Randomized clinical trial and economic analysis of four-layer compression bandaging for venous ulcers

BACKGROUND: The aim of this study was to compare the cost-effectiveness of four-layer compression bandaging for venous leg ulcers with that of other available treatments. METHODS: In this pragmatic trial, 200 patients with a venous leg ulcer were randomized either to four-layer bandaging (intervention group; n = 100) or to continue their usual system of care (control group; n = 100). The follow-up for each patient was 12 weeks. Analysis was by intention to treat; the main outcome measures were time to healing and cost to the health board per leg healed. RESULTS: Baseline characteristics were well matched in the two groups. The Kaplan-Meier estimate of the healing rate at 3 months was 54 per cent with four-layer bandaging and 34 per cent in the control group. Throughout the 3 months, four-layer bandaging healed leg ulcers significantly earlier (P = 0.006). There was a significant reduction in the median cost per leg healed with four-layer bandaging (euro 210 versus euro 234; P = 0.040). CONCLUSION: Four-layer bandaging is currently the most effective method of treating venous leg ulcers in a community setting.     

Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers

OBJECTIVES: Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid. METHODS: This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment. RESULTS: Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment. CONCLUSION: Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.     

Chronic venous leg ulcers are associated with high levels of metalloproteinases‐9 and neutrophil gelatinase‐associated lipocalin

Venous ulcers are related to dysfunctions in extracellular matrix. Both matrix metalloproteinases (MMP) and neutrophil gelatinase‐associated lipocalin (NGAL) could play a role in the healing process in patients with chronic venous ulcers. We evaluated the role of MMP‐9 and NGAL in the healing process in venous ulceration. We performed an open‐label, parallel groups, single clinical center study. Patients with chronic venous leg ulcers represented the test group (Group I), whereas patients without chronic ulcers represented the control group (Group II). In Group I plasma and wound fluid samples were collected at the time of admission, at the time of the surgery, and at the follow‐up, while ulcer tissues were taken at the time of the surgery. In Group II, plasma and wound fluid were collected at admission and at the time of the surgery, whereas skin tissues were collected at the time of the surgery. Enzyme‐linked immunosorbent assay test was used to evaluate the levels of MMP‐9 and NGAL in plasma and wound fluid, whereas Western blot analysis was performed to estimate the expression of MMP‐9 and NGAL in tissues. Enzyme‐linked immunosorbent assay tests revealed significantly higher levels of MMP‐9 and NGAL in both plasma and wound fluid of patients with ulcers compared to patients without ulcers (p < 0.01). Moreover, Western blot analysis documented an increased expression of MMP‐9 and NGAL in biopsy tissue of patients with ulcers compared to patients without ulcers (p < 0.01). In conclusion MMP‐9 and NGAL may correlate with the clinical course of venous ulcers.     

Healing rates and cost efficacy of outpatient compression treatment for leg ulcers associated with venous insufficiency.

OBJECTIVE: Although newer techniques to promote the healing of leg ulcers associated with chronic venous insufficiency are promising, improved healing rates and cost effectiveness are unproven. We prospectively followed a series of patients who underwent treatment with outpatient compression for venous stasis ulcers without adjuvant techniques to determine healing rates and costs of treatment. METHODS: Two hundred fifty-two patients with clinical or duplex scan evidence of chronic venous insufficiency and active leg ulcers underwent treatment with ambulatory compression techniques. The patients were prospectively followed with wound measurements at 1-week to 2-week intervals, and the factors that were associated with delayed healing were determined. RESULTS: Of all the ulcers, 57% were healed at 10 weeks of treatment and 75% were healed at 16 weeks. Ultimately, 96% of the ulcers healed, and only 1 major amputation was necessitated (0.4%). Initial ulcer size and moderate arterial insufficiency (ankle brachial index, 0.5 to 0.8; n = 34) were factors that were independently associated with delayed healing (P <.01). Patient age, ulcer duration before treatment, and morbid obesity did not significantly affect healing times. The cost of 10 weeks of outpatient treatment with compression techniques ranged from $1444 to $2711. CONCLUSION: The treatment of venous stasis ulcers with compression techniques results in reliable, cost-effective healing in most patients. Current adjuvant techniques may prove to be useful but are likely to be cost effective only in a minority of cases, particularly in patients with large initial ulcer size or arterial insufficiency.     

The effect of ankle range of motion on venous ulcer healing rates

Limitation of ankle movement may contribute to calf muscle pump failure, which is thought to contribute to venous leg ulcer formation, which affects nearly 1 million Americans. We therefore wished to study ankle movement in patients with venous leg ulcers and its effect on healing. Using goniometry, we measured baseline ankle range of motion in venous leg ulcer patients from a Phase 2 dose‐finding study of an allogeneic living cell bioformulation. Two hundred twenty‐seven patients were enrolled in four active treatment groups and one standard‐care control group, all receiving compression therapy. Goniometry data from a control group of 49 patients without venous disease, from a previous study, was used for comparison. We found patients with active venous leg ulcers had significantly reduced ankle range of motion compared with the control group (p = 0.001). After 12 weeks of therapy, baseline ankle range of motion was not associated with healing, as there was no significant difference between healed and nonhealed groups, suggesting that ankle range of motion is not important in venous leg ulcer healing or, more likely, is overcome by compression. However, patients with venous ulcers located on the leg (as opposed to the ankle) had significantly higher ankle range of motion for plantar flexion and inversion (p = 0.021 and p = 0.034, respectively) and improved healing with both cell bioformulation and standard care (p = 0.011), suggesting that wound location is an important variable for ankle range of motion as well as for healing outcomes.     

Randomized clinical trial of three-layer paste and four-layer bandages for venous leg ulcers: Meyer FJ,McGuinness CL,Lagattolla NRF,et al. Br J Surg 2003;90:934-40

ConclusionThree-layer compressive bandages are slightly more effective than four-layer compressive bandages for healing venous leg ulcers.SummaryOne hundred thirty-three patients with venous ulcers treated in a single clinic were stratified according to ulcer size and then randomized to receive three-layer or four-layer bandages. Ulcers were stratified by calculating the maximum length and breadth of the ulcer and multiplying these values. Ulcers were grouped into small (>0.25–<2.5 cm²), medium (2.5-25 cm² ), and large (25-100 cm² ) groups. Ulcers smaller than 0.25 cm² or larger than 100 cm² were excluded. Patients were excluded if they had diabetes, connective tissue disorders, rheumatoid arthritis, or human immunodeficiency virus, or were positive for sickle cell disease.Three-layer bandages consisted of a hypoallergenic paste, followed by a compression bandage, followed by Tubigrip. Four-layer bandages were comprised of orthopedic wool, a crepe bandage followed by a compressive bandage, and finally a Coban bandage. Patients were followed up for 1 year. Time to complete healing, defined as “restoration of entirely unbroken skin integrity without any purulent discharge after removal of all scabs,” was the primary end point.Complete ulcer healing occurred in 80% of patients treated with three-layer bandages and 65% of patients treated with the four-layer bandaging technique (P = .031). The median time to complete healing was 12 and 16 weeks, respectively (P = .04). The difference in healing did not become apparent until after 20 weeks of treatment. Large venous ulcers were less likely to heal. The adverse effect of ulcer size on healing was apparent in both the three-layer and four-layer bandage groups. Previous venous thrombosis or popliteal reflux did not affect ulcer healing.CommentBoth four-layer and three-layer bandaging techniques are effective in management of venous leg ulcers, with three-layer bandages apparently slightly more efficacious. Neither technique is suitable for all patients. In some patients allergy will develop to the paste component of the three-layer bandage, and other patients find the four-layer bandage bulky and uncomfortable. Not all forms of compression therapy are suitable for all patients. Physician and patient willingness to explore alternative management techniques is crucial to success of conservative therapy of venous ulcers.     

Evaluation of vascular and metabolic deficiency in patients with large leg ulcers.

A consecutive series of 50 patients with large leg ulcers (surface area > 100 cm2) were investigated for evidence of arterial, venous and nutritional problems. Arterial insufficiency was found in 34%, venous reflux in 50%. A group of eight patients had no arterial or venous problem but had serious deficiencies of vitamin C and zinc. Arterial bypass was performed successfully in 15 of the 17 patients with arterial disease. All patients had a mesh split-skin graft. The 25 with venous incompetence had compression bandaging; in these patients the ulcer had healed on discharge but 10 had recurrent ulceration within 6 months. The leg ulcers in patients with corrected arterial insufficiency healed significantly more rapidly than those with venous incompetence. The ulcers in those with nutritional deficiency healed promptly after skin grafting and correction of the deficiency. It is important to be aware of arterial insufficiency and nutritional deficiency in patients with leg ulcers, as such deficiencies may contribute to the non-healing of an apparently straightforward leg ulcer.     

Pulse oximetry: a new tool to assess patients with leg ulcers

The objective of the study was to investigate pulse oximetry as a guide to assessing patients with leg ulcers before treatment. Graduated elastic compression is the treatment of choice for uncomplicated venous leg ulcers, but is contra-indicated in patients with significant arterial disease. The standard assessment of arterial insufficiency by Doppler ultrasound ankle branchial pressure index (ABPI) has shortcomings which prompted this investigation of pulse oximetry as a possible additional, or alternative, method of assessment of patients with leg ulcers, prior to treatment with compression. The study, carried out on a population of patients attending hospital leg ulcer clinics, was designed to evaluate pulse oximetry assessment in the selection and monitoring of patients with venous leg ulceration leading to a prospective controlled study of ulcer healing in groups of patients with reduced and normal ABPI, selected for compression therapy by pulse oximetry criteria. Outcome measurement required follow-up of patients selected for compression therapy by pulse oximetry to record time to healing and rate of healing of leg ulcers. Results from the study show a fair correlation between the toe-finger oximetry index (TFOI) and Doppler ABPI. There is no difference between ulcer healing in patients with reduced and normal ABPI selected for treatment on the basis of pulse oximetry maximum compression pressure (MCP). In conclusion, pulse oximetry is an aid to the selection of patients who will benefit from compression therapy, but would be excluded on the basis of Doppler ABPI.     

Developing skills in leg ulcer nursing: the lessons learned

The high treatment costs of inappropriate leg ulcer management are well referenced. Wide variations in practice have also been reported. A training programme for community nurses has been in place in Leicestershire and Rutland NHS Trust for five years. Its objective is to promote evidence-based leg ulcer management. The aim of this prospective audit was to assess and compare the effectiveness of the compression bandage systems used in the trust: the original Charing Cross system (August 1996 to September 1997) and Robinson's Ultra Four kit (October 1997 to December 1998). All patients with leg ulceration were assessed using the Leicestershire leg ulcer assessment form. This was submitted along with an audit tool to the tissue viability service in exchange for a 12-week supply of compression bandages. The audit form was resubmitted after each subsequent 12-week period until the patient either had healed or was withdrawn from the audit. Differences between the two groups in mobility, previous deep vein thrombosis, fixed ankle deformity, the male to female ratio, duration of ulcer and ulcer surface area were noted. Patients using the Ultra Four kit had faster healing times than those given the Charing Cross system, but this was not statistically significant. Cost comparisons between the previous dressing regimen and compression bandaging showed a significance difference (p < 0.001). There was also a significant reduction in nurse time (p < 0.001). The audit results showed that compression bandaging therapy was an effective method of achieving healing in patients with venous leg ulcers and that significant cost savings were made in terms of dressing cost and nurse time. Furthermore, there were potential benefits in continuing compression therapy for the group of non-healers.     

Does the Pattern of Venous Insufficiency Influence Healing of Venous Leg Ulcers after Skin Transplantation?

AIMS: this study aimed to investigate the influence of venous insufficiency on results in venous leg ulcers treated with ulcer excision, meshed split-skin transplantation and correction of superficial venous insufficiency in the wound area. DESIGN: retrospective cohort study. SETTING: Copenhagen Wound Healing Center. METHODS: in 113 patients with venous leg ulceration, examined preoperatively with colour Duplex scanning (CDS), prognostic factors of healing and recurrence within 1 year were analysed using logistic regression. RESULTS:cumulative 1-year healing rate was 65% (73 patients) and 13 (12%) had recurrence of ulceration 1 year postoperatively. Initial ulcer size (OR: 0.97(95% CI: 0.96-0.99)), minor local superficial venous surgery (OR: 2.38 (95% CI: 1.04-5.46)), sufficient popliteal vein (2.97 (1.05-8.42)) and non-compliance with compression therapy (OR: 0.27 (95% CI: 0.11-0.71)) influenced the prognosis of healing positively. No statistically significant differences in healing and recurrence between patients with isolated superficial and mixed superficial/deep venous insufficiency was found. CONCLUSION: non-healing venous leg ulcers can be treated with ulcer excision, meshed split-skin transplantation and correction of superficial venous insufficiency in the wound area with beneficial results irrespective of underlying pattern of venous insufficiency as determined by CDS.     

The impact of differential expression of extracellular matrix metalloproteinase inducer, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-2 and PDGF-AA on the chronicity of venous leg ulcers.

INTRODUCTION: Alteration in the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-2 (MMP-2), tissue inhibitors of matrix metalloproteinases (TIMP-2) and platelet derived growth factor (PDGF-AA) may contribute to poor healing in venous leg ulcers. AIM: The aim of this study is to determine the expression of EMMPRIN, MMP-2, TIMP-2 and PDGF-AA in the ulcer exudates and perivascular tissue of healing and non-healing chronic venous ulcers. PATIENTS, MATERIALS AND METHODS: Forty patients with chronic venous ulcers were included in this study, with a mean age of 60 years. Eleven patients were males and 29 were females. All patients had normal ankle brachial index and a venous ulcer of at least 8 weeks duration. Immuno-histochemistry using monoclonal antibodies to PDGF-AA, MMP-2, TIMP-2 and EMMPRIN was carried out on paraffin embedded punch biopsy skin specimens from the ulcer edge. Enzyme linked immunosorbent assay for PDGF, MMP-2 and TIMP-2 were carried out on wound fluids collected from patients. The ulcer size and character at the initial assessment and after 8 weeks were assessed to determine the status of ulcer healing. RESULTS: No significant difference was seen in the expression of TIMP-2, MMP-2 and EMMPRIN between the two groups. However, in the non-healing group high levels of MMP-2 and low levels of TIMP-2 in the wound fluid suggest a strong correlation of these two markers in the state of healing. Analysis of wound fluid by ELISA demonstrated high PDGF-AA in the healing group (p = 0.021). Significantly increased levels of PDGF-AA (p<0001) was noted in the perivascular area on immuno-histochemistry of healing ulcers. These data suggest that PDGF-AA plays an important role in healing of venous ulcers. CONCLUSION: Non-healing venous ulcers are associated with greater activity MMP-2 activity. The ratio of MMPs to their inhibitors TIMPs, dictate the rate of healing of the ulcers. PDGF-AA activity is associated with ulcer healing, though the mechanism is unclear. EMMPRIN expression in chronic venous ulcers probably parallels the chronicity of the condition rather than propagate it. However, further studies with larger samples are needed.     

A prospective randomised trial of four-layer versus short stretch compression bandages for the treatment of venous leg ulcers.

This trial was undertaken to examine the safety and efficacy of four-layer compared with short stretch compression bandages for the treatment of venous leg ulcers within the confines of a prospective, randomised, ethically approved trial. Fifty-three patients were recruited from a dedicated venous ulcer assessment clinic and their individual ulcerated limbs were randomised to receive either a four-layer bandage (FLB)(n = 32) or a short stretch bandage (SSB)(n = 32). The endpoint was a completely healed ulcer. However, if after 12 weeks of compression therapy no healing had been achieved, that limb was withdrawn from the study and deemed to have failed to heal with the prescribed bandage. Leg volume was measured using the multiple disc model at the first bandaging visit, 4 weeks later, and on ulcer healing. Complications arising during the study were recorded. Data from all limbs were analysed on an intention to treat basis; thus the three limbs not completing the protocol were included in the analysis. Of the 53 patients, 50 completed the protocol. At 1 year the healing rate was FLB 55% and SSB 57% (chi 2 = 0.0, df = 1, P = 1.0). Limbs in the FLB arm of the study sustained one minor complication, whereas SSB limbs sustained four significant complications. Leg volumes reduced significantly after 4 weeks of compression, but subsequent volume changes were insignificant. Ulcer healing rates were not influenced by the presence of deep venous reflux, post-thrombotic deep vein changes nor by ulcer duration. Although larger ulcers took longer to heal, the overall healing rates for large (> 10 cm2) and small (10 cm2 or less) ulcers were comparable. Four-layer and short stretch bandages were equally efficacious in healing venous ulcers independent of pattern of venous reflux, ulcer area or duration. FLB limbs sustained fewer complications than SSB.     

The K-Four bandage system: evaluating its effectiveness on recalcitrant venous leg ulcers

This evaluation examined the effectiveness of the K-Four (Parema) high compression bandage system on 50 patients with recalcitrant 'hard-to-heal' venous leg ulcers and relates the outcome to an earlier randomised study which compared three other four-layer bandage systems. Twelve-week healing rates were 53.2% in the current series, which included patients with poor mobility, large ulcers and long pretreatment ulcer duration, rising to 69.5% at 20 weeks. When account was taken of known risk factors for delayed ulcer healing, no significant difference could be identified between between either K-Four or the earlier evaluated bandages, which included the original Charing Cross system, where the overall healing rates were 64.5% and 80%, respectively, at 12 and 20 weeks. It would seem more likely that treatment outcome is related to patient risk factors for delayed healing and bandaging expertise than to the bandage system employed.     

Management of mixed arterial and venous leg ulcers

BACKGROUND: The aim was to assess healing in patients with mixed arterial and venous leg ulcers after protocol-driven treatment in a specialist leg ulcer clinic. METHODS: The study included consecutive patients referred with leg ulceration and venous reflux over 6 years. Legs without arterial disease (ankle : brachial pressure index (ABPI) above 0.85) were treated with multilayer compression bandaging and patients with severe disease (ABPI 0.5 or less) were considered for immediate revascularization. Those with moderate arterial compromise (ABPI above 0.5 up to 0.85) were initially managed with supervised modified compression and considered for revascularization if their ulcer did not heal. Healing rates were determined using life-table analysis. RESULTS: Of 2011 ulcerated legs, 1416 (70.4 per cent) had venous reflux. Of these 1416, 193 (13.6 per cent) had moderate and 31 (2.2 per cent) had severe arterial disease. Healing rates by 36 weeks were 87, 68 and 53 per cent for legs with insignificant, moderate and severe arterial disease respectively (P < 0.001). Seventeen legs with moderate and 15 with severe arterial disease were revascularized. Of these, ulcers healed in four legs with moderate and seven with severe disease within 36 weeks of revascularization (P = 0.270). Combined 30-day mortality for revascularization was 6.5 per cent. CONCLUSION: A protocol including supervised modified compression and selective revascularization achieved good healing rates for mixed arterial and venous leg ulceration.     

Chemokine and inflammatory cytokine changes during chronic wound healing.

Wound healing is a complex process resulting from an interplay of processes including coagulation, inflammation, angiogenesis, and epithelialization. The chemokine family has been shown to contain members that are potent regulators of many of these pathways. Because we have previously shown that chemokines "pool" in biologic wound dressings, we studied the levels of CXC and CC chemokines, along with key inflammatory mediators, serially from a group of patients undergoing therapy for chronic venous leg ulcers. After 8 weeks, all patients had marked clinical healing of their ulcers (median 63.3% reduction in size) with two of 10 completely healed. Wound fluids extracted from dressings showed high levels of platelet factor-4 and interferon-gamma-inducible protein, with a trend toward increases in the ratio of the sums of the angiogenic versus angiostatic CXC chemokines (p = 0.082) in the tissues collected from the center of the ulcers during wound closure. Neutrophil-activating peptide-2 and interleukin-8 accounted for the most changes in wound fluid angiogenic chemokines, with significant differences both as compared with baseline levels and with patients' plasma level noted at various time points between weeks 0 and 8. The level of angiostatic chemokines, interferon-y inducible protein 10 and platelet-activating-4, fell most significantly between weeks 0 and 3 as compared with plasma levels. The observed shift toward angiogenic CXC chemokines suggests that effective healing in chronic venous insufficiency ulcers appears to "move" the ulcer bed toward a state more conducive to epithelialization,characteristic of the proliferative phase of wound healing. CC chemokines were also elevated at baseline in the wound fluid samples as compared with the patients' plasma levels. Macrophage inflammatory protein-1 (3 and regulated on activation, normal T expressed and secreted (RANTES) levels decreased with healing, whereas there were significant increases in the tissue levels of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 a over the first 4 weeks of therapy (p< or = 0.05 for both). Coincident with these changes was a steady increase in the ratio of interleukin-1 R/interleukin-1 receptor antagonist protein in the ulcer center tissues, which also correlated with healing (p < 0 .05) as compared with a decreasing ratio at the ulcer edge, and a biphasic response in the wound fluids. These findings suggest that advanced wound care techniques help move the ulcer from a chronic inflammatory state into one more characteristic of the late inflammatory/early proliferative phase of wound healing. Chemokines may play a critical role in the pathogenesis of chronic venous ulcers through their effects on angiogenesis and/or the progression of inflammatory reactions at the site of injury.     

Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines

Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non‐infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme‐linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP‐1 and MMP‐8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP‐2 and MMP‐9. We also documented higher levels of interleukin (IL)‐1, IL‐6, IL‐8, vascular endothelial growth factor and tumour necrosis factor‐alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.     

Randomized clinical trial of three‐layer tubular bandaging system for venous leg ulcers

The safety and efficacy of three‐layer (3L) tubular bandaging as a treatment for venous ulcer healing has not been evaluated despite its use in many clinical settings to treat people with venous leg ulcers. We evaluated the safety and efficacy of 3L tubular bandage compared with short‐stretch compression bandage to heal venous ulcers in a multicenter, open‐label, parallel‐group, randomized controlled trial. We randomized 45 patients with venous leg ulcers of up to 20 cm² area and an ankle brachial pressure index of >0.8 from hospital outpatient wound clinics in Victoria and Queensland, Australia. We measured time to healing and percentage reduction of wound size from baseline to week 12. Secondary outcomes were proportion of ulcers healed, self‐reported compliance of compression bandage, and health‐related quality of life, costs, recurrence rates, and adverse events. A total of 27 ulcers healed, the proportion of healed ulcers was higher for the 3L group (17/23 [74%] vs. 10/22 [46%]) (p = 0.05). Reported bandage tolerance at all treatment visits was 21 (91%) in 3L group vs. 17 (73%) (p = 0.10). There was no difference between the groups in adverse events. Costs were substantially less in 3L group.     

Role of matrix metalloproteinases in non‐healing venous ulcers

Chronic venous ulceration (CVU) of the lower limbs is a common condition affecting 1% of the adult population in Western countries, which is burdened with a high complication rate and a marked reduction in the quality of life often due to prolonged healing time. Several metalloproteinases (MMPs) such as MMP‐9 together with neutrophil gelatinase‐associated lipocalin (NGAL) appear to be involved in the onset and healing phases of venous ulcer, but it is still unclear how many biochemical components are responsible for prolonged healing time in those ulcers. In this study, we evaluate the role of MMP‐1 and MMP‐8 in long lasting and refractory venous ulcers. In a 2‐year period we enroled 45 patients (28 female and 17 male, median age 65) with CVU. The enroled population was divided into two groups: group I were patients with non‐healing ulcers (ulcers that had failed to heal for more than 2 months despite appropriate treatments) and group II were patients with healing ulcers (ulcers in healing phases). MMP‐1 and MMP‐8 were measured in fluids and tissues of healing and non‐healing ulcers by means of enzyme‐linked immunosorbent assay (ELISA) and Western blot analysis, respectively. In particular the patterns of the collagenases MMP‐1 and MMP‐8 in healing wounds were distinct, with MMP‐8 appearing in significantly greater amounts especially in the non‐healing group. Our findings suggest that MMP‐1, and MMP‐8 are overexpressed in long lasting CVU. Therefore, this dysregulation may represent the main cause of the pathogenesis of non‐healing CVU.     

A prospective,open, multicentre study to evaluate a new gelling fibre dressing containing silver in the management of venous leg ulcers

This study investigated the performance of a new gelling fibre dressing containing silver (DURAFIBER? Ag; Smith & Nephew, Hull, UK) in moderate to highly exuding venous leg ulcers with one or more clinical signs of infection. Fourteen patients with venous leg ulceration of median ulcer duration 12·5 weeks, recruited from three centres in South Africa, received treatment with the new dressing for a maximum of 8 weeks. Multilayer compression bandaging was used for all patients, at the majority of assessments. The objectives of this study were to assess the clinical acceptability of the dressing in terms of the following characteristics: antimicrobial properties, the progress of the wound towards healing, wear time, exudate management, conformability, patient comfort, pain on application, pain on removal and dressing integrity. The new dressing was rated as clinically acceptable for all characteristics, for all 14 patients (100%). It was easy to apply and remove; in 96·8% of removals, the dressing stayed intact on removal and could be removed in one piece. Fifty per cent of the wounds healed within the 8‐week study duration; between baseline and final assessment, the median percentage reduction in wound area was 98·2% and the median percentage reduction in devitalised tissue was 78%. Exudate levels and wound pain were significantly improved at final assessment compared to baseline assessment, and an increase in the number of patients with healthy peri‐wound skin between baseline and final assessment was observed. A reduction in bioburden and signs of clinical infection and an improvement in quality of life were observed over the 8‐week period. The average wear time was 6·4 days. This study supports the use of new dressing in the management of moderately to highly exuding venous leg ulcers with clinical signs of infection.     

A multicentre randomised controlled trial evaluating the efficacy of dehydrated human amnion/chorion membrane (EpiFix®) allograft for the treatment of venous leg ulcers

A randomised, controlled, multicentre clinical trial was conducted to evaluate the efficacy of dehydrated human amnion/chorion membrane (EpiFix) allograft as an adjunct to multilayer compression therapy for the treatment of non‐healing full‐thickness venous leg ulcers. We randomly assigned 109 subjects to receive EpiFix and multilayer compression (n = 52) or dressings and multilayer compression therapy alone (n = 57). Patients were recruited from 15 centres around the USA and were followed up for 16 weeks. The primary end point of the study was defined as time to complete ulcer healing. Participants receiving weekly application of EpiFix and compression were significantly more likely to experience complete wound healing than those receiving standard wound care and compression (60% versus 35% at 12 weeks, P = 0·0128, and 71% versus 44% at 16 weeks, P = 0·0065). A Kaplan–Meier analysis was performed to compare the time‐to‐healing performance with or without EpiFix, showing a significantly improved time to healing using the allograft (log‐rank P = 0·0110). Cox regression analysis showed that subjects treated with EpiFix had a significantly higher probability of complete healing within 12 weeks (HR: 2·26, 95% confidence interval 1·25–4·10, P = 0·01) versus without EpiFix. These results confirm the advantage of EpiFix allograft as an adjunct to multilayer compression therapy for the treatment of non‐healing, full‐thickness venous leg ulcers.