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.     

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.     

Adaptive compression therapy for venous leg ulcers: a clinically effective,patient‐centred approach

A prospective, randomised, 12‐week study was performed to evaluate the efficacy and tolerability of two compression methods for venous leg ulcers (VLUs); a new adaptive compression therapy (ACT) system, combining intermittent and sustained pneumatic compression (n = 38) and a conventional four‐layer bandage system (n = 52). Primary outcomes were ulcer healing and safety. Secondary outcomes were comfort, compliance, ulcer pain, patient‐perceived product performance and quality of life. Ulcer healing rate was similar (31·6% versus 42·3%, respectively, P = 0·30) between the treatments. Adverse events and patient‐rated comfort were also similar. Average daily usage for the dual system was 10·5 and 1·8 hours in the sustained and intermittent modes, respectively, representing its use during 71% of waking hours. Predicted final ulcer pain was also similar (P = 0·68). Performance was subjectively better for adaptive compression and significantly higher for exudate management (P = 0·04), skin protection (P < 0·001), removal ease (P = 0·0007), bathing (P < 0·0001) and sleep comfort (P = 0·0405). The adjusted final quality‐of‐life score was 0·1025 higher for adaptive compression (P = 0·0375). Subjects with healed ulcers attained higher final scores than unhealed subjects (P = 0·0004). This study provides evidence that ACT is comparably efficacious to successfully heal VLUs compared with four‐layer bandage management but is better accepted and achieves higher patient‐reported quality‐of‐life scores in these challenging patients.     

Clinical evaluation of gauze‐based negative pressure wound therapy in challenging wounds

The aim of this randomised clinical study was to evaluate the effectiveness and safety of gauze‐based negative pressure wound therapy (NPWT) in patients with challenging wounds. A total of 50 consecutive patients who had wound drainage for more than 5 days, required open wound management and had existence of culture positive infection were included the study. In this study, gauze‐based NPWT was compared with conventional dressing therapy in the treatment of patients with difficult‐to‐heal wounds. The patients were randomly divided into two groups. Group I (n = 25) was followed by conventional antiseptic (polyhexanide solution) dressings, and group II (n = 25) was treated with saline‐soaked antibacterial gauze‐based NPWT. The wounds' sizes, number of debridement, bacteriology and recurrence were compared between group I and group II. The mean age of the patients was 59·50 years (range 23–97). In group I, average wound sizes of pre‐ and post‐treatment periods were 50·60 ± 55·35 and 42·50 ± 47·92 cm², respectively (P < 0·001). Average duration of treatment was 25·52 ± 16·99 days, and average wound size reduction following the treatment was 19·99% in this group. In group II, the wounds displayed considerable shrinkage, accelerated granulation tissue formation, decreased and cleared away exudate. The average wound sizes in the pre‐ and post‐treatment periods were 98·44 ± 100·88 and 72·08 ± 75·78 cm², respectively (P < 0·001). Average duration of treatment was 11·96 ± 2·48 days, and average wound size reduction following the treatment was 32·34%. The patients treated with antibacterial gauze‐based NPWT had a significantly reduced recurrence (2 wounds versus 14 wounds, P = 0·001), and increased number of the culture‐negative cases (22 wounds versus 16 wounds, P < 0·047) in a follow‐up period of 12 months. There was a statistically significant difference between two groups in all measurements. As a result, we can say that the gauze‐based NPWT is a safe and effective method in the treatment of challenging infective wounds when compared with conventional wound management.     

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.     

Effect of local anaesthetic infiltration with bupivacaine and ropivacaine on wound healing: a placebo‐controlled study

Infiltration of surgical wounds with long‐acting local anaesthetics (LA) is used to reduce postoperative incisional pain. We hypothesised that infiltration with LA interferes with wound healing in rats. Seventy‐two rats were allocated into nine groups. After intraperitoneal anaesthesia, the interscapular dorsal region was infiltrated with equivolumes of saline, 0·5% bupivacaine or ropivacaine, in a randomised double‐blind fashion. A standardised incision was performed in the infiltrated area and sutured closed. The rats were euthanised on the 3rd or 14th day after the operation and tissue from the incision site was subjected to histochemical analyses and mechanical testing (MT). Compared with the control group, bupivacaine displayed a significant increase in the macrophage number on day 3 (+63% versus +27% for ropivacaine). The transforming growth factor β‐1 expression had a significant increase in the LA (versus saline) groups, +63% in ropivacaine group and +115% in bupivacaine group on day 3 (P < 0·05). The collagen fibres as measured by dyed area were significantly higher in the bupivacaine group on day 3 (+56%, P < 0·01 versus +15% for ropivacaine). CD34 was reduced in bupivacaine group (?51%, P < 0·05 versus +3% for ropivacaine). On day 14, no statistical differences were observed in either LA group (versus saline) with respect to histopathologic or inflammatory mediators. MT on day 14 showed no differences between the LA and saline groups. The LA‐induced increases in histological markers did not extend beyond the third day, suggesting that wound infiltration with long‐acting LA does not impair the wound healing process in rats.     

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.     

Evaluation of a muscle pump‐activating device for non‐healing venous leg ulcers

This evaluation involves an innovative muscle pump‐activating device (geko™) as an adjunctive therapy with best practices for non‐healing venous leg ulcers (VLUs). Stimulating the common peroneal nerve (at the fibular head), the geko™ device creates a response that acts as foot and calf muscle pumps, increasing venous, arterial and microcirculatory flow. The aim was to evaluate and determine if the geko™ is effective in this population and if it should be added to the medical supply formulary. In all, 12 patients with 18 recalcitrant VLUs (defined as less than 30% reduction in wound size in 30 days with best practices) in two community settings in Ontario consented to the evaluation and were treated with the geko™ for up to 20 weeks. A total of 44% of wounds healed, and 39% decreased in size. One patient non‐adherent with the geko™ and best practices had deterioration in his or her wounds. With the patients as their own control, the mean weekly healing rate with the geko™ was 9·35% (±SD 0·10) compared to 0·06% (±SD 0·10) prior to baseline, which was statistically significant (P < 0·01). Three patients not in optimal therapy increased compression due to decreased pain, further enabling healing. This study was not a randomised investigation, although the patients acted as their own controls. A pragmatic evaluation reflects the reality of the community sector; in spite of best practices or evidence‐based care, therapy is not uniformly applied, with some participants unable to tolerate or indeed comply with optimal compression therapy. Rash occurred under the devices in 7 of 12 (58%) patients. One patient stopped the device due to rash, while another had to take breaks from using the device. Subsequently, the manufacturer (FirstKind Ltd) has developed a new device and protocol specific to the requirements of wound therapy to minimise this response. This small case series demonstrated the highly significant effectiveness of the geko™ device in these hard‐to‐heal VLUs. Further evaluations to determine dose and patient selection criteria are underway.     

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.     

IPARZINE‐SKR study: randomized,double‐blind clinical trial of a new topical product versus placebo to prevent pressure ulcers

This study compared the efficacy of a new topical agent (IPARZINE‐4A‐SKR) on preventing category I pressure ulcers (PUs) over a 2‐week period, compared with a placebo. A double‐blind, randomised, multi‐centre, placebo‐controlled clinical trial in two parallel groups was conducted. The primary objective was to compare PU incidence between groups. Hospital and socio‐sanitary centre patients (n = 194) at risk of developing a PU (Braden scale) were randomised into two groups. The intervention group included 99 patients, and the placebo group comprised 95 patients. Patients were comparable in terms of age, sex and PU risk. In both groups, patients had a high risk of developing PUs. The product was applied on the sacrum, trochanters and heels. Six PUs (incidence = 6·1%) were detected in the intervention group versus seven (incidence = 7·4%) in the placebo group. Differences were not statistically significant (z = 0·08; P = 0·94), relative risk = 0·82 (95% confidence interval = 0·29–2·36). The main limitation of the study was the sample size and, therefore, the main difficulty encountered was in determining whether the product is ineffective or simply has not been used with sufficient patients. In conclusion, it is not possible to confirm that there are any differences between the studied and the placebo treatments in the prevention of PUs. The results obtained were similar to those obtained in studies of PU prevention using products based on topical fatty acids.     

Relationship between maceration and wound healing on diabetic foot ulcers in Indonesia: a prospective study

The aim of this study was to clarify the relationship between maceration and wound healing. A prospective longitudinal design was used in this study. The wound condition determined the type of dressings used and the dressing change frequency. A total of 62 participants with diabetic foot ulcers (70 wounds) were divided into two groups: non‐macerated (n = 52) and macerated wounds (n = 18). Each group was evaluated weekly using the Bates–Jensen Wound Assessment Tool, with follow‐ups until week 4. The Mann–Whitney U test showed that the changes in the wound area in week 1 were faster in the non‐macerated group than the macerated group (P = 0·02). The Pearson correlation analysis showed a moderate correlation between maceration and wound healing from enrolment until week 4 (P = 0·002). After week 4, the Kaplan–Meier analysis showed that the non‐macerated wounds healed significantly faster than the macerated wounds (log‐rank test = 19·378, P = 0·000). The Cox regression analysis confirmed that maceration was a significant and independent predictor of wound healing in this study (adjusted hazard ratio, 0·324; 95% CI, 0·131–0·799; P = 0·014). The results of this study demonstrated that there is a relationship between maceration and wound healing. Changes in the wound area can help predict the healing of wounds with maceration in clinical settings.     

Evaluating the effectiveness of a self‐management exercise intervention on wound healing,functional ability and health‐related quality of life outcomes in adults with venous leg ulcers: a randomised controlled trial

Exercise that targets ankle joint mobility may lead to improvement in calf muscle pump function and subsequent healing. The objectives of this research were to assess the impact of an exercise intervention in addition to routine evidence‐based care on the healing rates, functional ability and health‐related quality of life for adults with venous leg ulcers (VLUs). This study included 63 patients with VLUs. Patients were randomised to receive either a 12‐week exercise intervention with a telephone coaching component or usual care plus telephone calls at the same timepoints. The primary outcome evaluated the effectiveness of the intervention in relation to wound healing. The secondary outcomes evaluated physical activity, functional ability and health‐related quality of life measures between groups at the end of the 12 weeks. A per protocol analysis complemented the effectiveness (intention‐to‐treat) analysis to highlight the importance of adherence to an exercise intervention. Intention‐to‐treat analyses for the primary outcome showed 77% of those in the intervention group healed by 12 weeks compared to 53% of those in the usual care group. Although this difference was not statistically significant due to a smaller than expected sample size, a 24% difference in healing rates could be considered clinically significant. The per protocol analysis for wound healing, however, showed that those in the intervention group who adhered to the exercise protocol 75% or more of the time were significantly more likely to heal and showed higher rates for wound healing than the control group (P = 0·01), that is, 95% of those who adhered in the intervention group healed in 12 weeks. The secondary outcomes of physical activity, functional ability and health‐related quality of life were not significantly altered by the intervention. Among the secondary outcomes (physical activity, functional ability and health‐related quality of life), intention‐to‐treat analyses did not support the effectiveness of the intervention. However, per protocol analyses revealed encouraging results with those participants who adhered more than 75% of the time (n = 19) showing significantly improved Range of Ankle Motion from the self‐management exercise programme (P = 0·045). This study has shown that those participants who adhere to the exercise programme as an adjunctive treatment to standard care are more likely to heal and have better functional outcomes than those who do not adhere to the exercises in conjunction with usual care.     

A prospective,randomised, controlled,multi‐centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft,bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers

A prospective, randomised, controlled, parallel group, multi‐centre clinical trial was conducted at three sites to compare the healing effectiveness of treatment of chronic lower extremity diabetic ulcers with either weekly applications of Apligraf^® (Organogenesis, Inc., Canton, MA), EpiFix^® (MiMedx Group, Inc., Marietta, GA), or standard wound care with collagen‐alginate dressing. The primary study outcome was the percent change in complete wound healing after 4 and 6 weeks of treatment. Secondary outcomes included percent change in wound area per week, velocity of wound closure and a calculation of the amount and cost of Apligraf or EpiFix used. A total of 65 subjects entered the 2‐week run‐in period and 60 were randomised (20 per group). The proportion of patients in the EpiFix group achieving complete wound closure within 4 and 6 weeks was 85% and 95%, significantly higher (all adjusted P‐values ≤ 0·003) than for patients receiving Apligraf (35% and 45%), or standard care (30% and 35%). After 1 week, wounds treated with EpiFix had reduced in area by 83·5% compared with 53·1% for wounds treated with Apligraf. Median time to healing was significantly faster (all adjusted P‐values ≤0·001) with EpiFix (13 days) compared to Apligraf (49 days) or standard care (49 days). The mean number of grafts used and the graft cost per patient were lower in the EpiFix group campared to the Apligraf group, at 2·15 grafts at a cost of $1669 versus 6·2 grafts at a cost of $9216, respectively. The results of this study demonstrate the clinical and resource utilisation superiority of EpiFix compared to Apligraf or standard of care, for the treatment of diabetic ulcers of the lower extremities.     

A prospective evaluation of methylene blue and gentian violet dressing for management of chronic wounds with local infection

The objective of this prospective, non‐randomised study was to evaluate the performance of an antibacterial foam dressing containing methylene blue and gentian violet (Hydrofera Blue Classic dressing^®) for the management of chronic wounds with local infection. Patients in this study were ≥18 years of age (n = 29), and each had at least one chronic wound ≥1 cm² in size that showed signs of localised infection or critical colonisation but with good potential for healing based on clinical assessment. To all of these wounds, the dressing was applied and changed three times per week over the 4‐week study period. The primary endpoints of the study were: (i) changes in wound surface area measurement, (ii) changes in Pressure Ulcer Scale for Healing (PUSH) scores, (iii) changes in percent surface area of devitalised tissue (i.e., yellow slough or other necrotic tissue) and (iv) changes in clinical signs associated with localised wound infection/critical colonisation. Participants were evaluated at presentation (week 0 = baseline), week 2 and at week 4 (end of the study). The 29 patients completed the study, and at week 4, the following wound improvements were observed: (i) baseline mean wound surface area was significantly reduced by 42·5%, from 21·4 to 12·3 cm² at week 4 (P = 0·005); (ii) baseline mean PUSH score decreased significantly from 13·3 to 10·7 at week 4 (P < 0·001); (iii) baseline mean wound coverage by devitalised tissue (%) was significantly reduced, from 52·6 % to 11·4% at week 4 (P < 0·001) and (iv) the mean UPPER and LOWER wound infection scores were reduced from 3·6 at baseline to 0·9 at week 4 (75%; P < 0.001). These results indicate that the Hydrofera Blue Classic dressing was effective at managing these chronic wounds and helped them progress onto a healing trajectory.     

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.     

Randomised clinical trial to compare total contact casts,healing sandals and a shear‐reducing removable boot to heal diabetic foot ulcers

The objective of this study was to evaluate the efficacy of three off‐loading techniques to heal diabetic foot wounds: total contact casts (TCCs), healing sandals (HSs) and a removable boot with a shear‐reducing foot bed (SRB). This was a 12‐week, single‐blinded randomised clinical trial with three parallel treatment groups of adults with diabetes and a foot ulcer (n = 73). Ulcer healing was defined as full reepithelialisation with no drainage. Diabetic patients with grade UT1A or UT2A forefoot ulcers on the sole of the foot were enrolled. Patients with malignancy, immune‐compromising diseases, severe peripheral vascular disease (ankle‐brachial index < 0·60 or transcutaneous oxygen < 25 mm/Hg), alcohol or substance abuse within 6 months, untreated osteomyelitis or Charcot arthropathy with residual deformity that would not fit the HS or boot were excluded. In the intent‐to‐treat analysis, significantly higher proportion of patients were healed in the TCC group (69·6%) compared to those treated with the SRB (22·2%, P < 0·05). There was no difference in the rate of healed ulcers in the HS (44·5%) and TCC groups. Ulcers in the TCC group healed faster than those in the HS group (5·4 ± 2·9 versus 8·9 ± 3·5 weeks, P < 0·02). However, there was no difference in the time to healing in the TCC and SRB groups (6·7 ± 4·3 weeks, P = 0·28). Patients who used HS were significantly more active (4022 ± 4652 steps per day, P < 0·05) than those treated with TCCs (1447 ± 1310) or SRB (1404 ± 1234). It is concluded that patients treated with TCCs had the highest proportion of healed wounds and fastest healing time. The novel shear‐reducing walker had the lowest healing and highest rate of attrition during the study.     

Comparing the hydrosurgery system to conventional debridement techniques for the treatment of delayed healing wounds: a prospective,randomised clinical trial to investigate clinical efficacy and cost‐effectiveness

In these uncertain times of high health care costs, clinicians are looking for cost‐effective devices to employ in their everyday practices. In an effort to promote cost‐effective and proper wound repair, the hydrosurgical device allows accurate debridement of only unwanted tissue while precisely conserving viable structures for eventual repair. This prospective, randomised study compared procedures using the hydrosurgery system (VERSAJET?) with conventional debridement in order to assess clinical efficacy and cost‐effectiveness when treating subjects with chronic wounds. A total of 40 subjects were recruited. There was no difference in time to achieve stable wound closure between the treatment groups (P = 0·77). There were no significant differences between the two groups in terms of cost of the first operative procedure (P = 0·28), cost of surgical procedures during the study (P = 0·51), cost of study treatment (P = 0·29) or cost to achieve stable wound closure (P = 0·85). There were no differences in quantitative bacterial counts after debridement with either methods (P = 0·376). However, the time taken for the first excision procedure was significantly faster using the hydrosurgery system (VERSAJET) when compared with conventional debridement (P < 0·001). The total excision time for all procedures was significantly less for the Hydrosurgery group than for the conventional group (P = 0·005). Also, the Hydrosurgery group demonstrated significantly less intraoperative blood loss than conventional group for all procedures (P = 0·003). In this study, although there were no differences in time to stable wound closure or bacterial reduction between the two groups, the hydrosurgery system (VERSAJET) did offer advantages in terms of operative times and intraoperative blood loss and was cost‐neutral, despite the handpiece cost.     

C‐type natriuretic peptide slows down wound healing but promotes angiogenesis in SKH1‐hr hairless mice

C‐type natriuretic peptide (CNP) is known to increase growth rate of endothelial cells in vitro. In addition, gene transfer of CNP into ischaemic muscle was shown to induce angiogenesis. So far, no study has addressed the effect of CNP on dermal wound healing. The ear wound model in mice was used in this study. The first group was treated with dsRed‐CNP plasmid, whereas the second group was transfected with the empty dsRed‐sine plasmid, lacking sequence coding for CNP. The third group was sham operated and treated with saline to serve as second control. Wound size was measured on days 0, 1, 3, 5, 7, 9, 11 and 14. On days 7 and 14 capillary density was analysed. Wound closure rate was significantly reduced in mice treated with CNP [dsRed‐CNP 73·3 ± 3·2% versus dsRed‐sine 94·5 ± 2·4% versus saline 92·1 ± 2·4%, n = 8 per group, analysis of variance (ANOVA) P < 0·001] at day 7 postop. Capillary density was found to be significantly higher in CNP‐treated mice (dsRed‐CNP 18·7 ± 3·9 versus dsRed‐sine 12·3 ± 2·7 versus control 10·1 ± 4·7, CD31⁺ capillaries per microscope field, ANOVA P = 0·018) at day 14 postoperative. CNP significantly reduces wound closure rate in hairless mice but promotes the development of new blood vessels. A possible explanation is the dual effect of CNP, inhibiting growth of fibromyoblasts but stimulating growth of endothelial cells. Thus, CNP may serve as a therapeutic approach to diseases caused by hyperfibrosis.     

Low flow oxygenation of full‐excisional skin wounds on diabetic mice improves wound healing by accelerating wound closure and reepithelialization

Oxygen‐based therapies have proven effective in treating chronic and difficult‐to‐heal skin wounds, but the current therapeutic approaches suffer from major limitations and they do not allow for continuous wound treatment. Here we examined whether the continuous treatment of wounds with pure oxygen at low flow rates accelerates wound closure and improves wound healing in a murine model of diabetic skin wounds. Two full‐excisional dorsal skin wounds were generated on 15‐week‐old diabetic db/db mice and treated for 10 weeks continuously with pure oxygen (>99·9%) at low flow rates (3 ml/h). After 6 days, oxygen treatment resulted in a mean reduction of the original wound size by 60·2% as compared with only 45·2% in wounds on control mice that did not receive pure oxygen.(P = 0·022). After 10 days, oxygen‐treated wounds were 83·1% closed compared with 71·2% in wounds on control mice. While reepithelialisation was complete after 10 days in over 57% of wounds receiving low flow oxygen treatment, significant epithelial gaps remained in 75% wounds from mice that did not receive oxygen. Continuous low flow oxygenation significantly improves healing of diabetic skin wounds in mice and may therefore be an effective treatment for chronic cutaneous and possibly other slow‐healing wounds in diabetic patients.     

Efficacy and cost‐effectiveness of octenidine wound gel in the treatment of chronic venous leg ulcers in comparison to modern wound dressings

The aim of this study was to determine the efficacy, safety and cost‐effectiveness of an octenidine‐based wound gel in the treatment of chronic venous leg ulcers. For this purpose, 49 wounds were treated with either modern wound‐phase‐adapted dressings alone (treatment arm 1; n = 17), octenidine wound gel plus modern wound‐phase‐adapted dressings (treatment arm 2; n = 17) or octenidine wound gel alone (treatment arm 3; n = 15). During the study period of 42 days with dressing changes every 3–5 days, wound healing characteristics and treatment costs of different dressings were analysed. Wound size reduction was significantly better (P = 0·028) in both octenidine wound gel treatment arms compared to modern dressings alone with total reductions of 14·6%, 64·1% and 96·2% in treatment arms 1–3. Early wound healing was merely observed under octenidine wound gel treatment (n = 9), whereby lowest treatment costs were generated by octenidine wound gel alone (€20·34/dressing change). As a result, the octenidine wound gel is cost‐effective and well suitable for the treatment of chronic venous leg ulcers, considering both safety and promotion of wound healing.