Intest Res.  2022 Apr;20(2):171-183. 10.5217/ir.2021.00098.

SARS-CoV-2 vaccination for adult patients with inflammatory bowel disease: expert consensus statement by KASID

Affiliations
  • 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
  • 2Division of Gastroenterology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
  • 3Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
  • 4Department of Health Promotion Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, Korea
  • 5Division of Gastroenterology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University College of Korea, Jeju, Korea
  • 6Digestive Disease Center, CHA Bundang Hospital, CHA University, Seongnam, Korea
  • 7Division of Gastroenterology, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
  • 8Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
  • 9Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
  • 10Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
  • 11Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
  • 12Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Abstract

Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is threatening global health worldwide with unprecedented contagiousness and severity. The best strategy to overcome COVID-19 is a vaccine. Various vaccines are currently being developed, and mass vaccination is in progress. Despite the very encouraging clinical trial results of these vaccines, there is insufficient information on the safety and efficacy of vaccines for inflammatory bowel disease (IBD) patients facing various issues. After reviewing current evidence and international guidelines, the Korean Association for the Study of Intestinal Diseases developed an expert consensus statement on COVID-19 vaccination issues for Korean IBD patients. This expert consensus statement emphasizes that severe acute respiratory syndrome coronavirus 2 vaccination be strongly recommended for IBD patients, and it is safe for IBD patients receiving immunomodulatory therapy.

Keyword

COVID-19 vaccines; SARS-CoV-2; COVID-19; Inflammatory bowel disease

Cited by  4 articles

Update on SARS-CoV-2 vaccination of patients with inflammatory bowel disease: what clinicians need to know
Yoo Jin Lee, Seong-Eun Kim, Yong Eun Park, Ji Young Chang, Hyun Joo Song, Duk Hwan Kim, Young Joo Yang, Byung Chang Kim, Jae Gon Lee, Hee Chan Yang, Seung-Jae Myung
Intest Res. 2022;20(3):386-388.    doi: 10.5217/ir.2020.00172.

Vaccination in patients with inflammatory bowel disease–Asian perspectives: the results of a multinational web-based survey in the 8th Asian Organization for Crohn’s and Colitis meeting
Su Bum Park, Kyeong Ok Kim, Hong Sub Lee, Chang Hwan Choi, Shu Chen Wei, Min Hu Chen, Katsuyoshi Matsuoka
Intest Res. 2023;21(3):363-374.    doi: 10.5217/ir.2023.00015.

Beyond the survey, to the ideal therapy for Asian
Ki Jae Jo, Jong Pil Im
Intest Res. 2023;21(3):280-282.    doi: 10.5217/ir.2023.00075.

Effects of COVID-19 vaccines on patient-reported outcomes in patients with inflammatory bowel disease: a multicenter survey study in Korea
Jung Hyun Ji, Seung Hwan Shin, Yong Eun Park, Jihye Park, Jae Jun Park, Jae Hee Cheon, Tae Il Kim, Sang-Bum Kang, Sang Hyoung Park, Soo Jung Park
Intest Res. 2024;22(3):336-350.    doi: 10.5217/ir.2023.00077.


Reference

1. World Health Organization. WHO Coronavirus (COVID-19) Dashboard [Internet]. c2021 [cited 2021 Jul 6]. https://covid19.who.int/.
2. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017; 390:2769–2778.
Article
3. Yen HH, Weng MT, Tung CC, et al. Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide populationbased study. Intest Res. 2019; 17:54–62.
Article
4. Park SH, Kim YJ, Rhee KH, et al. A 30-year trend analysis in the epidemiology of inflammatory bowel disease in the Songpa-Kangdong district of Seoul, Korea in 1986-2015. J Crohns Colitis. 2019; 13:1410–1417.
Article
5. Kirchgesner J, Lemaitre M, Carrat F, Zureik M, Carbonnel F, Dray-Spira R. Risk of serious and opportunistic infections associated with treatment of inflammatory bowel diseases. Gastroenterology. 2018; 155:337–346.
Article
6. Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol. 2012; 107:1409–1422.
Article
7. D’Amico F, Danese S, Peyrin-Biroulet L. Systematic review on inflammatory bowel disease patients with coronavirus disease 2019: it is time to take stock. Clin Gastroenterol Hepatol. 2020; 18:2689–2700.
Article
8. D’Amico F, Rabaud C, Peyrin-Biroulet L, Danese S. SARS-CoV-2 vaccination in IBD: more pros than cons. Nat Rev Gastroenterol Hepatol. 2021; 18:211–213.
Article
9. Korea Disease Control and Prevention Agency. Q&A for SARS-CoV-2 Vaccination [Internet]. c2021 [cited 2021 Jul 10]. https://ncv.kdca.go.kr/menu.es?mid=a12207000000.
10. Amit S, Regev-Yochay G, Afek A, Kreiss Y, Leshem E. Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 vaccine recipients. Lancet. 2021; 397:875–877.
Article
11. Frenck RW Jr, Klein NP, Kitchin N, et al. Safety, immunogenicity, and efficacy of the BNT162b2 COVID-19 vaccine in adolescents. N Engl J Med. 2021; 385:239–250.
Article
12. Nair R, Aggarwal R, Khanna D. Methods of formal consensus in classification/diagnostic criteria and guideline development. Semin Arthritis Rheum. 2011; 41:95–105.
Article
13. Hong KS, Ko SB, Yu KH, et al. Update of the Korean clinical practice guidelines for endovascular recanalization therapy in patients with acute ischemic stroke. J Stroke. 2016; 18:102–113.
Article
14. Haas EJ, Angulo FJ, McLaughlin JM, et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet. 2021; 397:1819–1829.
Article
15. Hall VJ, Foulkes S, Saei A, et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study. Lancet. 2021; 397:1725–1735.
16. Alexander JL, Moran GW, Gaya DR, et al. SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement. Lancet Gastroenterol Hepatol. 2021; 6:218–224.
Article
17. Siegel CA, Melmed GY, McGovern DP, et al. SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting. Gut. 2021; 70:635–640.
Article
18. Rahier JF, Papay P, Salleron J, et al. H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy. Gut. 2011; 60:456–462.
Article
19. Mamula P, Markowitz JE, Piccoli DA, Klimov A, Cohen L, Baldassano RN. Immune response to influenza vaccine in pediatric patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007; 5:851–856.
Article
20. Fiorino G, Peyrin-Biroulet L, Naccarato P, et al. Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2012; 18:1042–1047.
Article
21. Korea Disease Control and Prevention Agency. Q&A for SARS-CoV-2 Vaccination [Internet]. c2021 [cited 2021 Jul 10]. https://ncv.kdca.go.kr/menu.es?mid=a12208000000.
22. See I, Su JR, Lale A, et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA. 2021; 325:2448–2456.
Article
23. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021; 384:2092–2101.
Article
24. European Medicines Agency. AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets [Internet]. c2021 [cited 2021 Jun 14]. https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-casesunusual-blood-clots-low-blood.
25. Expert Haematology Panel. Guidance produced from the Expert Haematology Panel (EHP) focussed on Covid-19 vaccine induced thrombosis and thrombocytopenia (VITT). c2021 [cited 2021 Jun 14]. https://b-s-h.org.uk/media/19530/guidance-version-13-on-mngmt-of-thrombosis-with-thrombocytopenia-occurring-after-c-19-vaccine_20210407.pdf.
26. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle P, Eichinger S. A prothrombotic thrombocytopenic disorder resembling heparin-induced thrombocytopenia following coronavirus-19 vaccination. Res Sq. [Preprint]. 2021 [cited 2021 Jun 16]. https://doi.org/10.21203/rs.3.rs-362354/v1.
Article
27. Medicines and Healthcare Products Regulatory Agency. Coronavirus vaccine-weekly summary of Yellow Card reporting [Internet]. c2021 [cited 2021 Jul 1]. https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting.
28. Centers for Disease Control and Prevention. Johnson & Johnson’s Janssen COVID-19 vaccine overview and safety [Internet]. c2021 [cited 2021 Jun 23]. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html.
29. Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010; 375:657–663.
Article
30. Koroku M, Omori T, Kambayashi H, et al. Granulocyte and monocyte apheresis therapy for patients with active ulcerative colitis associated with COVID-19. Intest Res. 2021; Mar. 12. [Epub]. https://doi.org/10.5217/ir.2020.00148.
Article
31. Bezzio C, Saibeni S, Variola A, et al. Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study. Gut. 2020; 69:1213–1217.
Article
32. Brenner EJ, Ungaro RC, Gearry RB, et al. Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry. Gastroenterology. 2020; 159:481–491.
Article
33. Ungaro RC, Brenner EJ, Gearry RB, et al. Effect of IBD medications on COVID-19 outcomes: results from an international registry. Gut. 2021; 70:725–732.
Article
34. Kennedy NA, Jones GR, Lamb CA, et al. British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic. Gut. 2020; 69:984–990.
Article
35. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020; 383:2603–2615.
Article
36. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021; 397:99–111.
37. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021; 384:403–416.
Article
38. Kennedy NA, Lin S, Goodhand JR, et al. Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD. Gut. 2021; 70:1884–1893.
Article
39. Wong SY, Dixon R, Martinez Pazos V, et al. Serologic response to messenger RNA coronavirus disease 2019 vaccines in inflammatory bowel disease patients receiving biologic therapies. Gastroenterology. 2021; 161:715–718.
Article
40. Melmed GY, Rubin DT, McGovern DPB. Winter is coming! Clinical, immunologic, and practical considerations for vaccinating patients with inflammatory bowel disease during the coronavirus disease-2019 pandemic. Gastroenterology. 2021; 160:639–644.
Article
41. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014; 58:309–318.
Article
42. Park SK, Choi CH, Chun J, et al. Prevention and management of viral hepatitis in inflammatory bowel disease: a clinical practice guideline by the Korean Association for the Study of Intestinal Diseases. Intest Res. 2020; 18:18–33.
Article
43. Crosby S, Schuh MJ, Caldera F, Farraye FA. Vaccination of patients with inflammatory bowel disease during the COVID-19 pandemic. Gastroenterol Hepatol (N Y). 2021; 17:18–30.
44. Queiroz N, Teixeira FV, Freire C, et al. Brazilian IBD study group position statement on SARS-COV2 vaccination. Arq Gastroenterol. 2021; 58:1–4.
Article
45. deBruyn J, Fonseca K, Ghosh S, et al. Immunogenicity of influenza vaccine for patients with inflammatory bowel disease on maintenance infliximab therapy: a randomized trial. Inflamm Bowel Dis. 2016; 22:638–647.
Article
46. Melmed GY, Agarwal N, Frenck RW, et al. Immunosuppression impairs response to pneumococcal polysaccharide vaccination in patients with inflammatory bowel disease. Am J Gastroenterol. 2010; 105:148–154.
Article
47. Pratt PK Jr, David N, Weber HC, et al. Antibody response to hepatitis B virus vaccine is impaired in patients with inflammatory bowel disease on infliximab therapy. Inflamm Bowel Dis. 2018; 24:380–386.
Article
48. Andrade P, Santos-Antunes J, Rodrigues S, Lopes S, Macedo G. Treatment with infliximab or azathioprine negatively impact the efficacy of hepatitis B vaccine in inflammatory bowel disease patients. J Gastroenterol Hepatol. 2015; 30:1591–1595.
Article
49. Park SH, Yang SK, Park SK, et al. Efficacy of hepatitis A vaccination and factors impacting on seroconversion in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2014; 20:69–74.
Article
50. Agarwal N, Ollington K, Kaneshiro M, Frenck R, Melmed GY. Are immunosuppressive medications associated with decreased responses to routine immunizations? A systematic review. Vaccine. 2012; 30:1413–1424.
Article
51. Wyant T, Leach T, Sankoh S, et al. Vedolizumab affects antibody responses to immunisation selectively in the gastrointestinal tract: randomised controlled trial results. Gut. 2015; 64:77–83.
Article
52. Andrisani G, Frasca D, Romero M, et al. Immune response to influenza A/H1N1 vaccine in inflammatory bowel disease patients treated with anti TNF-α agents: effects of combined therapy with immunosuppressants. J Crohns Colitis. 2013; 7:301–307.
Article
53. Sempere L, Almenta I, Barrenengoa J, et al. Factors predicting response to hepatitis B vaccination in patients with inflammatory bowel disease. Vaccine. 2013; 31:3065–3071.
Article
54. Kim SB, Park SJ, Chung SH, et al. Vaccination and complementary and alternative medicine in patients with inflammatory bowel disease. Intest Res. 2014; 12:124–130.
Article
55. Tinsley A, Navabi S, Williams ED, et al. Increased risk of influenza and influenza-related complications among 140,480 patients with inflammatory bowel disease. Inflamm Bowel Dis. 2019; 25:369–376.
Article
56. Kantsø B, Simonsen J, Hoffmann S, Valentiner-Branth P, Petersen AM, Jess T. Inflammatory bowel disease patients are at increased risk of invasive pneumococcal disease: a nationwide danish cohort study 1977-2013. Am J Gastroenterol. 2015; 110:1582–1587.
Article
57. Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. ACG clinical guideline: preventive care in inflammatory bowel disease. Am J Gastroenterol. 2017; 112:241–258.
Article
58. Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices. United States, 2020-21 influenza season. MMWR Recomm Rep. 2020; 69:1–24.
Article
59. Kim KO, Jang BI. Management of inflammatory bowel disease in the COVID-19 era. Intest Res. 2022; 20:3–10.
Article
60. Magro F, Rahier JF, Abreu C, et al. Inflammatory bowel disease management during the COVID-19 outbreak: the ten do’s and don’ts from the ECCO-COVID Taskforce. J Crohns Colitis. 2020; 14(14 Suppl 3):S798–S806.
Article
61. Zambrano LD, Ellington S, Strid P, et al. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status. United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69:1641–1647.
62. Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020; 370–m3320.
Article
63. Kotlyar AM, Grechukhina O, Chen A, et al. Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis. Am J Obstet Gynecol. 2021; 224:35–53.
Article
64. Rasmussen SA, Jamieson DJ. Pregnancy, postpartum care, and COVID-19 vaccination in 2021. JAMA. 2021; 325:1099–1100.
Article
65. Steinhoff MC, Katz J, Englund JA, et al. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. Lancet Infect Dis. 2017; 17:981–989.
Article
66. Winter K, Nickell S, Powell M, Harriman K. Effectiveness of prenatal versus postpartum tetanus, diphtheria, and acellular pertussis vaccination in preventing infant pertussis. Clin Infect Dis. 2017; 64:3–8.
Article
67. Adhikari EH, Spong CY. COVID-19 vaccination in pregnant and lactating women. JAMA. 2021; 325:1039–1040.
Article
68. Society of Obstetricians and Gynaecologists of Canada. SOGC COVID-19 vaccination in pregnancy FAQ for health care providers [Internet]. c2021 [cited 2021 Jul 10]. https://sogc.org/common/Uploaded%20files/Covid%20Information/EN_HCP-FAQ_SOGC_FINAL.pdf.
69. Centers for Disease Control and Prevention. Information about COVID-19 vaccines for people who are pregnant or breastfeeding [Internet]. c2021 [cited 2021 Jul 7]. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html.
70. U.S. Food and Drug Administration. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee meeting December 17, 2020: FDA briefing document Moderna COVID-19 vaccine [Internet]. c2021 [cited 2021 Jun 26]. https://www.fda.gov/media/144434/download.
71. Centers for Disease Control and Prevention. V-safe COVID-19 Vaccine Pregnancy Registry [Internet]. c2021 [cited 2021 Jul 7]. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/vsafepregnancyregistry.html.
72. Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary findings of mRNA COVID-19 vaccine safety in pregnant persons. N Engl J Med. 2021; 384:2273–2282.
Article
73. Gray KJ, Bordt EA, Atyeo C, et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol. 2021; 225:303.e1–303.e17.
Article
74. World Health Organization. Update on WHO Interim recommendations on COVID-19 vaccination of pregnant and lactating women [Internet]. c2021 [cited Jun 26]. https://www.who.int/publications/m/item/update-on-who-interim-recommendations-on-covid-19-vaccination-of-pregnant-and-lactating-women.
75. Department of Health & Social Care. Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination, 30 December 2020 [Internet]. c2020 [cited 2021 Jun 24]. https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020/joint-committee-on-vaccination-and-immunisation-advice-on-priority-groups-for-covid-19-vaccination-30-december-2020.
76. Public Health England. JCVI issues new advice on COVID-19 vaccination for pregnant women [Internet]. c2021 [cited 2021 Jul 5]. https://www.gov.uk/government/news/jcvi-issues-new-advice-on-covid-19-vaccination-for-pregnant-women.
77. Martins I, Louwen F, Ayres-de-Campos D, Mahmood T. EBCOG position statement on COVID-19 vaccination for pregnant and breastfeeding women. Eur J Obstet Gynecol Reprod Biol. 2021; 262:256–258.
Article
78. Medicines and Healthcare Products Regulatory Agency. UK regulator confirms that people should continue to receive the COVID-19 vaccine AstraZeneca [Internet]. c2021 [cited 2021 Jun 26]. https://www.gov.uk/government/news/uk-regulator-confirms-that-people-should-continue-to-receive-the-covid-19-vaccine-astrazeneca.
79. Choi WS. Comprehensive understanding and field application of COVID-19 vaccine. Korean J Med. 2021; 96:155–159.
Article
80. American College of Obstetricians and Gynecologists. Coronavirus (COVID-19), pregnancy, and breastfeeding: a message for patients [Internet]. c2021 [cited 2021 Jul 5]. https://www.acog.org/womens-health/faqs/coronavirus-covid-19-pregnancy-and-breastfeeding.
81. Perl SH, Uzan-Yulzari A, Klainer H, et al. SARS-CoV-2-specific antibodies in breast milk after COVID-19 vaccination of breastfeeding women. JAMA. 2021; 325:2013–2014.
Article
82. Royal College of Obstetricians and Gynaecologists. COVID-19 vaccines, pregnancy and breastfeeding [Internet]. c2021 [cited 2021 Jun 19]. https://www.rcog.org.uk/en/guidelines-research-services/coronavirus-covid-19-pregnancy-and-womens-health/covid-19-vaccines-and-pregnancy/covid-19-vaccines-pregnancy-and-breastfeeding/.
Full Text Links
  • IR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr