Skip to main content

Placebos and Nocebos in Migraine: Children and Adolescents

  • Chapter
  • First Online:
Placebos and Nocebos in Headaches

Part of the book series: Headache ((HEAD))

  • 560 Accesses

Abstract

Harnessing the placebo effect in clinical settings has been one of the goals of placebo research. However, most of the studies have been performed with healthy participants. Evaluating the placebo response constitutes a challenge in many conditions due to their ongoing nature and undulating processes that make interventions more complex in terms of identifying responsivity. Migraine, particularly episodic migraine, provides an ideal disease to evaluate placebo and nocebo responses because of its intermittent nature and the ability to evaluate a number of processes involved in treatment. The approach becomes even more interesting in the pediatric population where suggestibility may be more effective than in adults. In this chapter we present migraine as a model to investigate the impact of placebo and nocebo responsivity, provide a summary of placebo (and nocebo) in the pediatric migraine population, and offer a few suggestions related to the process, the utility, and the ethics of introducing placebo and managing nocebo into the pediatric clinic.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 99.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aamodt AH, Stovner LJ, Langhammer A, Hagen K, Zwart JA. Is headache related to asthma, hay fever, and chronic bronchitis? The Head-HUNT Study. Headache. 2007;47(2):204–12.

    Article  PubMed  Google Scholar 

  2. Annoni M, Miller FG. Placebo effects and the ethics of therapeutic communication: a pragmatic perspective. Kennedy Inst Ethics J. 2016;26(1):79–103.

    Article  PubMed  Google Scholar 

  3. Antonaci F, Voiticovschi-Iosob C, Di Stefano AL, Galli F, Ozge A, Balottin U. The evolution of headache from childhood to adulthood: a review of the literature. J Headache Pain. 2014;15:15.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Benedetti F, Carlino E, Pollo A. How placebos change the patient’s brain. Neuropsychopharmacology. 2011;36(1):339–54.

    Article  PubMed  Google Scholar 

  5. Benedetti F. How the doctor’s words affect the patient’s brain. Eval Health Prof. 2002;25(4):369–86.

    Article  PubMed  Google Scholar 

  6. Benedetti F. Placebo and the new physiology of the doctor-patient relationship. Physiol Rev. 2013;93(3):1207–46.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Benedetti F. Responding to nocebos through observation: social contagion of negative emotions. Pain. 2013;154(8):1165.

    Article  PubMed  Google Scholar 

  8. Bensing JM, Verheul W. The silent healer: the role of communication in placebo effects. Patient Educ Couns. 2010;80(3):293–9.

    Article  PubMed  Google Scholar 

  9. Bhugra D, Ventriglio A, Till A, Malhi G. Colour, culture and placebo response. Int J Soc Psychiatry. 2015;61(6):615–7.

    Article  PubMed  Google Scholar 

  10. Bille B. Migraine and tension-type headache in children and adolescents. Cephalalgia. 1996;16(2):78.

    Article  CAS  PubMed  Google Scholar 

  11. Bingel U, Wanigasekera V, Wiech K, Ni Mhuircheartaigh R, Lee MC, Ploner M, et al. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci Transl Med. 2011;3(70):70ra14.

    Article  PubMed  CAS  Google Scholar 

  12. Birnie KA, Chambers CT, Chorney J, Fernandez CV, McGrath PJ. Dyadic analysis of child and parent trait and state pain catastrophizing in the process of children’s pain communication. Pain. 2016;157(4):938–48.

    Article  PubMed  Google Scholar 

  13. Blankenship SL, Redcay E, Dougherty LR, Riggins T. Development of hippocampal functional connectivity during childhood. Hum Brain Mapp. 2017;38(1):182–201.

    Article  PubMed  Google Scholar 

  14. Borsook D, Maleki N, Becerra L, McEwen B. Understanding migraine through the lens of maladaptive stress responses: a model disease of allostatic load. Neuron. 2012;73(2):219–34.

    Article  CAS  PubMed  Google Scholar 

  15. Brascher AK, Kleinbohl D, Holzl R, Becker S. Differential classical conditioning of the nocebo effect: increasing heat-pain perception without verbal suggestions. Front Psychol. 2017;8:2163.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Brown KK, Gallant D. Impacting patient outcomes through design: acuity adaptable care/universal room design. Crit Care Nurs Q. 2006;29(4):326–41.

    Article  PubMed  Google Scholar 

  17. Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci. 2015;35(17):6619–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Casey BJ, Tottenham N, Liston C, Durston S. Imaging the developing brain: what have we learned about cognitive development? Trends Cogn Sci. 2005;9(3):104–10.

    Article  CAS  PubMed  Google Scholar 

  19. Colloca L, Benedetti F. Nocebo hyperalgesia: how anxiety is turned into pain. Curr Opin Anaesthesiol. 2007;20(5):435–9.

    Article  PubMed  Google Scholar 

  20. Colloca L, Benedetti F. Placebo analgesia induced by social observational learning. Pain. 2009;144(1–2):28–34.

    Article  PubMed  Google Scholar 

  21. Colloca L, Grillon C. Understanding placebo and nocebo responses for pain management. Curr Pain Headache Rep. 2014;18(6):419.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Colquhoun D, Novella SP. Acupuncture is theatrical placebo. Anesth Analg. 2013;116(6):1360–3.

    Article  PubMed  Google Scholar 

  23. Czerniak E, Biegon A, Ziv A, Karnieli-Miller O, Weiser M, Alon U, Citron A. Manipulating the Placebo response in experimental pain by altering doctor’s performance style. Front Psychol. 2016;7:874.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Danno K, Colas A, Masson JL, Bordet MF. Homeopathic treatment of migraine in children: results of a prospective, multicenter, observational study. J Altern Complement Med. 2013;19(2):119–23.

    Article  PubMed  Google Scholar 

  25. Davey G, Sedgwick P, Maier W, Visick G, Strachan DP, HR A. Association between migraine and asthma: matched case-control study. Br J Gen Pract. 2002;52(482):723–7.

    PubMed  PubMed Central  Google Scholar 

  26. Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1545–602.

    Article  Google Scholar 

  27. Dodd S, Dean OM, Vian J, Berk M. A review of the theoretical and biological understanding of the nocebo and placebo phenomena. Clin Ther. 2017;39(3):469–76.

    Article  PubMed  Google Scholar 

  28. Eidlitz-Markus T, Haimi-Cohen Y, Steier D, Zeharia A. Effectiveness of nonpharmacologic treatment for migraine in young children. Headache. 2010;50(2):219–23.

    Article  PubMed  Google Scholar 

  29. El-Chammas K, Keyes J, Thompson N, Vijayakumar J, Becher D, Jackson JL. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013;167(3):250–8.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ernst MM, O’Brien HL, Powers SW. Cognitive-behavioral therapy: how medical providers can increase patient and family openness and access to evidence-based multimodal therapy for pediatric migraine. Headache. 2015;55(10):1382–96.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Faria V, Erpelding N, Lebel A, Johnson A, Wolff R, Fair D, Burstein R, Becerra L, Borsook D. The migraine brain in transition: girls vs boys. Pain. 2015;156(11):2212–21.

    Article  PubMed  Google Scholar 

  32. Faria V, Fredrikson M, Furmark T. Imaging the placebo response: a neurofunctional review. Eur Neuropsychopharmacol. 2008;18(7):473–85.

    Article  CAS  PubMed  Google Scholar 

  33. Faria V, Gingnell M, Hoppe JM, Hjorth O, Alaie I, Frick A, Hultberg S, Wahlstedt K, Engman J, Månsson KNT, Carlbring P, Andersson G, Reis M, Larsson EM, Fredrikson M, Furmark T. Do you believe it? Verbal suggestions influence the clinical and neural effects of escitalopram in social anxiety disorder: a randomized trial. EBioMedicine. 2017;24:179–88.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Faria V, Kossowsky J, Petkov MP, Kaptchuk TJ, Kirsch I, Lebel A, Borsook D. Parental attitudes about placebo use in children. J Pediatr. 2017;181:272–8.e10.

    Article  PubMed  Google Scholar 

  35. Faria V, Linnman C, Lebel A, Borsook D. Harnessing the placebo effect in pediatric migraine clinic. J Pediatr. 2014;165(4):659–65.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Fernandes R, Ferreira JJ, Sampaio C. The placebo response in studies of acute migraine. J Pediatr. 2008;152(4):527–33, 33.e1.

    Article  PubMed  Google Scholar 

  37. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet. 2010;375(9715):686–95.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fiorio M, Recchia S, Corra F, Simonetto S, Garcia-Larrea L, Tinazzi M. Enhancing non-noxious perception: behavioural and neurophysiological correlates of a placebo-like manipulation. Neuroscience. 2012;217:96–104.

    Article  CAS  PubMed  Google Scholar 

  39. Francis M. Placebo spectacles-an excellent non pharmacological treatment for pediatric migraine. Cephalalgia. 2013;33:8–255.

    Google Scholar 

  40. Galli F, D’Antuono G, Tarantino S, Viviano F, Borrelli O, Chirumbolo A, et al. Headache and recurrent abdominal pain: a controlled study by the means of the Child Behaviour Checklist (CBCL). Cephalalgia. 2007;27(3):211–9.

    Article  CAS  PubMed  Google Scholar 

  41. German TP, Defeyter MA. Immunity to functional fixedness in young children. Psychon Bull Rev. 2000;7(4):707–12.

    Article  CAS  PubMed  Google Scholar 

  42. Grelotti DJ, Kaptchuk TJ. Placebo by proxy. BMJ. 2011;343:d4345.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hansen E, Zech N, Meissner K. [Placebo and nocebo: how can they be used or avoided?]. Internist (Berl). 2017;58(10):1102–10.

    Article  CAS  PubMed  Google Scholar 

  44. Harris P, Loveman E, Clegg A, Easton S, Berry N. Systematic review of cognitive behavioural therapy for the management of headaches and migraines in adults. Br J Pain. 2015;9(4):213–24.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Hauser W, Hansen E, Enck P. Nocebo phenomena in medicine: their relevance in everyday clinical practice. Dtsch Arztebl Int. 2012;109(26):459–65.

    PubMed  PubMed Central  Google Scholar 

  46. Ho TW, Fan X, Rodgers A, Lines CR, Winner P, Shapiro RE. Age effects on placebo response rates in clinical trials of acute agents for migraine: pooled analysis of rizatriptan trials in adults. Cephalalgia. 2009;29(7):711–8.

    Article  CAS  PubMed  Google Scholar 

  47. Howick J, Bishop FL, Heneghan C, Wolstenholme J, Stevens S, Hobbs FD, Lewith G. Placebo use in the United kingdom: results from a national survey of primary care practitioners. PLoS One. 2013;8(3):e58247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hunter T, Siess F, Colloca L. Socially induced placebo analgesia: a comparison of a pre-recorded versus live face-to-face observation. Eur J Pain. 2014;18(7):914–22.

    Article  CAS  PubMed  Google Scholar 

  49. Isik U, Ersu RH, Ay P, Save D, Arman AR, Karakoc F, Dagli E. Prevalence of headache and its association with sleep disorders in children. Pediatr Neurol. 2007;36(3):146–51.

    Article  PubMed  Google Scholar 

  50. Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, Burstein R. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med. 2014;6(218):218ra5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, Singer JP, Kowalczykowski M, Miller FG, Kirsch I, Lembo AJ. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One. 2010;5(12):e15591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kaptchuk TJ, Kelley JM, Conboy LA, Davis RB, Kerr CE, Jacobson EE, et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ. 2008;336(7651):999–1003.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Levinson W, Lesser CS, Epstein RM. Developing physician communication skills for patient-centered care. Health Aff (Millwood). 2010;29(7):1310–8.

    Article  Google Scholar 

  54. Lewis DW, Winner P, Wasiewski W. The placebo responder rate in children and adolescents. Headache. 2005;45(3):232–9.

    Article  PubMed  Google Scholar 

  55. Lewis DW. Almotriptan for the acute treatment of adolescent migraine. Expert Opin Pharmacother. 2010;11(14):2431–6.

    Article  CAS  PubMed  Google Scholar 

  56. Lichtenberg P, Heresco-Levy U, Nitzan U. The ethics of the placebo in clinical practice. J Med Ethics. 2004;30(6):551–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Linde K, Allais G, Brinkhaus B, Manheimer E, Vickers A, White AR. Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev. 2009;(1):CD001218.

    Google Scholar 

  58. Lucas S. Initial abortive treatments for migraine headache. Curr Treat Options Neurol. 2002;4(5):343–50.

    Article  PubMed  Google Scholar 

  59. Maas HJ, Danhof M, Della Pasqua OE. Analysis of the relationship between age and treatment response in migraine. Cephalalgia. 2009;29(7):772–80.

    Article  CAS  PubMed  Google Scholar 

  60. Malloy KM, Milling LS. The effectiveness of virtual reality distraction for pain reduction: a systematic review. Clin Psychol Rev. 2010;30(8):1011–8.

    Article  PubMed  Google Scholar 

  61. Melzack R. From the gate to the neuromatrix. Pain. 1999;(Suppl 6):S121–6.

    Article  Google Scholar 

  62. Merikangas KR, Angst J, Isler H. Migraine and psychopathology. Results of the Zurich cohort study of young adults. Arch Gen Psychiatry. 1990;47(9):849–53.

    Article  CAS  PubMed  Google Scholar 

  63. Neumann M, Edelhauser F, Kreps GL, Scheffer C, Lutz G, Tauschel D, et al. Can patient-provider interaction increase the effectiveness of medical treatment or even substitute it?--an exploration on why and how to study the specific effect of the provider. Patient Educ Couns. 2010;80(3):307–14.

    Article  PubMed  Google Scholar 

  64. Ng QX, Venkatanarayanan N, Kumar L. A systematic review and meta-analysis of the efficacy of cognitive behavioral therapy for the management of pediatric migraine. Headache. 2017;57(3):349–62.

    Article  PubMed  Google Scholar 

  65. Oppenheim D. Child, parent, and parent-child emotion narratives: implications for developmental psychopathology. Dev Psychopathol. 2006;18(3):771–90.

    Article  PubMed  Google Scholar 

  66. Powers SW, Coffey CS, Chamberlin LA, Ecklund DJ, Klingner EA, Yankey JW, et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376(2):115–24.

    Article  CAS  PubMed  Google Scholar 

  67. Rheims S, Cucherat M, Arzimanoglou A, Ryvlin P. Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy. PLoS Med. 2008;5(8):e166.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Rojas-Mirquez JC, Rodriguez-Zuniga MJ, Bonilla-Escobar FJ, Garcia-Perdomo HA, Petkov M, Becerra L, et al. Nocebo effect in randomized clinical trials of antidepressants in children and adolescents: systematic review and meta-analysis. Front Behav Neurosci. 2014;8:375.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Samiee-Zafarghandy S, Mazer-Amirshahi M, van den Anker JN. Trends in paediatric clinical pharmacology data in US pharmaceutical labelling. Arch Dis Child. 2014;99(9):862–5.

    Article  PubMed  Google Scholar 

  70. Sandler AD, Glesne CE, Bodfish JW. Conditioned placebo dose reduction: a new treatment in attention-deficit hyperactivity disorder? J Dev Behav Pediatr. 2010;31(5):369–75.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Sartory G, Muller B, Metsch J, Pothmann R. A comparison of psychological and pharmacological treatment of pediatric migraine. Behav Res Ther. 1998;36(12):1155–70.

    Article  CAS  PubMed  Google Scholar 

  72. Shang A, Huwiler-Muntener K, Nartey L, Juni P, Dorig S, Sterne JA, et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet. 2005;366(9487):726–32.

    Article  PubMed  Google Scholar 

  73. Sherman LE, Rudie JD, Pfeifer JH, Masten CL, McNealy K, Dapretto M. Development of the default mode and central executive networks across early adolescence: a longitudinal study. Dev Cogn Neurosci. 2014;10:148–59.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Simmons K, Ortiz R, Kossowsky J, Krummenacher P, Grillon C, Pine D, et al. Pain and placebo in pediatrics: a comprehensive review of laboratory and clinical findings. Pain. 2014;155(11):2229–35.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Simons LE, Goubert L, Vervoort T, Borsook D. Circles of engagement: childhood pain and parent brain. Neurosci Biobehav Rev. 2016;68:537–46.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Smith PB, Benjamin DK Jr, Murphy MD, Johann-Liang R, Iyasu S, Gould B, Califf RM, Li JS, Rodriguez W. Safety monitoring of drugs receiving pediatric marketing exclusivity. Pediatrics. 2008;122(3):e628–33.

    Article  PubMed  Google Scholar 

  77. Stewart WF, Wood C, Reed ML, Roy J, Lipton RB, Group AA. Cumulative lifetime migraine incidence in women and men. Cephalalgia. 2008;28(11):1170–8.

    Article  CAS  PubMed  Google Scholar 

  78. Strine TW, Okoro CA, McGuire LC, Balluz LS. The associations among childhood headaches, emotional and behavioral difficulties, and health care use. Pediatrics. 2006;117(5):1728–35.

    Article  PubMed  Google Scholar 

  79. Sun H, Bastings E, Temeck J, Smith PB, Men A, Tandon V, et al. Migraine therapeutics in adolescents: a systematic analysis and historic perspectives of triptan trials in adolescents. JAMA Pediatr. 2013;167(3):243–9.

    Article  PubMed  Google Scholar 

  80. Thompson JJ, Ritenbaugh C, Nichter M. Reconsidering the placebo response from a broad anthropological perspective. Cult Med Psychiatry. 2009;33(1):112–52.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Thompson-Schill SL, Ramscar M, Chrysikou EG. Cognition without control: when a little frontal lobe goes a long way. Curr Dir Psychol Sci. 2009;18(5):259–63.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Verheul W, Sanders A, Bensing J. The effects of physicians’ affect-oriented communication style and raising expectations on analogue patients’ anxiety, affect and expectancies. Patient Educ Couns. 2010;80(3):300–6.

    Article  PubMed  Google Scholar 

  83. Vijayakumar N, Whittle S, Dennison M, Yucel M, Simmons J, Allen NB. Development of temperamental effortful control mediates the relationship between maturation of the prefrontal cortex and psychopathology during adolescence: a 4-year longitudinal study. Dev Cogn Neurosci. 2014;9:30–43.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Vogtle E, Barke A, Kroner-Herwig B. Nocebo hyperalgesia induced by social observational learning. Pain. 2013;154(8):1427–33.

    Article  PubMed  Google Scholar 

  85. Wager TD, Atlas LY. The neuroscience of placebo effects: connecting context, learning and health. Nat Rev Neurosci. 2015;16(7):403–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Weimer K, Gulewitsch MD, Schlarb AA, Schwille-Kiuntke J, Klosterhalfen S, Enck P. Placebo effects in children: a review. Pediatr Res. 2013;74(1):96–102.

    Article  PubMed  Google Scholar 

  87. Weisz G, Cambrosio A, Keating P, Knaapen L, Schlich T, Tournay VJ. The emergence of clinical practice guidelines. Milbank Q. 2007;85(4):691–727.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Wendelken C, Ferrer E, Ghetti S, Bailey SK, Cutting L, Bunge SA. Frontoparietal structural connectivity in childhood predicts development of functional connectivity and reasoning ability: a large-scale longitudinal investigation. J Neurosci. 2017;37(35):8549–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Wilcox SL, Veggeberg R, Lemme J, Hodkinson DJ, Scrivani S, Burstein R, et al. Increased functional activation of limbic brain regions during negative emotional processing in migraine. Front Hum Neurosci. 2016;10:366.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Wober-Bingol C. Epidemiology of migraine and headache in children and adolescents. Curr Pain Headache Rep. 2013;17(6):341.

    Article  PubMed  Google Scholar 

  91. Woo KY. Unravelling nocebo effect: the mediating effect of anxiety between anticipation and pain at wound dressing change. J Clin Nurs. 2015;24(13–14):1975–84.

    Article  PubMed  Google Scholar 

  92. Yujiro I, Shunji N. A psychosomatic study of contagious dermatitis. Kyushu J Med Sci. 1962;13:335–50.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vanda Faria .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Faria, V., Borsook, D. (2019). Placebos and Nocebos in Migraine: Children and Adolescents. In: Mitsikostas, D., Benedetti, F. (eds) Placebos and Nocebos in Headaches. Headache. Springer, Cham. https://doi.org/10.1007/978-3-030-02976-0_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-02976-0_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-02975-3

  • Online ISBN: 978-3-030-02976-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics