Suprathel Versus Hypafix in the Management of Split-Thickness Donor Site Wounds in the Elderly: A Randomised Controlled Trial
Round 1
Reviewer 1 Report (Previous Reviewer 1)
Comments and Suggestions for AuthorsThis study presents the findings of a randomized trial comparing Hypafix to Suprathel. The authors reported no difference in any parameter.
1. The authors state that they calculated the need for 40 patients (20/group) but did not account for dropouts, making this study underpowered.
2. Please describe how you determined power in more detail.
3. Was the location of the donor site on the thigh consistent between groups?
Comments on the Quality of English Languageok, needs some cleaning up
Author Response
- The authors state that they calculated the need for 40 patients (20/group) but did not account for dropouts, making this study underpowered.
Thank you for this comment. The power calculations have been clarified in lines 130-132 of this paper to demonstrate that the study remains adequately powered with groups of 14 participants per side.
2. Please describe how you determined power in more detail.
Thank you for the comment, the final paragraph contains all the figures necessary to reconstruct the power calculation carried out in this study, and I hope with the amendments described above satisfies your concerns.
3. Was the location of the donor site on the thigh consistent between groups?
Yes thank you for your comment, this was referenced in line 97 of the paper and has been edited for clarity.
Reviewer 2 Report (Previous Reviewer 3)
Comments and Suggestions for AuthorsIn the present trial the authors compared Suprathel, an epidermal temporary skin substitute, against the local standard of care dressing Hypafix, an adhesive permeable gauze, for the indication of split thickness skin graft donor sites.
Although the methods are scientifically obviously sound, the questions the authors raised - namely whether a low-cost dressing may be equivalent to a skin substitute in the healing of partial thickness wounds in the elderly - cannot be adequately answered with the study. Although there seems to be no difference in wound healing in very small (<1% TBSA) split thickness skin graft donor sites, one also has to agree that these wounds very rarely develop wound healing problems as oposed to more extensive donor sites, let alone burn injuries.
Then, Suprathel - being a temporary epidermal substitute - has its primary indication in intermediate to deep dermal burns that would otherwise require skin grafting. This is also the indication where Suprathel has its biggest advantages, as there is no additional wound surface created through donor sites, and it has furthermore also been shown to produce more favourable scars on the long run. Of course, it can be used in superficial dermal burns, however, here also other equally effective and also cheaper dressing materials exist.
The donor site of a split thickness skin graft much rather resembles a superficial dermal burn were spontaneous healing can be expected and can be achieved with a great variety of dressing regimens.
Still, the authors propose an interesting method for coverage of skin graft donor sites - however, I cannot quite understand why it was compared to Suprathel for the abovementioned reasons. It seems that the outcome could be expected and does not really ad any novel insights.
Author Response
In the present trial the authors compared Suprathel, an epidermal temporary skin substitute, against the local standard of care dressing Hypafix, an adhesive permeable gauze, for the indication of split thickness skin graft donor sites.
Although the methods are scientifically obviously sound, the questions the authors raised - namely whether a low-cost dressing may be equivalent to a skin substitute in the healing of partial thickness wounds in the elderly - cannot be adequately answered with the study. Although there seems to be no difference in wound healing in very small (<1% TBSA) split thickness skin graft donor sites, one also has to agree that these wounds very rarely develop wound healing problems as oposed to more extensive donor sites, let alone burn injuries.
Then, Suprathel - being a temporary epidermal substitute - has its primary indication in intermediate to deep dermal burns that would otherwise require skin grafting. This is also the indication where Suprathel has its biggest advantages, as there is no additional wound surface created through donor sites, and it has furthermore also been shown to produce more favourable scars on the long run. Of course, it can be used in superficial dermal burns, however, here also other equally effective and also cheaper dressing materials exist.
The donor site of a split thickness skin graft much rather resembles a superficial dermal burn were spontaneous healing can be expected and can be achieved with a great variety of dressing regimens.
Still, the authors propose an interesting method for coverage of skin graft donor sites - however, I cannot quite understand why it was compared to Suprathel for the abovementioned reasons. It seems that the outcome could be expected and does not really ad any novel insights.
Thank you for your comments. We agree with the basic point that you make, but would like to highlight the fact that the methodology described in this paper is not without the current use practice of Suprathel.
The references of this paper include examples of people using both dressings for donor site coverage, and both are an established practice in various units with which the authors have had contact. I would refer you particularly to the Schwarze, Kaartinen and Kazanavicius papers referenced here, as well as the body of literature looking at superficial partial burn treatment with Suprathel.
Despite being focused on donor sites post skin cancer reconstruction, this paper still bears relevance to burn wounds. Indeed, the uniform depth of these injuries allows for greater comparison of patient groups that may potentially not be achieved in burns. This is referenced in the second paragraph of our discussion, where we acknowledge this research is limited to superficial partial injuries. This paragraph has been edited for clarity and to highlight the current body of evidence.
Hypafix is an inert dressing and also the standard dressing used in our unit. Suprathel has here therefore been compared against our standard practice.
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis paper reports the results of a noninferiority randomized trial comparing Hypafix and Suprathel dressings on donor sites in the elderly. The authors found no difference in any parameters between the two dressings.
1. Why did you choose a noninferiority study?
2. Was histology taken to confirm healing?
3. Why skin cancer? Why not other diseases with donor sites?
4. A total of 6 patients were lost to follow-up, making the numbers in this study even smaller. Did you really have sufficient numbers?
5. A 30 day healing time is long for a graft donor site. Did the patients have suitable nutrition?
6. Patients were only followed for 13 weeks after surgery. This does not provide sufficient data to make any comments on long term outcomes (generally considered to be donor site evaluation at 1 and 2 years post-grafting)
Author Response
Comment 1: Why did you choose a noninferiority study?
Response 1:This has now been explicitly addressed with amendments to paragraph 2 of our discussion.
Comment 2: Was histology taken to confirm healing?
Response 2: No histology was taken to confirm healing.
Comment 3: A total of 6 patients were lost to follow-up, making the numbers in this study even smaller. Did you really have sufficient numbers?
Response 3: These numbers are in keeping with similar studies as referenced in our discussion. We believe that the results still have value. There are specific challenges in large randomised controlled trials discussed in this paper, and we would be happy to collaborate on this in the future.
Comment 4: Why skin cancer? Why not other diseases with donor sites?
Response 4: Agree, this has been addressed with amendments to paragraph 2 of our discussion.
Comment 5: A 30 day healing time is long for a graft donor site. Did the patients have suitable nutrition?
Response 5: Agree, this has been addressed with amendments to paragraph 5 of our discussion.
Comment 6: Patients were only followed for 13 weeks after surgery. This does not provide sufficient data to make any comments on long term outcomes (generally considered to be donor site evaluation at 1 and 2 years post-grafting).
Response 6: We agree that longer follow-up may be preferable, however this is already addressed in paragraph 3 of our discussion with references to previous studies comparing follow-up at 13 weeks with longer term follow-up.
Reviewer 2 Report
Comments and Suggestions for Authors-Throughout the manuscript do not refer to the products by their tradenames. For example: Suprathel and Hypafix should not be mentioned at all except once in the methods section. Aside from that mention, they should be referred to as a generic name
-In Table 1, please present the p value between both groups for each of the 4 bullet points to show that there was no difference between groups
-Please provide a bit more information about the type of "skin cancer surgery" these patients were undergoing. Were they the same between groups?
-Please report the race/ethnicity and/or the Fitzpatrick skin types of the patients included in this study as these factors are known to have an effect on scar formation which is one of your outcomes
-Figure 3 should include labels for what time points post excision the photos are from and efforts should be made to crop the pictures so they are a similar size across time
-Figure 4 should include a y axis label
-Figure 4 should include error bars which would be representative of the variance exhibited among each patient within the group reported in each bar
Comments on the Quality of English Language-There are some minor spelling errors that should be corrected.
Author Response
Comment 1: Throughout the manuscript do not refer to the products by their tradenames. For example: Suprathel and Hypafix should not be mentioned at all except once in the methods section. Aside from that mention, they should be referred to as a generic name.
Response 1: Where possible product are now referred to by a generic name. Exceptions to this are once in the introduction, in the dressing formulation section of the methods, and any part of the discussion where evidence related to the specific dressing is being discussed.
Comment 2: In Table 1, please present the p value between both groups for each of the 4 bullet points to show that there was no difference between groups
Response 2: This has been done.
Comment 3: Please provide a bit more information about the type of "skin cancer surgery" these patients were undergoing. Were they the same between groups?
Response 3: Skin cancer has where applicable been appended with non-melanoma skin cancer.
Comment 4: Please report the race/ethnicity and/or the Fitzpatrick skin types of the patients included in this study as these factors are known to have an effect on scar formation which is one of your outcomes
Response 4: Thank you, this oversight has been ammended in paragraph 1 of the results section.
Comment 5: Figure 3 should include labels for what time points post excision the photos are from and efforts should be made to crop the pictures so they are a similar size across time
Response 5: Please refer to the legend. These are all different (consecutive) patients at 13 weeks. Cropping these images to look similar would be misleading as they are different patients at the same time point.
Comment 6: Figure 4 should include a y axis label
Response 6: This has been included
Comment 7: Figure 4 should include error bars which would be representative of the variance exhibited among each patient within the group reported in each bar
Comment 7: We believe the fact that none of these results are significantly different is explained in Table 2. There is already a substantial amount of information displayed in Figure 4 and error bars obfuscate this.
Reviewer 3 Report
Comments and Suggestions for AuthorsThe authors present the results of a randomized controlled trial concerning two different dressings for split thickness skin graft donor sites.
The introduction and methods section provide all necessary background information to enable the reader to follow the results and the deductions made.
The results are presented very clearly, there are two minor remarks:
1) There seems to be a mistake in lines 132 and 133, here the numbers for the mean donor site areas must have been mixed up. Please correct.
2) Figure 4 is quite difficult to read because of the four different colours used. Suggest to use only two colours, as the indications "observer" and "reported" of the POSAS items are pointed out clearly in the legends below the bars.
There are tow thoughts that should be included into the discussion:
As the primary indication for Suprathel are both superficial but also deep dermal burns (this is where its biggest advantages are), a mere donor site (depth equivalent to superficial partial thickness burn) study does not adequately reflect its potential in burn injuries in the elderly - consequently this study does only reflect a small part of the potentials of suprathel.
Furthermore, it does not seem feasible to use expensive dressings such as Suprathel for donor site coverage in elective indications with expectedly low rates of wound healing complications (apart from age, which is negilible in small donor areas such as presented in the study).
Those to aspects should be mentioned in the discussion section.
Author Response
Comment 1: There seems to be a mistake in lines 132 and 133, here the numbers for the mean donor site areas must have been mixed up. Please correct.
Response 1: We agree, thank you, this correction has been made. The values are correct, the comparator has been reversed to "smaller" from "larger".
Comment 2: Figure 4 is quite difficult to read because of the four different colours used. Suggest to use only two colours, as the indications "observer" and "reported" of the POSAS items are pointed out clearly in the legends below the bars.
Response 2: Thank you for the feedback regarding colour coding of the graph. We do think that there is value in being able to differentiate the observer and reporter responses, but understand that the multitude of colours may cause issue. The graph has been recolourised and we hope that this will be less challenging to the eye!
Thank you for your additional comments. These have been addressed in paragraphs 2 and 5 of the discussion. We believe costings are addressed in the final paragraph of the discussion and agree with your comments on feasibility.
