Debridement for surgical wounds

Cochrane Database of Systematic Reviews

Volumn 2024, Issue 5, 2024, Pages

  Smith, Fiona ^a   Donaldson, Jayne ^a   Brown, Tamara ^a,b  

^a UNIVERSITY OF STIRLING   (United Kingdom)

^b LEEDS METROPOLITAN UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DEXTRANOMER; ELASTOMER; EUSOL; POVIDONE; SILICONE; SODIUM CHLORIDE; STREPTODORNASE PLUS STREPTOKINASE; TOSYLCHLORAMIDE SODIUM; DEXTRAN;

ADVERSE EVENT; AUTOLYTIC DEBRIDEMENT; CHEMICAL DEBRIDEMENT; CLINICAL DECISION MAKING; COST EFFECTIVENESS ANALYSIS; DATA EXTRACTION; DEBRIDEMENT; ENDOSCOPY; FOLLOW UP; GRADE APPROACH; HAZARD RATIO; HOSPITALIZATION; HUMAN; INFECTION; LENGTH OF STAY; NECROSIS; OUTCOME ASSESSMENT; PATIENT SATISFACTION; PATIENT SELECTION; PUBLICATION; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK ASSESSMENT; SATISFACTION; SENSITIVITY ANALYSIS; SURGICAL DEBRIDEMENT; SURGICAL WOUND; SYSTEMATIC REVIEW; TECHNOLOGY; WOUND HEALING; ADOLESCENT; ADULT; AGED; CHILD; META ANALYSIS; MIDDLE AGED; PRESCHOOL CHILD; PROCEDURES; STATISTICAL BIAS; SURGICAL INFECTION; TIME FACTOR; VERY ELDERLY; YOUNG ADULT; METHODOLOGY;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; BANDAGES; BIAS; CHILD; CHILD, PRESCHOOL; DEBRIDEMENT; HUMANS; MIDDLE AGED; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SURGICAL WOUND; SURGICAL WOUND INFECTION; TIME FACTORS; WOUND HEALING; YOUNG ADULT; DEXTRANS; STREPTODORNASE AND STREPTOKINASE;

EID: 79959531056     PISSN: 14651858     EISSN: None     Source Type: Journal    
DOI: 10.1002/14651858.CD006214.pub5     Document Type: Review

References (99)

1. Goode AW, Glazer G, Ellis BW. The cost effectiveness of dextranomer and Eusol in the treatment of infected surgical wounds. British Journal of Clinical Practice 1979;33(11-2):325-6. x-wiley/crsRef/3222528
2. Michiels I, Christiaens MR. Dextranomer (Debrisan) paste in post-operative wounds: a controlled study. Clinical Trials Journal 1990;27(4):283-90. x-wiley/crsRef/3222530
3. Poulson J, Kristensen VN, Brygger HE, Delikaris P. Treatment of infected surgical wounds with Varidase. Acta Chirurgica Scandinavica 1983;149(3):245-8. x-wiley/crsRef/3222532
4. Sondergaard JO, Galatius H. Debrisan compared with chloramine packs in the treatment of postoperative infected wounds [Debrisan versus kloramin-mecheved postoperative inficerede cikatricer]. Ugeskrift for Laeger 1982;144(21):1523-5. x-wiley/crsRef/3222534
5. Wang H, Dou X, Hu X, Yu J, Wang S. Effectiveness and safety of endoscopy for treatment of surgical site infection: a randomised control trial. Experimental and Therapeutic Medicine 2014;8:1727-30. x-wiley/crsRef/3222536 [DOI: 10.3892/etm.2014.2028]
6. Young HL, Wheeler MH. Report of the prospective trial of dextranomer beads (Debrisan) and silicone foam elastomer (silastic dressings in surgical wounds). British Journal of Surgery 1982;69(1):33-4. x-wiley/crsRef/3222538
7. Acosta S, Monsen C, Dencker M. Clinical outcome and microvascular blood flow in VAC and Sorbalgon treated peri-vascular infected wounds in the groin after vascular surgery – an early interim analysis. International Wound Journal 2013;10(4):377-82. x-wiley/crsRef/3222540
8. Allie DE, Herbert CJ, Lirtzman MD, Wyatt CH, Keller VA, Souther SM, et al. Novel treatment strategy for leg and sternal wound complications after coronary graft surgery: bioengineered Apligraf. Annals of Thoracic Surgery 2004;78(2):673-8. x-wiley/crsRef/3222542
9. Bethell E. Why gauze dressings should not be the first choice to manage acute surgical cavity wounds. Journal of Wound Care 2003;12(6):237-9. x-wiley/crsRef/3222544
10. Cannavo M, Fairbrother G, Owen D, Ingle J, Lumley T. A comparison of dressings in the management of surgical abdominal wounds. Journal of Wound Care 1998;7(2):57-62. x-wiley/crsRef/3222546
11. Capasso VA, Munro BH. The cost and efficacy of two wound treatments. AORN Journal 2003;77(5):984-1004. x-wiley/crsRef/3222548
12. Cassino R, Ippolito AM. Aminoacid gel versus hydrogel: which is the quicker debrider? Acta Vulnologica 2013;11(4):149-59. x-wiley/crsRef/3222550
13. Cohn SM, Lopez PP, Brown M, Namias N, Jackowskl J, Li P, et al. Open surgical wounds: how does Aquacel compare with wet-to-dry gauze. Journal of Wound Care 2004;13(1):10-2. x-wiley/crsRef/3222552
14. De Feo M, De Sante LS, Ramano G, Renzulli A, Corter AD, Utili R, et al. Treatment of recurrent staphylococcal mediastinitis: still a controversial issue. Annals of Thoracic Surgery 2001;75(2):538-42. x-wiley/crsRef/3222554
15. De Feo M, Gregorio R, Corter AD, Marra C, Amarelli C, Renzulli A, et al. Deep sternal wound infection: the role of early debridement surgery. European Journal of Cardio-Thoracic Surgery 2003;19(6):811-6. x-wiley/crsRef/3222556
16. Doughty DB. Preventing and managing surgical wound dehiscence. Advances in Skin and Wound Care 2005;18(6):319-22. x-wiley/crsRef/3222558
17. Douville EC, Asaph JW, Dworkin RJ, Handy JR, Canepa CS, Grunkemeier GL, et al. Sternal preservation: a better way to treat most sternal wound complications after cardiac surgery. Annals of Thoracic Surgery 2004;78(5):1659-64. x-wiley/crsRef/3222560
18. Edwards RH, Killen DA. Comparison of two methods of management of clean surgical wounds. JAMA 1967;201(1):137-8. x-wiley/crsRef/3222562
19. Foster L, Moore P, Clark S. Comparison of hydrofibre and alginate dressings on open acute surgical wounds. Journal of Wound Care 2000;9(9):442-5. x-wiley/crsRef/3222564
20. Gliantsev SO, Savvina TV. Comparative evaluation of activity of proteolytic enzymes used in surgery. Biulleten Eksperimentalnoi Biologii 1996;121(6):16-20. x-wiley/crsRef/3222566
21. Gottrup F. The significance of dressings and topical agents in secondary healing [Betydningen af bandage og lokale midler ved sekundaert helede kirurgiske sar]. Ugeskrift for Laeger 2005;167(47):4473-6. x-wiley/crsRef/3222568
22. Granick MS, Posnett J, Jacoby M, Noruthun S, Ganchi PA, Datiashvili RO. Efficacy and cost-effectiveness of a high-powered parallel waterjet for wound debridement. Wound Repair and Regeneration 2006;14(4):394-7. x-wiley/crsRef/3222570
23. Guest JF, Ruiz FJ. Modelling the cost implications of using carboxymethylcellulose dressing compared with gauze in the management of surgical wound healing by secondary intention in the US and UK. Current Medical Research and Opinion 2005;21(2):94-101. x-wiley/crsRef/3222572
24. Kim SW, Lee JH, Soe BF, Rhie JW. Prospective RCT comparing two hydrocolloid dressings in acute trauma wounds in South Korea. Journal of Wound Care 2013;22(4):208-13. x-wiley/crsRef/3222574
25. Kuleshov SE, Kaem RI. The use of carbon dioxide laser in acute surgical infection of the soft tissues. Khirurgiia Moskva 1992;2:94-101. x-wiley/crsRef/3222576
26. Ma WJ, Zhou Y, Xu RH, Shrestha A, Li FY, Yang Q, et al. Healing time after hepatobiliary surgery treated by needle-free incision suture closure. World Journal of Gastroenterology 2014;20(42):15815-9. x-wiley/crsRef/3222578
27. Moore PJ, Foster L. Cost benefits of two dressings in the management of surgical wounds. British Journal of Nursing 2000;9(17):1128-32. x-wiley/crsRef/3222580
28. Moore OA, Smith LA, Campbell F, Seers K, McQuay HJ, Moore RA. Systematic review of the use of honey as a wound dressing. BMC Complementary and Alternative Medicine 2001;1(2):2. x-wiley/crsRef/3222582
29. Moues CM, Vos MC, van den Bemd GJ, Stijnen T, Hovius SE. Bacterial load in relation to vacuum-assisted closure wound therapy: a prospective randomised trial. Wound Repair and Regeneration 2004;12(1):11-7. x-wiley/crsRef/3222584
30. Mulder GD. Evaluation of three nonwoven sponges in the debridement of chronic wounds. Ostomy/Wound Management 1995;41(3):62-7. x-wiley/crsRef/3222586
31. NCT01237392. Ultrasonic wound debridement vs standard sharp debridement. clinicaltrials.gov/show/NCT01237392 (first received 9 November 2010). x-wiley/crsRef/16466995
32. NCT02482948. MEDIHONEY® Gel versus collagenase for wound debridement. clinicaltrials.gov/show/NCT02482948 (first received 26 June 2015). x-wiley/crsRef/16466997
33. TM Hyrdrosurgery system in the treatment of open tibia fractures: a prospective open label randomized controlled trial. International Journal of Burn Trauma 2014;4(2):53-8. x-wiley/crsRef/3222588
34. Rand RP, Cochran RP, Aziz S, Hofer BO, Allen MD, Verrier ED, et al. Prospective trial of catheter irrigation and muscle flaps for sternal wound infection. Annals of Thoracic Surgery 1998;65(4):1046-9. x-wiley/crsRef/3222590
35. Shoham Y, Shapira E, Haik J, Harats M, Egozi S, Robinson D, et al. Bromelain-based enzymatic debridement of chronic wounds: results of a multicentre randomized controlled trial. Wound Repair and Regeneration 2021;29:899-907. x-wiley/crsRef/25455920 [DOI: DOI: 10.1111/wrr.12958]
36. Soul JA. A trial of Debrisan in the cleansing of infected surgical wounds. British Journal of Clinical Practice 1978;32(6):172-3. x-wiley/crsRef/3222592
37. Tewarie L, Goetzenich A, Hatam N, Holtmannspötter O, Kuschel T, Autschbach R, et al. Ultrasonic debridement of deep surgical wound infection and mediastinitis after sternotomy. Thoracic and Cardiovascular Surgeon 2013;61:OP242. x-wiley/crsRef/3222594 [DOI: 10.1055/s-0032-1332481]
38. Tolstykh PI, Glostishchev VK, Khanin AG, Aboyants RK, Yusuf MY, Antsyshkin VA. The effect of biologically active dressings of wounds upon the development of the wound process. Vestnivk Khirurgh IM I I Grekova 1987;138(3):57-60. x-wiley/crsRef/3222596
39. Williams P, Howells RE, Miller E, Foster ME. A comparison of two alginate dressings used in surgical wounds. Journal of Wound Care 1995;4(4):170-2. x-wiley/crsRef/3222598
40. TM dressing with silver in wound healing after surgery for anal fistula. Chinese Journal of Tissue Engineering Research 2012;16(47):8835-41. x-wiley/crsRef/3222600
41. Zeitani J, Bertoldo F, Bassano C, Penta de Peppo A, Pellegrino AP, El Fakhri FM, et al. Superficial wound dehiscence after median sternotomy: surgical treatment versus secondary wound healing. Annals of Thoracic Surgery 2004;77(2):672-5. x-wiley/crsRef/3222602
42. NCT03798041. Early debridement within 24 hours after surgery for wound healing of abdominal incision. clinicaltrials.gov/show/NCT03798041 (first received 9 January 2019). x-wiley/crsRef/16467001
43. NCT03880331. Comparing outcomes of secondary intention wound care methods. clinicaltrials.gov/show/NCT03880331 (first received 19 March 2019). x-wiley/crsRef/16467003
44. Anderson I. Debridement methods in wound care. Nursing Standard 2006;20(24):65-72.
45. Atkin L, Acton C, Edmonds M, Fumarola S, Geraghty J, McIntosh C, et al. The role of larval debridement therapy in the management of lower limb wounds. www.wounds-uk.com/resources/details/the-role-of-larval-debridement-therapy-in-the-management-of-lower-limb-wounds (accessed 14 October 2022).
46. Bahr S, Mustafi N, Hättig P, Piatkowski A, Mosti G, Reimann K, et al. Clinical efficacy of a new monofilament fibre-containing wound debridement product. Journal of Wound Care 2011;20(5):242-8.
47. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection. JAMA Surgery 2017;152:784-91. [DOI: 10.1001/jamasurg.2017.0904]
48. Bradley M, Cullum N, Sheldon T. The debridement of chronic wounds: a systematic review. Health Technology Assessment 2001;3(3 (17 Pt 1)):1-78. [DOI: 10.3310/hta3171]
49. Brown A. Phases of the wound healing process. Nursing Times 2015;111(46):12-3.
50. Callaghan R. Treating difficult-to-debride wounds using a manuka honey dressing: a case study evaluation. Wounds UK 2014;10(2):104-9.
51. Cornell RS, Meyr AJ, Steinberg JS, Attinger CE. Debridement of the noninfected surgical wound. Journal of Vascular Surgery 2010;52(3 Suppl):31-6s.
52. Cornwell P, Arnold-Lang M, Bernahl Barss S, Varnado MF. The use of Dakin's Solution in chronic wounds. Journal of Wound, Ostomy and Continence Nursing 2010;37(1):94-104. [DOI: 10.1097/WON.06013e3181c78874]
53. Deeks JJ, Higgins JP, Altman DG. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
54. European Centre for Disease Prevention and Control. Healthcare-associated infections: surgical site infections. Annual Epidemiological Report for 2018-2023 2023:1-19.
55. European Wound Management Association. Debridement: an updated overview and clarification of the principle role of debridement. Journal of Wound Care 2013;22(3):S1-49.
56. Fletcher J, Probst A. Managing dry wounds in clinical practice: challenges and solutions. Wounds International 2020;11(2):47-52.
57. Glanville J, Dooley G, Wisniewski S, Foxlee R, Noel-Storr A. Development of a search filter to identify reports of controlled clinical trials within CINAHL Plus. Health Information and Libraries Journal 2019;36(1):73-90.
58. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.guidelinedevelopment.org/app/handbook/handbook.html.
59. Gray D, White R, Cooper P, Kingsley T, Young T. An introduction to applied wound management and its use in the assessment of wounds. Wounds UK 2009;5(4):4-9.
60. Gray D, Acton C, Chadwick P, Fumarola S, Leaper D, Morris C, et al. Consensus guidelines for the use of debridement techniques in the UK. Wounds UK 2011;7(1):77-84.
61. Haemmerle G, Duellii H, Abel M, Strohal R. The wound debrider: a new monofilament fibre technology. British Journal of Nursing 2011;20(6):S35-42.
62. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60.
63. Higgins JP, Altman DG, Sterne JA. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017), Cochrane, 2017. Available from training.cochrane.org/handbook/archive/v5.2.
64. Higgins JP, Eldridge S, Li T. Chapter 23: Including variants on randomized trials. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
65. International Wound Infection Institute (IWII). Wound infection in clinical practice. eprints.hud.ac.uk/id/eprint/30637/1/iwii-consensus_final-web.pdf (accessed 14 October 2022).
66. Janis J, Harrison B. Wound healing: part II. Clinical applications. Plastic and Reconstructive Surgery 2014;133(3):383-92e.
67. Lantis J, Paredes J. Permissive maintenance debridement – the role of enzymatic debridement in chronic wound care. Wounds International 2017;8(2):7-13.
68. Leak K. How to… Ten top tips for wound debridement. Wounds International 2012;2(2):21-3.
69. Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al. Chapter 4: Searching for and selecting studies. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
70. Liberati A, Altman DG, TetzlaF J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLOS Medicine 2009;6:e1000100.
71. Madhok BM, Vowden K, Vowden P. New techniques for wound debridement. International Wound Journal 2013;10:247-51.
72. McFarland A, Smith F. Wound debridement: a clinical update. Nursing Standard 2014;28(52):51-8.
73. Moore Z. The important role of debridement in wound bed preparation. Wounds International 2012;3(2):19-23.
74. National Institute for Health and Care Excellence. The MIST Therapy system for the promotion of wound healing. www.nice.org.uk/guidance/mtg5/documents/mist-therapy-system-for-the-promotion-of-wound-healing-in-chronic-and-acute-wounds-consultation-document (accessed prior to 12 April 2024).
75. National Institute for Health and Care Excellence. The Debrisoft monofilament debridement pad for use in acute or chronic wounds. guidance.nice.org.uk/mtg17 (accessed 14 October 2022).
76. National Institute for Health and Care Excellence. Surgical site infections: prevention and treatment. www.nice.org.uk/guidance/ng125 (accessed prior to 12 April 2024).
77. Norman G, Dumville JC, Mohapatra DP, Owens GL, Crosbie EJ. Antibiotics and antiseptics for surgical wounds healing by secondary intention. Cochrane Database of Systematic Reviews 2016, Issue 3. Art. No: CD011712. [DOI: 10.1002/14651858.CD011712.pub2]
78. Ousey K, Schofield A. Made easy: wound bed preparation. www.wounds-uk.com/download/resource/8995 (accessed prior to 12 April 2024).
79. Ovens L, Irving S. Advances in wound cleansing: an integrated approach. Wounds UK 2018;14(1):58-63.
80. Page MJ, Higgins JP, Sterne JA. Chapter 13: Assessing risk of bias due to missing results in a synthesis. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
81. Prince B, Young T. Debridement consensus: recommendations for practice. Wound Essentials 2013;8(1):71-6.
82. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2020.
83. Sainsbury DC. Evaluation of the quality and cost-effectiveness of Versajet hydrosurgery. International Wound Journal 2009;6(1):24-9.
84. Schultz GS, Sibbald RG, Falanga V, Ayello EA, Dowsett C, Harding K, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair and Regeneration 2003;11(Suppl 1):S1-28.
85. Schünemann HJ, Vist GE, Higgins JP, Santesso N, Deeks JJ, Glasziou P, et al. Chapter 15: Interpreting results and drawing conclusions. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
86. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing 'Summary of findings' tables and grading the certainty of the evidence. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
87. Seidelman JL, Mantyh CR, Anderson DJ. Surgical site infection prevention: a review. JAMA 2023;329:244-52. [DOI: 10.1001/jama.2022.24075]
88. Spear M. The necessity of wound debridement. Plastic Surgical Nursing 2010;30(1):54-6.
89. Spruce P, Bullough L, Johnson S, O'Brien D. Introducing HydroClean® plus for wound-bed preparation: a case series. Wounds International 2016;7(1):26-32.
90. Tao H, Butler JP, Litrell T. The role of whirlpool in wound care. Journal of the American College of Clinical Wound Specialists 2012;4(1):7-12.
91. Vowden K, Vowden P. Debridement made easy. Wounds UK 2011;7(4):1-4.
92. Wounds UK. Best Practice Statement: the Use of Topical Antimicrobial Agents in Wound Management. 3rd edition. London (UK): Wounds UK, 2013.
93. World Union of Wound Healing Societies (WUWHS). Principles of best practice: wound infection in clinical practice. An international consensus. www.woundsinternational.com/resources/details/wound-infection-clinical-practice-wuwhs-international-consensus (accessed prior to 12 April 2024).
94. World Union of Wound Healing Societies (WUWHS). Surgical wound dehiscence: improving prevention and outcomes. www.woundsinternational.com/resources/details/surgical-wound-dehiscence-improving-prevention-and-outcomes (accessed 14 October 2022).
95. World Union of Wound Healing Societies (WUWHS). WUWHS consensus document: wound exudate, effective assessment and management. www.woundsinternational.com/resources/details/wuwhs-consensus-document-wound-exudate-effective-assessment-and-management (accessed 14 October 2022).
96. Dryburgh N, Donaldson J, Mitchell M, Smith F. Debridement for surgical wounds. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No: CD006214. [DOI: 10.1002/14651858.CD006214]
97. Dryburgh N, Smith F, Donaldson J, Mitchell M. Debridement for surgical wounds. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No: CD006214. [DOI: 10.1002/14651858.CD006214.pub2]
98. Smith F, Dryburgh N, Donaldson J, Mitchell M. Debridement for surgical wounds. Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No: CD006214. [DOI: 10.1002/14651858.CD006214.pub3]
99. Smith F, Dryburgh N, Donaldson J, Mitchell M. Debridement for surgical wounds. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No: CD006214. [DOI: 10.1002/14651858.CD006214.pub4]