**Transcript of Cyberseminar**

**Spotlight on Evidence-based Synthesis Program**

**Advanced Wound Care Therapies for Non-Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review**

**Presenters:  Neal A. Foman, MD, MS; Nancy L. Greer, PhD**

**May 8, 2013**

**Advanced Wound Care Therapies for Non-Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review**

**May 8, 2013**

*This is an unedited transcript of this session. As such, it may contain omissions or errors due to sound quality or misinterpretation. For clarification or verification of any points in the transcript, please refer to the audio version posted at www.hsrd.research.va.gov/cyberseminars/catalog-archive.cfm or contact:**Nancy.Greer@va.gov*

Moderator: And we are just at the top of the hour here, so I am going to introduce our presenters and discussants for today’s call. Our first presenter today is Dr. Neil Foman. He is a clinical associate professor and residency program director for the department of dermatology at the University of Minnesota. He is also a fulltime staff dermatologist at the Minneapolis Veteran’s Affairs Healthcare System. Originally from Boston he received his BA from Cornell University, his MS from State University of New York at Buffalo and his MD form Albany Medical College. His areas of interest are wound care, graduate medical education, patient education and teaching dermatology to primary care providers. He is joined by Nancy Greer; she is a health science specialist at the Minneapolis VA Healthcare System and the Program Manger for the Minneapolis site of the VA Evidence Based Synthesis Program. She is also affiliated with the Minnesota Evidence Based Practice Center, of VA and University of Minnesota Collaborative under the Agency for Healthcare Research and Quality. Prior to joining the VA, she was the manager for healthcare evidence analysis at the Institute for Clinical Systems Improvement where her primary responsibility was the development of over 50 technology assessment reports. Our discussant for today is Jeffrey Robbins; he is the Director of the Veterans Health Administration Headquarters Podiatry services and the Chief of the Podiatry Section at the Louis Stokes Cleveland VA Medical Center. He is a graduate of the Ohio College of Podiatric Medicine, Cleveland Ohio where he also holds a faculty stature of Professor of Podiatric Medicine. He is board certified by the American Board of Podiatric Orthopedics and Primary Podiatric Medicine and the American Board of Podiatric Public Health, and is a fellow to the American College of Foot and Ankle Orthopedics and Medicine. With that I am going to turn things over to Dr. Foman.

Dr. Foman:Good morning everyone, pleasure to be here with all of you. For the next 45 minutes or so Dr. Greer and I will be discussing advanced wound care therapies for non healing diabetic venous and arterial ulcers, a systematic review. We know there are lots of experts on the line, thank you for joining us, at the end of our conversation today we would welcome dialogue, differing opinions and any questions that you might have. Before we begin I would like to acknowledge our coauthors and collaborators as well as our expert panel and reviewers who you see pictured on the slide in front of you. A little bit about the evidence based synthesis program before we begin talking about our topic, this report is based on research that was conducted by the evidence based synthesis program center which is located at the Minneapolis VA Medical Center. Funding for this does come from the Department of Veteran’s Affairs, the Veteran’s Health Administration, the Office of Research and Development as well as Quality Enhancement Research Initiative. It’s important to point out that the findings and conclusions in this document are those of the authors. The findings do not necessarily represent the views of the Department of Veteran’s Affairs or the United States government. I would also like to point out that no investigators have any affiliation or financial involvement that conflict with the material presented in this report. 

So the VA evidence based synthesis program was established to provide timely and accurate syntheses or reviews of healthcare topics that have been identified by VA clinicians, managers, and policy makers as they work to improve the health and healthcare of Veterans. There are currently four centers in the country that conduct evidence based research at the Durham VA Medical Center, the VA of the Greater Los Angeles Healthcare System, the Portland VA Medical Center and here at the Minneapolis VA Healthcare System. The purposes of the evidence syntheses are to develop clinical policies that are informed by evidence so then implement effective services to improve patient outcomes and to support VA Clinical Practice guidelines and performance measures. And lastly to guide the direction for future research to address gaps in clinical knowledge. There are many others that are involved in the evidence based synthesis program, there is a steering committee that represents research and operations and provides oversight and guides the program direction. There is a technical expert panel that is recruited for each topic to provide content expertise. They also help to guide topic development and refine the key questions. And there are external peer reviewers and policy partners who review and comment on the draft report. Final reposts are posted on the VA HSR&D website and the link to that is picture here.

So the repost that we’ll be discussing today is our report on advanced wound care therapies for non healing diabetic venous and arterial ulcers which was completed in November of 2012. If you are interested in reviewing the full length report, it is available on the ESP website and the link is in front of you. So some background for our work, non healing ulcers are wounds that are unresponsive to initial therapy or that persist despite appropriate care. If ulcers do not heal with standard treatment then advanced wound care therapies are considered. There is a large and growing array of advanced wound care therapies that are being developed, but their efficacy, comparative effectiveness and harm are not yet well established. Just want to present a little bit of the scope of this problem on a clinical level, approximately 1% to 3% of the US population or up to nine million people are affected with chronic leg ulcers. There are considerable costs associated with the diagnosis and treatment of leg ulcers to the tune of about eight to ten billion dollars per year in the United States alone. There is also significant morbidity associated with leg ulcers, again to the tune of about two million lost work days per year. So that you can see this is a very significant healthcare problem. 

The purpose of this review was to evaluate published randomized controlled trials of the efficacy and harms of advance wound care therapies compared to either usual care of another advance wound care therapy. In treating leg ulcers the most important step is to identify the pathophysiologic cause of the ulcer and then to direct treatment accordingly. Overall the goal is to preserve function of the limb and to prevent associated morbidities for the patient. Diabetic ulcers are ulcerations that are secondary to peripheral neuropathy and microvascular compromise seen in diabetes. These ulcers comprise up to 10% of chronic lower extremity ulcers. Approximately 20% of those who have diabetes will develop a foot ulcer in their lifetime and up to twenty 5% of these patients will require an amputation. So this is a picture of a typical diabetic foot ulcer, as you can see this is the bottom of the foot. These ulcers are very typically well defined, they have sharp borders, they can be very deep as you can see in the center and often they research surrounded by a thick callus. They tend to occur over pressure points on the bottom of the foot.

Going on to discuss the second type of ulcer that our work studied, venous ulcers; these are typically caused by venous insufficiency. They are often called stasis ulcers, these are by far the most common type of chronic leg ulcer accounting for seventy to 80% and they most commonly arise secondary to either varicose veins or postphlebitic syndrome. Here is a picture of a typical venous leg ulcer, often the edges are very serpiginous, jagged, they can be shallow or they can be deep. The surrounding skin will often give you a clue to whether or not this is a venous ulcer, the surrounding skin tends to be either very inflamed or red, or it might show brownish hyper pigmentation and often you might be able to appreciate some wrinkling here. Often there is edema in the extremity that will lend support to the notion that this patient has venous insufficiency. 

The last type of ulcers that our work considered is the arterial ulcer, this is usually caused by peripheral arterial disease, tends to be referred to as either arterial or ischemic ulcers. These comprise about 6% to 10% of all chronic leg ulcers and the major risk factors for these ulcers are peripheral arterial disease, cigarette smoking, and diabetes. A picture of a typical arterial ulcer, they’re often on the very distal parts of the extremity and as opposed to the diabetic ulcers which are often on the bottom of the feet, these tend to occur on the top of the feet. Again their borders are very sharp, very well marginated and there often is surrounding inflammation of the skin. So the key questions that our work considered are number one, what are the efficacy and harms of therapies for diabetic ulcers? Is the efficacy dependent on axillary therapies? Does efficacy differ according to patient demographics, comorbid conditions, treatment compliance or activity level? Our key questions two and three were the same questions in relation to venous ulcers and arterial ulcers. And I will turn the discussion over to DR Greer.

Dr. Greer:I’m going to go through the methods and results of our review, the methods were fairly typical and systematic reviews we did a Medline search from 1995 to august of 2012, plus we did a hand search of reference lists of eligible trials and recent systematic reviews. We did update the search in March of 2013 and found no additional studies that would have been eligible for inclusion. We focused on randomized controlled trials enrolling human subjects 18 and over and the trials had to be published in the English language. As Dr. Fomar said we focused on non healing lower extremity diabetic venous and arterial ulcers. We excluded acute wounds, surgical wounds and pressure ulcers and we included only studies reporting a percentage of ulcers healed at study completion or time to complete ulcer healing as an outcome, they had to report one of those out comes to be eligible. We included 11 categories of interventions, some biologics, some other kinds of products silver and oxygen and some mechanical types of interventions. We did find no trials of topical oxygen therapy that met our inclusion criteria. Our main outcomes of interest were the proportion of ulcers healed at study completion, time to complete ulcer healing, patient global assessment and return to daily activities. Secondary outcomes are listed there including infection reoccurrence, quality of life and adverse events. We organized our findings by the ulcer type, diabetic, venous, arterial, we found some studies that mixed the three different categories and then we also had one study of an amputation wound. We’re going to focus to day on the diabetic venous and arterial and we categorize the ulcer type based on the author of the trials description of what the ulcer types were. 

The quality of individual studies was assessed using established criteria for determining risk of bias and randomized controlled trials, modification of the Cochran approach with allocation concealment, blinding, intention to treat analysis and withdrawals explained. We did pooled analyses where it was feasible as you‘ll see it wasn’t’ feasible for many of the interventions. We determined strength of evidence fort the percentage of ulcers healed and time to complete ulcer healing using the method of Owens, a 2010 reference focusing on risk of bias, precision, directness and consistency. Our literature flow diagram, our literature search yielded over twelve hundred titles and abstracts. We did a full text review of 177 papers, we added 21 from hand searching reference lists and so on and ended up with a total of 68 articles representing 64 trials, 35 dealing with diabetic ulcers, 20 trials with venous ulcers and one with arterial ulcers. For the diabetic ulcer trials 25 compared advanced therapy to usual care or placebo, ten compared advanced therapy to another advanced therapy. Mean ulcer size and mean ulcer duration as you see on the screen, the location of the site of the ulcers as it was described by the author was a foot ulcer in 26 trials and a lower extremity ulcer in 7 trials. Trying to get at some of the other factors, 11 trials reported that the ulcer was neuropathic and 16 trials reported that the participants were required to have adequate circulation or they excluded people with severe arterial disease. 

This table summarizes our findings for the outcome of proportion of ulcers healed in the trials, the diabetic ulcer trials that compared an advanced therapy to standard care of placebo. On the left column you can see the different therapies that we found, we have eight categories overall, we separated out the two different types of biological skin equivalent. There were as you can see in the column next to that there were very few trials of each intervention category, one, two, three as you can see there and very...in some cases there were small trials. The next two columns the column title advanced therapy superior that’s showing the number of trials for a particular intervention that found the advanced therapy superior to the standard care or placebo and then the column next to that is the trials finding no difference. So for example for collagen, one trial found the advanced therapy of collagen superior, three trials found that there was no difference between the collagen and standard care of placebo. So you can see overall for most interventions the results are mixed, some trials finding positive outcomes, some not and our strength of evidence for these interventions again for the proportion of ulcers healed, was most low. Two acceptations, moderate strength of evidence for the biological skin equivalent apligraft and for negative pressure wounds therapy.

This next table is similar showing the proportions of ulcers healed in diabetic ulcer trials where an advanced therapy was compared to another advanced therapy and again we broke out the different biological skin equivalents so there are six categories of...we broke out silver cream and silver dressings so there were six categories, why aren’t there six rows of [inaud.] Anyway so we broke those out and overall six interventions again a few trials and small trials, 26 in a trial, 28, 24, and so on. So relatively small trials and this is showing that in with the exception of hyperbaric oxygen therapy, there was not difference found between the advanced therapy we were looking at or the focus of the trail and the comparator. In the hyperbaric oxygen therapy trail extracorporal shock wavy therapy was actually superior to hyperbaric oxygen therapy. And the strength of evidence for each of these comparisons was rated as low. The polled results and as I said we were not able to pool a whole lot because of even within a product category there were different product that were being used and different regiments and so on, so it was difficult to pool things. For the biological skin equivalent versus standard care there were three trials, the absolute risk difference was 11%, relative risk 1.49 and that was a non significant finding across the pool trials. For the biological skin equivalent Apligraf we did find a significant difference, the average risk difference of 21% and for the platelet derived growth factors we did also find a significant difference but it is important to note the I2 value, that’s a measure of heterogeneity showing that there was an 85% is a very high number, showing there was a lot of variation across trials and therefore our confidence in that conclusion is not strong. The I2 for Apligraf was zero which is obviously very good; the I2 for the dermograph was in the moderate range.

Other main outcomes, time to ulcer healing was reported in 24 of the trials and overall there were either no differences or mixed results as strength of evidence was rated as low or insufficient for all of the therapies. The global assessment was only reported in one trial and returned daily activities were not reported in any of the studies we included. Secondary outcomes, amputations, revascularization surgery, quality of life are ones that did find some differences or fewer amputations in one of two trials reporting on biological skin equivalent. There was only one trial of negative pressure wound therapy; they did report fewer amputations in the negative pressure wound therapy group. And hyperbaric oxygen, one of the three trials that reported amputations found fewer amputations. For revascularization surgery only five trials reported quality of life only one trail reported. There were not differences in any other outcomes and there were no differences in other adverse events such as reactions to therapy and so on. We did also look at mortality although the studies were not powered to assess mortality but we found no difference in mortality. And the second part of each of our key questions was dealing with demographics, comorbidic conditions and overall very very studies reported anything that would allow us to assess whether the efficacy or comparative effectiveness differed according to those factors. So we just have to conclude that there was insufficient evidence for that part of the question.

For the venous ulcers there were 16 trials that compared advanced therapy to usual care or placebo and four that compared advanced therapy to another advanced therapy. Mean ulcer sizes and ulcer durations are reported there, and again as far as how the ulcer was categorized, 14 trials listed the ulcer as a leg ulcer, three as a lower extremity ulcer. The location of the ulcers was not typically very specified to a great deal in these trials. The diagnosis was based on signs and symptoms of venous insufficiency in 12 trials and eight trials required adequate circulation. The same type of table as we saw for the diabetic ulcers, this again is proportion of ulcers healed. For venous ulcers in trials that compared advanced therapy to standard care, there were nine categories of interventions again we split the biological skin equivalents and the silver cream and silver dressing, and as with the diabetic one allowed one and two trials for each intervention category and some small sample sizes within those trials. You can see that for venous ulcers there were fewer studies that found the advanced therapy superior and in a lot of cases there were mixed findings, one trial positive, and one trial with no difference. And again our strength of evidence was low for all things except keratinocyte therapy. This table is showing the proportion of ulcers healed in the venous studies when advanced therapy was compared to another advanced therapy. And there were only two categories of products there, the keratinocytes and silver products with again small numbers of trials. In two cases there was no difference between the advanced product and another advanced product, in the one case silver cream was superior to a tripeptide copper cream. But given the low numbers and the strength of evidence was low.

Pooled results for the venous studies again we were only able to pool a few studies for a few interventions. Again this is looking at ulcers healed, there was a significant finding for the keratinocyte and with the I2 is low so that is indicating some confidence unless our moderate strength of evidenced for that intervention. Silver cream and silver dressing non significant findings with high I2 values so again heterogeneity and calling into question a lot of, any kind of conclusion we could make about those studies. Other main outcomes reported in the venous trials the time to ulcer healing was only reported in seven trials and you can see there no difference with the silver dressing and that was only reported in one trial. Shorter time to ulcer healing with biological skin equivalent also reported only in one trial. Mixed results or in several cases significance was not reported so the strength of evidence was low or insufficient for time to ulcer healing for all of the interventions. The global assessment of patient global assessment three trials reported a silver dressing and a silver cream trial finding a better outcome in electromagnetic therapy finding no difference. Return to daily activities again very little reported. Secondary outcomes ulcer infection was reported in eight trials only one of the eight, a collagen trial finding a significant difference with fewer infections. Ulcer recurrence reported in seven trials again, only a biological dressing finding fewer recurrences, pain similar. But again other outcomes and adverse events were no differences so I guess the conclusion could be that the therapies are no worse as far as adverse events than the existing or the comparators. And again the question about patient demographics, comorbid conditions, compliance, activity level, we were unable to answer that question because of insufficient evidence to report in technology trials.

For arterial ulcers we only found one small trial, 31 participants and ti compared an advanced therapy to usual care. Mean ulcer size was 4.8cm; this was treatment for the ulcer following revascularization surgery. There was a significant improvement in ulcer healing and time to healing with the advanced therapy. There were no differences in any other outcomes and no information on the affect of baseline characteristics treatment compliance or activity level on healing. So with that I am going to turn it back to Dr. Foman for the discussion.

Dr. Foman:Thank you, so where does the systematic review lead us clinically and how can this help us in the care of these patients? So again we know that chronic low extremity ulcers are a very common and very significant health problem. We’re all familiar with a wide range of standard treatment approaches that have been available for a long time such as off loading, compression and leg elevation. Many ulcers do heal within several weeks but up to a third either do not heal ever or actually become larger and deeper as time goes on. These are the difficult ulcer to treat and they can result in considerable clinical morbidity and healthcare costs. So fortunately an increasing number of advanced treatment modalities are becoming available to aid with these difficult wounds. Most advanced wound care therapies do come with a considerable cost and this is something that we all much consider when we select a treatment, especially when we compare the cost of standard care. However these costs might be justified if they result in improved ulcer healing, reduced morbidity, fewer lower extremity amputations and improved patient functional status. So as Dr. Greer pointed out there were many limitations to the studies that we reviewed. A lot of them had a very narrow patient population that is they had a limited enrollment. Many of the trials were industry sponsored; the definition of chronic ulcer did vary quite significantly from study to study. Few of the studies were of long duration, in many cases advanced therapies were compared only to standard therapy as opposed to being compared to another advanced therapy. The methodological quality of the studies was mostly fair or poor and one thing we don’t know is how effective standard care was for each patient prior to entering each of these study trials.

Our systematic review of randomized controlled trials found discouragingly low strength of evidence regarding the effectiveness of advanced wound care therapies for treatment of lower extremity ulcers. For each of the three major ulcer types, diabetic, venous and arterial, specific advance wound care therapies were only evaluated in a few studies, often in highly selected populations and frequently with conflicting findings. Regarding the diabetic ulcers, some conclusions that we can make are that there is moderate strength of evidence with the biological skin equivalent Apligraf and negative pressure wound therapy which both were seen to improve healing compared to standard care. There was low strength of evidence found for collagen, the biological skin equivalent Dermagraft, platelet derived growth factor, silver cream or hyperbaric oxygen, improving the percentage of ulcers healed compared to standard care. Also for diabetic ulcers, pooled analyses or data from a single good quality study demonstrated significant improvement in ulcer healing for Apligraf, one of the biological skin equivalents, platelet derived growth factor and negative pressure wound therapy again compared to standard care. No improvement was seen in ulcer healing for Dermagraft, another biological skin equivalent and no studies reported a significant difference in adverse events for any treatment comparison. 

For the venous ulcers some individual trials of Oasis which is a biological dressing, Apligraf again a biological skin equivalent, keratinocytes, silver cream and dressing and electromagnetic therapy noted significant benefit in the percentage of ulcers healed compared with standard therapy. Overall however, the results for each therapy were mixed, in pooled analyses with venous ulcers, keratinocytes resulted in significantly better healing compared to standard therapy. Strength of evidence was moderate for keratinocytes and low for all of the other therapies. And again no advance wound care therapy was observed to result in an increase in adverse events. And lastly for arterial ulcers only one study was identified for the purposes of this review. One thing to note though is that probably 10% to 20% of ulcers have a mixed etiology and many of these probably included an arterial component so that does need to be teased out in future work.

Apligraf increased ulcer healing and decreased time to healing compared to standard care and there was no difference in adverse events observed. So we found insufficient evidence to guide clinicians and policy makers regarding whether efficacy differs according to patient demographics, comorbid conditions, treatment compliance or activity level. It’s important to note that this review looked at only studies of FDA approved products, studies with wounds of multiple etiologies for example vascular ulcers, pressure ulcers or trauma indued ulcers were excluded if they did not report results by specific etiology. And the studies did not report primary outcomes of healed wounds or time to complete healing, these studies were all excluded. Also cost effective analyses were not conducted in this work, but despite the high cost of advanced wound care therapies, they may actually be cost effective or even cost saving if in the long run they lead to wound healing, decreases ulcer associated morbidity and improved functional status. 

So recommendations for future study, we need to find studies or see studies that will compare advanced therapies to each other and not just to standard care. Future research should also examine microvascular disease to more clearly distinguish diabetic from strictly arterial ulcers. More studies are also needed on advanced wound care therapies in patients with strictly arterial disease and several organizations have outlines overall methodological standards for future research of would heal therapies and these are found in the full report. So if there are further questions after today’s discussion you can certainly contact Dr. Greer and here is her contact information. Again the full report is available on this link. And what we’d like to do now is hand over the discussion to Dr. Robbins, thank you.

Dr. Robbins:Thank you both Dr’s Foman and Greer for that greater presentation and the outstanding work that you have done on this project. I know that many of you on the call will be wondering how we can use this information to derive meaningful change to our specific system of care. How do we operationalize this data? What is clear is that there is not a lot of strong evidence to support using a lot of our advanced wound care products currently in use at many medical centers. At the same time if they were to have researched debridement for example, they would have found little evidence to support its use either but it’s still considered the standard of care and we wouldn’t dream of not doing debridement. The level of evidence there is expert opinion and consensus so the real question is how do we balance the need to use the highest levels of evidence to make our clinical decisions with that are part of wound care? How do we use new and emerging products that show promise in healing wounds? 

Well currently we are discussing nationally this issue and plan to provide some guidance to the field on the criteria for use methodology that we help will drive the use of these products and technology and put some science behind them. The purpose is not to prevent their use but rather to set a standard for when they can be used and when they should be used. So for example it’s clear that all wound care providers should be doing the following at the presentation of a wound or an ulceration. They should be doing the appropriate wound assessment, assessing whether there’s infection, whether there’s ischemia, whether there’s a venous involvement, deswabing the characteristics of the wound, the location, the size, the wound, that odor erythema etc. At the same time keeping in mind that the protoplasm, the general medical conditions are essential for healing the wound and control of those systemic conditions, diabetes, hypertension, heart disease and so on. And then of course instituting proper initial wound care based on whatever that standard is and if you go back to the 1999 ADA guidelines, those would include a moist wound environment, debridement and offloading.

 If we can’t demonstrate these interventions, no amount of advance wound carte products is going to help; it’s just not going to heal. We understand that circumstances however present on occasion where a deviation from the standard of care is necessary and that’s okay as long as the rational for those deviations are documented in the assessment portion of the record. I think that is going to become increasingly more important. Not only will we be recommending an algorithm based on the evidence, we also plan to recommend local policies and decisions be made by either an existing pave committee, A Prevention Amputation and Veterans Everywhere or wound care committees based on the criteria for used recommendations. The idea here is to provide national recommendations but to have it driven locally, this will allow for local input in the process. For example the products and technologies that have moderate levels of evidence may be allowed for use trusting the providers will follow the algorithm or have documented a rational for not following it. This can be followed up with provider chart reviews and included in the mandatory local provider performance evaluations; the PPE’s that we have to do anyway. Those products that have low level of evidence may be restricted and require a request consult in which they indicate the necessary information for the use of the product that can be embedded right into that consult template. So it wouldn’t necessarily require a person identifying it or reviewing it although that is certainly an option.

For an example, a patient who failed to reduce by 50% in four weeks of standard therapy which included proper offloading and that really needs to be assessed, because that’s probably the single most important limiting factor in standard of care would therapy before you get to advanced wound care products is that offloading issue. But let’s say that they used proper offloading and that they failed to reduce by 50% in four weeks and the clinician decides they want to use an approved advanced wound care product, they can do so for an additional two weeks. And the committees, the local committees would make a determination for how long an advanced wound care product should be used before seeing some kind of improvements, so you may limit that to two weeks or three weeks, or four weeks that the committee preapproved for the use of that particular advanced wound care product before having to reconsult. And lets say that also failed to improve, and at that point the request for another advanced wound care product that may have low levels of evidence maybe be proper for approval. The point to all this is to ensure that we’re using sound principles in our decision making regarding wound care products and technologies to give our patients the best chance of healing. We anticipate providing this criteria, it’s still being discussed so I’m happy to receive any kind of feedback on those ideas and other ideas, but we hope to provide that for guidance in the not to distant future. And let me stop there and see if there are any questions for discussion for either Dr. Greer, myself or Dr. Foman.

Moderator: Great thank you, we actually have only received one question at this point, but just let the audience know that if you don’t know how to submit a question please use the Q&A screen and go to Webinar to submit that into us. The Q&A screen is located on the dashboard on the right hand side of your screen, just click on that orange arrow at the upper right-hand corner of your screen if it has collapsed against the side of your monitor. And the one question we’ve received so far, this has been a very interesting discussion, with all the new advanced wound care products being introduced all the time, how can you keep the provider or practitioner’s preference out of the decision process and be able to do a trial to prove it?

Dr. Robbins:I’m happy to start the discussion if I might, that was specifically the purpose for the second level of approval. If a clinician for example brings a particular product that they feel has merit, has value, and would like to try it, local medical centers can determine and basically by policy, allow for a field test at their facility to use that particular product. All of these products obviously have to be approved by the FDA and basically the FDA does that by showing that there’s no harm which is obvious because the level of evidence on most of these products is low and only a couple or few are moderate. So when, and that’s the real question here, how do we insure that clinicians can use new and emerging products and technologies, and the way to do that is to define an oversight system locally and that requires a special permission and oversight by this committee that they agree to in advance on those business rules. So for example the business rule may be that if you haven’t used photo contact casting as an offloading, we’re not going to allow you to use an advanced wound care product or an instant total contact cast or a cast [inaud.], whatever the offloading is because we know there’s high levels of evidence for that. So we can determine those, now if a patient can’t have those then we might want to reconsider. So this is going to have to be done on a committee structure basis as opposed to a single individual making those decisions based on a policy. A field test certainly can be done and approved with eyes wide open with the committee’s approval to do that. A limited number of patients defining the criteria for that particularly pilot and I think that that’s going to be a smart way of addressing it.

Dr. Greer: Sorry, I would just add...

Moderator:No, go ahead.

Dr. Greer:That it’s a difficult question when...  and ideally products could be blinded but that’s not feasible for many of these products. So at the very least in a research situation the outcome assessment should be blinded. The people doing the outcomes should be assessing the quality, the feeling and so on without knowledge of the intervention. And again I also realize that that’s not 100% possible either but that would be the goal in the research setting.

Dr. Robbins:Yes and I think that I was not addressing research or a trial and I think that that’s an important distinction. If you’re going to do a trial or a research project that requires IRB approval, absolutely. What I was referring to was a field test which is something different, that is this is a new product that has been approved by the FDA; we want to try it, that’s different than doing an actual research project.

Dr. Greer:Yes, I agree.

Moderator: Okay great thank-you, the next question we have here, is compression now considered standard therapy?

Dr. Foman:I’d like to start with a comment on that. Compression is definitely very important treatment for venous ulcer and I would say it really is the gold standard. Again as I mentioned earlier in the presentation, it’s extremely important to determine the etiology of an ulcer before you go ahead and treat it. You do not want to compress a leg in a patient who has significant peripheral arterial disease or they will end up with significant complications. But once you do determine that an ulcer is strictly venous in nature, compression absolutely must be part of that patient’s therapy.

Moderator: Okay great thank you, the next question I have here, this is directed towards one of you three, I’m not sure who. Basic care includes offloading moist environment and the questioner did not catch the third item.

Dr. Robbins:That was debridement.

Moderator: Great thank you, the next question here, I’m curious if you considered examining total contact casting as an advanced therapy?

Dr. Robbins:Actually total contact casting is not, or offloading is not considered an advanced wound care therapy. It is considered the gold standard for offloading. So id I had to write a hierarchy of offloading, total contact cast would be on the top, instant total contact cast would be the second and I’ll explain what that is, cast boot with cutout would be the third, and surgical shoe with cutout would be the last. Now the instant total contact cast is essentially a cast boot or a CamWalker with a removable pegs that can be removed to offload the lesion and what makes it significantly different than just simply that same device is that a piece of either plaster or fiberglass or even duct tape is placed around it so that the patient wears it all the time. The difference between one, two, three, and four is passive versus active. If a patient can remove the offloading, then it generally is not going to be effective because they will remove it despite what we tell them. So one and two, total contact cast and instant total contact cast are more passive in that they are worn all the time, they can’t walk, they can’t stand and do dishes, they can’t walk in their house without the offloading device and there are some very, very good papers done on those topics that show very definitively that they are much more effective than the ones that can be removed.

Moderator: Okay great, thank you, the next question I have here, do you know if any VA’s are running trials investigating one advanced therapy versus another?

Dr. Robbins:I do not, I’m unaware of any at this point in time but I don’t have my finger on the pulse of all the research.

Moderator: Okay, we can’t expect you to know everything so that’s fair. The next question I have here, you changed terminology from standard therapy to usual therapy in the study of presentation, how do you differentiate these terms?

Dr. Greer:I think in this context we were using them to be the same thing. We were looking at the individual studies to see what they reported, did they report offloading, debridement and so on as being required as part of the therapy. We rarely found any level of detail about that in the individual studies so I apologize, I think standard care and usual care were synonymous for today’s presentation.

Moderator:Okay great thank you, the next question I have here, one of the advanced products listed was collagen, was this actually collagen or collagenase?

Dr. Robbins:No, collagenase is a debriding enzyme, no these were collagen products that are generally used to lay down a scaffolding so that collagen can be deposited into the wound is the operational theory. So no, these are not collagenase, it’s actual collagen products.

Moderator: Okay great thank you, the next question here, has there been any discussion regarding monitoring of the wound care therapies at home, in acute care settings or in our community living centers? I think this would be very interesting given wounds that are slow healing of mixed etiology.

Dr. Robbins:Actually I am in discussions right now with the Telehealth folks at Central Office on just this topic. There are some issues that bothered me for a long time, for example we have patients with chronic wounds that we force to come to our clinics and walk on their wounds in order for us to check them once a week. When we could theoretically do that very easily in their homes especially now with all of the technology that we have and the ability to take high resolution images of that a clinician could remotely could be evaluating every week, three times a week if they could. So I am talking with the folks in Telehealth and we are looking to pilot a project like this at some point in time. CLS’s is another issues as well, we’re also trying to do that here, we do have some technological barriers to doing that but the same thing could be true. A remote clinician with a good nursing staff that is on site at the CLC could provide very high level care for those patients in Direct Vet care remotely. So I agree with you, I think its very exciting, I think it’s time has come but we need to workout some of those issues regarding the technology and sending images through the ether.

Moderator:Okay great thank you, the next question I have here, compression for how long is the best?

Dr. Foman:That really is very patient dependent, some wounds heal very quickly and some would heal very slowly. So really patients do need to be monitored on a very regular basis. We tend to see our patients once a week in our clinic and you adjust your compression therapy based on their response to your treatment.

Dr. Robbins:I would also add that after the wound is healed, the answer to that question is forever.

Dr. Foman:Absolutely.

Moderator:Okay great thank you, the next one I have there is actually a comment. We are increasingly seeing bariatric Veterans with long histories of poor or slow wound healing, unable to manage care at home, or they live in homes or in unstable housing settings with poor social supports or increased needs for support in ADL’s that have limited availablility in many community settings.

Dr. Robbins:Well that sounded like a statement.

Moderator: Yes, it was just a comment being sent in.

Dr. Robbins:Well I appreciate that comment, I just wanted to address that because I do appreciate that comment and that is precisely why I’m working with the office of Telehealth to see if we can develop some kind of a system that may provide some relief for even that group of patients. I think we have to maximally utilize the technologies that we have available to us to improve care and to do that kind of outreach, so I’m right there with you.

Moderator: Great thank you, the next question here; did all of these studies include offloading?

Dr. Greer:Again that was something we looked for but it was not consistently reported, and certainly even less reported was compliance with offloading. Some would say that they were getting the advanced therapy in addition to standard care, and they would mention offloading, debridement and so on, but then not report compliance with that. A few studies did report compliance but very few.

Moderator:Okay great thank you, the next question, will these policies affect any provider treating LE wounds in the VA system or only the podiatrists?

Dr. Robbins:Anyone providing care, these are not just podiatrists; the idea is this is for...these are a criteria for use for wounds not for a profession.

Dr. Foman:And I would just add that treatment of leg ulcers in general, foot ulcers in general is definitely a multidisciplinary approach where podiatrists are working with surgeons with dermatologists, with wound care nurses. It’s a very multipronged approach.

Moderator:Okay great thank you, the next question here, I’m going to be fully honest, there are a couple words in here I’ve never seen before and I am going to butcher them pretty badly when I am pronouncing them here. I apologize profusely, please bear with me if you guys don’t understand what I’m saying please ask me to repeat and I will repeat this question. Is the VA currently utilizing autologous therapy to stimulate angiogenesis for chronic non-healing wounds? It’s cheaper than negative pressure therapy as well as quicker.

Dr. Robbins:Which autologous therapy, well I can’t ask that question, if they’re talking about plasma rich proteins, then yes we are using those in some places and again the level of evidence is low and I have not seen the study that you’re referring to in terms of cost savings. But again the pharmacoeconomics data really has to be looked at with a grain of salt because it doesn’t address the efficacy of the product; it just looks at overall costs. And so it is suspect, it is not necessarily by itself a reason to use or not use so we really have to look at that information. And I’m assuming you are talking about plasma rich proteins and if not ask another question.

Moderator:Great thank you, the next question here, when do you recommend starting home based pumping for healing and continued therapy?

Dr. Foman:So again I can speak to largely the treatment of venous ulcers and as Dr. Robbins said earlier compression therapy is absolutely a permanent mainstay of treatment for all venous ulcers. In a perfect world you want to get a patient to the point where their edema is decreased enough that they’re able to use compression stockings on a daily basis. Some patients for whatever reason they might not be able to reach their lower extremities or their edema is just too significant. They may not be able to use compression stockings and that’s a case where a pneumatic compression device might be helpful for them, and someone would use one of those devices either daily or two or three times a week to help to minimize their edema.

Moderator: Okay great thank you, the next question, did any of the types of wounds discussed respond; heal better when compared to the other types once nutrition was adjusted?

Dr. Greer:I’m not sure if you’re comparing wound types or wound products, but we did not find any evidence that we wanted...we had that as a...in the back of our heads to look for nutritional status as a factor but we did not find any information about that.

Dr. Robbins:And I’d like to make a comment about that as well because I think that whoever asked this question is once again right on the money. I refer to that a little bit in my comments when I talked about the protoplasm of the...and the systemic conditions of the patient. We cannot prematurely focus on a wound, we need that macro look but we also need a micro look as well, and wee need to make sure that all of the variables that we can adjust and intervene with are adjusted and intervened. And certainly nutrition and nutritional status is one of them, so I agree and I know that in our wound care clinic, the nutritional status is one that is reviewed on a regular basis with patients to ensure that they get proper nutrition and that some of the clinical indicators are prealbumin, the albumin, are inline with norms and with wound healing.

Moderator: Okay great thank you and that actually does conclude all of the questions that we have received for todays, oh one just came out, I’ll try to sneak this in here. In light of the study and planned future recommendations, what is being done to improve access to vascular and podiatric services within the VA, particularly to the Veterans living in the areas services by CVOX?

Dr. Robbins:Well I will tell you that in many cases, and that is so VISN dependent and variable and it’s almost medical center dependent and variable, it really depends on the demand for care. I will tell you that in my VISN for example, almost every CBOC has podiatry and at least two or three times a week if not every single day, so it really is dependent on the particular VISN and what the demand is. As more demand comes in, then the more attention is paid, that’s the nature of our system.

Moderator: Okay great thank you, with that, that does conclude all the questions that we have received so I’m going to end that part of today’s’ session. I do want to thank our presenters and discussants for today’s presentation; we really appreciate the time that you all put into preparing and presenting for today’s cyber seminar. The audience obviously we got a ton of questions a ton of really great questions, the audience obviously really was very interested in today’s topic so thank you very much for the time you put into this. For our audience thank you for joining us for today’s ESP Cyber Seminar, as you leave today’s session you will be prompted with a feedback survey, if you could take a few moments to fill that out we do read through all of that feedback and we do make a lot of changes dependent on the responses that we get in the feedback survey. So thank you everyone for joining us for today’s spotlight on evidence based synthesis program cyber seminar, and we hope to see you at a future session, thank you.

Dr. Robbins:Thank you everyone.

Dr. Foman:Thank you.

Dr. Greer:Thanks.

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