Norman Gill, Westby Maggie J, Rithalia Amber D, Stubbs Nikki, Soares Marta O, Dumville Jo C
Division of Nursing, Midwifery and Social Work, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Jean McFarlane Building, Oxford Road, Manchester, UK, M13 9PL.
Cochrane Database Syst Rev. 2018 Jun 15;6(6):CD012583. doi: 10.1002/14651858.CD012583.pub2.
BACKGROUND: Venous leg ulcers are open skin wounds on the lower leg which can be slow to heal, and are both painful and costly. The point prevalence of open venous leg ulcers in the UK is about 3 cases per 10,000 people, and many people experience recurrent episodes of prolonged ulceration. First-line treatment for venous leg ulcers is compression therapy, but a wide range of dressings and topical treatments are also used. This diversity of treatments makes evidence-based decision-making challenging, and a clear and current overview of all the evidence is required. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents. OBJECTIVES: To assess the effects of (1) dressings and (2) topical agents for healing venous leg ulcers in any care setting and to rank treatments in order of effectiveness, with assessment of uncertainty and evidence quality. SEARCH METHODS: In March 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. We updated this search in March 2018; as a result several studies are awaiting classification. SELECTION CRITERIA: We included published or unpublished randomised controlled trials (RCTs) that enrolled adults with venous leg ulcers and compared the effects of at least one of the following interventions with any other intervention in the treatment of venous leg ulcers: any dressing, or any topical agent applied directly to an open venous leg ulcer and left in situ. We excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factors and other biological agents, larval therapy and treatments such as laser, heat or ultrasound. Studies were required to report complete wound healing to be eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction. We conducted this NMA using frequentist meta-regression methods for the efficacy outcome; the probability of complete healing. We assumed that treatment effects were similar within dressings classes (e.g. hydrocolloid, foam). We present estimates of effect with their 95% confidence intervals (CIs) for individual treatments focusing on comparisons with widely used dressing classes, and we report ranking probabilities for each intervention (probability of being the best, second best, etc treatment). We assessed the certainty (quality) of the body of evidence using GRADE for each network comparison and for the network as whole. MAIN RESULTS: We included 78 RCTs (7014 participants) in this review. Of these, 59 studies (5156 participants, 25 different interventions) were included in the NMA; resulting in 40 direct contrasts which informed 300 mixed-treatment contrasts.The evidence for the network as a whole was of low certainty. This judgement was based on the sparsity of the network leading to imprecision and the general high risk of bias in the included studies. Sensitivity analyses also demonstrated instability in key aspects of the network and results are reported for the extended sensitivity analysis. Evidence for individual contrasts was mainly judged to be low or very low certainty.The uncertainty was perpetuated when the results were considered by ranking the treatments in terms of the probability that they were the most effective for ulcer healing, with many treatments having similar, low, probabilities of being the best treatment. The two most highly-ranked treatments both had more than 50% probability of being the best (sucralfate and silver dressings). However, the data for sucralfate was from one small study, which means that this finding should be interpreted with caution. When exploring the data for silver and sucralfate compared with widely-used dressing classes, there was some evidence that silver dressings may increase the probability of venous leg ulcer healing, compared with nonadherent dressings: RR 2.43, 95% CI 1.58 to 3.74 (moderate-certainty evidence in the context of a low-certainty network). For all other combinations of these five interventions it was unclear whether the intervention increased the probability of healing; in each case this was low- or very low-certainty evidence as a consequence of one or more of imprecision, risk of bias and inconsistency. AUTHORS' CONCLUSIONS: More research is needed to determine whether particular dressings or topical agents improve the probability of healing of venous leg ulcers. However, the NMA is uninformative regarding which interventions might best be included in a large trial, largely because of the low certainty of the whole network and of individual comparisons.The results of this NMA focus exclusively on complete healing; whilst this is of key importance to people living with venous leg ulcers, clinicians may wish to take into account other patient-important outcomes and factors such as patient preference and cost.
背景:下肢静脉性溃疡是小腿部的开放性皮肤伤口,愈合缓慢,既疼痛又耗费高昂。英国开放性下肢静脉性溃疡的现患率约为万分之三,许多人经历过溃疡长期反复发作。下肢静脉性溃疡的一线治疗方法是加压治疗,但也会使用多种敷料和局部治疗。治疗方法的多样性使得基于证据的决策具有挑战性,因此需要对所有证据进行清晰且最新的概述。本综述是一项网状Meta分析(NMA),评估与替代敷料和局部用药相关的溃疡完全愈合的概率。 目的:评估(1)敷料和(2)局部用药在任何护理环境下治疗下肢静脉性溃疡的效果,并按有效性对治疗方法进行排序,同时评估不确定性和证据质量。 检索方法:2017年3月,我们检索了Cochrane伤口专业注册库、Cochrane对照试验中央注册库(CENTRAL)、Ovid MEDLINE、Ovid MEDLINE(在研及其他未索引引文)、Ovid Embase和EBSCO CINAHL Plus。我们还浏览了相关纳入研究的参考文献列表以及综述、Meta分析、指南和卫生技术报告,以识别其他研究。对语言、出版日期或研究环境没有限制。我们在2018年3月更新了此检索;因此有几项研究正在等待分类。 选择标准:我们纳入了已发表或未发表的随机对照试验(RCT),这些试验纳入了患有下肢静脉性溃疡的成年人,并比较了以下至少一种干预措施与治疗下肢静脉性溃疡的任何其他干预措施的效果:任何敷料,或直接应用于开放性下肢静脉性溃疡并留置原位的任何局部用药。我们将附着于外部设备的敷料排除在本综述之外,如负压伤口治疗、皮肤移植、生长因子和其他生物制剂、幼虫疗法以及激光、热或超声等治疗。研究需报告伤口完全愈合情况才有资格纳入。 数据收集与分析:两位综述作者独立进行研究选择、“偏倚风险”评估和数据提取。我们使用频率学派Meta回归方法对疗效结局(完全愈合的概率)进行此网状Meta分析。我们假设同一类敷料(如水胶体、泡沫敷料)内的治疗效果相似。我们给出了个体治疗效果的估计值及其95%置信区间(CI),重点是与广泛使用的敷料类别的比较,并且我们报告了每种干预措施的排序概率(成为最佳、次佳等治疗的概率)。我们使用GRADE对每个网状比较以及整个网状结构评估证据的确定性(质量)。 主要结果:我们在本综述中纳入了78项RCT(7014名参与者)。其中,59项研究(5156名参与者,25种不同干预措施)纳入了网状Meta分析;产生了40个直接对比,为300个混合治疗对比提供了信息。整个网状结构的证据确定性较低。这一判断基于网状结构的稀疏性导致的不精确性以及纳入研究中普遍存在的高偏倚风险。敏感性分析也表明网状结构的关键方面不稳定,并报告了扩展敏感性分析的结果。个体对比的证据主要被判定为低或极低确定性。当根据溃疡愈合最有效的概率对治疗方法进行排序来考虑结果时,不确定性依然存在,许多治疗方法成为最佳治疗的概率相似且较低。排名最高的两种治疗方法成为最佳治疗的概率均超过50%(硫糖铝和含银敷料)。然而,硫糖铝的数据来自一项小型研究,这意味着这一发现应谨慎解读。在将含银敷料和硫糖铝的数据与广泛使用的敷料类别进行比较时,有一些证据表明,与非粘贴性敷料相比,含银敷料可能会增加下肢静脉性溃疡愈合的概率:RR 2.43,95%CI 1.58至3.74(在低确定性网状结构背景下为中等确定性证据)。对于这五种干预措施的所有其他组合,尚不清楚该干预措施是否会增加愈合概率;在每种情况下,由于不精确性、偏倚风险和不一致性中的一项或多项原因,这都是低或极低确定性证据。 作者结论:需要更多研究来确定特定的敷料或局部用药是否能提高下肢静脉性溃疡愈合的概率。然而,网状Meta分析对于哪些干预措施可能最适合纳入大型试验并无指导意义,主要是因为整个网状结构以及个体比较的确定性较低。本网状Meta分析的结果仅关注完全愈合;虽然这对下肢静脉性溃疡患者至关重要,但临床医生可能希望考虑其他对患者重要的结局和因素,如患者偏好和成本。
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