Submission Title. The scourge of chronic venous leg ulcers is topical zinc the answer? A review of the literature. Category. Nursing & Midwifery

Transcription

1 Submission Title The scourge of chronic venous leg ulcers is topical zinc the answer? A review of the literature Category Nursing & Midwifery Word Count 3,393

2 Abstract Venous leg ulcers (VLUs) are chronic leg wounds which can have a debilitating effect on the physical and psychological health of patients. Older patients, who are a vulnerable group, suffer from VLUs more frequently and they are on the increase as the population ages. Venous leg ulcers also pose a serious cost to the health service. Zinc, in the form of topical creams and lotions has been used in wound care for over 3,000 years and today it is contained in a variety of wound care products which are used to treat chronic venous leg ulcers. Aim: This aim of this review is to undertake the first in-depth analysis of whether topical zinc based wound products are effective in promoting the healing of venous leg ulcers. Methods: Following a systematic search and review of literature, based on selected keywords, eleven studies were identified as being relevant and data extracted using content analysis. Results: The results show that there is currently very poor quality evidence to suggest that topical zinc based wound products are effective in healing venous leg ulcers; either in conjunction with compression therapy, as compression bandages themselves, or as a topical skin protectant. Some of the studies were sponsored by industry which calls into question the validity and reliability of their results. Conclusion: It is apparent that not only was much of the literature conducted on a small-scale, it is also outdated and methodologically inconsistent. There is scant high quality evidence to suggest that topical zinc based wound products are effective in promoting the healing of venous leg ulcers. New studies are urgently needed which are larger, scientifically rigorous and without bias from industry. This will enable nurses to implement evidenced based practice and choose the most appropriate wound management product to improve patient care and reduce costs to the health service. Keywords: venous leg ulcer, topical zinc, zinc oxide, management and treatment Page 2 of 23

3 Table of Contents Abstract... 2 Introduction... 4 Literature Review... 6 Search Strategy... 6 Zinc paste bandages with compression therapy... 6 Zinc impregnated bandages as compression therapy... 8 Topical zinc ointment as a skin protectant Discussion Conclusion Appendix A - References Appendix B - Table of literature reviewed Page 3 of 23

4 Introduction Venous leg ulcers (VLUs) are the most common type of leg ulcer. They are wounds which occur on the leg or foot which take longer than six weeks to heal. They are mainly due to incompetence valves in the blood vessels in the leg leading to venous stasis and hypertension, (Browne, 1982). VLUs are a chronic condition which can cause pain, exudate and odour, poor sleep, loss of mobility and social isolation for those who suffer from them, which can seriously affect patients morbidity and quality of life (Palfreyman, Nelson, Lochiel et al, 2006). Current Irish estimates put the prevalence rate of venous leg ulcers between %, with the rate rising markedly to 1.03% for those over seventy years of age (O Brien, Grace, Perry et al, 2000). This corresponds to an average of 9,000 people who suffer with chronic venous leg ulcers in Ireland (CSO, 2012). However these figures could more than double by 2041 as the population ages (McGill, 2010). In addition the cost of treating just one leg ulcer in the United Kingdom was estimated at 1,300 (Iglesias, 2004). Conservative estimates put the cost, to the Health Service Executive (HSE), of managing chronic venous leg ulcers to be in the region of 12 million annually. If VLUs are poorly managed and treated, they will not only cause a series of debilitating physical and psychological problems for a vulnerable age group but also create a serious financial and resource burden on an already overstretched local and national health service. Topical zinc, in the form of zinc oxide or calamine lotion, has been used medicinally in wound care for over 3,000 years and is still widely used in wound care products today (Lansdown, 1996). Zinc is the second most abundant trace element in the human body after iron and is an essential mineral in human nutrition. It is required for catalysing over 100 enzymes (Collins, 2003), and it is necessary for antibody production and immune cell function (Shankar and Prasad, 1998), as well as protein and DNA synthesis Page 4 of 23

5 (Gray, 2003). A study by Henzel, DeWeese & Lichti (1970) noted that post-operative wounds of some patients after major surgery were very slow to heal. Upon investigated they found that these patients had decreased serum zinc levels in their blood and split thickness skin biopsies revealed they also had up to 50% less zinc in the granulation tissue and wound margin compared to other post-operative patients. They attributed the deficit in serum zinc levels to the poor wound healing process, which along with other research prompted the use of topical zinc in wound care. Many wound care products contain topical zinc such as; 1) zinc pastes e.g. Steripaste, Viscopaste PB7 and Zincaband, 2) zinc paste and calamine products such as Calaband, 3) zinc paste caladmine and clioquinol e.g. Quinaband, 4) zinc paste and coal tar e.g. Coltapaste or Taraband, and 5) zinc paste and ichthammol products such as Ichtaband and Ichtopaste (Williams, 1999). These have been marketed as anti-inflammatory, anti-microbial and overall as contributing to the wound healing process (Molnlycke Healthcare, 2009; Smith & Nephew, 2012) and as such have been used to treat a variety of wounds such as chronic venous leg ulcers. However despite the widespread use of topical zinc in wound dressings used in the management of chronic venous leg ulcers, no in-depth literature review has ever been undertaken to assess its efficacy. Given that nursing practice should be grounded on high quality, rigorous scientific and social science research, this paper will examine literature to determine if the use of zinc based wound products, such as those mentioned above, are effective in promoting the healing of venous leg ulcers and the implications this can have for patients, nursing practice and the health services. Page 5 of 23

6 Literature Review Search Strategy A literature search was undertaken by querying the databases CINAHL, MEDLINE/PubMed, and the Cochrane Library using a combination of key search terms such as: topical zinc, zinc oxide, zinc paste, wound healing, zinc dressing, zinc bandage, zinc stocking and venous leg ulcer. Included in the search were peer-reviewed journals, written in English, between to ensure results were comprehensive and of a high quality. A hand search of textbooks was also undertaken to provide background information that supplemented the literature review. This resulted in eleven published studies (Appendix B). The literature revealed topical zinc is used in three main ways to promote the healing of venous leg ulcers. Firstly zinc paste bandages are used in conjunction with compression therapy, secondly zinc impregnated bandages are used as compression therapy and thirdly topical zinc ointment is used as a skin protectant. Zinc paste bandages with compression therapy Parbooteeah & Brown (2008) highlight that zinc impregnated bandages have been in use since 1854 and their modern day equivalents are still one of the main treatments for venous leg ulcers in conjunction with compression therapy. They are made with open-weave bleached cotton and are impregnated with a zinc oxide paste ranging in concentration from 6-15%. Strömberg and Agren (1984) examined the effect of a zinc oxide dressing on the healing of 18 venous leg ulcers and 19 arterial ulcers. Their randomised double blinded study compared two groups; one which used gauze impregnated with zinc oxide, and the second which used identical gauze without any topical ointment, on their leg ulcer. In both groups they looked at the size of the ulcer, granulation and debridement based on two treatments over 8 weeks. Patients with venous wounds received additional compression therapy. Although their results showed a Page 6 of 23

7 better healing rate among the patient who received zinc oxide (83%) compared to the control group (42%), the study s sample size, short time-frame and mixed wound type limit the generalisability of the results. Not only this but the study is nearly 30 years old and newer more effective wound care products have been developed since the 1980 s. Another randomised controlled study by Eriksson (1986) looked at the effectiveness of two types of occlusive bandages in treating thirty four venous leg ulcers. He concluded that over 10 weeks there was no difference in the healing rate between an aluminium foil dressing with compression bandaging and a double layered Tensoplast bandage, which consists of an inner stocking impregnated with zinc oxide paste and an outer elastic bandage. Brandrup, Menne, Agren et al (1990) compared a zinc oxide medicated dressing called Mezinc with a hydrocolloid dressings, Duoderm in a prospective, randomised trial over eight weeks. They investigated the effects of both dressing types on the healing rate and pain in both venous and arterial leg ulcers. Compression therapy was applied over the dressings on venous leg ulcers only. They reported a 65% reduction in wound area under adhesive zinc oxide tape compared to a 48% reduction in the size of ulcer when the hydrocolloid dressing was applied. Both wound dressings had similar analgesic effects but several patients had to withdraw from the study due to a sensitivity reaction to the Mezinc treatment. Overall they concluded that there was insufficient data for the results to be significant as only 31 patients in total participated in the study. A later study by Stacey, Jopp-Mckay, Rashid et al (1997) examined the effect of three different wound dressings on 133 leg ulcers due to venous disease. Their randomised controlled trial (RCT) revealed patients treated with a Viscopaste TM, a zinc paste bandage, had far higher healing rates (79%) than those who had zinc oxide stockingettes (59%) or a calcium alginate fibre dressings (56%) applied under compression bandaging. However the authors concluded that healing was mainly attributed to the extra Page 7 of 23

8 compression which improved venous return and not due to the dressing applied. Others argue that compression bandaging may have masked any beneficial effect that zinc oxide and the other dressings had during healing and recommended more in-depth, explicit research (Agren & Mirastschijski, 2004). More recently Parboteeah & Brown (2008) presented three detailed case studies involving the use of Viscopaste TM on venous leg ulcers in conjunction with K4 compression bandaging. Each of the patients in the case studies had tried a variety of wound dressings with compression bandaging to heal the leg ulcers which had failed. While they acknowledged that compression bandaging is the gold standard treatment for these types of wounds, their research based on clinical experience demonstrated that zinc paste bandages can be effective in treating venous leg ulcers that are difficult to heal. However this type of research while helpful is low quality evidence compared to a randomised controlled trial. Although the current body of evidence points towards the efficacy of zinc paste bandages, when applied in conjunction with compression therapy, in promoting the healing of venous leg ulcers the evidence is inconclusive. Zinc impregnated bandages as compression therapy Unna s boot is a zinc paste-containing bandage, wrapped around the patient's leg from above the toes to below the knee, which is used to treat venous leg ulcers mainly in the United States (Fletcher, Cullum & Sheldon, 1997). Hendricks & Swallow (1985) were the first to examine whether Unna s boot as a form of compression therapy was as effective as other interventions in promoting the healing of venous leg ulcers. They undertook a randomised trial and treated ten patients who had venous stasis leg ulcers with Unna s boot, while fourteen patients, also with venous leg ulcers, received elastic support stockings. Unfortunately both treatment groups were small and the results showed no statistically significant Page 8 of 23

9 difference between their success in healing the leg ulcers (p=0.9394). However the average healing time was much shorter for patients who received Unna s boot, 7.3 weeks, while it took on average 18.4 weeks for venous leg ulcers to heal for patients who were treated with support stockings. A subsequent study by Cordts, Hanrahan, Rodriguez et al (1992) compared a Duoderm CGF dressing plus compression (Coban wrap) to Unna s boot. They reported healing rates, for 30 patients with chronic venous leg ulcers, were faster on Duoderm CGF ( / cm 2 /wk/cm perimeter) than patients on Unna s boot ( / cm 2 /wk/cm perimeter) during the first four weeks of therapy. Again at twelve weeks they found the cohort using Duoderm CGF had better healing rates although the results at that stage were not statistically significant (p = 0.11). Overall they concluded that Duoderm CGF with compression may be more effective for promoting the healing of chronic VLUs than Unna s boot. A longitudinal study by Kerstein & Gahtan (2000) looked at the outcomes of treating venous leg ulcers in a homecare versus an outpatient setting. They used three types of treatments; 1) a saline gauze dressing, 2) a hydrocolloid dressing, both in conjunction with compression therapy, and 3) an Unna s boot. Patients with the hydrocolloid dressing had the best results as they had the lowest rates of ulcers which failed to heal or which reoccurred at 13%. This was followed closely by Unna s boot with a reoccurrence or failed healing rate of 21% while the saline dressing was the least effective with a rate of 88%. Later research has compared a four layered compression bandaging system called PROFORE against Unna s boot (Poligano, Boneado, Gasboro et al, 2004). This prospective randomised parallel-group trial followed sixty-eight patients over 24 weeks. Although the results showed that the ease of applying the Page 9 of 23

10 Profore dressing was rated more highly than Unna s boot, there was no significant difference in the time taken for the venous leg ulcers to heal. Furthermore the research was funded by Smith and Nephew a manufacturer of PROFORE products which could have biased the study design and skewed the results in favour of their wound care product. The use of Unna s boot is becoming less common as it is being replaced by elastic compression bandaging which provides sustained pressure, is easier to use, better shaped for the leg and does not have to be changed as frequently (dearaujo, Valencia, Federman et al, 2003). It is impossible to say if zinc bandages as a form of compression therapy alone are effective in promoting the healing of venous leg ulcers although it is unlikely given the major advancements in wound dressings and compression bandaging over the last number of years. Topical zinc ointment as a skin protectant Zinc oxide ointment is also used as a barrier film on skin to protect it from wound exudate, reduce inflammation and stimulate wound healing (Rostan, DeBuys, Madeey et al, 2002). Cameron, Hoffman, Wilson et al (2005) studied the effects of different types of peri-wound skin protectants on venous leg ulcers. They compared the effectiveness of using Cavilon No Sting Barrier Film (NSBF) as opposed to a zinc paste compound, as they both help create a barrier film to protect skin surrounding venous leg ulcers from irritation and maceration. Their small randomised controlled trial revealed that there was very little difference, in terms of the decrease in wound size or the healing rate of the ulcers, between the two products. They did report that nurses found Cavilon was much faster and easier to apply than the zinc oxide paste, and Cavilon was preferred from a patient comfort point of view. However the results of their study are overshadowed by the fact that it was sponsored by 3M Health Care, a manufacturer of Cavilon which could have biased the results. Page 10 of 23

11 Other research has identified issues with using topical zinc paste as a barrier film. Schuren, Becker and Sibbald (2005) undertook a systematic review and meta-analysis of peri-wound skin protectants and warned that zinc paste can actually obscure the wound margin and make it more difficult to observe. In essence they found no difference between different barrier methods to protect the skin surrounding chronic venous leg ulcers. Moffatt, Martin & Smithdate (2007) also highlighted the possibility of sensitivity reactions to zinc paste and recommended doing a patch test on patients skin as a test first. They suggested applying a small amount of zinc paste to normal skin for three days, then remove it and do a follow up examination of the patients skin on day five to ensure there is no reaction. However Newton & Cameron (2003) stress that many nurses do not leave the patch test for a long enough period to enable them to accurately determine if the patient has a reaction. In conclusion there is insufficient evidence to suggest that topical zinc ointment improves the healing of venous leg ulcers or better protects the skin surrounding these types of wounds over other products. Discussion Given the plethora of nursing research on wound care and wound management, the widespread use of zinc in wound care products, as well as the serious effects of chronic venous leg ulcers on both patients and the health services, it is surprising that no review has been conducted to date that examines the efficacy of topical zinc for promoting healing in VLUs. This paper represents the first in-depth analysis of the application of a range of topical zinc based wound care products on venous leg ulcers and the value of this therapy compared with other wound management methods. The results highlight several issues in the current empirical research. Page 11 of 23

12 Firstly and most worryingly, the majority of literature on this topic is out of date, with only three out of the twelve research studies reviewed occurring within the last decade. Even the most recent evidence from 2008 is already five years old and consisted of very low quality evidence from three case studies. Newer wound care products and procedures are continuously being developed and tested, and are replacing older treatments as is evident from the phasing out of Unna s boot in favour of more modern techniques for managing chronic venous leg ulcers such as four layered compression bandaging (O Meara, Cullum, Nelson & Dumville, 2012). Therefore more up to date research is needed to examine the effects of a variety of zinc based wound products on the healing of venous leg ulcers. This is essential to ensure nurses select the most appropriate dressing for patients which minimises pain, exudate and odour, stress and anxiety, and shortens the time it takes for them to heal. These improvements will then help reduce the cost of treating venous leg ulcers and free up time for nursing staff to concentrate on other activities. Another issue is that most of the research is on a small scale, typically with fewer than forty two participants. While some of the larger studies were able to undertake statistical analysis and produce results with some significance the majority were too small to draw generalisable conclusions from. This is compounded by the fact that the research also applied a variety of design types from randomised clinical trials, to longitudinal studies and case studies, which represents varying levels of quality on the hierarchy of evidence and makes the results of one study difficult to assess against another. A further complication is that the literature also examined a diverse range of dressings, such as zinc oxide impregnated dressings like Mezinc, double layered Tensoplast bandages and zinc oxide stockingettes e.g. Acoban. In parallel the studies also looked at several different criteria to rate the effect of the wound dressings, from healing times and rates using various measurements, to the size of the ulcerated area, the Page 12 of 23

13 presence or absence of granulation, handling properties, patient comfort, and pain levels to name a few which makes comparison difficult. The inconsistency of the methodological approaches makes it impossible for nurses to assess the real impact of zinc based wound products in promoting the healing of chronic venous leg ulcers as no definitive conclusion can be drawn as to their efficacy. Nurses are therefore left to a apply their best clinical judgement as well as a trial and error approach which could delay the wound healing process, causing excess pain and burden to the patient, and add additional cost and time constraints to the health service. A final point of note is the involvement and sponsorship of industry in some of the research. Although the authors state any such conflict of interest it is always questionable whether the research was undertaken with scientific rigour. Lexchin, Bero, Djulbegovic and Clark (2008) cite industrial sponsorship as being associated with choosing unsuitable comparators, reporting more favourable analysis and overall the research results are pro-industry. Bekelman and Gross (2003) also highlight that commercial support for research is also associated with restrictions on publication and data sharing. Furthermore a comparison of industry sponsored meta-analyses versus Cochrane reviews was undertaken by Jorgensen, Hilden & Gotzsche (2006). They concluded that research produced with industry support was less transparent, played down the significance of any methodological restrictions, and overall was more favourable than the equivalent Cochrane review. Given that the UK wound care market was estimated to be worth in the region of 4.4 billion in 2011 and projected to grow by 4% every year for the next five years (HealthInvestor, 2013) it is hard not to be sceptical of research backed by industry as they have a vested interest in promoting the widespread use of their wound care products. Page 13 of 23

14 Based on all of this evidence, it is clear that much more research is needed. A Cochrane systematic review of wound dressings used to heal venous leg ulcers came to the same conclusion stating; there is insufficient evidence that any type of treatment heals ulcers more quickly than others (Palfreyman, Nelson, Lochiel et al, 2006). They called for larger, high quality trials to determine the effectiveness of wound dressings on venous leg ulcers which should include a priori sample size calculation, have a time to total healing as their primary outcome measure, and include cost-effectiveness and quality of life data. This would give nurses more definitive guidance as to what wound products, zinc based or otherwise, to apply help heal venous leg ulcers, reduce patient morbidity, improve their quality of life and reduce the costs to the health service. Conclusion It is clear from the literature reviewed that there is insufficient evidence to determine if topical zinc based wound products are effective in healing venous leg ulcers. Anecdotal evidence from historical practices, small scale limited research which is out of date, and incorrect assumptions about wound care products based on advertising, should not form the knowledge basis for the nursing profession. Nursing practice must be grounded on high quality, rigorous scientific and social science research. Therefore new research is urgently needed to determine the effect, if any, of topical zinc healing of venous leg ulcers. Page 14 of 23

15 Appendix A - References Agren, M.S., and Mirastschijski, U. (2004) The release of zinc ions from and cytocompatibility of two zinc oxide dressings. Journal of Wound Care 13(9), Bekelman, J.E., Li, Y., and Gross, C.P. (2003) Scope and impact of financial conflicts of interest in biomedical research: a systematic review. Journal of the American Medical Association 289(4), Brandrup, F., Menné, T., Agren, M.S. et al (1990) A randomised trial of two occlusive dressings in the treatment of leg ulcers. Acta Dermato-Venereologica 70(3), Browse, N.L. (1982) The cause of venous ulceration. Lancet 2(8292), Cameron, J., Hoffman, D., Wilson, J. and Cherry, G. (2005) Comparison of two peri-wound skin protectants in venous leg ulcers: a randomised controlled trial. Journal of Wound Care 14(5), Central Statistics Office (2012) Census 2011 Profile 2 Older and Younger. Available at: Collins, N. (2003) Zinc supplementation: yea or nay? Advances in Skin Wound Care 16(5), Page 15 of 23

16 Cordts, P.R., Hanrahan, L.M., Rodriguez, A.A., Woodson, J., LaMorte, W.W. and Menzoian, J.O. (1992) A prospective, randomised trial of Unna s boot versus Duoderm CGF hydroactive dressing plus compression in the management of venous leg ulcers. Journal of Vascular Surgery 15(3), dearaujo, T., Valencia, T., Federman, D.G. and Kirsner, R.S. (2003) Managing the Patient with Venous Ulcers. Annals of Internal Medicine 138(4), Eriksson, G. (1986) Comparison of two occlusive bandages in the treatment of venous leg ulcers. British Journal of Dermatology 114(1), Fletcher, A., Cullum, N. and Sheldon, T.A. (1997) A systematic review of compression treatment for venous leg ulcers. British Medical Journal 315 (7108), Gray, M. (2003) Does oral zinc supplementation promote healing of chronic wounds? Journal Wound Ostomy Continence Nursing 30(6), Health Investor (2013) M&A Activity set to rise in wound care market. Available at: ZmNTUtYjc4Zi00MTJmLTlhZWUtYmRhNTI4M2RjNzhh_TT2gjh4TpbrwBhf2fdQzKJJXFY1))/Sho warticlenews.aspx?id=2736&aspxautodetectcookiesupport=1 Henzel, J.H., DeWeese, M.S. and Lichti, E.L. (1970) Zinc concentrations within healing wounds. Significance of postoperative zincuria on availability and requirements during tissue repair. Archives of Surgery 100(4), Page 16 of 23

17 Hendricks, W.M. and Swallow, B.A. (1985) Management of stasis leg ulcers with Unna s boot versus elastic support stockings. Journal of the American Academy of Dermatology 12(1), Iglesias, C.P., Nelson, E.A., Cullum, N., Torgerson, D.J. and VenUS I collaborators (2004) Economic analysis of VenUS I, a randomized trial of two bandages for treating venous leg ulcers. British Journal of Surgery 91(10), Jorgensen, A.W., Hilden, J. and Gotzsche, P.C. (2006) Cochrane reviews compared with industry supported meta-analyses and other meta-analyses of the same drugs: systematic review. British Medical Journal 333(7572), 782. Kerstein, M.D. and Gahtan, V. (2000) Outcomes of venous ulcer care: results of a longitudinal study. Ostomy Wound Management 46(6), 22-6, Lansdown, A.B. (1996) Zinc in the healing wound. Lancet 347(9003), Lexchin, J., Bero, L.A., Djulbegovic, B. and Clark, O. (2003) Pharmaceutical industry sponsorship and research outcome and quality: systematic review. British Medical Journal 326(7400), McGill, P. (2010) Illustrating Ageing in Ireland and North & South Key Facts and Figures. Centre for Ageing Research and Development in Ireland (CARDI), Dublin. Available at: Page 17 of 23

18 Moffatt, C., Martin, R. and Smithdate, R. (2007) Leg Ulcer Management. Blackwell Publishing, Oxford. Molnlycke Healthcare (2009) Steripaste TM Preservative-free Sterile Zinc Paste Bandage: Wound Care Product Sheet. Molnlycke Healthcare, Bedfordshire, UK. Available at: eripaste.pdf Newton, H. and Cameron, J. (2003) Skin Care in Wound Management. Medical Communications UK Limited, Holsworthy, UK. O Brien, J.F., Grace, P.A., Perry, I.J. and Burke, P.E. (2000) Prevalence and aetiology of leg ulcers in Ireland. Irish Journal of Medical Science 169(2), O'Meara, S., Cullum, N., Nelson, E.A. and Dumville, J.C. (2012) Compression for venous leg ulcers. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD DOI: / CD pub3. Palfreyman, S.S.J., Nelson, E.A., Lochiel, R. and Michaels, J.A. (2006) Dressings for healing venous leg ulcers. Cochrane Database of Systematic Reviews 3(CD001103) DOI: / CD pub2. Parboteeah, S. and Brown, A. (2008) Managing chronic venous leg ulcers with zinc oxide paste bandages. British Journal of Nursing 17(6), Page 18 of 23

19 Polignano, R., Boneado, P., Gasbarro, S. and Allegra, C. (2004) A randomised controlled study of four layer compression versus Unna s boot for venous ulcers. Journal of Wound Care 13(1), Rostan, E.F., DeBuys, H.V., Madey, D.L. and Pinnell, S.R. (2002) Evidence supporting zinc as an important antioxidant for skin. International Journal of Dermatology 41(9), Schuren, J., Becker, A. and Sibbald, R.G. (2005) A liquid film-forming acrylate for peri-wound protection: a systematic review and meta-analysis (3M Cavilon no-sting barrier film). International Wound Journal 2(3), Shankar, A.H. and Prasad, A.S. (1998) Zinc and immune function: the biological basis of altered resistance to infection. The American Journal of Clinical Nutrition 68(2 Suppl), 447S-463S. Smith & Nephew (2012) Product Catalogue: ICHTHOPASTE Available at: Stacey, M.C., Jopp-Mckay, A.G., Rashid, P., Hoskin, S.E. and Thompson, P.J. (1997) The influence of dressings on venous ulcer healing a randomised trial. European Journal of Vascular and Endovascular Surgery 13(2), Stromberg, H.E. and Agren, M.S. (1984) Topical zinc oxide treatment improves arterial and venous leg ulcers. British Journal of Dermatology 111(4): Page 19 of 23

20 Williams, C. (1999) Examining the range of medicated and paste impregnated bandages. British Journal of Nursing 8(15), Page 20 of 23

21 Appendix B - Table of literature reviewed Author, Yr Setting Sample Study Design Methodology Analysis Key findings Brandup, Menne, Agren et al (1990) Odense University Hospital, Denmark N=61 patients with venous and arterial leg ulcers Prospective randomised trial over 8 weeks Comparison of zinc oxide impregnated dressing Mezinc, and a hydrocolloid dressing Duoderm. Patch test done, Colophony allergy was an exclusion criteria. SPSS predictive analytics software Both dressings were well tolerated by patients similar analgesia effects. No major difference in the efficacy of the two occlusive dressings. Cameron, Hoffman, Wilson et al (2005) Weekly dressing clinic, Whitney Community Hospital, Oxfordshire. N=35 patients with venous leg ulcers. 12 week randomised control trial. Observational study comparing Cavilon NSBF against zinc paste compound. Weekly wound measurements and post study questionnaire for nursing staff. SPSS predictive analytics software. Minimal difference between the two products in terms of healing rate. Time required to remove and reapply the products was significantly shorter for Cavilon NSBF. Cordts, Hanrahan, Rodriguez et al (1992) Dressing clinic at Boston City Hospital, USA. N=30 patients with Grade III venous leg ulcers. Randomised control trial 12 week study. Comparison of Duoderm CGF with a Coban compression bandage against Unna s boot. Weekly wound dressings, photograph and measurements. Post study patient and nurse survey on treatment provided. SPSS software, Student s t test, Wilcoxon rank sum test, chi-square test, linear regression analysis, ANOVA, correlation analysis. Ulcers with the Duoderm CGF and Coban wrap healed more quickly than those treated with Unna s boot within a 12 week period although the results were not statistically significant.

22 Author, Yr Setting Sample Study Design Methodology Analysis Key findings Eriksson (1986) Wound clinic, Danderyd Hospital, Sweden N=34 patients with venous leg ulcers. Randomised controlled study 10 weeks. Comparison of a hydrocolloid dressing (alinimum foil) and a double layered Tensoplast bandage (inner zinc and outer elastic bandage). Evaluated against stereophotogrammetric measurement of ulcer area and volume, and bacterial counts. SPSS predictive analytics software. No difference was found in the healing rate between the dressings Hendricks & Swallow (1985) Asheboro Dermatology Clinic, North Carolina, USA N=21 patients with stasis leg ulcers Randomly assigned two groups to Comparison of Unna s boot versus an elastic support stocking with graded compression. SPSS software - Wilcoxon rank sum test, Cox regression analysis No statistically significant difference between their success rate (p=0.9394). Healing time was shorter for patients treated with Unna s boot Kerstein & Gahtan (2000) Mount Sinai Medical Centre, New York N=81 patients with venous ulcers Longitudinal study Explore the outcomes and cost of wound in a home healthcare setting and an outpatient setting. Ulcers managed with saline gauze, or a hydrocolloid dressing and compression therapy, or an Unna s boot. Patients preferred homecare but the costs were higher. Data suggests hydrocolloid dressings are the most cost effective. Lower recurrence of ulcers in hydrocolloid (13%) and Unna s boot (21%) group Parboteeah & Brown (2008) Vascular clinic, Leicester Hospital, UK. N=3 patients with venous leg ulcers. Three studies. case Clinical case studies of Vistopaste TM slab applied to venous leg ulcers under K4 compression bandaging ranging from 4 months to 1 year. Clinical observations and analysis. Zinc oxide paste therapy in conjunction with compression bandaging can be effective in healing venous leg ulcers that are proving difficult to treat by other methods. Polignano, Boneado, Gasboro et al (2004) Camerata Hospital, Florence, Italy N=68 patients with venous leg ulcers Prospective randomised trial over 24 weeks Comparison of healing rates, handling properties, and patient comfort in PROFORE four layer bandage system versus Unna s boot No difference in time to closure (p=0.13). Profore was easier to apply (p=0.013). PROFORE is as effective as Unna s boot in treating venous leg ulcers, it was easier to apply. Page 22 of 23

23 Author, Yr Setting Sample Study Design Methodology Analysis Key findings Schuren, Becker Sibbald (2005) & 3M Germany Laboratory, Carl- Schurz-Strasse, Neuss, Germany N=9 studies Systematic Review Evaluate the clinical performance and cost effectiveness of a film-forming liquid acrylate in the protection of the chronic ulcer peri-wound skin. Meta-analysis There is no difference between the protective properties of different barrier methods to protect the peri-wound skin around chronic ulcers. Stacey, Jopp- Mckay, Rashid et al (1997) Leg ulcer clinic, Fremantle Hospital, Australia. N=133 patients venous ulcers. with leg Prospective randomised clinical trial. Comparison of a zinc oxide impregnated paste bandage (Vistopaste) with a zinc oxide stockingette (Acoban) and a calcium alginate fibre dressing (Kaltostat). Weekly dressings for 9 months. Rate of reduction of ulcer size in cm2 was measured weekly Chi-squared analysis, Kruskal-Wallis one way analysis of variance, Wilcoxon rank sum test, Cox regression analysis, Bonferroni test. Improved healing with the zinc oxide impregnated paste bandage under compression compared to the other dressings. Strömberg and Agren (1984) Dressing clinic, Stockholm University Hospital, Sweden N=37 patients with arterial and venous leg ulcers Randomised double blinded study over 8 weeks Comparison of gauze compress medicated with zinc oxide compared with identical gauze without zinc oxide. Weekly measurements of ulcer size, presence of granulation and ulcer debridement. Chi-squared analysis and Wilkcoxon test using SPSS The zinc treated patients responded significantly better (p<0.05) than the control group. Healing of leg ulcers can be improved after the addition of topical zinc. Page 23 of 23