iWounds News 1 - October 2019 (US Edition)

October 2019 | Issue 01

Clinical trials confirm efficacy of TLC-NOSF dressing for the safe treatment of leg ulcers

Michael Edmonds:

Diabetic foot care: A new era

Page 6

William Ennis:

Profile

Results from two open prospective trials have revealed that the TLC-NOSF sucrose octasulphate dressing, with poly-absorbent fibres, represents an effective and safe treatment for the local management of leg ulcers. In addition, cost-effectiveness studies examining the economic impact of the dressing have demonstrated that significant annual cost savings can be achieved with TLC-NOSF sucrose octasulphate dressings.

Page 12

IWGDF unveils new infection and PAD guidelines for diabetic foot patients

Members of the International Working Group on the Diabetic Foot (IWGDF) presented up-to-date guidelines for the diagnosis, prognosis and treatment of diabetic foot ulcers at the 29th conference of the European Wound Management Association (EWMA; 5–7 June, Gothenburg, Sweden), highlighting development on the areas of infection and peripheral arterial disease (PAD).

S

ylvie Meaume (Hôpital Rotschild, Paris, France) presented the findings of the NEREIDES and CASSIOPEE multicentre trials at the European Wound Management Association’s (EWMA) 29th conference (5–7 June, Gothenburg, Sweden). She said: “It is difficult to treat these wounds and 40–50% of venous leg ulcers remain unhealed after 12 months.

Also, the problem of recurrence is a major issue, with there being more than a 70% recurrence rate within three months.”

An effective treatment of leg ulcers

The NEREIDES and CASSIOPEE trials aimed to assess the efficacy and safety of the TLC-NOSF dressing in the local management of leg ulcers at different stages of the healing process, and were conducted across a total of 35 centres, hospitals and private practices in France. Patients with non-infected, moderately to heavily exudative leg ulcers—either of venous or mixed aetiology—were treated with the dressing and Continued on page 2

FIRST REVEALED AT the 8th International Symposium on the Diabetic Foot (22–25 June 2019, The Hague, The Netherlands), the eight new documents also include guidelines for the prevention of wounds, wound classification and wound healing.

The process of making the guidelines, according to Benjamin A Lipsky (University of Washington, Seattle, USA), involved the formulation, by a multidisciplinary working group, of clinical questions and key outcome measures “that clinicians would care about” when treating patients with diabetic foot problems. These questions were reviewed by clinicians and a systematic review of the complete scientific literature was subsequently performed. Once this had been achieved, recommendations were graded to establish how useful they might be.

Continued on page 5

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October 2019 | Issue 01

Conference coverage

Clinical trials confirm efficacy of TLC-NOSF dressing for the safe treatment of leg ulcers Continued from page 1

appropriate compression therapy over the course of 12 weeks. The primary outcome, in both studies, was the relative wound area reduction (RWAR) at week 12.

Thirty-seven patients with wounds in the desloughing stage (70% or more sloughy tissue) entered into the NEREIDES trial, while 51 with wounds in the granulating stage (50% or more granulation tissue) were part of the CASSIOPEE study.

Other than the percentage of sloughy tissue on wound bed at baseline, the cohorts of both studies were very similar and consisted of 90% or more outpatients that were predominantly female and had an average age of over 75 years. In addition to this, a majority of the patients in both NEREIDES and CASSIOPEE had a marked history of suffering with venous ulcers.

Regarding the characteristics of the patients’ wounds,

It is difficult to treat these wounds and 40–50% of venous leg ulcers remain unhealed after 12 months.”

Meaume said: “If we look at the wound, it is a very similar duration and area. Half of the wounds have a duration of more than six months despite previous compression therapy, and a third of the wounds have an area of more than 10cm³. It is important to notice that there are not just simple wounds, but also arterial wounds included in the study.”

After 12 weeks of treatment, the RAWR measured in both trials presented a beneficial outcome, with patients in the NEREIDES study experiencing a 60% reduction compared to an 81% RAWR in the CASSIOPEE trial.

A wound closure rate of 18% was recorded for ulcers treated with the dressing as part of NEREIDES, and 20% for wounds in CASSIOPEE. These results are consistent with the findings of previous RCTs conducted with TLC-NOSF matrix dressings.

Wound healing outcomes depending on wound duration at initiation were also revealed, and Meaume described these findings as “the major result of these

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studies”. In the NEREIDES study, RAWR for wounds with a duration of less than six months was 85%, whereas wounds with a duration of six months or more had a reduction rate of 43%. These results were consistent with the wound closure rate measured in the CASSIOPEE test, with 30% of ulcers less than six months old closing compared to just 11% of wounds six months or older, as disocvered in the NEREIDES study.

“The conclusion of these two studies is that you can use this dressing, and the sooner is better,” said Meaume.

In terms of safety, the dressing was well tolerated in all healing stages; a total of 19 adverse events—none of which were serious—were recorded throughout both studies. The nature of these adverse events was also

The main cost driver was the efficacy of TLC-NOSF compared to neutral advanced wound care dressings.”

Intractable leg ulcer above the ankle

similar in both studies and consistent with the good safety profiles of the poly-absorbent fibres and of the TLC-NOSF dressings.

Meaume concluded: “This result corroborates with the findings of previous clinical trials on TLC-NOSF dressings and confirms the clinical interest of this new TLC-NOSF dressing with poly-absorbent fibres in the local treatment of exuding chronic wounds, at their different wound healing stages and until wound closure, in the accepted standard of wound care.”

Significant annual cost savings

Following the recent recommendation of the TLC-NOSF dressing by the UK National Institute for Health and Care Excellence (NICE), Isaac Odeyemi (Manchester, UK) also spoke at EWMA and presented the results of two cost-effectiveness studies that were conducted across the healthcare systems of the UK and Germany.

Both studies involved a Markov-model cost-

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effectiveness design using four states of patient health, with a further distinction made between pre- and post-amputation wounds. Referring to the EXPLORER double-blind randomised controlled trial, which also demonstrated the safety and efficacy of the dressing, Odeyemi noted that the trial informed the model efficacy parameters of their analysis, supplemented by estimates from the literature. In models for the UK, the EXPLORER study’s endpoint of 20 weeks was extrapolated to a base-case time horizon of one year, which was further extended to 100 weeks in the German model.

During the study, costs were analysed from individual countries’ perspectives and adjusted for 2017 prices.

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As reported by NICE in their recommendation for UrgoStart dressings, Odeyemi quoted an average costsaving of “up to £5.4 million each year, if only 25% of people having treatment with diabetic foot ulcers in the UK use UrgoStart”.

In the UK, Odeyemi reported that the study demonstrated a cost saving of £342 per patient over one year, with a healing time reduced by “up to 60 days”. In the German study, on the other hand, the model demonstrated a lower cost per effectively treated bleed of €6,77.58 for the UrgoStart group, compared to €10,375.56 for the control group over the same 100week period.

Surprisingly, Odeyemi revealed that “sensitivity analyses also showed UrgoStart was dominant in terms of all the model input varied. You could give any other dressing in the healthcare system for free—and UrgoStart would still be cost-saving.” This is a rare result in a health economics analysis, emphasising that the dressing was economically dominant in both the UK and the German studies, both of which provided exactly the same result.

In conclusion, Odeyemi also emphasised the importance of the finding: “This is actually quite significant—it is a lot of money that healthcare systems can actually save.”

“The main cost driver was the efficacy of TLC-NOSF compared to neutral advanced wound care dressings.

Furthermore, earlier use of the dressing resulted in even better efficacy, higher cost savings and better quality of life.”

Please contact the iWounds News team with news or advertising queries Tel: +44 (0) 20 7736 8788 Published by: BIBA Medical, 526 Fulham Road London, UK SW6 5NR Tel: +44 (0) 20 7736 8788 Printed by: Buxton Press

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October 2019 | Issue 01

Wound technology

Endovenous laser ablation to offer faster treatment for chronic venous ulcers Endovenous laser ablation (EVLA) of perforating veins has been established as an effective method of treating chronic venous ulcers in patients with diabetes mellitus, according to a new study conducted in Azerbaijan.

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esults of the study, which enrolled 42 patients suffering from chronic venous ulcers, were presented at the European Wound Management Association’s (EWMA) 29th conference (5–7 June, Gothenburg, Sweden) by principal investigator Vugar Fattah-Pur (Azerbaijan State Advanced Training Institute for Doctors, Baku, Azerbaijan), who carried out the trial with the support of colleagues Ismayil Asgarov and Elmaddin Akhundov, as well as Uzeyir Ismayilov (“ISTANBUL NS” Clinic, Baku, Azerbaijan).

Fattah-Pur explained that a deficiency of perforated veins causes venous insufficiency, which as a consequence leads to the development of chronic venous ulcers in the lower limbs. He said: “The standard treatment of chronic venous ulcers (CVU) is compression therapy, traditional surgery and foam sclerotherapy. But, at the same time there are frequent recurrences reported. It should be noted that diabetes mellitus in its turn aggravates the course of

determine whether or not this process can offer a truly viable alternative to traditional surgical treatment and compression therapy.

The 42 patients taking part in the study—all of whom had diabetes mellitus—were divided into one of three groups. The first group of 21 underwent EVLA by a diode laser with a wavelength of 1470nm, while a second cohort of 10 patients were subject to epifascial ligation of the perforated vein. Finally, a third group of 11 were treated with compression therapy until the wound had healed.

EVLA is a safe, effective and less traumatic method of ablating deficient perforated veins that is performed on an outpatient basis.”

Vugar Fattah-Pur

disease and impacts the results of treatment of CVU.” By evaluating the efficiency of EVLA in the treatment of patients with chronic venous ulcers, the study’s goal was to

In addition to EVLA, a simultaneous miniphlebectomy was performed on five of the patients from the first group, while six others from the same group underwent foam sclerotherapy. These extra treatments were conducted in order “to achieve expedient satisfactory aesthetic results,” according to FattahPur. All three groups were also required to wear compression hosiery: the first and second cohorts for 4–6 weeks, and the

Diagnostic biomarkers and fluorescence imaging may have the potential to advance wound care “A lot more bacteria than anticipated” have been discovered on wounds in a patient cohort consisting of 89% venous leg ulcers, and using fluorescence imaging proved superior for detecting infection in wounds. This was the conclusion of Thomas Serena (Warren, USA), president of the Association for the Advancement of Wound Care, presenting the results in the iWounds programme at the Charing Cross Symposium (CX; 15–18 April, 2019).

THE RECENT DISCOVERY follows years of clinical assessment, fluorescence imaging and research, Serena noted. Serena opened his presentation with a case, as he told the CX audience about a patient with a venous leg ulcer who was placed into a clinical trial.

Although the wound did not look infected, the patient was subsequently treated, as he tested positive for generic staph aureus. Serena described this experience: “When the person who controls your budget for the next 10 years is in your clinic and you get the diagnosis of infection incorrect […] you begin a journey into how to do a better job, and that is what we have been on for 14–15 years.”

He argued at the meeting that symptoms can vary widely between patients and many may even be asymptomatic. This idea stimulated Serena and colleagues to initially conduct a pilot study to evaluate the diagnostic accuracy when fluorescence imaging was used adjunctively to the clinical severity score (CSS) assessment, to identify wounds with moderate to heavy bacterial loads.

Adult wound care patients were recruited for a prospective, single-blinded, single-centre clinical trial.

With 89% of the cohort having venous leg ulcers, the average wound area was 10.81cm², and the majority had been living with their wound for over 12 months. “It was a three-step process. First, the investigator carried out a CSS assessment, then we took a picture, to see if the fluorescent image demonstrated infection. Finally, we did a quantitative tissue biopsy and histology to confirm [infection],” Serena explained.

A positive fluorescent image, Serena said, has a 100% accuracy rate of detecting infection. He added that the low number of true negatives in this population prevented the calculation or statistical analysis of specificity and negative predictive value.

According to Serena, the results of the clinical questionnaire highlighted the fact that fluorescence images guided at least one aspect of wound care in 90% of study patients. He reported that clinician confidence was seen to increase by 21%, while such images enabled the identification of true positive wounds missed by CSS

third group for 14–18 weeks.

The first group included nine men and 33 women with an average age of 54.7 years. This group also had an average ulcer area of 2.16±0.73cm².

Following EVLA, nearly 30% of these patients experienced pain, while around two thirds of the study group were affected by ecchymosis. In addition to this, induration was noted in the postoperative period for approximately half of the patients, and around 40% of patients complained of paraesthesia.

However, Fattah-Pur asserted that “none of the above complications have ever influenced the daily physical capabilities of patients”.

Comparing the results of these 21 patients who underwent EVLA to both the second and third groups, the speaker underlined that the average wound healing period for those in the first group was 26 days. Moreover, the second group of 10 patients who underwent epifascial ligation of the perforated vein had a wound healing period of 25 days, whereas the final set of 11 patients treated with compression therapy had a wound healing period of 78 days.

Fattah-Pur concluded: “EVLA is a safe, effective and less traumatic method of ablating deficient perforated veins that is performed on an outpatient basis. This allows us to consider this technique as a successful method of eliminating reflux in perforated veins, rapid treatment of CVU and a possible replacement of the traditional surgical treatment.” It was also stated that further research is needed to evaluate the long-term efficacy of EVLA as a treatment for patients with diabetes mellitus.

alone in 47% of wound treatment plans.

Outlining next steps in this field, Serena noted an additional project that he and his team have been working on: “We are now developing biomarkers for infection, to be used in clinical trials.” Although he said that these are currently available in Europe, they are not presently approved for use in the USA. Thus, Serena et al set out to develop an assay to detect bacterial proteases from commonly known wound pathogens.

Of the 366 patients studied, Serena said the most interesting finding was the 133 patients who were not clinically diagnosed with infection, but tested positive for bacterial protease activity (BPA). This indicated that the initial stages of pathogenicity do not necessarily result in observable clinical signs of infection.

According to Serena, the US Food and Drug Administration (FDA) responded to this finding by implying that there remains no proof that bacteria are bad for wounds. Acknowledging the truth in this, Serena and colleagues initiated a large trial aimed to prove that BPA has prognostic power in predicting the time for wounds to heal. What they found was that positive tests for BPA indicated a high likelihood that wound healing would be impaired.

“It actually is a really good surrogate endpoint,” noted Serena, as he put forward that BPA should be viewed as a point-of-care immediate predictor of healing, which has been derived prospectively in a randomised controlled trial. “We have been in contact with the FDA, and are hopeful we can get this approved in the USA,” Serena said. “I think we can conclude that, from both of these diagnostic methods, we have found a lot more bacteria than we anticipated, and bacteria locations—we did not anticipate these. The question now: What do we do about it?”

Issue 01 | October 2019

Diabetic foot care

5

IWGDF unveils new infection and PAD guidelines for diabetic foot patients Continued from page 1

Diagnosis and treatment of foot infections

It is estimated that at least 25% of all persons with diabetes will eventually develop a foot infection, and this problem remains the most common cause of both diabetes-related hospitalisations and lower extremity amputations. As non-specialists are usually responsible for treating these infections, a new guideline was considered necessary by the IWGDF, expanding what was published in 2016 on the diagnosis and management of foot infections in persons with diabetes.

In addition to this, the updated recommendations aim to combat a “global antimicrobial crisis”. Lipsky said: “We are not producing new antibiotics and the ones we have are not as useful because of the developing resistance of micro-organisms, so we have to use the antibiotics we have available in the wisest possible way.”

In support of the guideline, the infection committee of the IWGDF produced an update of a 2015 systematic review of interventions for treating infection, and a first time systematic review on the diagnosis of infection. The guideline updates the severity of infection classification scheme (see below) that the infection committee developed in 2004, with osteomyelitis—an infection of the bone—now having the separate designation of “O”.

Key recommendations on diagnosis, as explained by Lipsky, encourage physicians to assess all diabetic foot ulcers according to the IWGDF classification system, which grades diabetic foot patients from 1–4 depending on whether they have no infection, a mild infection, a moderate infection or a severe infection. In cases of serious infection, recommendations state that a patient should be hospitalised, while outpatient treatment would be suitable for most moderate and mild cases.

The performance characteristics of a number of helpful diagnostic tests are detailed in the guidelines, such as a probe-to-bone test, various serum inflammatory markers and imaging techniques. Lipsky added that if there is an infected wound “you should culture tissue, not send swab specimens,” and (for now) process them using standard methods as opposed to newer molecular techniques. In selected cases, potentially infected bone should be sampled for a definitive diagnosis of osteomyelitis or to establish the causative pathogen(s) and antibiotic susceptibility results.

Turning his focus to guidelines for treating infection, Lipsky emphasised that antibiotics shown to be effective in clinical trials should be selected based on the likely pathogen(s), severity of infection and risk of adverse events, and be administered orally in mild and most moderate cases. Regarding the duration of therapy, he stated: “Most of us treat much too long. There is good evidence based on randomised controlled trials that no more than one to two weeks of treatment is necessary for the vast majority of soft tissue infections, and no more than six weeks for bone infections.”

Treating patients with PAD

Presented by Nicolaas Schaper (Maastricht, The Netherlands), the new guideline on the management of PAD in patients with a foot ulcer and diabetes aims to tackle its association with a poor prognosis and support non-vascular specialists with diagnosis and treatment,

Nicolaas Schaper

especially as there is currently “weak evidence” to underpin clinical practice.

Looking at those affected by PAD, Schaper underlined that in developed countries 30−40% of persons with diabetes, including younger people, have PAD. These patients face a much higher risk of amputation as the PAD frequently progresses faster and is associated with more severe disease, compared to persons without diabetes. Schaper explained this situation using the results of a study: “If a patient has claudication, one in 20 of those with diabetes underwent amputation. If a patient does not have diabetes, the amputation rate is one in a 100, so it is a huge increased risk.” Once a diabetic foot ulcer has developed, up to 50% of the patients have signs of PAD. The first part of the guideline centres around the diagnosis of PAD, asserting that the disease should be excluded in diabetic foot patients as soon as possible.

We are not producing new antibiotics and the ones we have are not as useful because of the developing resistance of micro-organisms.”

This cannot be achieved with a clinical examination alone, as even those with severe PAD can demonstrate a good pulse in the foot; instead, more advanced examinations to test ankle and toe pressure are required. While there is no single modality in place, PAD is considered unlikely if triphasic pedal Doppler waveforms are measured, the ankle-brachial index is between 0.9 and 1.3, and the toe-brachial index is 0.75 or higher.

Once PAD has been diagnosed, the physician must assess the probability of healing when estimating the need for revascularisation. Using the WIfI classification system, which considers other key aspects such as the wound, ischaemia and foot infection, it is possible to estimate the amputation risk and determine whether revascularisation would be beneficial.

Although this system is a useful guide, there is still a great amount of uncertainty and physicians must be

prepared to change strategy. Schaper said: “We advise that if a patient has PAD and does not heal within 4–6 weeks, then go to imaging and revascularise.

If all your initial tests are normal and you treat the patient optimally, there is still a chance that the patient has PAD, because all the tests are to a certain extent unreliable.” For diabetic foot patients with both PAD and infection, Schaper further emphasised the need to treat immediately, as once there is an infection as well as PAD, the risk of amputation rises greatly.

“Time is tissue in these patients,” he said. Following the completion of these two stages (diagnosing and estimation of prognosis), any approach to treatment should involve a multidisciplinary team of vascular specialists and aim to direct blood flow to one or more arteries, preferably in the anatomical region of the ulcer. The revascularisation technique should also be selected based on the individual factors of each patient and local factors.

In their closing remarks, both speakers considered the key controversies and conclusions raised by their respective guidelines and discussed the best approach moving forward. For patients with PAD, Schaper affirmed that revascularisation decisions are complex due to the potential for spontaneous healing, and called

Benjamin A Lipsky

upon physicians to optimise other aspects of care, as described in practical guidelines of the IWGDF. Lipsky also raised a number of important questions about what the best approach to imaging bone and soft tissue infections might be, as well as the potential viability and usefulness of topical or local antimicrobial therapies, which are among the topics that will be explored further with the foundation of a new guideline established.

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October 2019 | Issue 01

Diabetic foot care

A new dawn in diabetic foot care: Evidence-based treatments for ulceration Michael Edmonds Comment & Analysis Michael Edmonds, a pioneer in the treatment of the diabetic foot, has underlined the need for innovation and development in the wound care field. Presently, the emergence of multiple randomised controlled trials (RCTs) is driving the effort to upgrade treatments and provide better care to patients. In his article, Edmonds discusses a number of studies that are testing the efficacy of advanced wound dressings and therapies for diabetic foot patients, from LeucoPatch to topical wound oxygen.

U

nhealed diabetic foot ulcers are a prelude to 84% of lower extremity amputations,¹ so it is important to heal ulcers quickly.

However, the evidence base to promote the healing of diabetic foot ulcers has been deficient, leading to a call for welldesigned clinical trials.² In response to this, there has been a renewed interest in diabetic foot care and several randomised controlled foot ulcer trials have been published.

1. In a randomised, double-blinded controlled study, a sucrose octasulphate dressing—which is a polyester mesh impregnated with a lipidocolloid matrix, containing sucrose octasulfate potassium salt—has been demonstrated as beneficial in non-infected, neuroischaemic diabetic foot ulcers that were difficult to heal, despite best standard of care.³ In total, 126 participants were randomised to the sucrose octasulphate dressing and 114 to the control dressing, and after 20 weeks wound closure occurred in 60 patients (48%) from the sucrose octasulfate dressing group and 34 patients (30%) from the control dressing group (95% CI 5–30; adjusted odds ratio 2.60, 95% CI 1.43–4.73; p=0·002). Compared with the average healing time in the control group of 180 days, there was a significantly shorter healing time (reduced by 60 days) in participants treated with the sucrose octasulphate dressing.

2. A multicentre randomised controlled trial assessed LeucoPatch in people

with diabetes and hard-to-heal diabetic foot ulcers, including ischaemic feet down to an ABI of 0.5. The weekly application of LeucoPatch, which provides autologous leucocytes, platelets, and fibrin, resulted in the healing of 45 (34%) out of 132 ulcers within 20 weeks, compared to 29 (22%) out of 134 ulcers in the standard care group without LeucoPatch treatment (odds ratio 1.58, 96% CI 1.04–2.40; p=0.0235) by intention-to-treat analysis. Time to healing was also shorter in the LeucoPatch group (p=0.0246) than in the standard care group.4 3. Diabetic patients with chronic lower extremity ulcers who received the weekly human amnion/chorion membrane dHACM allograft were significantly more likely to heal in 12 weeks compared with those not receiving dHACM (intention-to-treat 70% vs. 50%, P = 0.0338, Per-Protocol-81% vs.

wound reduction size was 7.2% for the treatment group versus 4.8% for the control group (p=0.012).7

Toe ulcer with cellulitis

a significantly improved time to healing with the use of allograft (P < 0.0187).5 4. The safety and efficacy of EDX110, a medical device that generates nitric oxide for the treatment of diabetic foot ulcers, was assessed in a multicentre randomised controlled trial.6 The cohort consisted of 135 participants with 148 ulcers—30% of which were clinically infected at baseline—were recruited (75 participants in the EDX110 group and 75 in the control group).

Treatment lasted 12 weeks, or until healed, and saw both arms given optimal debridement, offloading and antimicrobial treatment. EDX110 achieved its primary endpoint by attaining a median percentage area reduction of 88.6% compared to 46.9% for the control group (p = 0.016) at 12 weeks.

5. Integra Dermal Regeneration Template was used to treat diabetic foot ulcers in a two-phase study consisting of 307 patients. The first phase of the study was a 14-day period which saw patients receive 0.9% sodium chloride gel, along with a secondary dressing and standard offloading. After the initial 14 days, the patients with less than 30% re-epithelialisation entered into the second phase, which was randomised with a control group treated with 0.9% sodium chloride gel and a treatment group treated with Integra bilayer graft. After the 16-week follow-up, patients

the evidence base to promote the healing of diabetic foot ulcers has been deficient, leading to a call for welldesigned clinical trials.”

55%, P=0.0093), according to a prospective, randomised controlled multicentre clinical trial of 110 patients. A Kaplan-Meier analysis was performed to compare the time-to-healing performance with and without dHACM, showing

who received the Integra graft had a significantly greater complete closure rate (51%) versus the control group (32%) (p=0.001). The mean time to closure in the treatment group was 43 days versus 78 days for the control group, and weekly

6. A further randomised trial was undertaken to explore the efficacy of topical wound oxygen (TWO2) homecare therapy for diabetic foot ulcers that had failed to heal with standard of care alone.8 All subjects were enrolled into a standard of care run-in that included gold-standard offloading and sharp debridement.

Only ulcers not on a proven healing trajectory with standard of care alone (<30% wound area reduction) were randomised into the active phase of the study, where they were assigned (double blind) to either active, or sham TWO2 device treatment arms. The primary endpoint of the study was ulcers healed at 12 weeks. At the first interim analysis point of 73 subjects, the active TWO2 arm was shown to be significantly superior to the sham arm (Pearson’s chi-square = 7.2707, P=0.007), increasing the likelihood of healing in 12 weeks by up to four times.

The goal should be to heal ulcers as quickly as possible and avoid the catastrophe of losing a leg to infection. These studies have described interventions that significantly improve healing, and it is hoped that this new dawn will usher in an age of enlightenment in the study of the basic and clinical science of diabetic foot ulcers, finally preventing major amputations which result from complications with unhealed foot ulcers.

Michael Edmonds is a professor of diabetic foot medicine, King’s College London, and consultant physician, King’s College Hospital, London, UK. References: 1. Pecoraro R, Reiber G, and Burgess E. Pathways to diabetic limb amputation: a basis for prevention.

Diabetes Care 1990; 13: 513–521.

2. Jeffcoate WJ, Bus SA, Game FL, et al. International Working Group on the Diabetic Foot and the European Wound Management Association.

Reporting standards of studies and papers on the prevention and management of foot ulcers in diabetes: required details and markers of good quality. Lancet Diabetes Endocrinol 2016; 4: 781-788.

3. Edmonds M, Lazaro-Martinez JL, Alfayate-Garcia JM, et al. Sucrose octasulfate dressing versus control dressing in patients with neuroischaemic diabetic foot ulcers (Explorer): an international, multicentre, double-blind, randomised, controlled trial. Lancet Diabetes Endocrinol 2018; 6: 186-96.

4. Game F, Jeffcoate W, Tarnow L, Jacobsen JL, et al.

LeucoPatch II trial team. LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observermasked, randomised controlled trial. Lancet Diabetes Endocrinol. 2018 Nov; 6(11), 870–878. doi: 10.1016/ S2213–8587(18)30240–7.

5. Tettelbach W, Cazzell S, Reyzelman AM, et al. A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: A prospective, multicentre, randomised, controlled study of 110 patients from 14 wound clinics.

International Wound Journal 2018.

6. Edmonds ME, Bodansky HJ, Boulton AJ, et al.

Multicenter, randomized controlled, observer-blinded study of a nitric oxide generating treatment in foot ulcers of patients with diabetes - ProNOx1 study.

Wound Repair Regen 2018 Apr 4. doi: 10.1111/ wrr.12630.

7. Driver V, Lavery L, Reyzelman A, Dutra T. A clinical trial of Integra Template for diabetic foot ulcer treatment. Wound Rep Regen 2015; 23(6), 891–900.

8. Frykberg R, Franks P, Edmonds M, et al.

Multinational, Multicenter, Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen Therapy (TWO2) in the Treatment of Chronic Diabetic Foot Ulcers Diabetes 2018 Jul; 67 (Supplement 1).

Available from: https://doi.org/10.2337/db18-43-LB.

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October 2019 | Issue 01

Advertorial

SPONSORED ADVERTORIAL

Tracy’s story: Facing the challenge of a chronic wound

It is estimated that chronic wounds cost the NHS more than £5 billion every year, but even more devastating is the impact those same wounds can have on patients. Leanne Atkin (University Huddersfield, UK), chair of the Legs Matter Campaign, speaks to iWounds News about Tracy’s story, from the damaging effects of her venous leg ulcer to a potential solution for hard-to-heal wounds.

resulted in deep vein thrombosis (DVT) during pregnancy, ultimately causing venous insufficiency and the start of her ulceration. Clinicians, especially nurses, tend to think of the average venous leg ulcer patient as being in their seventies, not their thirties. The effect on a patient’s quality of life is significant, no matter the age of the patient, but there is added complexity with patients of a younger age including issues with sexual relationships, parenting, working, career, ambition, and their ability to exercise, all of which impact self-worth and confidence. This was one of the reasons that Tracy became part of the Legs Matter campaign: to share her story and the impact this can have on an individual, to try to ensure the appropriate assessment and treatment of sufferers of lower limb ulceration, and also to raise awareness that leg ulceration affects any age group.

How did EpiFix help with the progression of healing for Tracy’s ulcer following the presentation at Wound Care Today 2018?

As part of the Legs Matter awareness campaign, Tracy presented her story of living day-to-day with an active leg ulcer at the Wound Care Today conference. In the audience was a member of the company who produced EpiFix and they approached Tracy and I following her presentation, offering to support a free evaluation of their product. I must admit that I was very sceptical, as we had previously tried every wound care product with little long-term success. However, both myself and Tracy were open to new suggestions and desperate to try anything which may help. Truthfully, neither of us expected any true benefit from using this but agreed we had very little to lose!

Permission was gained from the NHS to evaluate this product for Tracy and within a few months of her presentation, the first application of EpiFix was completed. The changes in Tracy’s wound were dramatic. Within weeks, the wound bed appeared active Leanne Atkin (left) and Tracy Goodwin (right)

When did you first meet Tracy, and how did you find out about her story?

I first met Tracy over 15 years ago, and at that time she was suffering from her first venous leg ulcer. This ulcer was challenging, but eventually she did go on to heal. Unfortunately, about 10 years ago she suffered a recurrence of her ulceration and despite deep venous bypass surgery, high compression therapy, appropriate wound bed preparation and intervention to treat superficial venous incompetence, healing was slow. For many years there was little progress with her wound and she experienced frequent infections, resulting in increased pain, odour and exudate, all of which directly affected Tracy’s quality of life.

What were the biggest challenges faced during the treatment of Tracy’s ulcer?

One of the biggest challenges I personally faced was the fact that despite high quality evidence-based care, there were a number of months and years in which very little progress was made in terms of wound improvement. This was very frustrating as I desperately wanted to help Tracy and reduce her suffering. I simply felt like I was failing her!

In what ways did the leg ulcer affect Tracy’s day-to-day life?

When Tracy first developed her leg ulcer she was a wife, running a business and a mother of two young children. The impact this had on her life was enormous.

She was taking morphine for the pain which affected her ability to drive, she could not take her children swimming, struggled to walk for any length of time,

and had issues with the smell and exudate that made her increasingly anti-social: all of this had an impact on her marriage. However, it was her recollection of the wound’s impact on her self-worth and self-confidence which really brings the difficulty of living with a leg ulcer home to me as a clinician. These are Tracy’s words: “I am upset about the life I could have had, the career I should have had and for the person that I should have been.

“I always thought I would be somebody and achieve something in life but I feel like I have had that opportunity stolen away. I hate feeling self-conscious, disabled and unattractive and I hate that this leg ulcer has taken away my self-confidence.”

I am upset about the life I could have had, the career I should have had and for the person I should have been.”

Is there enough awareness of how venous leg ulcers can affect people of a younger age?

Definitely not and if you ask a clinician to identify younger patients with venous disease they will often picture morbidly obese patients or patients with a history of intravenous drug use. Tracy was neither of these: she had a pre-thrombotic tendency which

EpiFix

with improved quality and amount of granulation tissue. Over time, epithelisation was evident and within 24 weeks the wound was completely healed. I believe in an evidence base and am completely aware that a single case is not a robust form of evidence, therefore I am unable to state whether it was the EpiFix which truly healed Tracy. However, there had been no progress for over 6 years, having tried every wound product on the market with very little success. Therefore, EpiFix potentially provides a real solution for chronic non-healing wounds and further investigation into this product is urgently required by patients.

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October 2019 | Issue 01

Conference coverage

iWounds Workshop debuts at CX 2019 This year’s Charing Cross Symposium (CX; 15–18 April, London, UK) introduced a new strand of care to Europe’s leading vascular meeting, with the debut of the iWounds Workshop.

Complementing a plenary programme with hands-on activities, the iWounds Workshop highlighted the importance for early diagnosis of underlying conditions in leg and foot tissue loss, and interdisciplinary management and collaboration for wound therapy.

DEMONSTRATIONS WERE split across three workstreams— interdisciplinary and interprofessional education, early referral, and implementation. Michael Edmonds (London, UK) told iWounds News: “We have had good attendance. There was a wide array of techniques for diagnosis and treatment for various different aetiologies—for diabetic ulcers, venous ulcers and arterial ulcers. The workshops displayed recent innovations in stateof-the-art wound healing technology and wound care dressings, as well as techniques in debridement and footwear technology.”

The buzz within the iWounds Workshop was all about collaborative working on wound management between disciplines, with demonstrators

and attendees alike positive about the potential for the strand to raise awareness of an often overlooked and expensive aspect of patient care.

Andy Holman (Medi UK) was demonstrating products that offer debridement and compression solutions.

“The value of the iWounds Workshop is that it is interactive; it is more than just looking. We need to unite all the disciplines who look at wounds—tissue viability, podiatry, diabeticians, the whole range of people who are looking at these patients in isolation potentially. iWounds can bring them all together.”

Mike Griffiths (Advanced Oxygen Therapy) was demonstrating a topical wound oxygen therapy at the workshop.

“Vascular surgeons deal with wounds a lot,” Griffiths said. “iWounds lets

them know about alternatives to healing difficult refractory wounds. It is nice to see a focus on wounds. Wound care involves everybody from radiologists to infection control specialists to the vascular surgeon, and the iWounds Workshop promotes that.”

Speaking to iWounds News, William Ennis (Chicago, USA), head of the American College of Wound Healing and Tissue Repair and a facilitator at the workshops, said there was potential for showcasing technologies on wound imaging to measure healing pre- and post-bypass, and video live cases based on wound anatomy that could help physicians to decide on revascularisation strategies. He said: “The concept of iWounds is novel and different. You are only taking care of one component of the problem if you focus on the vessel, whether it is the artery or the vein.

Twenty-something per cent of those people are going to have some kind of soft tissue injury, and then you have

Reflux elimination study reveals effective ultrasound method of treating leg ulcer patients A study into the efficacy of early reflux elimination for venous leg ulcer (VLU) patients has revealed that the combination of ultrasound-guided foam sclerotherapy (UGFS) only, and a hybrid method of endovenous laser treatment (EVLT) with UGFS, could present a minimally invasive method of treating superficial venous reflux.

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leksandra Jaworucka-Kaczorowska (Gorzów Wielkopolski, Poland) presented the results of the study at the European Venous Forum (EVF; 27–29 June, Zurich, Switzerland), outlining how both the UGFS-only and hybrid methods can be associated with high healing rates and low mid-term recurrence rates. In addition, both approaches may prove more costeffective and popular by replacing life-long compression therapy with a single intervention.

While compression therapy is still the “mainstay of treatment” for VLU patients, JaworuckaKaczorowska emphasised that “more than 85% have superficial venous reflux and are therefore candidates for intervention”. In response to the findings of the ESCHAR and EVRA trials, the elimination of axial and perforating reflux has been suggested as an adjunctive therapy for reducing recurrence rates and accelerating healing.

In order to assess the efficacy of early reflux elimination, the study aimed to determine ulcer healing rate at 24 weeks and one year, as well as ulcer recurrence rate at one year, after the elimination of axial and perforator reflux in patients with active VLU. All of the participants, 69% of whom had first-time ulcers, were also treated with compression therapy as part of

the study.

Prior to the beginning of treatment, and one, three, six and 12 months afterwards, each participant underwent a clinical assessment to measure ulcer dimensions and the wound at risk of infection (W.A.R) score, as well as a duplex assessment to determine the condition of deep and superficial veins, the presence of reflux and any post-treatment venous occlusion.

Explaining the findings of the duplex assessment, Jaworucka-Kaczorowska said: “I found perforating vein incompetency in 63% of patients and segmental deep vein incompetency in almost 16% of patients. Also, 61%

Since long-term patient compliance to compression is relatively poor, it may prove more effective as well as costefficient to provide a single intervention.”

no solution for them, or you just refer them on. It does not mean that [vascular surgeons and interventionalists] are going to physically do [wound care], per se, but it is increasing their knowledge of it. It is about raising awareness.”

Una Adderley, director of the National Wound Care Strategy, UK, pointed out: “There is a pressing need for a greater focus on implementation of existing evidence-informed guidance. More interdisciplinary working that achieves genuine collaboration between all those who provide care is needed to deliver better outcomes for patients.”

Summing up the iWounds philosophy, Edmonds concluded: “iWounds, through both the formal sessions and the workshops, has very much promoted interdisciplinary care, which CX has always espoused; in a sense, this is a continuation of that tradition. It has promoted the ethos of interdisciplinary care, and enriches one of the traditions of CX.”

of segmental deep vein reflux disappeared after ablation of the incompetent superficial veins.”

Following the first clinical and duplex assessment, patients received one of three treatments: UGFS of the incompetent superficial veins, perforating veins and tributaries (34.2%); UGFS of the incompetent perforating veins and tributaries (35%); or a hybrid method of both UGFS and EVLT (30.8%). All patients underwent pharmacotherapy and a wound care strategy of surgical debridement, antiseptic and wound dressing in addition to their treatment.

The results of the trial showed an ulcer healing rate at 24 weeks of 92%, which rose to more than 98% after one year with only two leg ulcer patients failing to heal, and a median VLU healing time of 3.4 months.

Furthermore, the estimated one-year recurrence rate was just 4.4%. “I also assessed the time of healing according to ulcer area, and the bigger it was at the beginning, the longer it took to heal” added Jaworucka-Kaczorowska.

Similar results were also recorded in terms of ulcer duration, with those that had newer wounds taking less time to heal.

All of the patients with isolated superficial reflux healed in three or less months, while the presence of incompetent perforating veins prolonged the healing time; 50% of patients with additional perforating vein incompetence healed in more than three months.

Patients with isolated perforating vein incompetence demonstrated the lowest healing rate, as none healed in less than six months.

“UGFS and hybrid approaches appear to be attractive, minimally invasive methods of treating superficial venous reflux. Since long-term patient compliance to compression is relatively poor, it may prove more effective as well as cost-efficient to provide a single intervention to reduce recurrence, rather than life-long treatment with compression,” Jaworucka-Kaczorowska concluded.

Issue 01 | October 2019

Establishing a pathway for the assessment and pre-treatment of venous leg ulcers In her presentation at the Royal Society of Medicine Venous Forum (RSMVF; 17–19 June, London, UK), consultant vascular surgeon Emma Wilton (Oxford University Hospitals, Oxford, UK) outlined the important process for identifying which patients with leg ulceration require deep venous intervention. Upon the suspicion of the obstructive venous pathology, Wilton argued that there are a number of steps which should be taken before treatment is applied, including imaging and an in-flow assessment.

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hronic venous insufficiency affects 7–9% of the UK population and is caused by such complications as valvular incompetence, chronic obstruction and calf pump failure, “all of which lead to the final pathway of elevated ambulatory venous pressure within the lower limb and venous hypertension,” according to Wilton. Other problems that can result in this insufficiency range from both superficial and deep venous reflux to causes of outflow obstruction, including post-thrombotic syndrome and either malignant or non-malignant iliac veins.

Explaining the assessment procedure which should

Conference coverage be followed in cases like this, Wilton said: “At our institution, we have a pathway for chronic obstructive venous disease. If suspected, the patient undergoes imaging, a multidisciplinary team meeting, clinic follow-up and further investigation before finally agreeing on treatment.”

The first clinical assessment stage involves an analysis of the symptoms and of venous insufficiency, and a review of the patient’s history. Key areas of attention, as listed by the speaker during her presentation, include aching or cramping, swollen limbs and skin discolouration, in addition to more obvious and immediate symptoms such as varicose veins and venous ulcers. Patients with either their own or a family history of venous disease should be noted, as well as any patient who has been an intravenous drug user in the past.

Following this initial review, the imaging stage is conducted, and everyone undergoes a venous duplex scan of the lower limb with a full assessment of deep and superficial systems. According to Wilton, this is highlights the presence of deep vein thrombosis, chronic scarring and venous reflux and helps to determine, or at least offer a suspicion, of deep venous disease.

The next step would involve a magnetic resonance venography or computed tomographic venography ranging from the upper thigh to the lower diaphragm.

While the former aids with a clinical assessment of venous reflux and reveals the extent of occlusive disease, the latter helps to identify post-thrombotic stenotic change and can be performed on either directly or indirectly. In order to establish the adequacy of inflow vessels of patients identified as having venous disease, direct venography would also be performed.

By following this sequence of assessments, it becomes clearer which patients should receive treatment. Wilton said: “We would suggest that you treat patients with symptoms of chronic venous insufficiency that you can see is due to severe post-thrombotic syndrome or significant venous disease attributable to iliac veins and

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outflow obstruction.” Other factors that should influence the decision of whether or not to treat the patient include life expectancy, functional status and their bleeding risk.

Pregnancy and ongoing intravenous drug use were also listed as contraindications to treatment.

Wilton concluded: “As mentioned, they need to have at least a good, if not adequate, inflow; they need to be able to be fully anticoagulated, they need to be compliant with their medication, and they need to be fully informed about the procedure and follow-up schedule, as well as the potential need for reintervention.”

We would suggest that you treat patients with symptoms of chronic venous insufficiency that you can see is due to severe post-thrombotic syndrome or significant venous disease.”

On the potential of deep venous stenting for treating leg ulcers, she added: “The evidence is relatively limited, though here have been some retrospective case series looking at deep venous stenting and the healing up of leg ulcers, showing about a 60% healing rate.” On the potential of deep venous stenting for treating leg ulcers, she added: “The evidence is relatively limited, though there have been some retrospective case series looking at deep venous stenting and the healing of leg ulcers, showing about a 60% healing rate.”

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October 2019 | Issue 01

Interview

Profile

William Ennis

William Ennis is currently Catherine and Francis Burzik professor of Wound Healing and Tissue Repair, and chief of Wound Healing Section, University of Illinois, Chicago, USA. With his 25 years of experience practising wound care, Ennis speaks about what led him to the wound field, how it is changing with the increasing application of new technologies, and the importance of new vascular guidelines.

What led you to a career in medicine and why did you decide to specialise in wound healing and repair?

I had every intention of doing biological research when I went to college. While in my senior year, I was lucky to get a position doing research at Brookhaven National Lab in New York and my director, an MD/PhD, encouraged me to get a medical degree so that I could do both basic and clinical research. During the second year of medical school I became extremely fascinated with anatomy. I spent hours doing dissections and simulating surgical procedures with my anatomy teacher, who himself had been a practising surgeon. That experience convinced me to do general and vascular surgery training. My interest and exposure to wound care grew from the vascular surgery department in Chicago.

Who were some of your key mentors and influences as you trained to become a physician?

Walter Reagan was my first surgical mentor, as his expertise in the operating room and command of cellular physiology truly inspired me to become an academic.

Drâ&#x20AC;&#x2122;s Sloan and McBrayer allowed me to pursue wound care during and after my vascular fellowship.

I established a wound care clinic in my first year of vascular surgery practice and with Dr Meneses, my collaborating PhD for 20 years, embarked on creating both a clinical and research approach to wound care that I still follow today.

In what ways has the wound care and healing space changed during your time in medicine?

When I first started, no one had a clue what a wound clinic was and there were only a few advanced dressings on the market to choose from. My surgical training allowed me to realise that the key to wound care is to maximise the medical condition of the patient, surgically prepare the wound bed, control the bacterial load and ensure adequate tissue perfusion. Those principles are just as important today despite the thousands of advanced wound care products that are on the market.

Our biggest advancement has been the understanding of the wound healing process at the cellular and biochemical level. These research findings have driven product innovation and therapeutic options for todayâ&#x20AC;&#x2122;s wound care provider.

What technologies are you watching closely, and how do you hope to see technological development impact wound care in the next few years?

In our field, advances in therapy have outpaced those in diagnostics. This is very different from most other specialties in medicine. Over the past few years, however, we are beginning to see diagnostic tools that measure cytokines in the wound fluid, tissue microcirculation status, oxygen levels and the biochemical composition of the wound tissue. Continued advances in these diagnostic tools will allow providers to more accurately identify the aetiology of the wound and to better target treatment options.

Do artificial intelligence and predictive analytics have the potential to majorly impact wound healing and repair?

I am a strong believer in big data and predictive analytics in medicine in general, and wound care specifically. One of the problems in wound care is that many individual practitioners do not see the volume of cases that allow for the development of internal expertise. Pattern recognition and machine learning algorithms can provide adjunctive knowledge for the provider and in a way democratise wound expertise to a broader clinician base.

Do you think that there should be more of an emphasis on new interventional wound healing techniques, as well as developing advanced dressings?

Yes, I think we have plateaued in dressing technology and now require more advanced techniques to help the wave of wound care patients that are descending on the healthcare system due to an aging population and epidemics in diabetes and obesity. Futuristic techniques such as 3D-printing of skin is an example of a breakthrough technology that could revolutionise how we care for wounds.

Is there a recent paper on an aspect of wound healing that stands out to you, and why?

I think that the level of scientific rigour in wound care publications over the past few years is what really stands out to me as opposed to a specific paper. The field had to mature from using case studies and anecdotes into a credible field of medicine. The healthcare system now demands this approach.

What progress has the American College of Wound Healing and Tissue Repair (ACWHTR) made during your tenure as president and CEO?

The mission of the organisation is to create a formal specialty status for wound care. Our creation of several wound care fellowships and the application to the American Council for Graduate Medical Education (ACGME) for accreditation of this training have been the biggest highlights thus far.

Has there been any significant movement on securing fellowship status for wound care specialists?

As we await a final ACGME decision on the formal fellowship programmes, we are also attempting to create a hybrid fellowship that would include both face-to-face and virtual training so that mid-career physicians could advance their education without having to take time away from their careers. This is done all the time in nonclinical graduate education but would be disruptive in medicine. The ACWHTR is also leading this charge.

How important will the new vascular guidelines and classification system for wounds be?

I believe they are extremely important, not only so that

we are speaking the same language, but so that we can better predict the likelihood of whether a specific wound will heal or not. The CX meeting and others like it, play a pivotal role in ensuring that these guidelines are disseminated to the wound care community. For example, many wound care meetings have lectures on venous ulcers without any mention to this day of the CEAP classification. Meetings that ensure cross pollination of guidelines, advances and enhance team-based clinical collaboration play an enormous role in improving wound care outcomes moving forward.

Are there any other wound healing initiatives you have encountered that are driving change?

Likely the biggest initiative that will impact wound care is that payers are calculating the total cost of care and we will likely have wound care bundles in the future.

Issue 01 | October 2019

Interview

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Fact File

The field had to mature from using case studies and anecdotes into a credible field of medicine.”

Qualifications

1980 BS, State University of New York 1985 DO, New York College of Osteopathic Medicine 1999 MBA, Keller Graduate School of Management 2016 MMM, University of Southern California 2017 CPE, American Association for Physician Leadership

Academic Appointments (selected)

2005–Present Clinical professor of surgery, Midwestern University, Chicago College of Osteopathic Medicine 2013–Present Catherine and Francis Burzik Professorship in Wound Healing and Tissue Repair 2014–Present Professor of surgery with tenure, University of Illinois

Professional Appointments (selected)

this event marked the formal beginning of our field becoming a specialty. The other proud moment was receiving the Catherine and Francis Burzik endowed professorship in wound healing, the first of its kind in the USA, also at UIC.

Could you tell us about one of your most memorable wound cases?

While this is a US-based phenomenon, it will force us to emphasise the provision of value-based outcomes in wound care, defined as improved outcomes for less cost.

What are some of the proudest moments of your career?

The day we graduated our first fellow from the University of Illinois at Chicago (UIC) along with the surgical residents stands out for me. I knew that

I distinctly remember, early in my career, a 48-year-old diabetic with a motorcycle injury and exposed distal tibia. He refused a flap procedure which was the standard of care. We tried a new device, negative pressure wound therapy, which at the time was considered experimental, and we were gathering data for Medicare. The bone completely granulated over and we were able to place a skin graft and completely heal the patient. He and his wife named their child after the name of our subacute unit!

What are some of your hobbies and interests outside of medicine?

I was a musician throughout high school and college and played in many bands. I still love music and listen almost all day, every day. I also love to run, bike, swim and compete in triathlons.

1998–2006 Attending physician and director of wound programme, Advocate Christ Medical Centre 2008–Present Professor of clinical surgery and attending physician, University of Illinois Hospital and Health Sciences System 2017–Present Chief medical officer, Healogics Inc.

Offices (selected)

1990–Present Member of American College of Osteopathic Surgeons 1995–1997 Founding board member of the Association for the Advancement of Wound Care 1995–Present Member of Wound Healing Society 2008–2010 President of the Association for the Advancement of Wound Care

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October 2019 | Issue 01

Surgical wounds

The management pathway of surgical wounds healing by secondary intention Ian Chetter Catherine Arundel Comment & Analysis At the Charing Cross Symposium (15–18 April 2019, London, UK), Ian Chetter (Hull, UK) presented on the pathway from assessment to treatment for patients with surgical wounds healing by second intention (SWHSI), discussing the impact this may have on such factors as quality of life. In this article on the work conducted by SWHSI and SWHSI-2 researchers, Chetter and Catherine Arundel (York, UK) explore the range of treatments available, comparing their efficacy and popularity with patients.

O

ver 10 million surgical operations occur within the NHS each year,¹ with associated surgical incisions usually closed with sutures or staples.

However, it may not always be possible to close the wound and, even if it is, the wound might dehisce following closure.

In such situations, the wound may be left open to heal by secondary intention— from the bottom up through formation of granulation tissue.

SWHSI may require frequent dressing changes, with a range of options available from simple, non-adherent dressings to more expensive, complex treatments such as negative pressure wound therapy (NPWT). The management of these wounds can also be challenging given their prolonged healing trajectory and the potential need for extended hospitalisation or additional treatments.² Despite the complexity of these wounds, and the extensive treatments required, there is a limited evidence base relating to patient and wound characteristics, healing rates and the effectiveness of treatments for SWHSI³.

A recently completed NIHR-funded Programme Grant for Applied Research (reference: RP-PG-0609-10171) has resulted in a better understanding of the management of SWHSI through a range of research methods, including a cross-sectional survey, cohort study, econometric modelling, and a pilot, feasibility trial.

Cross-sectional survey data4 identified that SWHSI are a relatively common occurrence with an estimated prevalence of 4.1 per 10,000 population (95% CI: 3.5–4.7). Of the 187 participants included in the survey, SWHSI were frequently seen following colorectal (n=80, 42.8%), plastic (n=24, 12.8%) and vascular (n=22, 11.8%) surgeries, with the majority of these wounds being planned before surgery (n=90, 48.1%).

Most patients received wound treatment (n=109, 58.3%), with the majority of patients receiving their wound care in community settings (n=109, 58.3%).4 To build on this evidence, a prospective cohort study³ was completed, producing data which concurred with the cross-sectional survey findings with regards to associated surgical specialty

and the planning of SWHSI prior to operation. The cohort data also indicated that hydrofibre dressings (n=259, 65.9%) were the most common treatment, yet a number of patients (n=115, 29.3%) used the more complex NPWT. The cohort study also afforded identification of patient healing trajectories with healing occurring in 81.4% (n=320) of participants at a median of 86 days (95% CI: 75–103). Duration of healing was longer in patients with leg (median: 127; 95%CI: 92–210) days) or foot (median: 182; 95%CI: 150–231 days) wounds.

Utilising the data collected, predictors

of prolonged healing were identified: baseline wound area (p=<0.01), surgical wound contamination (determined during surgery) (p=0.04) and wound infection at any time (baseline or post-operatively) (p=<0.01).³ Using the cohort data, two econometric models (Model A—least ordinary least squares with imputation; Model B— two stage model—logistic and linear regression) assessed the clinical and cost effectiveness of NPWT as a treatment for SWHSI.5 NPWT was found to be less effective than standard dressing treatments for the healing of SWHSI; Model A—73 days longer (than those who did not receive NPWT) (95% Credible Interval (CrI): 33.8–112.8); Model B—46 days longer (95% CrI: 19.6–72.5). Using incremental quality adjusted life years, NPWT was also found to be less cost effective than standard dressing treatments; Model A: -0.012 (SE 0.005) (observables); -0.008 (SE 0.011) (unobservables); Model B: -0.007 (observables) and -0.027 (unobservables) (SE 0.017).5 It is important, however, to note that effectiveness estimates are derived from observational data and so confounding may reduce confidence in these findings.

Qualitative interviews with patients (n=20) identified initial shock and disbelief from patients experiencing a SWHSI.6 Quality of life was notably impaired for patients living with a SWHSI, especially those with dependents or in paid employment. For patients, wound healing was a key outcome, with a willingness to try any treatment that promised wound healing. Interviews with

health professionals (n=12) identified that they had variable knowledge of SWHSI treatments, and frequently favoured NPWT despite the lack of robust evidence.6 As the final element of the NIHRfunded Programme Grant for Applied Research (RP-PG-0609-10171), a pilot, feasibility randomised controlled trial (RCT) was conducted.7,8 In total, 248 patients were screened for eligibility, with 40 participants (16%) subsequently recruited and randomised to receive NPWT or usual care (no NPWT). During the three-month follow-up period, 10

(25%) wounds were determined to have healed. The pilot, feasibility RCT demonstrated that it would be possible to complete a full RCT to provide definitive evidence for the effectiveness of NPWT as a treatment for SWHSI.8 The NIHR Health Technology Assessment programme has subsequently funded (reference: 17/94/42) a pragmatic, multicentre RCT to assess the clinical and cost-effectiveness of NPWT as a treatment for SWHSI, compared to standard dressings. This study will recruit 696 participants from across surgical specialities, and patients will be allocated 1:1 to receive either NPWT or usual care (standard dressings). The study will aim to ascertain the difference in time to wound healing (in days since randomisation) between the two study arms as the primary outcome. Secondary outcomes include significant clinical events, wound infection, wound pain, patient quality of life and healthcare resource use.

Ian Chetter is a vascular surgeon and chair of surgery at Hull York Medical School (York, UK). He is an NIHR senior investigator, chairs the Research Committee of the Vascular Society of Great Britain & Ireland and is chief investigator for both the SWHSI Programme Grant for Applied Research and the SWHSI-2 randomised controlled trial.

Catherine Arundel is a trial methodologist based at York Trials Unit, University of York, Uk. She has extensive experience coordinating and managing large scale randomised controlled trials and associated research. This has included coordinating the SWHSI Programme Grant for Applied Research and currently the SWHSI-2 randomised controlled trial.

References: 1. NHS Confederation. Key statistics on the NHS 2016 Available from: http://www.nhsconfed.org/resources/ key-statistics-on-the-nhs.

2. Mees J, Mardin WA, Senninger N, Bruewer M, Palmes D, and Mees ST,. Treatment options for postoperatively infected abdominal wall wounds healing by secondary intention. Lagenbecks Arch Surg. 2012;397(8):1359-66.

3. Chetter IC, Oswald AV, McGinnis E, Stubbs N, Arundel C, Buckley H, et al. Patients with surgical wounds healing by secondary intention: A prospective, cohort study. Int J Nurs Stud.

2019;89:62-71.

4. Chetter IC, Oswald AV, Fletcher M, Dumville JC and Cullum NA. A survey of patients with surgical wounds healing by secondary intention; an assessment of prevalence, aetiology, duration and management. J Tissue Viability. 2016;26(2):103-7.

5. Saramago P, Claxton K, Welton NJ, and Soares M,.

Bayesian econometric modelling of observational data for cost-effectiveness analysis - Establishing the value of negative pressure wound therapy in the healing of open surgical wounds. Unpublished. 2019.

6. McCaughan D, Sheard L, Dumville J, Cullum N, and Chetter IC,. Patients’ perceptions and experiences of living with a surgical wound healing by secondary intention: A qualitative study. Int J Nurs Stud.

2018;77:29-38.

7. Arundel C, Buckey H, Clarke E, Cullum N, Dixon S, Dumville J, et al. Surgical Wounds Healing by Secondary Intention (SWHSI): study protocol for a randomised controlled pilot trial comparing negative pressure wound therapy versus usual care. . Trials.

2016;17(535).

8. Arundel C, Fairhurst C, Corbacho-Martin B, Buckley H, Clarke E, Cullum N, et al. Pilot feasibility randomized clinical trial of negative‐pressure wound therapy versus usual care in patients with surgical wounds healing by secondary intention. BJS Open.

2018;2(3):99-111.

Acknowledgements: The SWHSI project was funded by the National Institute for Health Research (NIHR) Programme Grant for Applied Research (Reference: RP-PG-0609-10171).

The SWHSI-2 trial is funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (Reference: 17/42/94).

The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Issue 01 | October 2019

Cell therapy may provide benefit for “no option” critical limb ischaemia patients at two years

Critical limb ischaemia

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et al also looked at the effect of cBMA in certain subgroups—those with and without diabetes and those with Rutherford stage 4 versus those with Rutherford stage 5. This part of the post-hoc analysis found that while cBMA did provide a significant benefit for patients without diabetes and Rutherford stage 4, it did not provide a benefit for diabetic patients and/or those with Rutherford stage 5.

According to Leckie, she and colleagues also found that the quantity of CD105+/CD34dim was relevant to the effect of cell therapy. The mean cell count in non-diabetic patients who did not have an amputation was significantly higher than non-diabetic patients who Two-year results from the MOBILE (Marrowstim treatment of limb ischaemia in patients did have an amputation: 134.1 vs. 34.3 (p=0.0452). with severe peripheral arterial disease) trial indicate that injecting concentrated bone However, there was no significant difference in mean marrow aspirate (cBMA, Zimmer Biomet), versus placebo, into patients with critical limb cell count between diabetic patients who underwent ischaemia is associated with a significant increase in amputation-free survival at two years. amputation and those who did not.

However, the results also suggest that diabetic/Rutherford 5 patients do not benefit from “Cell therapy becomes significantly effective at two the therapy. years with a 50% reduction in death/major amputation, the quantity of CD105+/CD34dim is KATHERIN E LECKIE (Division of Vascular Surgery, amputation and no all-cause mortality) associated with freedom from amputation Department of Surgery, Indiana University School of at 52 weeks, with a secondary endpoint in non-diabetics, but the Rutherford 5 Medicine, Indianapolis, USA) presented the results being the rate of major amputation of diabetic is unresponsive to autologous cell of the MOBILE trial at the 2019 Society for Vascular the index limb. At one year, there was therapy,” Leckie concluded. She added Surgery (SVS) Vascular Annual Meeting (VAM; 12–15 no significant difference in the rate of that that MOBILE trial provides important June, National Harbor, USA). She reported that the amputation-free survival between groups: information to inform future trials but it trial focused on the 30% of patients with critical limb 79.8% for cBMA vs. 69.5% for placebo also raised questions such as is there a ischaemia who have “no options for revascularisation”. (p=0.224). “more potent cell population” and whether She added the lack of revascularisation treatment However, Leckie and colleagues such a population would benefit patients options for these patients leads to 53,000 major performed a post-hoc analysis to review with diabetes. amputations being performed in the USA each year, the results at two years. This showed that Leckie told iWounds News: “The results noting that—when all costs were considered— there was a significant difference—76.5% Katherin E Leckie of the two-year analysis indicate that amputation was the “sixth most expensive operation” in for cBMA vs. 55.9% for placebo the positive effect of cell therapy is later the country and cost US$6 billion dollars per year. (p=0.028)—with a hazard ratio of 0.49 in favour of than we anticipated. In fact, it was at 56 weeks that the In MOBILE, 152 patients (155 limbs) with Rutherford cBMA. Leckie reported that the separation between divergence between the cell treated and placebo groups 4 or Rutherford 5 critical limb ischaemia were cBMA and placebo occurred at 56 weeks (i.e. after the in amputation free-survival became significant. This randomised to receive an injection of cBMA (119) or primary endpoint). delay in therapeutic effect suggests that cell therapy may placebo (36). The cells used were mesenchymal stem Furthermore, with the post-hoc analysis, Leckie slow or halt the progression of disease.” cells, which Leckie explained can be taken from “bone She adds that, with a NIH grant, she and her marrow, the umbilical cord, adipose tissue, teeth, and colleagues are now investigating the mechanisms “by the placenta” but were taken from bone marrow for this which cell therapy, both autologous bone marrow study. She said that a benefit of MOBILE, compared derived cells and allogeneic mesenchymal stem cells, with previous stem cell trials, was that the extraction of may prevent amputations”. “These studies are focusing cells from the bone marrow and subsequent injection on what the cells secrete after injection into ischaemic back into the patient only involved one procedure for the human skeletal muscle, how these secreted factors patient. promote angiogenesis and muscle fibre regeneration, The primary endpoint of the study was the rate of and ways to potentiate these effects using hydrogels and amputation-free survival (a combined endpoint of no genetic modification of the cells,” Leckie notes.

The results of the two-year analysis indicate that the positive effect of cell therapy is later than we anticipated.”

World vascular societies announce new global guidelines for chronic limb-threatening ischaemia Four years ago, vascular experts from around the world had a “quixotic quest”, to get all surgeons and providers to agree on the best ways to treat a common and debilitating illness: chronic limb-threatening ischaemia. The goal has come to fruition, with the publication of new global guidelines, produced by the European Society for Vascular Surgery (ESVS), Society for Vascular Surgery (SVS), and the World Federation of Vascular Societies (WFVS).

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hronic limb-threatening ischaemia (CLTI)—the term now adopted for what is also known as critical limb ischaemia—is the end-stage of peripheral vascular disease. Patients with CLTI are at risk of amputation or even death from the effects of vascular disease.

Co-editors were Michael Conte from the SVS, Philippe Kolh from the ESVS and Andrew Bradbury from the WFVS.

Nearly 60 additional authors worked on the project. Participants spanned six continents and represented all specialties that treat CLTI. The collaboration between expert vascular specialists from around the world has created a unique practice guideline, reflecting the spectrum of the disease and approaches seen worldwide, said Conte. An extensive evidence

review was undertaken, directed by a methodologist, to support the writing group’s work.

“This guideline provides a new foundation for describing and treating CLTI, an escalating public health problem around the world that involves a broad array of health professionals,” Conte said. “By improving the staging of CLTI, we believe that optimal care pathways can be defined and based on more accurate clinical and epidemiologic evidence going forward.”

Conte noted with pride that the multispecialty, international group of vascular experts emphasised the importance of a patient- and limb-centric approach to the care of CLTI. “With the continuous evolution of vascular technology, we must remain focused on the primary goals of treatment, in contradistinction to a lesioncentric emphasis on technical success,” he said.

Another major change is the name itself. The term “critical limb ischaemia (CLI)” is “outdated and fails to encompass the full spectrum” of patients evaluated and treated for limb-

threatening ischaemia, the authors said.

Conte attributes the success of the diverse, international group to a process of consensus development. “A key aspect of our success was broad agreement on the importance of creating a new set point for CLTI around the world. CLTI is one of the most common conditions treated by vascular specialists, and often the most challenging. We also recognised that where evidence is limited the recommendations must be carefully considered to encompass the scope of practice,” he said.

Kolh added: “This is a huge achievement. We took time, but overall it went very smoothly and we developed a great amount of collaboration between colleagues across the Atlantic and worldwide.”

Major recommendations cover the need for comprehensive assessments in patients with suspected CLTI, optimal medical therapy and prompt and effective revascularisation for patients with advanced ischaemia and limb threat. The document also outlines the importance of an individualised approach to improve patient care and reduce limb loss.

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Oxygen therapy

October 2019 | Issue 01

Thousands of diabetic foot ulcer patients could benefit from topical oxygen therapy An Expert Panel report published in The Diabetic Foot Journal has recommended a new treatment algorithm for topical oxygen therapy in patients with diabetic foot ulcers (DFUs) and called for it to be considered as an adjunct to standard of care after four weeks if the wound area has not reduced by 40%.

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n addition, the report advises that the early initiation of topical oxygen therapy—before four weeks— could be beneficial for patients with peripheral arterial disease (PAD), especially where there is ulcer pain, non-healing after amputation, or sloughy wounds.

There are approximately 169,000 people suffering with a DFU in the UK, 65% of which are complicated

by PAD. In response to this, the Expert Panel states that advanced treatment options are needed as healing rates under standard of care are often poor. The sustained delivery of oxygen, either from the blood supply or an external source such as topical oxygen, is vital to heal non-healing wounds, especially for DFUs. Paul Chadwick, visiting professor at Birmingham City University and chair of the Expert Panel Report, said: “The evidence for topical oxygen therapy is growing and is shown to be beneficial, improving outcomes in suitable patients. This new consensus document and simple treatment pathway provides clarity on the role of topical oxygen therapy and when it should be introduced to help manage and heal these difficult-to-heal wounds.

The patients of biggest concern for me are those with severe ulcers, as they are four times more likely to need a major amputation and almost twice as likely to die within one year.” of DFUs should be undertaken by the One product demonstrating results in multidisciplinary foot care service or a topical oxygen therapy is Granulox, a clinician experienced in diabetic foot care, haemoglobin spray from Mölnlycke that before being undertaken thereafter by the binds oxygen from the atmosphere and community. transports it to the wound bed where it is Diabetic foot disease is the most released. A European Wound Management common reason for hospital admissions Association (EWMA) evaluation of among people with diabetes, and DFUs oxygen therapies currently available in cost the NHS an estimated £1 billion per wound care awarded the haemoglobin year, while the additional social costs to spray a treatment recommendation of the patient, such as reduced mobility and Grade 1B, indicating a positive benefit– Paul Chadwick sickness absence, are estimated at £13.9 risk value with moderate quality of billion per year. The indirect costs for evidence and very strong observational studies. people with diabetic foot disease are also high, as many In a single-blinded randomised controlled trial on 72 experience a poorer quality of life than those without patients with venous leg ulcers, the average wound size foot disease. In total, 85% of amputations are preceded reduction was 53% at 13 weeks (p<0.01) in the group

by DFUs, which also incur a greater risk of premature treated with the spray. By comparison, no significant death, myocardial infarction and fatal stroke. reduction in wound size was seen in the control group.

Speaking to iWounds News, Chadwick commented Studies have also shown that twice as many chronic on why topical oxygen therapy should be considered wounds are healed at 8–16 weeks with the haemoglobin as an adjunct to best practice, and how this can spray compared to standard of care, with shorter improve outcomes for patients: “Oxygen is a welltime (50%) to heal. More than 70% of patients have known requirement to promote cell metabolism and reported lower average pain scores at four weeks with pathways for wound healing, such as the angiogenesis the haemoglobin spray than with standard of care in and revascularisation, cell metabolism and energy chronic wounds, while 99% have shown less slough in production, synthesis of connective tissue and infection chronic wounds after four weeks compared to 33% with resistance. Topical oxygen therapy, in particular, plays standard of care. a vital role for the healing of non-healing wounds, The Expert Panel report recommends that the especially for wounds associated with peripheral arterial initiation of topical oxygen therapy for the treatment disease and diabetic foot ulcers.

The evidence for topical oxygen therapy is growing and is shown to be beneficial, improving outcomes in suitable patients.”

“Patients who could benefit from topical oxygen therapy are those with peripheral arterial disease who are not suitable for revascularisation, patients who have undergone unsuccessful revascularisation, persons with ulcer pain, and patients who are not healing after amputation. Therefore, the panel members recommended—in an updated treatment algorithm— that topical oxygen therapy should be considered as an adjunct to standard of care after four weeks if the wound area has not reduced by 40%.

“The report also looked at product innovations and reviewed clinical data to form a basis of recommendations. Granulox (Mölnlycke), an oxygenating haemoglobin spray, is showing promising results in topical oxygen therapy. Studies have shown that diabetic patients can benefit with a reduction in their foot ulcer size when haemoglobin spray is used as an adjunct to standard care.”

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October 2019 | Issue 01

Wound specialisation

Wound care specialisation: Where are we now?

Karen Imma Gellada Comment & Analysis The impact of chronic wounds—a global “healthcare problem”—is felt by patients and the medical community, yet there is limited education on the management of wounds and no standard training programme currently in place. Karen Imma Gellada, a member of the American College of Wound Healing and Tissue Repair (ACWHTR), explains wound care’s “long, arduous road” to specialisation and the current status of a proposed wound healing and tissue repair fellowship.

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hronic wounds have been becoming more prevalent in the past years, affecting around 6.5 million patients and especially the elderly population¹. In the USA alone, 3% of individuals over 65 years old have an open wound². From 1993 to 2003, the number of pressure ulcers in hospitalised patients has increased by 63%,¹ and the prevalence of venous ulcers in the USA continues to be about 600,000 annually.³ With diabetic persons having a 15–25% risk of developing neuropathic ulcers, the number of diabetic foot ulcers has climbed with the rising incidence and prevalence of the disease.4 Unfortunately, with an ageing population and higher rates of diabetes, hypertension, obesity, and other chronic illnesses, these numbers will continue to increase. In the same regard, acute wounds—particularly surgical and traumatic wounds, abrasions, or superficial burns—are also on the rise, emphasising the need for post-surgical wound care as well as emergency and calamity care.5 All of these issues translate to the increased cost of healthcare, decreased productivity, lost wages and poor quality of life for the patients.

Despite the threat imposed by

chronic wounds to public health and the economy, its importance has been overshadowed by other major health concerns. Research funding for the study of chronic wounds is very low compared to its overall impact as a healthcare problem4 and wound education has not kept up, despite advances in wound dressings and the development of various wound technologies.

In the USA, wound education in medical schools is limited to two to three hours on the physiology of tissue injury and wound healing,6 and there is no consensus for the minimum education needed to become a wound expert. There have been multiple wound care societies with “certifying examinations” to become wound “certified”, but no standard training programme. At present, wound care has not been officially recognised as a medical “specialty” by the American Medical Association (AMA) and the American Board of Medical Specialties (ABMS).7 It is globally understood that safe patient care of a high quality can only be provided if doctors are well trained.

Inappropriate wound management is further associated with unfavourable outcomes and higher treatment costs,

as well as prolonged suffering for the patient. Answering the call to further elevate the standards of wound education in the country, ACWHTR was started by key leaders from the clinical, research and industry divisions of the field. In response to the need for advancing wound care as a boardcertified medical specialty, the main objective of the college is to create fellowship programmes, examinations and certification processes using the guidelines of the ABMS and American College of Graduate Medical Education (ACGME). This is to increase awareness of non-healing wounds and thereby promote more research in the field, along with supporting the development of appropriate health policies.8 The University of Illinois Hospital and Health Sciences System became the first academic sponsor for the fellowship under the direction of William Ennis, and the Wound Healing and Tissue Repair Section was developed within the Vascular Surgery Division in January 2008. This fellowship is available to residents who have completed residency programmes and are board eligible or certified in Internal Medicine, Family Medicine or General Surgery. The curriculum involves a two to four week rotation in different areas that are pertinent to wound care, including vascular surgery, plastic surgery, general surgery, orthopaedic surgery, dermatology/pathology, rheumatology, endocrinology, infectious disease, geriatrics, palliative care, nutrition, and physical therapy.

The programme is a total of 12 months and trains the fellow in managing a variety of wounds, both acute and chronic, in different settings, as well as understanding the multidisciplinary nature of the field.9 The first fellow was accepted in July 2008 and, at present, a total of seven fellows have completed the programme and begun practicing as wound care specialists. Since this programme started, other institutions have followed suit. Stanford University, Cleveland Clinic, Wake Forest University and Innova Health have all started wound fellowship programmes and graduated several fellows.

On June 2018, ACWHTR submitted an application to the ACGME for the accreditation of a Fellowship Programme in Wound Healing and Tissue Repair, which was opened for comment through

NAWCO launches first professional credential in advanced wound care The National Alliance of Wound Care and Ostomy (NAWCO) has announced the first professional credential to recognise clinical expertise in advanced wound care at the 2019 Wild On Wounds (WOW) national conference in Las Vegas, USA. ACCORDING TO A statement, the new Advanced Wound Care Certified (AWCC) credential validates the higher-level knowledge and skills required to use today’s advanced wound therapies, such as negative pressure wound therapy (NPWT), biologic skin equivalents, and hyperbaric oxygen treatments.

For clinicians who have previously earned NAWCO’s

Wound Care Certification (WCC), or other eligible wound certifications, achieving the AWCC credential is said to offer an additional opportunity to elevate their organisations’ wound care programmes and develop their own careers.

“Until now, most wound management certifications have stressed a broad command of skin and wound care

the ACGME website in February 2019 and is now awaiting approval of the board.

The path to the specialisation of wound care has been a long, arduous road and in the era of quality-based healthcare, wound care will be one of the standards that is measured. As wound care providers, it is our duty to our patients to continue learning and keep up with changes in the field that will allow us to provide appropriate, effective and evidence-based care that will impact not just cost, but, more importantly, quality of life for patients.

There is now a better recognition of the differences between various types of wounds and their pathologies down to the molecular level, yet this is not sufficient.

Understanding and addressing the current concerns and misconceptions that physicians and patients deal with on a daily basis would expedite advancement of this field. In addition, more research and evidence-based therapies are essential to advance the specialty of wound care. With the increasing number of fellowship programmes and trained physicians, the recognition of wound care as a specialty is long overdue.

Karen Imma Gellada is a former fellow for the section of wound healing and tissue repair at the University of Illinois at Chicago, USA. She finished her family medicine residency at the University of Illinois College of Medicine at Peoria, USA. She is currently a practicing wound care physician in Rockford, Illinois, USA. References: 1. Sen C, Gordillo G, Roy S, Kirsner R, Lambert L, Hunt T, Gottrup F, Gurnter G, Longaker M. Human Skin Wounds: A Major and Snowballing Threat to Public Health and Economy. Wound Repair Regen. 2009: 17(6): 763–771.

2. Serena TE. Are you at risk for chronic wounds? 2015. www.futreofpersonalhealth.com/prevention-andtreatment/are-you-at-ris-for-chronic-wounds.

3. Abbade LP, Lastoria S. Venous ulcer: epidemiology, physiopathology, diagnosis and treatment. Int J Dermatol 2005;44: 449–56.

4. Sen C. Human wounds and its burden: an updated compendium of estimates. Advances in Wound Care.

2019: 8(2): 39–48.

5. US Surgery. Executive Summary. US Surgery.

2008. http://www.touchbriefings.com/cdps/editem. cfm?cid=5&nid=2358 6. Patel NP, Granick MS. Wound education: American medical students are inadequately trained in wound care. Ann Plast Surg. 2007; 59:53–5.

7. Darrah J. Measuring the value of wound care certification in a quality-based healthcare system. Today’s Wound Clinic. https://www. todayswoundclinic.com/articles/measuring-valuewound-care-certification-quality-based-healthcaresystem.

8. Gellada K, Ruggiero M. Pursuing the path to specialized wound care: the ACWHTR perspective.

Today’s Wound Clinic. 2017: 11(8).

9. Ennis W. Wound care specialization: the current status and future plans to move wound care into the medical community. Advances in Wound Care. 2012: 1(5): 184–188.

principles,” said Cindy Broadus, executive director of NAWCO. “With healthcare facilities demanding more clinical mastery in advanced wound care, the new AWCC programme will supercharge certificants’ professional growth in this arena.”

The pathway to the AWCC credential includes rigorous education and experience requirements, as well as an exam. Anna Gable Mackie became the first clinician to earn the certification on 5 September 2019, while five other candidates received passing scores on the AWCC exam at the 2019 WOW national conference to join Mackie as the first cohort of AWCC clinicians.

The candidates satisfied education requirements through an online course provided by Healiant, meeting the criteria established by the NAWCO certification committee.

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October 2019 | Issue 01

Wound healing

Measuring success in venous ulcer healing: “Ambiguous and difficult to define” Defining success in wound healing remains a nebulous concept, with no consensus on what constitutes a successful outcome. Dave Bosanquet (University of Bristol, Bristol, UK) outlined the difficulties at the Charing Cross Symposium (CX; 15–18 April, London, UK), arguing that a “core outcomes set” was needed to help characterise success.

SYSTEMATIC REVIEWS OF wound healing literature have found that “over 100 different outcomes are being reported in the RCTs [randomised controlled trials]”, said Bosanquet, asking: “How do you pick the outcomes that are meaningful, clinically relevant and important to patients? In order to address such variation, the key thing that is needed is a core outcomes set, where you decide what outcomes are so important that they should be reported in all trials involving wound care.”

The US Food and Drug Administration (FDA) definition of wound healing has been widely accepted as the industry gold standard, defined as 100% reepithelialisation of a wound surface, without exudate, drainage or dressing, that is confirmed, once healed, two weeks later. “RCTs and cohort studies are good at reporting the first two aspects,” Bosanquet pointed out.

“What we are not good at doing is checking that those wounds do not reoccur after a couple of weeks.”

Surrogate outcomes are also used to define endpoints: “Wound healing is a complex process comprising a number of stages. It is not just complete closure—you have a lot of studies that report an outcome of a 50% reduction in wound size after four weeks […], and we are talking about surrogate outcomes.

“Rather than the end outcome of actual wound healing, you are evaluating a half-way outcome. And we know that wounds do not necessarily heal in a linear fashion, and that the percentage change can be exaggerated when we look at small wounds compared to large wounds. We have also got to recognise that some wounds are never going to heal.”

How do you pick the outcomes that are meaningful, clinically relevant and important to patients? The key thing that is needed is a core outcomes set where you decide what outcomes are so important they should be reported in all trials.”

Measures can be based on efficacy, efficiency or effectiveness, broadly referring to healing (and recurrence), the speed at which that happens (the number of visits, time to heal, and number of dressing changes), and the cost, both financial and patientrelated. They can also be grouped into symptoms, such as exudate, oedema, odour and pain, quality of life measures, patient preference and acceptability, resource usage (in terms of staff time, number of visits, cost), and the tissue type: granulation or necrosis.

“When we have all these varying outcomes, how on earth do we synthesise the data? How do we perform meaningful meta-analysis?” he asked. Bosanquet highlighted comments from the European Wound Management Association: “If the only gold standard was total wound closure, no therapy would ever be considered efficacious,” and: “Conversely, if a nonspecific endpoint is chosen, any positive findings may not translate into a clear clinical benefit at the bedside.” Development of a core outcome set involves an exhaustive systematic review to summarise outcomes currently being reported, then gathering together a large group of key individuals comprising patients, healthcare professionals and industry, “and through a Delphi process achieve consensus on what are the actual outcomes that are important to report for patients undergoing clinical trials”.

Bosanquet concluded: “Healing itself, as defined by the FDA, is generally well done in the literature, with the exception of checking that your wound has not recurred after a couple of weeks. Surrogate outcomes, such as a 50% area of reduction after a few weeks, are done quite frequently, but have inherent problems, as all surrogate outcomes do. There are a number of other outcomes, inconsistently reported, which make comparison difficult. We await the results of the core outcome set to help decide how we should define success in wound healing.”

The benefit of early ankle-brachial pressure index measurement for vascular wound care CX Executive Board member Una Adderley (University of Leeds, Leeds, UK), director of the National Wound Care Strategy Programme for the National Health Service (NHS) England, spoke at the Charing Cross Symposium (CX; 15–18 April, London, UK) this year, on the challenge of ankle-brachial pressure index (ABPI) for managing vascular disease. Adderley argued for the benefits of introducing ABPI assessment for the early detection of arterial disease, claiming the data support that a significant majority of amputations could be prevented with its use.

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dderley told CX delegates attending the wound care session that an “accurate diagnosis is the foundation of any treatment decision”.

The ABPI is, she argued, a “relatively accurate” test for arterial insufficiency— “more valid and reliable than pedal pulse palpation and more portable than duplex scanning”. Furthermore, Adderley pointed to literature that raises issues of interpretation with other diagnostic methods, such as peripheral pulse palpation.

In addition to allegedly inaccurate diagnostic tools, Adderley directed the audience’s attention to an All-Party Parliamentary Group report on vascular and venous disease in the UK, which highlighted that “every two hours, a patient in England loses their leg due to complications” related to peripheral arterial disease. Adderley described

this as an opportunity for improvement, telling the audience at CX: “With early arterial assessment, 80% of these amputations could be prevented.”

Adderley then commented on what she perceived as the “suboptimal use of compression for venous leg ulceration”.

Citing support from articles published in Journal of Wound Care and Journal of Tissue Viability, she informed attendees

With early arterial assessment, 80% of these amputations could be prevented.”

Una Adderley

that in North East England, 23.6% of leg and foot ulcers are not assessed using Doppler ultrasound for the detection

of arterial disease, and 46% of venous leg ulcers in the same region are not in compression.

Data from an individual English healthcare district evidenced that 33.6% of leg ulcers are not assessed using Doppler ultrasound, and 25% of venous leg ulcers are not in compression.

Published in the Journal of Wound Care, the study by Narasimhaiah Srinivasaiah and colleagues at the University of Hull (Hull, UK) set out to “review current wound-care practice and the standard of wound care” in an area of England, concluding that wounds represent a “significant cause of morbidity” and recommending a structured focus to tackle this issue. The study found a cumulative wound prevalence for the region at 12%, with community nurses involved in caring for 70.1% of patients with wounds, and 52.7% of wounds being treated in the patients’ homes.

Srinivasaiah et al write: “A systematic focus is necessary on effective and timely diagnosis, on ensuring treatment is appropriate to the cause and condition of the wound and on active measures to prevent complications.”

Adderley said that the solution for detecting arterial disease was the early use of the ABPI measurement, ensuring the clinical safety of patients who might suffer from mixed arterial and venous disease. She also called for a service redesign, creating benefits such as “opportunities for deliberate practice, access to equipment, and knowledge reinterpretation”.

Issue 01 | October 2019

Market watch

Product News MolecuLight agrees loan to expand FDA-approved fluorescence imaging tech

MolecuLight, a provider of handheld fluorescence imaging for the real-time visualisation of bacteria in chronic wounds, has announced it has secured a US$7.5 million term loan from Oxford Finance LLC, a specialty finance firm which provides senior debt to life sciences and healthcare services companies worldwide.

This news follows the announcement of a “major regulatory milestone”, as the company revealed on 14 August 2019 that the FDA had granted De Novo clearance for its i:X fluorescence imaging device. Ralph DaCosta, founder, chief scientific officer and director of MolecuLight, commented on the new round of funding: “The MolecuLight i:X platform is a significant advancement in the management of chronic wounds, that is already revolutionising wound care practice in Canada and Europe.”

MolecuLight’s financial position as it provides us the additional resources to build our global commercial organisation to support the significant demand from wound care practitioners for our MolecuLight i:X device,” said Anil Amlani, MolecuLight CEO. “There is no other real-time pointof-care method other than the i:X by which to visualise fluorescence, which is indicative of clinically significant bacteria and therefore allowing wound care clinicians to optimise their decision-making about treatment pathways.

“With hundreds of MolecuLight devices deployed globally and a breadth of clinical, peer-reviewed evidence, the demand for the device is understandable,” Amlani added.

“Oxford provides financing for high growth, high potential medical device companies and we feel that MolecuLight is such an opportunity,” said Christopher A Herr, senior managing director at Oxford Finance LLC. “The combination of their i:X device, its powerful value proposition against a significant clinical problem, and the experienced team at MolecuLight make this the ideal company for us to finance.”

Huntleigh launches advanced treatment device for lower limb wound healing

Moleculight fluorescence imaging

“Thousands of patients to date have already experienced a change in their assessment and treatment by clinicians who feel empowered by the wound fluorescence images they are seeing. As reported in multi-centered published clinical studies, clinicians used the images to inform their wound management practices in real-time, in particular, for guided wound sampling, cleaning and debridement,” DaCosta said.

According to a statement, the new round of financing will further support MolecuLight’s commercial expansion and allow them to the meet “growing global demand” for its technology.

MolecuLight i:X is described as a safe and portable fluorescent imaging device that assists clinicians in visualising significant bacteria in chronic wounds in real time, digitally measuring the wounds and assisting in optimising the treatment pathway at the point-of-care.

Furthermore, i:X is indicated as a handheld imaging tool that allows clinicians responsible for diagnosing and treating skin wounds, at the pointof-care, to view and digitally record images of a wound, as well as images of fluorescence emitted from a wound when exposed to an excitation light.

“Securing this funding bolsters

Huntleigh has announced the UK release of a technology that is designed to assist in the management of hard-toheal leg ulcers. Developed at the Arjo R&D Faculty in Cardiff, the Wound Express Advanced Wound Therapy Device should be used in conjunction with standard treatment techniques and has been shown to significantly reduce the size of both hard-to-heal wounds of venous and mixed aetiology in some patients, and other wounds completely in just eight weeks of use.

The ongoing treatment of venous leg ulcers is currently very expensive, creating a large economic burden for health services in many countries; the NHS, for instance, manages an estimated 278,000 venous leg ulcers every year—47% of which (130,660) do not heal within 12 months—costing over £1.7 billion. To help reduce this burden, Huntleigh has developed a new concept in wound healing. According to a statement, the Wound Express device uses Intermittent Pneumatic Compression (IPC) to increase blood flow around the leg ulcer.

Furthermore, the Wound Express system has a specially designed three chamber garment that attaches to the pump, which has a unique, patented timing cycle that augments venous and arterial blood flow. Unlike standard treatment, the Wound Express universal garment has also been designed to be placed on the thigh and not on the wound site.

Many patients adapt their lives to accommodate a wound, which often affects their day-to-day activities.

Nicky Ivins, clinical research director at the Welsh Wound Innovation Centre, spoke about how this new technology can improve patients’ quality of life:

Wound Express

“Wound Express provides the patient an opportunity to apply additional compression with the aim of increasing the rate of healing, reducing the level of oedema and exudate, and consequently reducing the overall pain experienced in the lower leg. Importantly, patients can self-manage at a time that suits them and apply a daily therapy without being dependent on a health care provider.”

Keith Harding, medical director of the Welsh Wound Innovation Initiative, describes Wound Express as “An innovative and exciting new approach for treating patients with lower limb problems”. “It has the potential to be a real game changer in managing a difficult aspect of clinical practice,” he said.

This device is ideally suited for patients to use at home, and includes portable, quiet pump which allows the two-hour therapy cycle to be delivered whilst minimising disruption to a patient’s lifestyle and daily activities.

Patients can therefore become more empowered in the self-management of their condition. Released to the UK market in September 2019, Wound Express has the potential to enable wound care specialists to increase efficiencies and to reduce nursing time visits substantially.

Pilot study of BioLexa Platform on diabetic skin ulcers achieves positive results

Hoth Therapeutics, a biopharmaceutical company focused on targeted therapeutics for patients suffering from indications such as dermatological and chronic wound disorders, has announced the initial results of a pilot study conducted on the application of the BioLexa Platform, a therapeutic compound on diabetic skin ulcers.

According to a statement, this trial was designed to establish foundational protocols for assessing the effectiveness of the BioLexa Platform—a therapeutic compound—for accelerating and improving wound healing in the context of acute and chronic diabetic ulcers, using an animal model of impaired wound healing developed at Massachusetts General Hospital (MGH), Boston, USA.

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Specific objectives of the study included optimising the method of application of the therapeutic compound (BioLexa) on diabetic skin wounds in animal models (mice) of both acute and chronic diabetic wound healing established at MGH’s Vaccine and Immunotherapy Centre (VIC). In addition to this, the trial aimed to optimise the Staphylococcus aureus (S.aureus) inoculation dose to achieve biofilm growth in the infected diabetic wound model.

An animal protocol amendment was submitted to and approved by the MGH Institutional Animal Care and Use Committee (IACUC) to allow the application of the BioLexa compound on wounds in the established mouse model chosen for the study. A full biosafety protocol was also submitted to and approved by the Partners Institutional Biosafety Committee (IBC), allowing the use of pathogens such as S.aureus, and all work as part of the study was performed in compliance with these institutionally approved protocols.

After 22 days post-injury, the animals were euthanised and the dressings on the wounds were removed in order to reveal the wounds and allow for the collection of tissue biopsies. Upon removal of the wound dressings and the obscuring cream, Ruxandra Sirbulescu (Boston, USA), who designed and conducted the pilot study at MGH, observed that the majority of the wounds, treated with either BioLexa or the carrier base control of BioLexa, were fully closed and re-epithelialised.

While the present pilot study did not include wounds treated with saline solution, previous studies in this model have shown that wounds treated with control solutions, such as saline, remain fully open ulcers at 22 days post-injury.

Preliminary data from the study suggest a benefit of BioLexa treatment over placebo in certain categories, although the company has also stated that a larger, well-controlled study is required before any clear conclusion can be drawn on treatment efficacy.

Sirbulescu remarked: “We observed complete closure in all treated wounds, which is not typical for this experimental model. Moreover, several parameters associated with the quality of tissue regeneration were significantly improved after treatment of the open ulcers with BioLexa, including better collagen deposition and increased angiogenesis.

“Our next studies will aim to confirm the observed regenerative effects of the BioLexa platform in the context of chronic diabetic ulcers, with and without substantial bacterial burden.”

Robb Knie, CEO of Hoth Therapeutics, also commented on the findings, looking forward to the next stage of development: “Preliminary results indicated that, as a wound care product, Biolexa performed extremely well in a mouse model of diabetic ulcers. Hoth is excited about the next phase of our pilot programme and look forward to sharing results upon the completion of the next module.”

22

October 2019 | Issue 01

Market watch

Industry News House of Commons debates the importance of a national wound care strategy

A member of the UK parliament has emphasised the need for a national wound care strategy during a recent debate in the House of Commons, highlighting that “diagnosis is difficult, but rapid diagnosis is absolutely essential”. Ann Clywd, MP for the Welsh constituency of Cynon Valley, brought forward the debate due to her own experience of suffering with a chronic wound.

Describing it as “the most painful thing I have ever come across,” Clywd arrived at Parliament straight from her hospital bed to speak on the subject of lower limb wound care. In response to a debate held in the House of Lords, which revealed that wound care is a massive challenge to the NHS—but one that lacks priority or investment—the MP called for urgent action to improve the standard of care.

Clywd added that “while 60% of all wounds heal within a year, a huge ​resource has to be committed to managing untreated wounds”, with the cost of treating two million patients with wounds every year estimated to be over

£5 billion.

“I am told that, ideally, 70% of venous leg ulcerations should heal within 12 to 16 weeks, and 98% in 24 weeks. In reality, however, research shows that healing rates at six months have been reported as low as 9%, with infection rates as high as 58%.”

Looking ahead to the future, Clywd warned that without a national strategy which prioritises faster diagnoses and the prevention of infection, as well as providing more investment, patients will receive worse care for their injuries, while costs for other parts of the NHS will continue to rise.

Caroline Dinenage, Minister of State for Social Care, responded: “Our priority is for leg ulcers of this type to be treated early and in the community when that is possible, without the need for further hospital admissions or GP appointments. I think that a preventative approach is right for patients and for the system. It is key for wound care to be delivered effectively and efficiently.

“That is why NHS England and NHS Improvement have commissioned the Academic Health Science Network to develop and deliver a national wound care strategy programme for England,

which aims to improve the quality of wound care provision.”

The programme, which began its work in 2018, aims to take a data-driven approach to developing national clinical standards of care, improving patient experience and outcomes, as well as working alongside the industry to ensure that wound care products are reaching patients at the right time. There are also plans to improve the provision of wound care training.

According to a statement, Crichton is working with Jenna Cash (Edinburgh, UK), a specialist in wound healing immunology, on the two-year project.

He said: “We want to understand what

Sensor technology for the monitoring of wound healing in development

Engineers at Heriot-Watt University, Edinburgh, UK, are developing a sensor that will help patients, doctors and nurses manage how wounds heal.

Wounds cost the NHS between £4.5 and £5.1 billion each year to manage, while burns, diabetic ulcers, caesarean section scars, surgical incisions and simple cuts cause significant pain to patients.

In addition, their treatment consumes a huge amount of clinical resources annually.

Michael Crichton (Edinburgh, UK), a biomedical engineer at Heriot-Watt University, has been awarded £360,000 from the Engineering and Physical Sciences Research Council (EPSRC) to develop a microsensor that will detect wound healing by monitoring the tiny, microscale mechanical changes that happen to the body’s tissue.

Heriot-Watt sensor technology

actually happens in a wound. Lots of research has looked at the biological properties of wounds, but we know very little about the mechanics of how wounds heal, especially at the microscale, which is where changes are happening at sub-hair width scales.

“The sensor will make small mechanical measurements, much like how a doctor would prod a lump, and will tell us how the tissue is changing, or whether the wound needs a different dressing or treatment.

Cash added: “Our work on the immunological response during healing is reflected in mechanical changes, and anything that combines these has the potential for new therapies in this area.”

Calendar of events 2–4 October AMP Europe: Amputation Prevention Symposium Lugano, Switzerland

11–12 October ACWH: American College of Wound Healing and Tissue Repair Chicago, USA

europe.amptheclimeeting.com

www.acwound.org

3–6 October Wounds Canada Niagra Falls, Canada

12–14 October SAWC Fall: Symposium on Advanced Wound Care Las Vegas, USA

www.woundscanada.ca

17–19 October DF Con: Diabetic Foot Global Conference Los Angeles, USA www.dfcon.com

2–4 November The VEINS at VIVA Las Vegas, USA www.vivaphysicians.org

4–6 November Wounds UK Harrogate UK www.wounds-uk.com

19–23 November VEITHsymposium New York, USA www.veithsymposium.org

26–28 January Conference of the French Society for Wound Care Paris, France www.cicatrisations2020.org

26–27 February Wound Care Today Milton Keynes, UK www.woundcare-today.com

www.sawcfall.com

June 2019

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