A Live Video Mind-Body Treatment to Prevent Persistent Symptoms Following Mild Traumatic Brain Injury: Protocol for a Mixed Methods Study

Jonathan Greenberg, Tanya Singh, Grant L Iverson, Noah D Silverberg, Eric A Macklin, Robert A Parker, Joseph T Giacino, Gloria Y Yeh, Ana-Maria Vranceanu, Jonathan Greenberg, Tanya Singh, Grant L Iverson, Noah D Silverberg, Eric A Macklin, Robert A Parker, Joseph T Giacino, Gloria Y Yeh, Ana-Maria Vranceanu

Abstract

Background: Every year, approximately 42 million people sustain a mild traumatic brain injury (mTBI, also known as concussion), with particularly high rates among college-aged individuals. A substantial proportion of these people (44%-64%) develop persistent symptoms that are challenging to treat, costly, and associated with significant disability. Anxiety has emerged as a risk factor for progression from acute to persistent mTBI symptoms.

Objective: This study aims to develop, adapt, and establish the feasibility of the Toolkit for Optimal Recovery after Concussions (TOR-C), an innovative mind-body program aimed at preventing persistent symptoms among young adults with mTBI and comorbid anxiety. Here, we describe the proposed study design, methodology, measurement, and treatment manuals.

Methods: In phase 1, we will conduct individual, live video qualitative interviews (up to n=20) with college-aged individuals with mTBI and comorbid anxiety to inform adaptation of the intervention and study procedures. In phase 2, an open pilot of the live video TOR-C (n=5) with exit interviews will be conducted to explore the initial feasibility, acceptability, and credibility of the program and to refine the study procedures. Phase 3 will involve conducting a feasibility randomized controlled trial (N=50) of the TOR-C versus a health education control (Health Enhancement for Concussions; HE-C), both delivered via live video, to establish feasibility of recruitment procedures (screening, eligibility, and enrollment) and data collection; feasibility, credibility, and acceptability of the live video TOR-C and HE-C (adherence, retention, fidelity, and satisfaction) following prespecified benchmarks; and a signal of improvement in outcomes.

Results: Phase 1 of the study has been approved by the Massachusetts General Hospital Institutional Review Board. Study completion is anticipated by early 2025.

Conclusions: We will develop and test the first mind-body intervention focused on prevention of persistent symptoms following mTBI in young adults with comorbid anxiety problems. This will allow us to establish feasibility markers in postconcussive symptoms, anxiety, disability, and fear avoidance to inform a future efficacy trial of the TOR-C versus HE-C.

International registered report identifier (irrid): PRR1-10.2196/25746.

Keywords: anxiety; intervention development; mild traumatic brain injury; mixed methods.

Conflict of interest statement

Conflicts of Interest: GLI has a clinical and consulting practice in forensic neuropsychology, including expert testimony, involving individuals who have sustained mild TBIs (including athletes). He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs, and Psychological Assessment Resources (PAR, Inc.). He has received research support from the Harvard Integrated Program to Protect and Improve the Health of NFLPA Members, and grant support from the National Football League. He serves as a scientific advisor for Sway Operations, LLC, Highmark, Inc., and for NanoDX® (formerly BioDirection, Inc.). EAM reports grants from Acorda Therapeutics, personal fees from Shire Human Genetic Therapies, grants from Amylyx Pharmaceuticals, grants from Mitsubishi Tanabe Pharmaceuticals America, grants from GlaxoSmithKline, personal fees from Biogen, personal fees from Novartis Pharmaceuticals, personal fees from Cerevance, personal fees from Inventram, other from Biohaven Pharmaceuticals, other from Clene Nanomedicine, other from Prilenia Therapeutics, other from Ra Pharmaceuticals, personal fees from Partners Therapeutics, personal fees from Stoparkinson Healthcare LLC, all outside the submitted work.

©Jonathan Greenberg, Tanya Singh, Grant L Iverson, Noah D Silverberg, Eric A Macklin, Robert A Parker, Joseph T Giacino, Gloria Y Yeh, Ana-Maria Vranceanu. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 14.01.2021.

Figures

Figure 1
Figure 1
Phases of development of the Toolkit for Optimal Recovery after Concussion. RCT: randomized controlled trial; TOR-C: Toolkit for Optimal Recovery after Concussion.

References

    1. Gardner RC, Yaffe K. Epidemiology of mild traumatic brain injury and neurodegenerative disease. Mol Cell Neurosci. 2015 May;66(Pt B):75–80. doi: 10.1016/j.mcn.2015.03.001.
    1. Ponsford J, Willmott C, Rothwell A, Cameron P, Kelly AM, Nelms R, Curran C, Ng K. Factors influencing outcome following mild traumatic brain injury in adults. J Int Neuropsychol Soc. 2000 Jul;6(5):568–79. doi: 10.1017/s1355617700655066.
    1. Boake C, McCauley SR, Levin HS, Pedroza C, Contant CF, Song JX, Brown SA, Goodman H, Brundage SI, Diaz-Marchan PJ. Diagnostic criteria for postconcussional syndrome after mild to moderate traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2005;17(3):350–6. doi: 10.1176/jnp.17.3.350.
    1. Dikmen S, Machamer J, Fann JR, Temkin NR. Rates of symptom reporting following traumatic brain injury. J Int Neuropsychol Soc. 2010 May;16(3):401–11. doi: 10.1017/S1355617710000196.
    1. Nelson LD, Temkin NR, Dikmen S, Barber J, Giacino JT, Yuh E, Levin HS, McCrea MA, Stein MB, Mukherjee P, Okonkwo DO, Diaz-Arrastia R, Manley GT, Adeoye O, Badjatia N, Boase K, Bodien Y, Bullock MR, Chesnut R, Corrigan JD, Crawford K, Duhaime A, Ellenbogen R, Feeser VR, Ferguson A, Foreman B, Gardner R, Gaudette E, Gonzalez L, Gopinath S, Gullapalli R, Hemphill JC, Hotz G, Jain S, Korley F, Kramer J, Kreitzer N, Lindsell C, Machamer J, Madden C, Martin A, McAllister T, Merchant R, Noel F, Palacios E, Perl D, Puccio A, Rabinowitz M, Robertson CS, Rosand J, Sander A, Satris G, Schnyer D, Seabury S, Sherer M, Taylor S, Toga A, Valadka A, Vassar MJ, Vespa P, Wang K, Yue JK, Zafonte R. Recovery after mild traumatic brain injury in patients presenting to US level I trauma centers: a transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) study. JAMA Neurol. 2019 Jun 3;76(9):1049–59. doi: 10.1001/jamaneurol.2019.1313.
    1. Barker-Collo S, Theadom A, Jones K, Ameratunga S, Starkey N, Dudley M, Kahan M. Reliable individual change in post concussive symptoms in the year following mild traumatic brain injury: data from the longitudinal, population-based brain injury incidence and outcomes New Zealand in the community (Bionic) study. JSM burn trauma. JSM Burn Trauma. 2016 Aug 18;1(1)
    1. Silverberg ND, Gardner AJ, Brubacher JR, Panenka WJ, Li JJ, Iverson GL. Systematic review of multivariable prognostic models for mild traumatic brain injury. J Neurotrauma. 2015 Apr 15;32(8):517–26. doi: 10.1089/neu.2014.3600.
    1. Zahniser E, Nelson LD, Dikmen SS, Machamer JE, Stein MB, Yuh E, Manley GT, Temkin NR, TRACK-TBI Investigators The temporal relationship of mental health problems and functional limitations following mtbi: a TRACK-TBI and TED study. J Neurotrauma. 2019 Jun;36(11):1786–93. doi: 10.1089/neu.2018.6172.
    1. Silverberg ND, Panenka WJ, Iverson GL. Fear avoidance and clinical outcomes from mild traumatic brain injury. J Neurotrauma. 2018 Aug 15;35(16):1864–73. doi: 10.1089/neu.2018.5662.
    1. Zale EL, Lange KL, Fields SA, Ditre JW. The relation between pain-related fear and disability: a meta-analysis. J Pain. 2013 Oct;14(10):1019–30. doi: 10.1016/j.jpain.2013.05.005.
    1. Greenberg J, Mace R, Funes C, Silverberg N, Iverson G, Caplan D, Ana-Maria V. Pain catastrophizing and limiting behavior mediate the association between anxiety and postconcussion symptoms. Psychosomatics. 2020;61(1):49–55. doi: 10.1016/j.psym.2019.09.004.
    1. Silverberg ND, Iverson GL. Is rest after concussion 'the best medicine?: recommendations for activity resumption following concussion in athletes, civilians, and military service members. J Head Trauma Rehabil. 2013;28(4):250–9. doi: 10.1097/HTR.0b013e31825ad658.
    1. Leddy JJ, Haider MN, Ellis M, Willer BS. Exercise is medicine for concussion. Curr Sports Med Rep. 2018 Aug;17(8):262–70. doi: 10.1249/JSR.0000000000000505.
    1. Silverberg ND, Martin P, Panenka WJ. Headache trigger sensitivity and avoidance after mild traumatic brain injury. J Neurotrauma. 2019 May 15;36(10):1544–50. doi: 10.1089/neu.2018.6025.
    1. Silverberg ND, Iverson GL, Panenka W. Cogniphobia in mild traumatic brain injury. J Neurotrauma. 2017 Jul 1;34(13):2141–6. doi: 10.1089/neu.2016.4719.
    1. Kontos A, Pan R, Emami K. Mental health manifestations of concussion. In: Hong E, Rao AL, editors. Mental Health in the Athlete Modern Perspectives and Novel Challenges for the Sports Medicine Provider. Cham, Switzerland: Springer; 2020. May 31, pp. 149–63.
    1. DiFazio M, Silverberg ND, Kirkwood MW, Bernier R, Iverson GL. Prolonged activity restriction after concussion: are we worsening outcomes? Clin Pediatr (Phila) 2016 May;55(5):443–51. doi: 10.1177/0009922815589914.
    1. Mayer AR, Quinn DK, Master CL. The spectrum of mild traumatic brain injury: a review. Neurology. 2017 Aug 8;89(6):623–32. doi: 10.1212/WNL.0000000000004214.
    1. Wahbeh H, Elsas S, Oken BS. Mind-body interventions: applications in neurology. Neurology. 2008 Jun 10;70(24):2321–8. doi: 10.1212/01.wnl.0000314667.16386.5e.
    1. Astin JA, Shapiro SL, Eisenberg DM, Forys KL. Mind-body medicine: state of the science, implications for practice. J Am Board Fam Pract. 2003;16(2):131–47. doi: 10.3122/jabfm.16.2.131.
    1. Hofmann SG, Sawyer AT, Witt AA, Oh D. The effect of mindfulness-based therapy on anxiety and depression: a meta-analytic review. J Consult Clin Psychol. 2010 Apr;78(2):169–83. doi: 10.1037/a0018555.
    1. Ungar T, Knaak S. Mental health stigma and the mind-body problem: making the case for strategic collusion. Aust N Z J Psychiatry. 2013 Nov;47(11):1088. doi: 10.1177/0004867413498279.
    1. Erwin Wells R, Phillips RS, McCarthy EP. Patterns of mind-body therapies in adults with common neurological conditions. Neuroepidemiology. 2011;36(1):46–51. doi: 10.1159/000322949.
    1. Rose RD, Buckey JC, Zbozinek TD, Motivala SJ, Glenn DE, Cartreine JA, Craske MG. A randomized controlled trial of a self-guided, multimedia, stress management and resilience training program. Behav Res Ther. 2013 Feb;51(2):106–12. doi: 10.1016/j.brat.2012.11.003.
    1. Greenberg J, Romero VL, Elkin-Frankston S, Bezdek MA, Schumacher EH, Lazar SW. Reduced interference in working memory following mindfulness training is associated with increases in hippocampal volume. Brain Imaging Behav. 2019 Apr;13(2):366–76. doi: 10.1007/s11682-018-9858-4.
    1. Glueckauf RL, Ketterson TU. Telehealth interventions for individuals with chronic illness: research review and implications for practice. Prof Psychol: Res Pract. 2004;35(6):615–27. doi: 10.1037/0735-7028.35.6.615.
    1. Social Distancing: Keep a Sage Distance to Slow the Spread Internet. Centers for Disease Control and Prevention (CDC) 2020. Nov 17, [2020-12-14]. .
    1. Coronavirus Disease (COVID-19) Advice for the Public. World Health Organization. 2020. Dec 08, [2020-08-14]. .
    1. Kaut KP, de Pompei R, Kerr J, Congeni J. Reports of head injury and symptom knowledge among college athletes: implications for assessment and educational intervention. Clin J Sport Med. 2003 Jul;13(4):213–21. doi: 10.1097/00042752-200307000-00004.
    1. NIH Consensus Development Panel on Rehabilitation of Persons With Traumatic Brain Injury Rehabilitation of persons with traumatic brain injury. J Am Med Assoc. 1999 Sep 8;282(10):974–83. doi: 10.1001/jama.282.10.974.
    1. Bruns J, Hauser WA. The epidemiology of traumatic brain injury: a review. Epilepsia. 2003;44(s10):2–10. doi: 10.1046/j.1528-1157.44.s10.3.x.
    1. Beiter R, Nash R, McCrady M, Rhoades D, Linscomb M, Clarahan M, Sammut S. The prevalence and correlates of depression, anxiety, and stress in a sample of college students. J Affect Disord. 2015 Mar 1;173:90–6. doi: 10.1016/j.jad.2014.10.054.
    1. Lungu A, Sun M. Time for a change: college students' preference for technology-mediated versus face-to-face help for emotional distress. Telemed J E Health. 2016 Dec;22(12):991–1000. doi: 10.1089/tmj.2015.0214.
    1. Vranceanu A, Jacobs C, Lin A, Greenberg J, Funes CJ, Harris MB, Heng MM, Macklin EA, Ring D. Results of a feasibility randomized controlled trial (RCT) of the toolkit for optimal recovery (TOR): a live video program to prevent chronic pain in at-risk adults with orthopedic injuries. Pilot Feasibility Stud. 2019;5:30. doi: 10.1186/s40814-019-0416-7.
    1. Czajkowski SM, Powell LH, Adler N, Naar-King S, Reynolds KD, Hunter CM, Laraia B, Olster DH, Perna FM, Peterson JC, Epel E, Boyington JE, Charlson ME. From ideas to efficacy: the ORBIT model for developing behavioral treatments for chronic diseases. Health Psychol. 2015 Oct;34(10):971–82. doi: 10.1037/hea0000161.
    1. Framework for Developing and Testing Mind and Body Interventions. National Center for Complementary and Integrative Health. 2017. [2020-12-14]. .
    1. Iverson GL, Lange RT, Wäljas M, Liimatainen S, Dastidar P, Hartikainen KM, Soimakallio S, Ohman J. Outcome from complicated versus uncomplicated mild traumatic brain injury. Rehabil Res Pract. 2012;2012:415740. doi: 10.1155/2012/415740. doi: 10.1155/2012/415740.
    1. Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092–7. doi: 10.1001/archinte.166.10.1092.
    1. McCrory P, Meeuwisse W, Dvořák J, Aubry M, Bailes J, Broglio S, Cantu RC, Cassidy D, Echemendia RJ, Castellani RJ, Davis GA, Ellenbogen R, Emery C, Engebretsen L, Feddermann-Demont N, Giza CC, Guskiewicz KM, Herring S, Iverson GL, Johnston KM, Kissick J, Kutcher J, Leddy JJ, Maddocks D, Makdissi M, Manley GT, McCrea M, Meehan WP, Nagahiro S, Patricios J, Putukian M, Schneider KJ, Sills A, Tator CH, Turner M, Vos PE. Consensus statement on concussion in sport-the 5 international conference on concussion in sport held in Berlin, October 2016. Br J Sports Med. 2017 Jun;51(11):838–47. doi: 10.1136/bjsports-2017-097699.
    1. Bellg AJ, Borrelli B, Resnick B, Hecht J, Minicucci DS, Ory M, Ogedegbe G, Orwig D, Ernst D, Czajkowski S, Treatment Fidelity Workgroup of the NIH Behavior Change Consortium Enhancing treatment fidelity in health behavior change studies: best practices and recommendations from the NIH behavior change consortium. Health Psychol. 2004 Sep;23(5):443–51. doi: 10.1037/0278-6133.23.5.443.
    1. Vranceanu A, Zale EL, Funes CJ, Macklin EA, McCurley J, Park ER, Jordan JT, Lin A, Plotkin SR. Mind-body treatment for international English-speaking adults with neurofibromatosis via live videoconferencing: protocol for a single-blind randomized controlled trial. JMIR Res Protoc. 2018 Oct 23;7(10):e11008. doi: 10.2196/11008.
    1. Reichman M, Riklin E, Macklin E, Vranceanu A. Virtual mind-body treatment for adolescents with neurofibromatosis: study protocol for a single-blind randomized controlled trial. Contemp Clin Trials. 2020 Aug;95:106078. doi: 10.1016/j.cct.2020.106078.
    1. Truong JQ, Ciuffreda KJ, Han MH, Suchoff IB. Photosensitivity in mild traumatic brain injury (mTBI): a retrospective analysis. Brain Inj. 2014;28(10):1283–7. doi: 10.3109/02699052.2014.915989.
    1. Kurowski BG, Wade SL, Dexheimer JW, Dyas J, Zhang N, Babcock L. Feasibility and potential benefits of a web-based intervention delivered acutely after mild traumatic brain injury in adolescents: a pilot study. J Head Trauma Rehabil. 2016;31(6):369–78. doi: 10.1097/HTR.0000000000000180.
    1. Belanger HG, Barwick F, Silva MA, Kretzmer T, Kip KE, Vanderploeg RD. Web-based psychoeducational intervention for postconcussion symptoms: a randomized trial. Mil Med. 2015 Feb;180(2):192–200. doi: 10.7205/MILMED-D-14-00388.
    1. Dexheimer JW, Kurowski BG, Anders SH, McClanahan N, Wade SL, Babcock L. Usability evaluation of the SMART application for youth with mTBI. Int J Med Inform. 2017 Jan;97:163–70. doi: 10.1016/j.ijmedinf.2016.10.007.
    1. Babcock L, Kurowski BG, Zhang N, Dexheimer JW, Dyas J, Wade SL. Adolescents with mild traumatic brain injury get SMART: an analysis of a novel web-based intervention. Telemed J E Health. 2017 Jul;23(7):600–7. doi: 10.1089/tmj.2016.0215.
    1. Mahaffey B, Mackin D, Vranceanu A, Lofaro L, Bromet E, Luft B, Gonzalez A. The stony brook health enhancement program: the development of an active control condition for mind-body interventions. J Health Psychol. 2020;25(13-14):2129–40. doi: 10.1177/1359105318787024.
    1. Vranceanu A, Riklin E, Merker VL, Macklin EA, Park ER, Plotkin SR. Mind-body therapy via videoconferencing in patients with neurofibromatosis: an RCT. Neurology. 2016 Aug 23;87(8):806–14. doi: 10.1212/WNL.0000000000003005.
    1. Zale EL, Pierre-Louis C, Macklin EA, Riklin E, Vranceanu A. The impact of a mind-body program on multiple dimensions of resiliency among geographically diverse patients with neurofibromatosis. J Neurooncol. 2018 Apr;137(2):321–29. doi: 10.1007/s11060-017-2720-5.
    1. EZ Texting. [2020-12-22]. .
    1. Greenberg J, Popok PJ, Lin A, Kulich RJ, James P, Macklin EA, Millstein RA, Edwards RR, Vranceanu A. A mind-body physical activity program for chronic pain with or without a digital monitoring device: proof-of-concept feasibility randomized controlled trial. JMIR Form Res. 2020 Jun 8;4(6):e18703. doi: 10.2196/18703.
    1. Greenberg J, Lin A, Zale E, Kulich RJ, James P, Millstein R, Shapiro H, Schatman M, Edwards R, Vranceanu A. Development and early feasibility testing of a mind-body physical activity program for patients with heterogeneous chronic pain; the getActive study. J Pain Res. 2019;12:3279–97. doi: 10.2147/JPR.S222448. doi: 10.2147/JPR.S222448.
    1. Lovell MR, Collins MW. Neuropsychological assessment of the college football player. J Head Trauma Rehabil. 1998 Apr;13(2):9–26. doi: 10.1097/00001199-199804000-00004.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361–70. doi: 10.1111/j.1600-0447.1983.tb09716.x.
    1. Snell DL, Iverson GL, Panenka WJ, Silverberg ND. Preliminary validation of the world health organization disability assessment schedule 2.0 for mild traumatic brain injury. J Neurotrauma. 2017 Dec 1;34(23):3256–61. doi: 10.1089/neu.2017.5234.
    1. Snell D, Siegert R, Silverberg N. Rasch analysis of the world health organization disability assessment schedule 2.0 in a mild traumatic brain injury sample. Brain Inj. 2020 Apr 15;34(5):610–8. doi: 10.1080/02699052.2020.1729417.
    1. Waddell G, Newton M, Henderson I, Somerville D, Main CJ. A fear-avoidance beliefs questionnaire (FABQ) and the role of fear-avoidance beliefs in chronic low back pain and disability. Pain. 1993 Feb;52(2):157–68. doi: 10.1016/0304-3959(93)90127-b.
    1. Sullivan MJ, Bishop SR, Pivik J. The pain catastrophizing scale: development and validation. Psychol Assess. 1995;7(4):524–32. doi: 10.1037/1040-3590.7.4.524.
    1. Feldman G, Hayes A, Kumar S, Greeson J, Laurenceau J. Mindfulness and emotion regulation: the development and initial validation of the cognitive and affective mindfulness scale-revised (CAMS-R) J Psychopathol Behav Assess. 2006 Nov 7;29(3):177–90. doi: 10.1007/s10862-006-9035-8.
    1. Spence M, Moss-Morris R, Chalder T. The behavioural responses to illness questionnaire (BRIQ): a new predictive measure of medically unexplained symptoms following acute infection. Psychol Med. 2005 Apr;35(4):583–93. doi: 10.1017/s0033291704003484.
    1. Attkisson CC, Zwick R. The client satisfaction questionnaire. Psychometric properties and correlations with service utilization and psychotherapy outcome. Eval Program Plann. 1982;5(3):233–7. doi: 10.1016/0149-7189(82)90074-x.
    1. Devilly GJ, Borkovec TD. Psychometric properties of the credibility/expectancy questionnaire. J Behav Ther Exp Psychiatry. 2000 Jun;31(2):73–86. doi: 10.1016/s0005-7916(00)00012-4.
    1. Miles M, Huberman A. Qualitative Data Analysis: An Expanded Sourcebook, 2nd Edition. California, USA: SAGE Publications; 1994.
    1. Gale NK, Heath G, Cameron E, Rashid S, Redwood S. Using the framework method for the analysis of qualitative data in multi-disciplinary health research. BMC Med Res Methodol. 2013 Sep 18;13:117. doi: 10.1186/1471-2288-13-117.
    1. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006 Jan;3(2):77–101. doi: 10.1191/1478088706qp063oa.
    1. Rounsaville B, Carroll K, Onken L. A stage model of behavioral therapies research: getting started and moving on from stage I. Clin Psychol Sci Pract. 2006;8(2):133–42. doi: 10.1093/clipsy.8.2.133.
    1. Cohen J. Statistical power analysis. Curr Dir Psychol Sci. 2016 Jun 24;1(3):98–101. doi: 10.1111/1467-8721.ep10768783.
    1. Leon AC, Davis LL, Kraemer HC. The role and interpretation of pilot studies in clinical research. J Psychiatr Res. 2011 May;45(5):626–9. doi: 10.1016/j.jpsychires.2010.10.008.
    1. Kistin C, Silverstein M. Pilot studies: a critical but potentially misused component of interventional research. J Am Med Assoc. 2015 Oct 20;314(15):1561–2. doi: 10.1001/jama.2015.10962.
    1. Dworkin SL. Sample size policy for qualitative studies using in-depth interviews. Arch Sex Behav. 2012 Dec;41(6):1319–20. doi: 10.1007/s10508-012-0016-6.
    1. Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004 May;10(2):307–12. doi: 10.1111/j..2002.384.doc.x.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する