Safety and performance evaluation of a next‐generation antimicrobial dressing in patients with chronic venous leg ulcers

The objective of this study was to investigate the safety and performance of AQUACEL? Ag+ dressing, a wound dressing containing a combination of anti‐biofilm and antimicrobial agents, in the management of chronic wounds. Patients (n = 42) with venous leg ulcers exhibiting signs of clinical infection were treated for 4 weeks with AQUACEL? Ag+ dressing, followed by management with AQUACEL? wound dressings for 4 weeks. Wound progression, wound size, ulcer pain and clinical evolution of the wound were assessed for up to 8 weeks. Adverse events were recorded throughout the study. AQUACEL? Ag+ dressing had an acceptable safety profile, with only one patient discontinuing from the study, because of a non‐treatment‐related adverse event. After 8 weeks, substantial wound improvements were observed: 5 patients (11·9%) had healed ulcers and 32 patients (76·2%) showed improvement in ulcer condition. The mean ulcer size had reduced by 54·5%. Patients reported less pain as the study progressed. Notable improvements were observed in patients with ulcers that were considered to require treatment with systemic antibiotics or topical antimicrobials at baseline (n = 10), with a mean 70·2% reduction in wound area. These data indicate that AQUACEL? Ag+ dressing has an acceptable safety profile in the management of venous leg ulcers that may be impeded by biofilm.     

Systematic review and meta‐analysis of the efficacy of epidermal grafting for wound healing

Autologous skin grafting is an important method for wound coverage; however, it is an invasive procedure and can cause donor site morbidity. Epidermal grafting (EG) enables epidermal transfer to wounds with minimal donor site morbidity. However, data to date have been heterogeneous. This study aims to synthesise the current evidence on EG for wound healing to establish the efficacy of this surgical technique. A comprehensive search in the MEDLINE, EMBASE and CENTRAL databases was conducted. The endpoints assessed were proportion of wounds healed and mean wound‐healing time. This systematic review was conducted and reported according to the Meta‐Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We identified 1568 articles, of which seven articles were included in this review – a total of 209 wounds in 190 patients. The mean wound duration was 17·06 weeks (95% CI 8·57–25·55). Of these, 71·5% (95% CI 56·7–84·2) of the wounds achieved complete healing. Mean time for complete wound healing was 5·53 weeks (95% CI 3·18–7·88). The mean donor site healing time was 7·48 days (95% CI 4·83–10·13), with no reported donor site morbidity. The current data are small and lack level 1 evidence.     

Treatment of chronic diabetic lower leg ulcers with activated protein C: a randomised placebo‐controlled,double‐blind pilot clinical trial

Lower leg ulcers are a serious and long‐term complication in patients with diabetes and pose a major health concern because of the increasing number of patients diagnosed with diabetes each year. This study sought to evaluate the clinical benefit of topical activated protein C (APC) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either APC (N = 6) or physiological saline (placebo; N = 6) in a randomised, placebo‐controlled, double‐blind pilot clinical trial. Treatment was administered topically, twice weekly for 6 weeks with final follow‐up at 20 weeks. Wound area was significantly reduced to 34·8 ± 16·4% of week 0 levels at 20 weeks in APC‐treated wounds (p = 0·01). At 20 weeks, three APC‐treated wounds had completely healed, compared to one saline‐treated wound. Full‐thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following APC treatment. Patient stress scores were also significantly reduced following APC treatment (p < 0·05), demonstrating improved patient quality of life as assessed by the Cardiff Wound Impact Questionnaire. This pilot trial suggests that APC is a safe topical agent for healing chronic lower leg ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial.     

Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a prospective,randomised, controlled,multi‐centre comparative study examining clinical efficacy and cost

Advanced therapies such as bioengineered skin substitutes (BSS) and dehydrated human amnion/chorion membrane (dHACM) have been shown to promote healing of chronic diabetic ulcers. An interim analysis of data from 60 patients enrolled in a prospective, randomised, controlled, parallel group, multi‐centre clinical trial showed that dHACM (EpiFix®, MiMedx Group Inc., Marietta, GA) is superior to standard wound care (SWC) and BSS (Apligraf®, Organogenesis, Inc., Canton, MA) in achieving complete wound closure within 4–6 weeks. Rates and time to closure at a longer time interval and factors influencing outcomes remained unassessed; therefore, the study was continued in order to achieve at least 100 patients. With the larger cohort, we compare clinical outcomes at 12 weeks in 100 patients with chronic lower extremity diabetic ulcers treated with weekly applications of Apligraf (n = 33), EpiFix (n = 32) or SWC (n = 35) with collagen‐alginate dressing as controls. A Cox regression was performed to analyse the time to heal within 12 weeks, adjusting for all significant covariates. A Kaplan–Meier analysis was conducted to compare time‐to‐heal within 12 weeks for the three treatment groups. Clinical characteristics were well matched across study groups. The proportion of wounds achieving complete closure within the 12‐week study period were 73% (24/33), 97% (31/32), and 51% (18/35) for Apligraf, EpiFix and SWC, respectively (adjusted P = 0·00019). Subjects treated with EpiFix had a very significant higher probability of their wounds healing [hazard ratio (HR: 5·66; adjusted P: 1·3 x 10^?7] compared to SWC alone. No difference in probability of healing was observed for the Apligraf and SWC groups. Patients treated with Apligraf were less likely to heal than those treated with EpiFix [HR: 0·30; 95% confidence interval (CI): 0·17–0·54; unadjusted P: 5·8 x 10^?5]. Increased wound size and presence of hypertension were significant factors that influenced healing. Mean time‐to‐heal within 12 weeks was 47·9 days (95% CI: 38·2–57·7) with Apligraf, 23·6 days (95% CI: 17·0–30·2) with EpiFix group and 57·4 days (95%CI: 48·2–66·6) with the SWC alone group (adjusted P = 3·2 x 10^?7). Median number of grafts used per healed wound were six (range 1–13) and 2·5 (range 1–12) for the Apligraf and EpiFix groups, respectively. Median graft cost was $8918 (range $1,486–19,323) per healed wound for the Apligraf group and $1,517 (range $434–25,710) per healed wound in the EpiFix group (P < 0·0001). These results provide further evidence of the clinical and resource utilisation superiority of EpiFix compared to Apligraf for the treatment of lower extremity diabetic wounds.     

Effectiveness of an acellular synthetic matrix in the treatment of hard‐to‐heal leg ulcers

Hard‐to‐heal leg ulcers are a major cause of morbidity in the elderly population. Despite improvements in wound care, some wounds will not heal and they present a significant challenge for patients and health care providers. A multi‐centre cohort study was conducted to evaluate the effectiveness and safety of a synthetic, extracellular matrix protein as an adjunct to standard care in the treatment of hard‐to‐heal venous or mixed leg ulcers. Primary effectiveness criteria were (i) reduction in wound size evaluated by percentage change in wound area and (ii) healing assessed by number of patients healed by end of the 12 week study. Pain reduction was assessed as a secondary effectiveness criteria using VAS. A total of 45 patients completed the study and no difference was observed between cohorts for treatment frequency. Healing was achieved in 35·6% and wound size decreased in 93·3% of patients. Median wound area percentage reduction was 70·8%. Over 50% of patients reported pain on first visit and 87·0% of these reported no pain at the end of the study. Median time to first reporting of no pain was 14 days after treatment initiation. The authors consider the extracellular synthetic matrix protein an effective and safe adjunct to standard care in the treatment of hard‐to‐heal leg ulcers.     

Analysis of pressure ulcer wound fluid using two‐dimensional electrophoresis

The incidence rate of pressure ulcers in the USA ranges from 0·4% to 38% in acute care settings and from 2·2% to 23·9% in long‐term care settings, and their treatment costs are in the billions of dollars yearly. The proteome of wound fluid may contain early indicators or biomarkers associated with healing in pressure ulcers that would enable treatment regimes to be optimised for each individual. Wound fluid was collected from the interior and periphery of 19 chronic pressure ulcers at 15 time points during 42 days for an analysis of protein expression. Proteins were fractionated using two‐dimensional polyacrylamide gel electrophoresis. A comparison of the spot distributions indicates a biochemical difference between the interior and the periphery of wounds. Pressure ulcers that healed show a greater number of spots for interior and peripheral locations combined over time when compared with wounds that did not heal. Using this technique, protein S100A9 was identified as a potential biomarker of wound healing. The identification of differences within the proteome of healing versus non healing pressure ulcers could have great significance in the use of current treatments, as well as the development of new therapeutic interventions.     

Efficacy and safety of a gauze pad containing hyaluronic acid in treatment of leg ulcers of venous or mixed origin: a double‐blind,randomised, controlled trial

Topical hyaluronic acid (HA) is routinely used in the local treatment of chronic wounds, but few data have been reported to date. A 60‐day double‐blind, randomised, controlled superiority trial was designed to investigate the efficacy and safety of a gauze pad containing HA in local treatment of venous leg ulcers, compared with its neutral vehicle. The primary endpoint was the percentage of wound size reduction after 45 days. Totally 89 patients were included. At day 45, the percentage of ulcer surface reduction was significantly greater in the HA group (73 ± 4·6%) versus neutral vehicle group (46 ± 9·6%) (P = 0·011). The number of healed ulcers was significantly higher in the HA group at day 45 (31·1% versus 9·3% respectively) and day 60 (37·8% versus 16·3% respectively; P < 0·05). At day 30, pain intensity based on visual analogue scale was significantly lower in the HA group (12·4 mm ± 2·6 versus 22·8 mm ± 3·8; P = 0·026). Tolerance of both treatments was comparable in the two groups. HA gauze pad, in local treatment of venous leg ulcers, was significantly more effective than the neutral vehicle on wound size reduction, healed ulcers rate and pain management with a good safety profile.     

The effectiveness of intralesional injection of platelet‐rich plasma in accelerating the healing of chronic ulcers: an experimental and clinical study

The purpose of this prospective experimental and clinical study is to evaluate the effectiveness of the intralesional injection of platelet‐rich plasma (PRP), in the management of non‐healing chronic wounds. Skin defects were created in the ears of 20 white New Zealand rabbits. In the study group, autologous PRP was injected intralesionally. The control group was treated conservatively. Nineteen out of 20 cases of the study group healed within a mean time of 24·9 days. In the control group, seven defects healed within a mean period of 26·7 days, seven ulcers did not heal at day 28 and in six cases a full thickness ear defect was recorded. For a 3‐year period, 26 patients with chronic ulcers underwent surgical debridement and intralesional injection of PRP. A histological study was performed before and 7 days after PRP injection. Ten patients healed within a mean period of 7 weeks. In 16 cases, PRP prepared the wound bed for the final and simpler reconstructive procedure. Intralesional injection is a newly described method for application of PRP and represents an effective therapeutic option when dealing with non‐healing wounds.     

Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing

HYPOTHESIS: In patients with diabetic foot and pressure ulcers, early intervention with biological therapy will either halt progression or result in rapid healing of these chronic wounds. DESIGN: In a prospective nonrandomized case series, 23 consecutive patients were treated with human skin equivalent (HSE) after excisional debridement of their wounds. SETTING: A single university teaching hospital and tertiary care center. PATIENTS AND METHODS: Twenty-three consecutive patients with a total of 41 wounds (1.0-7.5 cm in diameter) were treated with placement of HSE after sharp excisional debridement. All patients with pressure ulcers received alternating air therapy with zero-pressure alternating air mattresses. MAIN OUTCOME MEASURE: Time to 100% healing, as defined by full epithelialization of the wound and by no drainage from the site. RESULTS: Seven of 10 patients with diabetic foot ulcers had complete healing of all wounds. In these patients 17 of 20 wounds healed in an average of 42 days. Seven of 13 patients with pressure ulcers had complete healing of all wounds. In patients with pressure ulcers, 13 of 21 wounds healed in an average of 29 days. All wounds that did not heal in this series occurred in patients who had an additional stage IV ulcer or a wound with exposed bone. Twenty-nine of 30 wounds that healed did so after a single application of the HSE. CONCLUSIONS: In diabetic ulcers and pressure ulcers of various durations, the application of HSE with the surgical principles used in a traditional skin graft is successful in producing healing. The high success rate with complete closure in these various types of wounds suggests that HSE may function as a reservoir of growth factors that also stimulate wound contraction and epithelialization. If a wound has not fully healed after 6 weeks, a second application of HSE should be used. If the wound is not healing, an occult infection is the likely cause. All nonischemic diabetic foot and pressure ulcers that are identified and treated early with aggressive therapy (including antibiotics, off-loading of pressure, and biological therapy) will not progress.     

A prospective,randomised comparative study of weekly versus biweekly application of dehydrated human amnion/chorion membrane allograft in the management of diabetic foot ulcers

The aim of this study is to determine if weekly application of dehydrated human amnion/chorion membrane allograft reduce time to heal more effectively than biweekly application for treatment of diabetic foot ulcers. This was an institutional review board‐approved, registered, prospective, randomised, comparative, non‐blinded, single‐centre clinical trial. Patients with non‐infected ulcers of ≥ 4 weeks duration were included for the study. They were randomised to receive weekly or biweekly application of allograft in addition to a non‐adherent, moist dressing with compressive wrapping. All wounds were offloaded. The primary study outcome was mean time to healing. Overall, during the 12‐week study period, 92·5% (37/40) ulcers completely healed. Mean time to complete healing was 4·1 ± 2·9 versus 2·4 ± 1·8 weeks (P = 0·039) in the biweekly versus weekly groups, respectively. Complete healing occurred in 50% versus 90% by 4 weeks in the biweekly and weekly groups, respectively (P = 0·014). Number of grafts applied to healed wounds was similar at 2·4 ± 1·5 and 2·3 ± 1·8 for biweekly versus weekly groups, respectively (P = 0·841). These results validate previous studies showing that the allograft is an effective treatment for diabetic ulcers and show that wounds treated with weekly application heal more rapidly than with biweekly application. More rapid healing may decrease clinical operational costs and prevent long‐term medical complications.     

Health economic burden that different wound types impose on the UK's National Health Service

The aim of this study was to estimate the patterns of care and annual levels of health care resource use attributable to the management of different wound types by the UK's National Health Service (NHS) in 2012/2013 and the annual costs incurred by the NHS in managing them. This was a retrospective cohort analysis of the records of 2000 patients in The Health Improvement Network (THIN) Database. Patients' characteristics, wound‐related health outcomes and all health care resource use were quantified, and the total NHS cost of patient management was estimated at 2013/2014 prices. The NHS managed an estimated 2·2 million patients with a wound during 2012/2013. Patients were predominantly managed in the community by general practitioners (GPs) and nurses. The annual NHS cost varied between £1·94 billion for managing 731 000 leg ulcers and £89·6 million for managing 87 000 burns, and associated comorbidities. Sixty‐one percent of all wounds were shown to heal in an average year. Resource use associated with managing the unhealed wounds was substantially greater than that of managing the healed wounds (e.g. 20% more practice nurse visits, 104% more community nurse visits). Consequently, the annual cost of managing wounds that healed in the study period was estimated to be £2·1 billion compared with £3·2 billion for the 39% of wounds that did not heal within the study year. Within the study period, the cost per healed wound ranged from £698 to £3998 per patient and that of an unhealed wound ranged from £1719 to £5976 per patient. Hence, the patient care cost of an unhealed wound was a mean 135% more than that of a healed wound. Real‐world evidence highlights the substantial burden that wounds impose on the NHS in an average year. Clinical and economic benefits to both patients and the NHS could accrue from strategies that focus on (a) wound prevention, (b) accurate diagnosis and (c) improving wound‐healing rates.     

Rapid healing of chronic venous stasis leg ulcers treated by the application of a novel serum‐free cultured autologous epidermis

The efficacy and durability of wound closure was examined in a prospective randomized unbalanced clinical trial using the application of a living serum‐free cultured epidermal autograft in conjunction with wound‐area debridement and a four‐layer compression wrap (N=10) compared with wound‐area debridement and a four‐layer compression wrap in patients with hard‐to‐heal leg ulcers arising from confirmed venous stasis (N=5). All 15 patients who presented with full‐thickness venous ulceration were treated weekly for 8 weeks, with a 12‐week final evaluation. The average time to wound closure for the grafted wounds was 4.1 weeks for 80% (8/10) of the cases that closed in 12 weeks compared with 12 weeks for the one closed in the control case. All of the grafted wounds remained closed at 12‐month follow‐up and one more healed at 30 weeks postenrollment. In the control group, one additional wound healed at 21 weeks postenrollment after the placement of an autograft. No serious adverse events were reported and subjective pain assessment was substantially reduced immediately after graft application. The graft treatment significantly improved outcome and provided durable wound closure. The data suggest that this adaption of this procedure may reduce the management costs of these wound types.     

Aetiology,comorbidities and cofactors of chronic leg ulcers: retrospective evaluation of 1 000 patients from 10 specialised dermatological wound care centers in Germany

Numerous comorbidities and cofactors have been known to influence wound healing processes. In this multicentre study, clinical data of 1 000 patients with chronic leg ulcers from ten specialised dermatological wound care centers were analysed. The patient cohort comprised 567 females and 433 males with an average age of 69·9 years. The wounds persisted on average for 40·8 months and had a mean size of 43·7 cm². Venous leg ulcers represented the most common entity accounting for 51·3% of all chronic wounds, followed by mixed‐type ulcers in 12·9% and arterial ulcerations in 11·0% of the patients. Vasculitis was diagnosed in 4·5%, trauma in 3·2%, pyoderma gangrenosum in 2·8%, lymphoedema in 1·7%, neoplasia in 1·0% and delayed post‐surgical wound healing in 0·6% of the included patients. In total, 70·5% of patients suffered from arterial hypertension, 45·2% were obese, 27·2% had non‐insulin dependent diabetes, and 24·4% dyslipidaemia. Altogether 18·4% suffered from metabolic syndrome. Cofactors and comorbidities of patients with chronic leg ulcers have previously been studied but not in detail. Here, we were able to demonstrate the existence of several potentially relevant cofactors, comorbidities of their associations and geographical distributions, which should be routinely examined in patients with chronic leg ulcers and – if possible – treated.     

A pilot study evaluating non‐contact low‐frequency ultrasound and underlying molecular mechanism on diabetic foot ulcers

Non‐contact low‐frequency ultrasound (NCLF‐US) devices have been increasingly used for the treatment of chronic non‐healing wounds. The appropriate dose for NCLF‐US is still in debate. The aims of this pilot study were to evaluate the relationship between dose and duration of treatment for subjects with non‐healing diabetic foot ulcers (DFUs) and to explore the correlation between wound healing and change of cytokine/proteinase/growth factor profile. This was a prospective randomised clinical study designed to evaluate subjects with non‐healing DFUs for 5 weeks receiving standard of care and/or NCLF‐US treatment. Subjects were randomly assigned to one of the three groups: application of NCLF‐US thrice per week (Group 1), NCLF‐US once per week (Group 2) and the control (Group 3) that received no NCLF‐US. All subjects received standard wound care plus offloading for a total of 4 weeks. Percent area reduction (PAR) of each wound compared with baseline was evaluated weekly. Profiles of cytokines/proteinase/growth factors in wound fluid and biopsied tissue were quantified to explore the correlation between wound healing and cytokines/growth factor expression. Twelve DFU patients, 2 (16·7%) type 1 and 10 (83·3%) type 2 diabetics, with an average age of 58 ± 10 years and a total of 12 foot ulcers were enrolled. Average ulcer duration was 36·44 ± 24·78 weeks and the average ABI was 0·91 ± 0·06. Group 1 showed significant wound area reduction at weeks 3, 4 and 5 compared with baseline, with the greatest PAR, 86% (P < 0·05); Groups 2 and 3 showed 25% PAR and 39% PAR, respectively, but there were no statistically significant differences between Groups 2 and 3 over time. Biochemical and histological analyses indicated a trend towards reduction of pro‐inflammatory cytokines (IL‐6, IL‐8, IL‐1β, TNF‐α and GM‐CSF), matrix metalloproteinase‐9 (MMP‐9), vascular endothelial growth factor (VEGF) and macrophages in response to NCLF‐US consistent with wound reduction, when compared with control group subjects. This proof‐of‐concept pilot study demonstrates that NCLF‐US is effective in treating neuropathic diabetic foot ulcers through, at least in part, inhibiting pro‐inflammatory cytokines in chronic wound and improving tissue regeneration. Therapeutic application of NFLU, thrice (3) per week, renders the best wound area reduction.     

Medications affecting healing: an evidence‐based analysis

The purpose of this arm of the study was to investigate the impact of medication on healing times of the various wound types, including acute wounds and leg ulcers. A prospective longitudinal study design was used, with de‐identified data collected using an electronic mobile wound care database system. Three main categories of data were collected, including patients' demographics, wounds types and treatment characteristics. For acute wounds, there was a total of 1732 patients with 2089 acute wounds. The average healing time was about 35 days. The only significant association was with chemotherapy, which increased healing time by 21 days (P = 0·048). There were non‐significant trends towards reduced healing times with antibiotics (0·5 days; P = 0·853), anticoagulants (1·7 days, P = 0·673) and corticosteroids (4·98 days, P = 0·303). Non‐steroidal anti‐inflammatory drugs (NSAIDs) were associated with a non‐significant increase in healing time (2·17 days, P = 0·707). For leg ulcers, there was a total of 264 patients with 370 leg ulcers. We only examined the impact of antibiotics, anticoagulants, corticosteroids and NSAIDs on healing times as they had an adequate number of wounds to analyse. The average healing times of leg ulcers were found to be 73 days. None of the classes of medications had any significant impact on healing time. Both anticoagulants and NSAIDs increased healing time by (22·5 days, P = 0·08) and (12·5 days, P = 0·03), respectively. On the other hand, antibiotics and corticosteroids decreased healing times non‐significantly by (9·1 days, P = 0·33) and (21·6 days, P = 0·84), respectively.     

A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB‐approved, prospective, randomised, single‐centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4‐week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32·0% ± 47·3% versus 97·1% ± 7·0% (P < 0·001) after 4 weeks, whereas at 6 weeks wounds were reduced by ?1·8% ± 70·3% versus 98·4% ± 5·8% (P < 0·001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0·001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing.     

Intralesional administration of epidermal growth factor‐based formulation (Heberprot‐P) in chronic diabetic foot ulcer: treatment up to complete wound closure

Previous studies have shown that an epidermal growth factor‐based formulation (Heberprot‐P) can enhance granulation of high‐grade diabetic foot ulcers (DFU). The aim of this study was to explore the clinical effects of this administration up to complete wound closure. A pilot study in 20 diabetic patients with full‐thickness lower extremity ulcers of more than 4 weeks of evolution was performed. Mean ulcer size was 16·3 ± 21·3 cm². Intralesional injections of 75 μg of Heberprot‐P three times per week were given up to complete wound healing. Full granulation response was achieved in all 20 patients in 23·6 ± 3·8 days. Complete wound closure was obtained in 17 (85%) cases in 44·3 ± 8·9 days. Amputation was not necessary in any case and only one relapse was notified. The most frequent adverse events were tremors, chills, pain and ardour at site of administration and local infection. The therapeutic scheme of intralesional Heberprot‐P administration up to complete closure can be safe and suitable to improve the therapeutic goal in terms of healing of chronic DFU.     

Cost‐effectiveness of treating vascular leg ulcers with UrgoStart® and UrgoCell® Contact

Although chronic wounds have a high socio‐economic impact, data on comparative effectiveness of treatments are rare. UrgoStart^® is a hydroactive dressing containing a nano‐oligosaccharide factor (NOSF). This study aimed at evaluating the cost‐effectiveness of this NOSF‐containing wound dressing in vascular leg ulcers compared with a similar neutral foam dressing (UrgoCell^® Contact) without NOSF. Cost‐effectiveness analysis from the perspective of the German statutory health care system was performed using a decision tree model for a period of 8 weeks. Cost and outcome data were derived from the clinical study ‘Challenge’ suggesting a response rate (≥40% wound size reduction) of UrgoStart^® of 65·6% versus 39·4% for the comparator. In the treatment model, effect‐adjusted costs of €849·86 were generated after 8 weeks for treatment with UrgoStart^® versus €1335·51 for the comparator resulting in an effect‐adjusted cost advantage of €485·64 for UrgoStart^®. In linear sensitivity analyses, the outcomes were stable for varying assumptions on prices and response rates. In an 8‐week period of treatment for vascular leg ulcers, UrgoStart^® shows superior cost‐effectiveness when compared with the similar neutral foam dressing without any active component (NOSF). As demonstrated within a randomised, double‐blind clinical trial, UrgoStart^® is also more effective in wound area reduction than the neutral foam dressing. Wound healing was not addressed in this clinical trial. Follow‐up data of 12 months to allow for reulceration assessment were not generated.     

The efficacy and safety of Grafix® for the treatment of chronic diabetic foot ulcers: results of a multi‐centre,controlled, randomised,blinded, clinical trial

In a randomised, controlled study, we compared the efficacy of Grafix^®, a human viable wound matrix (hVWM) (N = 50), to standard wound care (n = 47) to heal diabetic foot ulcers (DFUs). The primary endpoint was the proportion of patients with complete wound closure by 12 weeks. Secondary endpoints included the time to wound closure, adverse events and wound closure in the crossover phase. The proportion of patients who achieved complete wound closure was significantly higher in patients who received Grafix (62%) compared with controls (21%, P = 0·0001). The median time to healing was 42 days in Grafix patients compared with 69·5 days in controls (P = 0·019). There were fewer Grafix patients with adverse events (44% versus 66%, P = 0·031) and fewer Grafix patients with wound‐related infections (18% versus 36·2%, P = 0·044). Among the study subjects that healed, ulcers remained closed in 82·1% of patients (23 of 28 patients) in the Grafix group versus 70% (7 of 10 patients) in the control group (P = 0·419). Treatment with Grafix significantly improved DFU healing compared with standard wound therapy. Importantly, Grafix also reduced DFU‐related complications. The results of this well‐controlled study showed that Grafix is a safe and more effective therapy for treating DFUs than standard wound therapy.     

Noncontact low‐frequency ultrasound therapy in the treatment of chronic wounds: A meta‐analysis

Our objective was to summarize and quantify the effects of a noncontact low‐frequency ultrasound (NLFU) therapy on healing of chronic wounds. We performed a meta‐analysis of eight published studies reporting effects of NLFU on wound size and healing rate of chronic wounds in 444 NLFU‐treated patients. A search of the PubMed database was conducted in January 2010 and updated in October 2010. We used random‐effects linear regression models to estimate the proportional reductions in wound area and volume and the proportion of wounds healed from baseline to last follow‐up. In four studies (N=188) reporting change in wound area from baseline, NLFU was associated with 85.2% area reduction (95% CI 64.7%–97.6%) over a mean 7 weeks. In four studies (N=278) reporting reduction in wound volume, NLFU was associated with 79.7% volume reduction (95% CI 46.1%–98.8%) over a mean 12 weeks. In seven studies (N=429) reporting proportion of wounds healing by study end (mean time to healing 8.2 weeks; median 6.8 weeks), meta‐analyzed healing rates over time suggest 32.7% of wounds healed on average by 6 weeks (95% CI 23.3%–42.1%) and 41.7% by 12 weeks. NLFU for treatment of chronic wounds was associated with consistent and substantial wound size reductions, as well as favorable rates of healing.