實 證 期 刊 閱 讀 報 告 EBM-style Journal Reading 報告人： PGY夏紹剛 Email:143920@cch.org.tw 指導臨床教師：何昌益醫師/謝堯棚醫師 日期：2009/10/29 地點：一般內科82討論室

Clinical Scenario （臨床情境） 個案為73歲已婚男性，有高血壓及糖尿病病史，右腳糖尿病足於97年9月接受高壓氧治療後痊癒，本次因雙足潰瘍已兩週入院，診斷為糖尿病足，右足壞疽嚴重經外科清瘡治療後，外科醫師建議植皮以加速復原，病人僅希望再次進行高壓氧治療不願植皮。􀇻

Clinical Uncertainty → PICO 問題 對於糖尿病足部潰瘍患者，單純接受高壓氧治療相較於植皮是否仍有理想的復原能力？

Type of Question: Therpy 臨床個案的PICO Patient / Problem Patient who has Type 2 DM with foot ulcers (foot ulcer or diabetic foot) Intervention HBO OR hyperbaric oxygenation Comparison skin graft or skin transplantation Outcome enhance the wound healing Type of Question: Therpy

Search Terms & Strategy: （搜尋關鍵字與策略） 資料庫： Pubmed 搜尋日期： 2009/10/23 搜尋關鍵字與隅策略： 如圖表

Best available evidence: （挑選可獲得之最佳研究證據） Citation/s: A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes(2008) Lead author's name : R.J.Hinchliffe, G.D.Valk, J.Apelqvist, D.G.Armstrong, K.Bakker, F.L.Game, A.Hartemann-Heurtier, M.Londahl, P.E.Price, W.H.van Houtum,W. J.Jeffcoate

The Study: （研究效度）- 1 Prospective and retrospective controlled studies, published in any language, that evaluated interventions for the treatment of chronic foot ulcers in people aged 18 years or older with either type 1 or type 2 diabetes mellitus were considered. Randomized controlled trials (RCTs), case-control studies, prospective and retrospective cohort studies, control before-and-after (CBA) design and interrupted time series (ITS) designs were included. MEDLINE (1966 - 2006) EMBASE(1980 - 2006) The Cochrane database of systematic reviews, and the Cochrane Central Controlled Trials Register (2006)

The Study: （研究效度）- 2 One reviewer assessed all identified references by title and abstract on the basis of patient group, intervention and outcome. Full paper copies of identified articles were then assessed for eligibility by two independent reviewers (agreement was reached). Each included paper was further assessed by two reviewers, working independently, and information was extracted on study design, patient group, intervention, outcomes, duration of and loss to followup, using standard data extraction sheets.

The Study: （研究效度）- 3 Each study was scored for methodological quality using designspecific scoring, based on checklists developed by the Dutch Cochrane Center(RCT score:1-9). The SIGN instrument : (1) RCTs and (2) studies with case-control, cohort, CBA or ITS design. Studies were also rated as: ++ (high quality with low risk of bias), + (well conducted with low risk of bias) and – (low quality with higher risk of bias).

The Study: （研究效度）- 5 Level of Evidence: 1A(SR of RCTs) HBO therapy 6篇RCT(114 studies identified ) Bioengineered skin and skin grafts 6篇RCT(72 papers identified) Level of Evidence: 1A(SR of RCTs)

The Study: （研究效度）- 6 本篇文獻的PICO (T) Patient / Problem chronic foot ulcers in people aged 18 years or older with either type 1 or type 2 diabetes Mellitus Intervention Dressings, Debridement, Bioengineered skin and skin grafts, Electromagnetic, laser and ultrasound, Stem cell therapy, Abnormalities of wound biology and gene therapy, Reduction of tissue oedema, Hyperbaric oxygen, Resection of the chronic wound/surgical procedures Comparison Outcome The healing of chronic ulcer, ulcer area, amputation rate Time 3 months – 1 years

The Evidence: （研究重要結果）- 1 Topical HBO inclusion of the affected foot into a sealed chamber containing hyperbaric oxygen (HBO) Systemic HBO the patient spending prolonged periods of time in a large HBO chamber

The Evidence: （研究重要結果）- 2 HBO-1

The Evidence: （研究重要結果）- 3 HBO-2

The Evidence: （研究重要結果）- 4 Bioengineered skin and skin grafts-1

The Evidence: （研究重要結果）- 5 Bioengineered skin and skin grafts-2

Comment & Discussion: -1 Systemic HBO may reduce the incidence of major amputation. While further evidence of effectiveness and cost-effectiveness, is required from larger, more robust and blinded studies. The benefit of topically administered HBO is not established.

Comment & Discussion: -2 Bioengineered skin products and skin grafts are widely used in some areas, but their benefit has not been clearly established. Many clinicians will reserve the use of these relatively expensive treatments for ulcers that fail to respond to simpler approaches and yet bioengineered skin products have not been evaluated in such populations.

Comment & Discussion: -3 本篇review針對高壓氧、植皮等各種糖尿病足部潰瘍之治療方法進行探討，關鍵字及搜尋範圍拉到十分大故各種療法皆有許多篇paper被identified(高壓氧114篇，植皮72篇)，但最後對此兩種療法僅各評值6篇RCT，雖應可推論這幾篇為證據等級較高之paper，但評值的文章數或許過少而無法充分代表其療法之療效結論。 關於自體植皮方面僅有一篇文章被選出，並且是兩種植皮方法的比較，故未針對植皮本身之療效進行評值，而結論提出植皮的益處仍未清楚確立，或許是因以其篩選之方法，目前關於植皮療效之文章之嚴謹程度仍未達其篩選標準（文章中僅聲稱Reduction of tissue oedema, Hyperbaric oxygen, Resection 有療效）

Comment & Discussion: -4 回顧以(foot ulcer or diabetic foot) AND (skin graft or skin transplantation) 搜尋出的8篇相關randomized controlled trial文章中，雖大部分支持植皮之療效，但仍有少部份認為無明顯助益（2篇）。 (autologous dermal and epidermal grafts versus nonadherent paraffin gauze) The autologous tissue-engineered treatment exhibited improved healing in dorsal ulcers when compared with the current standard dressing. For plantar ulcers, the off-loading cast was presumably paramount and masked or nullified the effects of the autologous wound treatment.

Comment & Discussion: -5 針對此本次的臨床問題，未能搜尋到高壓氧及植皮兩者之療效比較的直觀研究，僅能由本篇review對兩者各自的療效性以較迂迴的方式對臨床個案作出外推性的決策底線：

Clinical bottom line 臨床決策底線 回到臨床個案情境 Clinical bottom line 臨床決策底線 對於糖尿病足部潰瘍患者，單純接受高壓氧治療仍可提高傷口復原能力，降低截肢機率 證據等級1A, 建議等級B

References: 1: Belov VV: [Effects of short-term immunosuppression on the engraftment of skin transplants at syndrome of the diabetic foot]. Vestn Khir Im I I Grek. 2007;166(5):32-5. 2: Puttirutvong P. Meshed skin graft versus split thickness skin graft in diabetic ulcer coverage. J Med Assoc Thai. 2004 Jan;87(1):66-72. 3: Caravaggi C: HYAFF 11-based autologous dermal and epidermal grafts in the treatment of noninfected diabetic plantar and dorsal foot ulcers: a prospective, multicenter, controlled, randomized clinical trial. Diabetes Care. 2003 Oct;26(10):2853-6 4: Hanft JR: Healing of chronic foot ulcers in diabetic patients treated with a human fibroblast-derived dermis. J Foot Ankle Surg. 2002 Sep-Oct;41(5):291-9.

References: 5: Veves A: Diabetic Foot Ulcer Study. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care. 2001 Feb;24(2):290-5. 6: Chang DW:Can a tissue-engineered skin graft improve healing of lower extremity foot wounds after revascularization? Ann Vasc Surg. 2000 Jan;14(1):44-9. 7: Naughton G:A metabolically active human dermal replacement for the treatment of diabetic foot ulcers. Artif Organs. 1997 Nov;21(11):1203-10 8: Sabolinski ML: Cultured skin as a ‘smart material’ for healing wounds: experience in venous ulcers. Biomaterials. 1996 Feb;17(3):311-20.

結 論 （標題 Title） Systemic HBO may improve the healing of of DM foot ulcer and reduce the incidence of major amputation Update By（下次更新日期）: Oct. 29, 2010

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