    1. CIHI . Anaphylaxis and allergy in the emergency department, 2015. Available: [Accessed 18 Dec 2015].
    1. Sheikh A, Hippisley-Cox J, Newton J, et al. . Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England. J R Soc Med 2008;101:139–43. 10.1258/jrsm.2008.070306
    1. Wood RA, Camargo CA, Lieberman P, et al. . Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol 2014;133:461–7. 10.1016/j.jaci.2013.08.016
    1. Moro-Moro M, Múgica-García MV, Tejedor-Alonso M A . Epidemiology of anaphylaxis: contributions from the last 10 years. J Investig Allergol Clin Immunol 2015;25:163–75.
    1. Simons FER, Sampson HA. Anaphylaxis epidemic: fact or fiction? J Allergy Clin Immunol 2008;122:1166–8. 10.1016/j.jaci.2008.10.019
    1. Lieberman P, Camargo CA, Bohlke K, et al. . Epidemiology of anaphylaxis: findings of the American College of allergy, asthma and immunology epidemiology of anaphylaxis Working group. Ann Allergy Asthma Immunol 2006;97:596–602. 10.1016/S1081-1206(10)61086-1
    1. Canada S. The impact on emergency department utilization of the CFHI healthcare collaborations and initiatives, 2013. Available:
    1. Hochstadter E, Clarke A, De Schryver S, et al. . Increasing visits for anaphylaxis and the benefits of early epinephrine administration: A 4-year study at a pediatric emergency department in Montreal, Canada. J Allergy Clin Immunol 2016;137:1888–90. 10.1016/j.jaci.2016.02.016
    1. Gabrielli S, Clarke A, Morris J, et al. . Evaluation of prehospital management in a Canadian emergency department anaphylaxis cohort. J Allergy Clin Immunol Pract 2019;7:2232–8. 10.1016/j.jaip.2019.04.018
    1. Lee AYM, Enarson P, Clarke AE, et al. . Anaphylaxis across two Canadian pediatric centers: evaluating management disparities. J Asthma Allergy 2017;10:1–7. 10.2147/JAA.S123053
    1. Motosue MS, Bellolio MF, Van Houten HK, et al. . National trends in emergency department visits and hospitalizations for food-induced anaphylaxis in US children. Pediatr Allergy Immunol 2018;29:538–44. 10.1111/pai.12908
    1. Grabenhenrich LB, Dölle S, Moneret-Vautrin A, et al. . Anaphylaxis in children and adolescents: the European anaphylaxis registry. J Allergy Clin Immunol 2016;137:1128–37. 10.1016/j.jaci.2015.11.015
    1. Canadian Society of Allergy and Clinical Immunology . Anaphylaxis in Schools & Other Settings, 2016. Available: [Accessed 10 Dec 2016].
    1. Lieberman P, Nicklas RA, Randolph C, et al. . Anaphylaxis—a practice parameter update 2015. Annals of Allergy, Asthma & Immunology 2015;115:341–84. 10.1016/j.anai.2015.07.019
    1. Muraro A, Roberts G, Worm M, et al. . Anaphylaxis: guidelines from the European Academy of allergy and clinical immunology. Allergy 2014;69:1026–45. 10.1111/all.12437
    1. Lieberman P. Biphasic anaphylactic reactions. Ann Allergy Asthma Immunol 2005;95:217–26. 10.1016/S1081-1206(10)61217-3
    1. Tole JW, Lieberman P. Biphasic anaphylaxis: review of incidence, clinical predictors, and observation recommendations. Immunol Allergy Clin North Am 2007;27:309–26. 10.1016/j.iac.2007.03.011
    1. Lertnawapan R, Maek-a-nantawat W. Anaphylaxis and biphasic phase in Thailand: 4-year observation. Allergol Int 2011;60:283–9. 10.2332/allergolint.10-OA-0256
    1. Orhan F, Canitez Y, Bakirtas A, et al. . Anaphylaxis in Turkish children: a multi-centre, retrospective, case study. Clin Exp Allergy 2011;41:1767–76. 10.1111/j.1365-2222.2011.03859.x
    1. Inoue N, Yamamoto A. Clinical evaluation of pediatric anaphylaxis and the necessity for multiple doses of epinephrine. Asia Pac Allergy 2013;3:106. 10.5415/apallergy.2013.3.2.106
    1. Lee J, Garrett JPD, Brown-Whitehorn T. Biphasic reactions in children undergoing oral food challenges. Allergy and Asthma Proceedings, 2013: 220–6.
    1. Nagano C, Ishiguro A, Yotani N. Anaphylaxis and biphasic reaction in a children Hospital. Japanese J Allergol 2013;62:163–70. 10.15036/arerugi.62.163
    1. Vezir E, Erkoçoǧlu M, Kaya A. Characteristics of anaphylaxis in children referred to a tertiary care center. Allergy and Asthma Proceedings, 2013: 239–46.
    1. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992;327:380–4. 10.1056/NEJM199208063270603
    1. Liew WK, Chiang WC, Goh AE, et al. . Paediatric anaphylaxis in a Singaporean children cohort: changing food allergy triggers over time. Asia Pac Allergy 2013;3:29. 10.5415/apallergy.2013.3.1.29
    1. Brown SGA, Stone SF, Fatovich DM, et al. . Anaphylaxis: clinical patterns, mediator release, and severity. J Allergy Clin Immunol 2013;132:1141–9. 10.1016/j.jaci.2013.06.015
    1. Grunau BE, Li J, Yi TW, et al. . Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis. Ann Emerg Med 2014;63:736–44. 10.1016/j.annemergmed.2013.10.017
    1. Rohacek M, Edenhofer H, Bircher A, et al. . Biphasic anaphylactic reactions: occurrence and mortality. Allergy 2014;69:791–7. 10.1111/all.12404
    1. Lee S, Bellolio MF, Hess EP, et al. . Predictors of biphasic reactions in the emergency department for patients with anaphylaxis. J Allergy Clin Immunol Pract 2014;2:281–7. 10.1016/j.jaip.2014.01.012
    1. Oya S, Nakamori T, Kinoshita H. Incidence and characteristics of biphasic and protracted anaphylaxis: evaluation of 114 inpatients. Acute Med Surg 2014;1:228–33. 10.1002/ams2.48
    1. Sricharoen P, Sittichanbuncha Y, Wibulpolprasert A, et al. . What clinical factors are associated with biphasic anaphylaxis in Thai adult patients? Asian Pac J Allergy Immunol 2015;33:8–13. 10.12932/AP0477.33.1.2015
    1. Manuyakorn W, Benjaponpitak S, Kamchaisatian W, et al. . Pediatric anaphylaxis: triggers, clinical features, and treatment in a tertiary-care Hospital. Asian Pac J Allergy Immunol 2015;33:281–8. 10.12932/AP0610.33.4.2015
    1. Alqurashi W, Stiell I, Chan K, et al. . Epidemiology and clinical predictors of biphasic reactions in children with anaphylaxis. Ann Allergy Asthma Immunol 2015;115:217–23. 10.1016/j.anai.2015.05.013
    1. Ko BS, Kim WY, Ryoo SM, et al. . Biphasic reactions in patients with anaphylaxis treated with corticosteroids. Ann Allergy Asthma Immunol 2015;115:312–6. 10.1016/j.anai.2015.07.015
    1. Douglas DM, Sukenick E, Andrade WP, et al. . Biphasic systemic anaphylaxis: an inpatient and outpatient study. J Allergy Clin Immunol 1994;93:977–85. 10.1016/S0091-6749(94)70044-3
    1. Saleh-Langenberg J, Flokstra-de Blok BMJ, AlAgla N, et al. . Late reactions in food-allergic children and adolescents after double-blind, placebo-controlled food challenges. Allergy 2016;71:1069–73. 10.1111/all.12923
    1. Irani A-M. Further evaluations of factors that may predict biphasic reactions in emergency department anaphylaxis patients. Pediatrics 2018;142:S222–3. 10.1542/peds.2018-2420Y
    1. Kim T-H, Yoon SH, Lee S-Y, et al. . Biphasic and protracted anaphylaxis to iodinated contrast media. Eur Radiol 2018;28:1242–52. 10.1007/s00330-017-5052-0
    1. Brady WJ, Luber S, Carter CT, et al. . Multiphasic anaphylaxis: an uncommon event in the emergency department. Acad Emerg Med 1997;4:193–7. 10.1111/j.1553-2712.1997.tb03739.x
    1. Popa VT, Lerner SA. Biphasic systemic anaphylactic reaction: three illustrative cases. Ann Allergy 1984;53:151–5.
    1. Stark BJ, Sullivan TJ. Biphasic and protracted anaphylaxis. J Allergy Clin Immunol 1986;78:76–83. 10.1016/0091-6749(86)90117-X
    1. Ellis AK, Day JH. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients. Ann Allergy Asthma Immunol 2007;98:64–9. 10.1016/S1081-1206(10)60861-7
    1. Scranton SE, Gonzalez EG, Waibel KH. Incidence and characteristics of biphasic reactions after allergen immunotherapy. J Allergy Clin Immunol 2009;123:493–8. 10.1016/j.jaci.2008.10.026
    1. Mehr S, Liew WK, Tey D. Clinical predictors for biphasic reactions in children presenting with anaphylaxis. Clin Exp Allergy 2010;18:83. 10.1111/j.1365-2222.2009.03276.x
    1. Confino-Cohen R, Goldberg A. Allergen immunotherapy-induced biphasic systemic reactions: incidence, characteristics, and outcome: a prospective study. Ann Allergy Asthma Immunol 2010;104:73–8. 10.1016/j.anai.2009.11.001
    1. Alqurashi W, Ellis AK. Do corticosteroids prevent biphasic anaphylaxis? J Allergy Clin Immunol Pract 2017;5:1194–205. 10.1016/j.jaip.2017.05.022
    1. Shaker MS, Wallace DV, Golden DBK, et al. . Anaphylaxis-a 2020 practice parameter update, systematic review, and grading of recommendations, assessment, development and evaluation (grade) analysis. J Allergy Clin Immunol 2020;145:1082–123. 10.1016/j.jaci.2020.01.017
    1. Lee S, Bellolio MF, Hess EP, et al. . Time of onset and predictors of biphasic anaphylactic reactions: a systematic review and meta-analysis. J Allergy Clin Immunol Pract 2015;3:408–16. 10.1016/j.jaip.2014.12.010
    1. Kemp SF. The post-anaphylaxis dilemma: how long is long enough to observe a patient after resolution of symptoms? Curr Allergy Asthma Rep 2008;8:45–8. 10.1007/s11882-008-0009-7
    1. Lee S, Sadosty AT, Campbell RL. Update on biphasic anaphylaxis. Curr Opin Allergy Clin Immunol 2016;16:346–51. 10.1097/ACI.0000000000000279
    1. Parlaman JP, Oron AP, Uspal NG, et al. . Emergency and hospital care for food-related anaphylaxis in children. Hosp Pediatr 2016;6:269–74. 10.1542/hpeds.2015-0153
    1. Michelson KA, Monuteaux MC, Neuman MI. Variation and trends in anaphylaxis care in United States children's hospitals. Acad Emerg Med 2016;23:623–7. 10.1111/acem.12922
    1. Gupta R, Holdford D, Bilaver L, et al. . The economic impact of childhood food allergy in the United States. JAMA Pediatr 2013;167:1026–31. 10.1001/jamapediatrics.2013.2376
    1. Shaker M, Wallace D, Golden DBK, et al. . Simulation of health and economic benefits of extended observation of resolved anaphylaxis. JAMA Netw Open 2019;2:e1913951. 10.1001/jamanetworkopen.2019.13951
    1. Simons FER, Ardusso LR, Bilò MB, et al. . International consensus on (icon) anaphylaxis. World Allergy Organ J 2014;7:9. 10.1186/1939-4551-7-9
    1. Sicherer SH, Allen K, Lack G, et al. . Critical issues in food allergy: a national academies consensus report. Pediatrics 2017;140. 10.1542/peds.2017-0194
    1. National Academies of Sciences and Medicine E . Finding a path to safety in food allergy: assessment of the global burden, causes, prevention, management, and public policy. Washington: National Academies Press, 2017.
    1. National Institute for Health and Clinical Excellence . Anaphylaxis: assessment and referral after emergency treatment | guidance and guidelines | NICE, 2016. Available: [Accessed 12 Dec 2016].
    1. Bialy L, Plint AC, Freedman SB, et al. . Pediatric emergency research Canada (PERC): Patient/Family-informed research priorities for pediatric emergency medicine. Acad Emerg Med 2018;25:1365–74. 10.1111/acem.13493
    1. Stiell IG, Wells GA, Vandemheen K, et al. . The Canadian CT head rule for patients with minor head injury. Lancet 2001;357:1391–6. 10.1016/S0140-6736(00)04561-X
    1. McGinn TG, Guyatt GH, Wyer PC, et al. . Users' guides to the medical literature: XXII: how to use articles about clinical decision rules. evidence-based medicine Working group. JAMA 2000;284:79–84. 10.1001/jama.284.1.79
    1. Wynants L, Collins GS, Van Calster B. Key steps and common pitfalls in developing and validating risk models. BJOG 2017;124:423–32. 10.1111/1471-0528.14170
    1. Reilly BM, Evans AT. Translating clinical research into clinical practice: impact of using prediction rules to make decisions. Ann Intern Med 2006;144:201–9. 10.7326/0003-4819-144-3-200602070-00009
    1. Green SM, Schriger DL, Yealy DM. Methodologic standards for interpreting clinical decision rules in emergency medicine: 2014 update. Ann Emerg Med 2014;64:286–91. 10.1016/j.annemergmed.2014.01.016
    1. Steyerberg EW, Vergouwe Y. Towards better clinical prediction models: seven steps for development and an ABCD for validation. Eur Heart J 2014;35:1925–31. 10.1093/eurheartj/ehu207
    1. Steyerberg EW, Uno H, Ioannidis JPA, et al. . Poor performance of clinical prediction models: the harm of commonly applied methods. J Clin Epidemiol 2018;98:133–43. 10.1016/j.jclinepi.2017.11.013
    1. Riley R. Prognostic model research, 2020. Available:
    1. Harrell FE. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. In: Publishing SI, ed. 2, 2015.
    1. Steyerberg EW. Clinical prediction models: a practical approach to development, validation, and updating. In:. Springer, 2009.
    1. Riley RD, Hayden JA, Steyerberg EW, et al. . Prognosis research strategy (progress) 2: prognostic factor research. PLoS Med 2013;10:e1001380. 10.1371/journal.pmed.1001380
    1. Steyerberg EW, Moons KGM, van der Windt DA, et al. . Prognosis research strategy (progress) 3: prognostic model research. PLoS Med 2013;10:e1001381. 10.1371/journal.pmed.1001381
    1. Collins GS, Reitsma JB, Altman DG, et al. . Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. Br J Surg 2015;102:148–58. 10.1002/bjs.9736
    1. Turner PJ, Worm M, Ansotegui IJ, et al. . Time to revisit the definition and clinical criteria for anaphylaxis? World Allergy Organ J 2019;12:100066. 10.1016/j.waojou.2019.100066
    1. Campbell RL, Li JTC, Nicklas RA, et al. . Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol 2014;113:599–608. 10.1016/j.anai.2014.10.007
    1. Australian Society of Clinical Immunology and Allergy . Acute management of anaphylaxis, 2021. Available:
    1. Bialy L, Plint A, Zemek R, et al. . Pediatric emergency research Canada: origins and evolution. Pediatr Emerg Care 2018;34:138–44. 10.1097/PEC.0000000000001360
    1. Dribin TE, Sampson HA, Camargo CA, et al. . Persistent, refractory, and biphasic anaphylaxis: A multidisciplinary Delphi study. Journal of Allergy and Clinical Immunology 2020;146:1089–96. 10.1016/j.jaci.2020.08.015
    1. Muñoz-Cano R, Pascal M, Araujo G, et al. . Mechanisms, cofactors, and augmenting factors involved in anaphylaxis. Front Immunol 2017;8:1193. 10.3389/fimmu.2017.01193
    1. Nagata S, Ohbe H, Jo T, et al. . Glucocorticoids and rates of biphasic reactions in patients with Adrenaline-Treated anaphylaxis: a propensity score matching analysis. Int Arch Allergy Immunol 2022;183:939–45. 10.1159/000524612
    1. Gupta RS, Sehgal S, Brown DA, et al. . Characterizing biphasic food-related allergic reactions through a US food allergy patient registry. J Allergy Clin Immunol Pract 2021;9:3717–27. 10.1016/j.jaip.2021.05.009
    1. Alqurashi W, Anaphylaxis: B. Epidemiology, Predictors, and Management.. In: Ellis AK, ed. Anaphylaxis: A Practical Guide. Springer Nature, 2020: 43–60.
    1. Riley RD, Ensor J, Snell KIE, et al. . Calculating the sample size required for developing a clinical prediction model. BMJ 2020;368:m441. 10.1136/bmj.m441
    1. Riley RD, Snell KIE, Ensor J, et al. . Minimum sample size for developing a multivariable prediction model: Part I - Continuous outcomes. Stat Med 2019;38:1262–75. 10.1002/sim.7993
    1. Schuh S, Babl FE, Dalziel SR, et al. . Practice variation in acute bronchiolitis: a pediatric emergency research networks study. Pediatrics 2017;140. 10.1542/peds.2017-0842
    1. Dalziel SR, Thompson JM, Macias CG, et al. . Predictors of severe H1N1 infection in children presenting within pediatric emergency research networks (PERN): retrospective case-control study. BMJ 2013;347:f4836. 10.1136/bmj.f4836
    1. Kraft M, Scherer Hofmeier K, Ruëff F, et al. . Risk factors and characteristics of biphasic anaphylaxis. J Allergy Clin Immunol Pract 2020;8:3388–95. 10.1016/j.jaip.2020.07.036
    1. Worm M, Francuzik W, Renaudin J-M, et al. . Factors increasing the risk for a severe reaction in anaphylaxis: an analysis of data from the European anaphylaxis registry. Allergy 2018;73:1322–30. 10.1111/all.13380
    1. R Core Team . R: a language and environment for statistical computing. R found. STAT. Comput, 2021. Available:
    1. Royston P, Moons KGM, Altman DG, et al. . Prognosis and prognostic research: developing a prognostic model. BMJ 2009;338:b604. 10.1136/bmj.b604
    1. Harrell FE, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996;15:361–87. 10.1002/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>;2-4
    1. Steyerberg EW, Eijkemans MJ, Harrell FE, et al. . Prognostic modeling with logistic regression analysis: in search of a sensible strategy in small data sets. Med Decis Making 2001;21:45–56. 10.1177/0272989X0102100106
    1. Vadas P, Perelman B, Liss G. Platelet-Activating factor, histamine, and tryptase levels in human anaphylaxis. J Allergy Clin Immunol 2013;131:144–9. 10.1016/j.jaci.2012.08.016
    1. Vadas P, Perelman B. Effect of epinephrine on platelet-activating factor-stimulated human vascular smooth muscle cells. J Allergy Clin Immunol 2012;129:1329–33. 10.1016/j.jaci.2012.02.027
    1. Alba AC, Agoritsas T, Walsh M, et al. . Discrimination and calibration of clinical prediction models: users' guides to the medical literature. JAMA 2017;318:1377–84. 10.1001/jama.2017.12126
    1. Vickers AJ, Van Calster B, Steyerberg EW. Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests. BMJ 2016;352:i6. 10.1136/bmj.i6
    1. Steyerberg EW, Vickers AJ, Cook NR, et al. . Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 2010;21:128. 10.1097/EDE.0b013e3181c30fb2
    1. Steyerberg EW, Harrell FE. Prediction models need appropriate internal, internal-external, and external validation. J Clin Epidemiol 2016;69:245–7. 10.1016/j.jclinepi.2015.04.005
    1. Toll DB, Janssen KJM, Vergouwe Y, et al. . Validation, updating and impact of clinical prediction rules: a review. J Clin Epidemiol 2008;61:1085–94. 10.1016/j.jclinepi.2008.04.008
    1. Steyerberg EW, Harrell FE, Borsboom GJ, et al. . Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol 2001;54:774–81. 10.1016/s0895-4356(01)00341-9
    1. Moons KGM, Altman DG, Reitsma JB, et al. . Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med 2015;162:W1–73. 10.7326/M14-0698
    1. Grady D, Berkowitz SA. Why is a good clinical prediction rule so hard to find? Arch Intern Med 2011;171:1701–2. 10.1001/archinternmed.2011.482
    1. Collins GS, de Groot JA, Dutton S, et al. . External validation of multivariable prediction models: a systematic review of methodological conduct and reporting. BMC Med Res Methodol 2014;14:1–11. 10.1186/1471-2288-14-40
    1. Ban J-W, Emparanza JI, Urreta I, et al. . Design characteristics influence performance of clinical prediction rules in validation: a meta-epidemiological study. PLoS One 2016;11:e0145779. 10.1371/journal.pone.0145779
    1. Alisic E, Hoysted C, Kassam-Adams N, et al. . Psychosocial care for injured children: worldwide survey among hospital emergency department staff. J Pediatr 2016;170:227–33. 10.1016/j.jpeds.2015.10.067
    1. Sullivan LM, Massaro JM, D’Agostino Sr RB. Likelihood Modelling: Presentation of Multivariate Data for Clinical Use: The Framingham Study Risk Score Functions. In: D’Agostino Sr RB, ed. Tutorials in Biostatistics: Statistical Modelling of Complex Medical Data. Wiley Online Library, 2004: 445–76.
    1. Bonnett LJ, Snell KIE, Collins GS, et al. . Guide to presenting clinical prediction models for use in clinical settings. BMJ 2019;365:l737. 10.1136/bmj.l737
    1. Bowen S, Graham ID. Integrated knowledge translation. In: Graham ID, Strauss SE, Tetroe J, eds. Knowledge translation in health care: Moving from evidence to practice. Wiley Blackwell Oxford, 2013: 14–21.
    1. Gagliardi AR, Berta W, Kothari A, et al. . Integrated knowledge translation (IKT) in health care: a scoping review. Implementation Sci 2015;11:1–12. 10.1186/s13012-016-0399-1
    1. CIHR . Guide to knowledge translation planning at CIHR: integrated and End-of-Grant approaches, 2012. Available: [Accessed 11 Apr 2016].
    1. Lomas J, Diffusion LJ. Diffusion, Dissemination, and implementation: who should do what? Ann N Y Acad Sci 1993;703:226–37. 10.1111/j.1749-6632.1993.tb26351.x
    1. P. Available: [Accessed 11 Apr 2016].
    1. Tca. Available: [Accessed 10 Jan 2017].
    1. Turner PJ, Gowland MH, Sharma V, et al. . Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012. J Allergy Clin Immunol 2015;135:956–63. 10.1016/j.jaci.2014.10.021
    1. Motosue MS, Bellolio MF, Van Houten HK, et al. . Risk factors for severe anaphylaxis in the United States. Ann Allergy Asthma Immunol 2017;119:356–61. 10.1016/j.anai.2017.07.014
    1. Mullins RJ, Wainstein BK, Barnes EH, et al. . Increases in anaphylaxis fatalities in Australia from 1997 to 2013. Clin Exp Allergy 2016;46:1099–110. 10.1111/cea.12748
    1. Xing Y, Zhang H, Sun S, et al. . Clinical features and treatment of pediatric patients with drug-induced anaphylaxis: a study based on pharmacovigilance data. Eur J Pediatr 2018;177:145–54. 10.1007/s00431-017-3048-z
    1. Smith PK, Hourihane Jonathan O'B, Lieberman P. Risk multipliers for severe food anaphylaxis. World Allergy Organ J 2015;8:30–6. 10.1186/s40413-015-0081-0
    1. Hompes S, Köhli A, Nemat K, et al. . Provoking allergens and treatment of anaphylaxis in children and adolescents--data from the anaphylaxis registry of German-speaking countries. Pediatr Allergy Immunol 2011;22:568–74. 10.1111/j.1399-3038.2011.01154.x
    1. Niggemann B, Beyer K. Factors augmenting allergic reactions. Allergy 2014;69:1582–7. 10.1111/all.12532
    1. Smit DV, Cameron PA, Rainer TH. Anaphylaxis presentations to an emergency department in Hong Kong: incidence and predictors of biphasic reactions. J Emerg Med 2005;28:381–8. 10.1016/j.jemermed.2004.11.028
    1. Brazil E, MacNamara AF. "Not so immediate" hypersensitivity--the danger of biphasic anaphylactic reactions. Emergency Medicine Journal 1998;15:252–3. 10.1136/emj.15.4.252
    1. Oya S, Kinoshita K, Daya M, et al. . Characteristics of anaphylactic reactions: a prospective observational study in Japan. J Emerg Med 2020;59:812–9. 10.1016/j.jemermed.2020.07.004
    1. Campbell RL, Bashore CJ, Lee S, et al. . Predictors of repeat epinephrine administration for emergency department patients with anaphylaxis. J Allergy Clin Immunol Pract 2015;3:576–84. 10.1016/j.jaip.2015.04.009
    1. Lee JM, Greenes DS. Biphasic anaphylactic reactions in pediatrics. Pediatrics 2000;106:762–6. 10.1542/peds.106.4.762
    1. Poachanukoon O, Paopairochanakorn C. Incidence of anaphylaxis in the Emer-gency department: a 1-year study in a university hospital. Asian Pacific J allergy Immunol 2006;24:111.
    1. Brown SGA. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 2004;114:371–6. 10.1016/j.jaci.2004.04.029

Source: PubMed

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