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A systematic review of cost-effectiveness analyses of complex wound interventions reveals optimal treatments for specific wound types

BMC Medicine volume 13, Article number: 90 (2015) Cite this article

Abstract

Background

Complex wounds present a substantial economic burden on healthcare systems, costing billions of dollars annually in North America alone. The prevalence of complex wounds is a significant patient and societal healthcare concern and cost-effective wound care management remains unclear. This article summarizes the cost-effectiveness of interventions for complex wound care through a systematic review of the evidence base.

Methods

We searched multiple databases (MEDLINE, EMBASE, Cochrane Library) for cost-effectiveness studies that examined adults treated for complex wounds. Two reviewers independently screened the literature, abstracted data from full-text articles, and assessed methodological quality using the Drummond 10-item methodological quality tool. Incremental cost-effectiveness ratios were reported, or, if not reported, calculated and converted to United States Dollars for the year 2013.

Results

Overall, 59 cost-effectiveness analyses were included; 71% (42 out of 59) of the included studies scored 8 or more points on the Drummond 10-item checklist tool. Based on these, 22 interventions were found to be more effective and less costly (i.e., dominant) compared to the study comparators: 9 for diabetic ulcers, 8 for venous ulcers, 3 for pressure ulcers, 1 for mixed venous and venous/arterial ulcers, and 1 for mixed complex wound types.

Conclusions

Our results can be used by decision-makers in maximizing the deployment of clinically effective and resource efficient wound care interventions. Our analysis also highlights specific treatments that are not cost-effective, thereby indicating areas of resource savings.

Please see related article: http://dx.doi.org/10.1186/s12916-015-0288-5

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Background

Complex wounds are those that do not heal after a period of 3 months or more [1]. These types of wounds are a significant burden on the healthcare system and result in patient and caregiver stress, economic loss, and decreased quality of life. At least 1% of individuals living in high economy countries will experience a complex wound in their lifetime [2], and over 6.5 million individuals have a complex wound in the United States alone [3]. Moreover, these types of wounds have a significant economic impact. For example, $10 billion United States dollars (USD) per year in North America is spent managing complex wounds [4], and 4% of the annual National Health Service expenditure in the United Kingdom is spent on care for patients with pressure ulcers [5].

There are three main categories of complex wounds: i) wounds resulting from chronic disease (e.g., venous insufficiency, diabetes), ii) pressure ulcers, and iii) non-healing surgical wounds [6-8]. Treatment is targeted to the type of wound. Managing complex wounds resulting from disease usually involves improving the underlying disease; for example, optimizing diabetes control for patients with diabetes [9]. A clinical assessment and history of mobility and neurological disability is often necessary to treat patients with pressure ulcers [9]. Considerations for managing surgical wound infections include previous antibiotic treatment and immune response [3].

It is estimated that the global wound care market will reach over $22 billion USD annually by 2020 [10]. Due to the burgeoning costs from the management of patients requiring complex wound care, policymakers are interested in finding cost-effective treatments. However, the cost-effectiveness of all interventions available to treat complex wounds is currently unclear. As such, we sought to elucidate cost-effective treatment strategies for complex wounds through a systematic review of cost-effectiveness analyses.

Methods

Protocol

The systematic review question was posed by members of the Toronto Central Local Health Integrated Network. In collaboration with the Toronto Central Local Health Integrated Network, our research team prepared a draft protocol that was revised to incorporate feedback from systematic review methodologists, policymakers, and clinicians with expertise in wound care (Additional file 1). Our protocol also included conducting a related project comprising an overview of systematic reviews for treating complex wounds, and these results are available in a separate publication [11].

Information sources and search strategy

On October 26, 2012, an experienced librarian conducted comprehensive literature searches in the following electronic databases from inception onwards: MEDLINE, EMBASE, and the Cochrane Library. The literature search was limited to adult patients and economic studies. The Peer Review of Electronic Search Strategies (PRESS) checklist [12] was used by another expert librarian to peer review the literature search. The search was revised, as necessary, and the final MEDLINE search is presented in Additional file 2. Full literature searches for the other databases are available upon request. The reference lists of the included studies were searched to identify additional relevant studies.

Eligibility criteria

Inclusion criteria were defined using the ‘Patients, interventions, comparators, outcomes, study designs, timeframe’ (PICOST) framework [13], as follows:

Patients

Adults aged 18 years and older experiencing complex wounds. Complex wounds included those due to chronic disease (such as diabetic foot ulcers or venous leg ulcers), pressure ulcers (such as decubitus ulcers or bed sores), and non-healing surgical wounds.

Interventions

All complex wound care interventions were included, as identified from our overview of systematic reviews [11] and outlined in Additional file 3.

Comparators

All comparators were eligible for inclusion, including any of the eligible interventions in comparison with each other or versus no treatment or placebo or usual care.

Outcomes

Cost-effectiveness (i.e., both incremental cost and incremental effectiveness) was included, where effectiveness was measured by at least one of the following outcomes: quality-adjusted life-years (QALYs), wounds healed, ulcer-free/healing time, wound size reduction/improvement, or hospitalizations (number/length of stay).

Study designs

Economic evaluations were included in which the incremental cost-effectiveness ratios (ICERs) were reported or could be derived.

Timeframe

We did not limit inclusion to year of publication.

Other limitations

We limited cost-effectiveness analyses to those based on a study with a control group, and where the data were from direct comparisons (versus a review using indirect data). Both published and unpublished studies were eligible for inclusion. Although we focused inclusion on those studies written in English, we contacted the authors of potentially relevant non-English studies to obtain the English translation.

Screening process for study selection

The team pilot-tested the pre-defined eligibility criteria using a random sample of 50 included titles and abstracts. After 90% agreement was reached, each title and abstract was screened by two team members, independently, using our Synthesi.SR tool [14]. Discrepancies were resolved by discussion or the involvement of a third reviewer. The same process was followed for screening full-text articles that were identified as being potentially relevant after screening their titles and abstracts.

Data abstraction and data collection process

The team pilot-tested data abstraction forms using a random sample of five included cost-effectiveness analyses. Subsequently, two investigators independently read each article and abstracted relevant data. Differences in abstraction were resolved by discussion or the involvement of a third reviewer. Data items included study characteristics (e.g., type of economic evaluation, time horizon, treatment interventions examined, study comparators), patient characteristics (e.g., clinical population, wound type), and cost-effectiveness results (e.g., ICERs, cost per QALY, cost per wound healed). The perspective of the economic evaluation was categorized as: patient, public payer, provider, healthcare system, or society [15].

Cost-effectiveness studies can have four possible overall results, which are often represented graphically in quadrants on a cost-effectiveness plane [16]. The possibilities for the intervention versus a comparator are: 1) more effective and less costly, which we noted as ‘dominant’; 2) more effective and more costly; 3) less effective and less costly; and 4) less effective and more costly, which we noted as ‘dominated’. The first possibility is considered to be cost-effective; whereas possibility 4 is not cost-effective. Situations 2 and 3 requires judgment by the decision-maker to interpret [17], and in such cases, the decision is often dependent on the decision-maker’s willingness to pay. For interventions that were found to be more effective yet more costly (i.e., situation 2) or less effective and less costly (situation 3), ICERs were reported or derived from both the differences in cost (i.e., incremental cost) and effectiveness (i.e., incremental effectiveness) between the study’s intervention and comparator groups using the formula:

(Cost of the intervention – Cost of the comparator) ÷ (Effectiveness of the intervention – Effectiveness of the comparator)

To assess key variables influencing the cost-effectiveness results, sensitivity analyses, level of uncertainty in the cost and benefit estimates, and incremental variabilities (i.e., the variability of the incremental cost and the variability of the incremental effectiveness), were reported.

Authors of the included cost-effectiveness analyses were contacted for data verification, as necessary. Further, multiple studies reporting the same economic data were sorted into the major publication (e.g., most recent paper or largest sample size) and companion report. Our results focus on the major publications and the companion reports were used to provide supplementary material.

Methodological quality appraisal

The methodological quality of the cost-effectiveness analyses was appraised using a 10-item tool developed by Drummond et al. (Additional file 4) [18]. The items on this tool include the appraisal of question definition, description of competing alternatives, effectiveness of the intervention, consideration of all relevant costs, measurement of costs, valuation of costs and consequences, cost adjustment/discounting, incremental analysis, uncertainty/sensitivity analysis, and discussion of study results. The Drummond score can range from 0 to 10. Each included cost-effectiveness analysis was appraised by two team members and conflicts were resolved by discussion or the involvement of a third reviewer.

Synthesis

Since the purpose of this systematic review was to summarize the cost-effectiveness of interventions for complex wound care, the results are reported descriptively. The costing data from all studies were converted to 2013 USD to increase the comparability of the economic results across cost-effectiveness studies. This process entailed first converting the currencies into USD using purchasing power parities for the particular year of the data [19,20], and then adjusting these for inflation to the year 2013 (rounded to the nearest dollar) using the consumer price index for medical care in the United States [21].

Results

Literature search and screening

The literature search identified 422 potentially relevant full-text articles after screening 6,200 titles and abstracts (Figure 1). There were 59 included cost-effectiveness analyses that fulfilled our eligibility criteria and were included [22-80], plus an additional three companion reports [81-83].

Figure 1
figure 1

Study flow diagram.

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Study and patient characteristics

The cost-effectiveness analyses evaluated interventions to treat venous ulcers (41%), diabetic ulcers (27%), and pressure ulcers (24%) (Table 1). The studies were published between 1988 and 2012. Most of the papers were conducted in the United Kingdom (29%) and United States (27%). Almost half (49%) reported private or mixed (private and public) funding sources of the studies, while one-third (34%) did not report a source of funding.

Table 1 Summary characteristics of all cost-effectiveness analyses (CEAs)
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While the majority of studies based effectiveness on a (single) randomized clinical trial (75%), only a few based effectiveness on a systematic review (9%) and 15% were based on observational studies (Tables 2, 3, 4, 5 and 6). Almost half (46%) of the economic studies included a sample size of 10 to 100 patients and the rest had a sample of >100 patients. In addition, 48% were conducted in a timeframe of 12 weeks or less, while the other studies had a duration of >12 weeks follow-up. Across the 59 economic studies, 9 different units of effectiveness were used, with the most common ones being healed wound (44%) and QALY (17%). Regarding the perspective of the cost-effectiveness analysis, almost half (46%) did not report this explicitly and 29% reported using the public payer perspective.

Table 2 Characteristics of each cost-effectiveness analysis (CEA) for venous ulcers (n = 24)
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Table 3 Characteristics of each cost-effectiveness analysis (CEA) for venous and venous/arterial ulcers (n = 2)
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Table 4 Characteristics of each cost-effectiveness analysis (CEA) for diabetic ulcers (n = 16)
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Table 5 Characteristics of each cost-effectiveness analysis (CEA) for pressure ulcers (n = 14)
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Table 6 Characteristics of each cost-effectiveness analysis (CEA) for mixed wound types (n = 3)
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Methodological quality appraisal

Approximately 71% (42 out of 59) of the cost-effectiveness analyses had a score of 8 or higher out of a total possible score of 10 (Additional file 5, Figure 2). Using the Drummond 10-item tool [18], the key methodological shortcoming across the cost-effectiveness analyses was that only 51% (30 out of 59) had established the ‘effectiveness’ of the intervention using data from efficacy studies (i.e., systematic reviews, randomized clinical trials or observational studies) that had sufficiently large sample sizes according to the International Conference on Harmonisation guidelines for establishing efficacy [84]. Consistent methodological strengths across the cost-effectiveness analyses included a clear research question, costs and consequences measured in appropriate physical units, credibly valued costs and consequences, and discounted costs (when applicable).

Figure 2
figure 2

Drummond methodological quality summary results (n = 59). Items: 1. Well-defined question. 2. Competing alternatives well described. 3. Effectiveness established. 4. All important and relevant costs and consequences identified. 5. Measurement accurately performed. 6. Valuation credibility. 7. Discounting. 8. Incremental analysis performed. 9. Allowance made for uncertainty. 10. Discussion.

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Cost-effectiveness results

Due to the large number of cost-effectiveness studies included and the numerous results, we have focused on dominant results in the text. However, all of the cost-effectiveness results are presented in Tables 7, 8, 9, 10 and 11 and the sensitivity analyses, level of uncertainty, and incremental variabilities are outlined in Additional file 6.

Table 7 Cost-effectiveness analysis (CEA) outcomes for venous ulcers (n = 24)
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Table 8 Cost-effectiveness analysis (CEA) outcomes for venous and venous/arterial ulcers (n = 2)
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Table 9 Cost-effectiveness analysis (CEA) outcomes for diabetic ulcers (n = 16)
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Table 10 Cost-effectiveness analysis (CEA) outcomes for pressure ulcers (n = 14)
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Table 11 Cost-effectiveness analysis (CEA) outcomes for mixed wound types (n = 3)
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Venous ulcers

Twenty-four cost-effectiveness analyses examined interventions for venous ulcers (Table 7) [22-45,83]. Sixteen studies found the interventions were dominant (i.e., more effective and less costly) [22-24,26-29,31,32,35,38,42-45], and 12 of these were studies with a Drummond score ≥8 [24,26-29,32,35,38,39,42,44,45]. These included Apligraf (Graftskin) vs. Unna’s Boot [42], Unna’s boot vs. hydrocolloid (DuoDERM) [32], micronized purified flavonoid fraction plus usual care vs. usual care alone [24], durable barrier cream vs. no skin protectant [26], pentoxifylline plus compression vs. placebo plus compression [27], Manuka honey dressing vs. usual care [29], amelogenin plus compression therapy vs. compression therapy only [45], and four-layer compression bandaging vs. usual care [35,38,44]. Although four-layer compression bandaging vs. short-stretch compression bandaging was found to be dominant in two studies [28,39]], this intervention was more effective and more costly in another economic evaluation [41].

Dominant interventions from four studies scoring <8 on the Drummond tool [22,23,31,43] included hydrocolloid dressing vs. Vaseline gauze dressing [22], hydrocolloid dressing plus compression hosiery vs. Unna’s boot [31], Thera-boot vs. Unna’s boot [23], and community leg ulcer clinic vs. usual care clinic [43].

Mixed venous and venous/arterial ulcers

Two cost-effectiveness analyses evaluated interventions for mixed venous and venous/arterial ulcers (Table 8) [46,47]. Only one study found an intervention to be dominant (and had a Drummond score ≥8); hydrocolloid (DuoDERM) dressing was dominant compared to saline gauze [47].

Diabetic ulcers

Sixteen cost-effectiveness analyses examined interventions for diabetic ulcers (Table 9) [48-63]. Twelve studies found the interventions were dominant [48-50,52-54,56,57,59,61-63], and 10 of these were studies with a Drummond score ≥8 [49,50,52-54,56,57,59,61,62]. These included becaplermin gel (containing recombinant human platelet-derived growth factor) plus good wound care (GWC) vs. GWC alone (note: the various GWC definitions used are outlined in Table 9) [57,62], cadexomer iodine ointment vs. usual care [49], filgrastim vs. placebo [50], intensified treatment vs. usual care [52], staged management diabetes foot program vs. usual care [53], ertapenem vs. piperacillin/tazobactam [54], ampicillin/sulbactam vs. imipenem/cilastatin [56], Apligraf (skin substitute) plus GWC vs. GWC alone [59], and promogran dressing plus GWC vs. GWC alone [61]. Hyperbaric oxygen therapy plus usual care vs. usual care alone was found to be dominant in one study [63], yet was more effective and more costly in another economic evaluation [51].

Dominant interventions from studies scoring <8 on the Drummond tool included hyperbaric oxygen therapy vs. control [48], and hyperbaric oxygen therapy plus standard care vs. standard care alone [63].

Pressure ulcers

Fourteen cost-effectiveness analyses evaluated pressure ulcer interventions (Table 10) [64-77]. Ten studies found the interventions were dominant [64,67,69,71-77], and four of these were studies with a Drummond score ≥8 [69,71,76,77]. These included moisture vapor permeable dressing vs. gauze [for grade II pressure ulcers] [77], advanced dressings vs. simple dressings [69], and hydrocolloid (DuoDERM) vs. gauze [76]. Collagenase-containing ointment (Novuxol) vs. hydrocolloid (DuoDERM) dressing was found to be dominant in one study [71], while collagen (Medifil) vs. hydrocolloid (DuoDERM) was more effective and more costly in another cost-effectiveness analysis [70].

The following interventions were dominant in six studies with a Drummond score <8: constant force technology mattress vs. low-air-loss mattress [64], silver mesh dressing vs. silver sulfadiazine cream [67], balsam Peru plus hydrogenated castor oil plus trypsin ointment vs. balsam Peru plus hydrogenated castor oil plus trypsin ointment plus other treatment (unspecified) for stage 1 and 2 wounds [72], balsam Peru plus hydrogenated castor oil plus trypsin ointment plus other treatment (unspecified) vs. other treatment (unspecified) for stage 1 wounds [72], balsam Peru plus hydrogenated castor oil plus trypsin ointment vs. other treatment (unspecified) for stage 2 wounds [72], polyurethane foam dressing vs. saline gauze [73], sequential granulocyte-macrophage/colony-stimulating factor and basic fibroblast growth factor vs. basic fibroblast growth factor alone [74], sequential granulocyte-macrophage/colony-stimulating factor and basic fibroblast growth factor vs. granulocyte-macrophage/colony-stimulating factor alone [74], and new hospital incentive system vs. non-introduced control [75].

Mixed wound types

Three cost-effectiveness analyses evaluated mixed complex wound types (Table 11) [78-80]. One study with a Drummond score ≥8 found that a multidisciplinary wound care team was dominant compared to usual care [80].

Discussion

We conducted a comprehensive systematic review to summarize the cost-effectiveness of interventions for complex wound care including data from 59 cost-effectiveness analyses. These economic studies examined numerous interventions and comparators and used different outcomes to assess effectiveness. In a few situations, the intervention considered in one cost-effectiveness analysis comprised the comparator in another cost-effectiveness analysis. Therefore, cost-effectiveness results are presented as comparisons of one treatment option relative to another.

Based on evidence from 42 cost-effectiveness studies with a Drummond score ≥8, 22 intervention comparisons were dominant (Additional file 7). For venous ulcers, these were four-layer compression bandaging vs. usual care, skin replacement vs. Unna’s Boot, Unna’s boot vs. hydrocolloid, micronized purified flavonoid fraction plus usual care vs. usual care, durable barrier cream vs. no skin protectant, pentoxifylline plus compression vs. placebo plus compression, Manuka honey dressing vs. usual care, and amelogenin plus compression therapy vs. compression therapy only. For mixed venous and venous/arterial ulcers, only hydrocolloid dressing vs. saline gauze was dominant according to high quality cost-effectiveness analyses. For diabetic ulcers, cadexomer iodine ointment vs. usual care, filgrastim vs. placebo, intensified treatment vs. usual care, staged management diabetes foot program vs. usual care, ertapenem vs. piperacillin/tazobactam, ampicillin/sulbactam vs. imipenem/cilastatin, skin replacement plus GWC vs. GWC alone, promogran dressing plus GWC vs. GWC alone, and becaplermin gel (containing recombinant human platelet-derived growth factor) plus GWC vs. GWC alone were dominant. For pressure ulcers, moisture vapor permeable dressing vs. gauze, advanced dressings vs. simple dressings, and hydrocolloid vs. gauze were dominant. Finally, for mixed wound types, multidisciplinary wound care team was dominant vs. usual care.

Our results highlight a need for a future network meta-analysis given the numerous interventions and comparators available. Network meta-analysis is a statistical technique that can be used to combine direct evidence of effectiveness from head-to-head studies and indirect evidence of the relative benefits of interventions versus a common comparator (usually placebo). This powerful statistical approach can also be used to select the best treatment option available from a ranking of all treatments. An attractive property of network meta-analysis is that it allows researchers and health economists the opportunity to use the ranking analysis to generate a de novo cost-effectiveness analysis more efficiently. Another potential future study is to conduct a systematic review of clinical practice guidelines on complex wounds, and compare the interventions recommended in these with those found to be cost-effective in our review.

The major methodological quality limitation found in the included cost-effectiveness analyses was that the majority did not adequately establish the effectiveness of the wound care intervention using data from systematic reviews, randomized clinical trials, or observational studies that had sufficiently large sample sizes. Moreover, many of the included economic studies did not report on uncertainty of the cost-effectiveness estimates, incremental variabilities, or sensitivity analyses, thereby further limiting the utility of those results. Further, many of the cost-effectiveness analyses did not assess long-term cost-effectiveness, and the choice of timeframe for an economic evaluation might significantly affect the cost-effectiveness results. Given the chronic nature of many types of wounds, economic modeling of a longer time horizon would provide a clearer picture in many circumstances. As an example, an intervention might be more effective yet more costly in the first 2 months of usage but it might be cost saving over a 1 year or longer timeframe due to overall fewer additional interventions required. Furthermore, most of the cost-effectiveness studies did not include information on patient-reported quality of life, which is a major limitation of this literature.

The majority of the included economic studies were from European countries and 16 were from the United States. When trying to apply the cost-effectiveness results to a country-specific context, several factors need to be assessed such as the perspective of the economic evaluation (e.g., public payer, healthcare provider), the type of healthcare system (e.g., publicly-funded healthcare), the local practice of medicine, and local costs.

There are a few limitations related to our systematic review process worth noting. Due to resource constraints, we only included studies written in English. However, we contacted authors of non-English studies to obtain the English translations. In addition, although we contacted authors to share their unpublished data, only published literature was identified for inclusion. Finally, due to the numerous number of cost-effectiveness analyses included, we focused reporting on those with dominant results and a score ≥8 on the Drummond tool in the main text. We note that this is an arbitrary cut-off, and there is not an agreed upon method to provide a summary score on this tool. However, all of our results for all studies are presented in the tables and appendices despite dominance and score on the Drummond tool.

Conclusions

We conducted a comprehensive systematic review of cost-effectiveness studies for interventions to treat adult patients with complex wounds. Our results can be used by decision-makers to assist in maximizing the deployment of clinically effective and resource efficient wound care interventions. Our analysis also highlights specific treatments that are not cost-effective, thus indicating areas for potential improvements in efficiency. A network meta-analysis and de novo cost-effectiveness analysis will likely bring additional clarity to the field, as some of the findings were conflicting.

Abbreviations

GWC:

Good wound care

ICER:

Incremental cost-effectiveness ratio

QALY:

Quality-adjusted life-year

USD:

United States dollar

References

  1. Mustoe TA, O’Shaughnessy K, Kloeters O. Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg. 2006;117:35S–41.

    Article  CAS  PubMed  Google Scholar 

  2. Gottrup F. A specialized wound-healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. Am J Surg. 2004;187:38S–43.

    Article  PubMed  Google Scholar 

  3. Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17:763–71.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Swanson L. Solving stubborn-wound problem could save millions, team says. CMAJ. 1999;160:556.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Miller PS. In economics as well as medicine prevention is better than cure. Age Ageing. 2004;33:217–8.

    Article  PubMed  Google Scholar 

  6. Canadian Association of Wound Care. Best practice articles. http://cawc.net/index.php/resources/resources/clinical-practice/.

  7. Jull AB, Rodgers A, Walker N. Honey as a topical treatment for wounds. Cochrane Database Syst Rev. 2008;4, CD005083.

    PubMed  Google Scholar 

  8. Lazarus GS, Cooper DM, Knighton DR, Percoraro RE, Rodeheaver G, Robson MC. Definitions and guidelines for assessment of wounds and evaluation of healing. Wound Repair Regen. 1994;2:165–70.

    Article  CAS  PubMed  Google Scholar 

  9. Werdin F, Tennenhaus M, Schaller HE, Rennekampff HO. Evidence-based management strategies for treatment of chronic wounds. Eplasty. 2009;9:e19.

    PubMed  PubMed Central  Google Scholar 

  10. Global Industry Analysts. Advanced wound care: a global strategic business report. http://www.marketresearch.com/Global-Industry-Analysts-v1039/Advanced-Wound-Care-8102385/.

  11. Tricco A, Antony J, Vafaei A, Khan PA, Cogo E, Wilson C, et al. Seeking effective interventions to treat complex wounds: an overview of systematic reviews. BMC Med. 2015, DOI: 10.1186/s12916-015-0288-5.

  12. Sampson M, McGowan J, Cogo E, Grimshaw J, Moher D, Lefebvre C. An evidence-based practice guideline for the peer review of electronic search strategies. J Clin Epidemiol. 2009;62:944–52.

    Article  PubMed  Google Scholar 

  13. Stone PW. Popping the (PICO) question in research and evidence-based practice. Appl Nurs Res. 2002;15:197–8.

    Article  PubMed  Google Scholar 

  14. Newton D. Synthesi.SR. http://knowledgetranslation.ca/sysrev/login.php.

  15. Centers for Disease Control and Prevention. Public health economics and tools. http://www.cdc.gov/stltpublichealth/pheconomics/.

  16. Black WC. The CE, plane: a graphic representation of cost-effectiveness. Med Decis Making. 1990;10:212–4.

    Article  CAS  PubMed  Google Scholar 

  17. Government of Ontario. Ontario guidelines for economic analysis of pharmaceutical products: interpretation of cost-effectiveness ratios. http://www.health.gov.on.ca/english/providers/pub/drugs/economic/econ_ratios.html.

  18. Drummond MF. Methods for the economic evaluation of health care programmes. 3rd ed. Oxford, New York: Oxford University Press; 2005.

    Google Scholar 

  19. OECD. StatExtracts, PPPs and exchange rates. http://stats.oecd.org/Index.aspx?datasetcode=SNA_TABLE4.

  20. Economy Watch. Implied PPP conversion rate data for year 1997, all countries. http://www.economywatch.com/economic-statistics/economic-indicators/Implied_PPP_Conversion_Rate/1997/.

  21. US Bureau of Labor Statistics. Consumer price index – all urban consumers (current series). http://data.bls.gov/pdq/querytool.jsp?survey=cu.

  22. Augustin M, Siegel A, Heuser A, Vanscheidt W. Chronic leg ulcers: cost evaluation of two treatment strategies. J Dermatolog Treat. 1999;10:S21–5.

    Google Scholar 

  23. DePalma RG, Kowallek D, Spence RK, Caprini JA, Nehler MR, Jensen J, et al. Comparison of costs and healing rates of two forms of compression in treating venous ulcers. Vasc Surg. 1999;33:683–90.

    Article  Google Scholar 

  24. Glinski W, Chodynicka B, Roszkiewicz J, Bogdanowski T, Lecewicz-Torun B, Kaszuba A, et al. The beneficial augmentative effect of micronised purified flavonoid fraction (MPFF) on the healing of leg ulcers: An open, multicentre, controlled, randomised study. Phlebology. 1999;14:151–7.

    Article  Google Scholar 

  25. Gordon L, Edwards H, Courtney M, Finlayson K, Shuter P, Lindsay E. A cost-effectiveness analysis of two community models of care for patients with venous leg ulcers. J Wound Care. 2006;15:348–53.

    Article  CAS  PubMed  Google Scholar 

  26. Guest JF, Taylor RR, Vowden K, Vowden P. Relative cost-effectiveness of a skin protectant in managing venous leg ulcers in the UK. J Wound Care. 2012;21:389–94.

    Article  CAS  PubMed  Google Scholar 

  27. Iglesias CP, Claxton K. Comprehensive decision-analytic model and Bayesian value-of-information analysis: pentoxifylline in the treatment of chronic venous leg ulcers. Pharmacoeconomics. 2006;24:465–78.

    Article  PubMed  Google Scholar 

  28. Iglesias CP, Nelson EA, Cullum N, Torgerson DJ, VenUS I Collaborators. Economic analysis of VenUS I, a randomized trial of two bandages for treating venous leg ulcers. Br J Surg. 2004;91:1300–6.

    Article  CAS  PubMed  Google Scholar 

  29. Jull A, Walker N, Parag V, Molan P, Rodgers A. Randomized clinical trial of honey‐impregnated dressings for venous leg ulcers. Br J Surg. 2008;95:175–82.

    Article  PubMed  Google Scholar 

  30. Junger M, Arnold A, Zuder D, Stahl HW, Heising S. Local therapy and treatment costs of chronic, venous leg ulcers with electrical stimulation (Dermapulse): a prospective, placebo controlled, double blind trial. Wound Repair Regen. 2008;16:480–7.

    Article  PubMed  Google Scholar 

  31. Kerstein MD, Gahtan V. Outcomes of venous ulcer care: results of a longitudinal study. Ostomy Wound Manage. 2000;46:22–6.

    CAS  PubMed  Google Scholar 

  32. Kikta MJ, Schuler JJ, Meyer JP, Durham JR, Eldrup-Jorgensen J, Schwarcz TH, et al. A prospective, randomized trial of Unna’s boots versus hydroactive dressing in the treatment of venous stasis ulcers. J Vasc Surg. 1988;7:478–83.

    Article  CAS  PubMed  Google Scholar 

  33. Michaels JA, Campbell WB, King BM, Macintyre J, Palfreyman SJ, Shackley P, et al. A prospective randomised controlled trial and economic modelling of antimicrobial silver dressings versus non-adherent control dressings for venous leg ulcers: the VULCAN trial. Health Technol Assess. 2009;13:1–114.

    Article  CAS  Google Scholar 

  34. Morrell CJ, Walters SJ, Dixon S, Collins KA, Brereton LM, Peters J, et al. Cost effectiveness of community leg ulcer clinics: randomised controlled trial. BMJ. 1998;316:1487–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. O’Brien JF, Grace PA, Perry IJ, Hannigan A, Clarke Moloney M, Burke PE. Randomized clinical trial and economic analysis of four-layer compression bandaging for venous ulcers. Br J Surg. 2003;90:794–8.

    Article  PubMed  Google Scholar 

  36. Oien RF, Hakansson A, Ahnlide I, Bjellerup M, Hansen BU, Borgquist L. Pinch grafting in hospital and primary care: a cost analysis. J Wound Care. 2001;10:164–9.

    Article  CAS  PubMed  Google Scholar 

  37. Sibbald RG, Torrance GW, Walker V, Attard C, MacNeil P. Cost-effectiveness of Apligraf in the treatment of venous leg ulcers. Ostomy Wound Manage. 2001;47:36–46.

    CAS  PubMed  Google Scholar 

  38. Taylor AD, Taylor RJ, Marcuson RW. Prospective comparison of healing rates and therapy costs for conventional and four-layer high-compression bandaging treatments of venous leg ulcers. Phlebology. 1998;13:20–4.

    Google Scholar 

  39. Ukat A, Konig M, Vanscheidt W, Munter KC. Short-stretch versus multilayer compression for venous leg ulcers: a comparison of healing rates. J Wound Care. 2003;12:139–43.

    Article  CAS  PubMed  Google Scholar 

  40. Watson JM, Kang’ombe AR, Soares MO, Chuang LH, Worthy G, Bland JM, et al. VenUS III: a randomised controlled trial of therapeutic ultrasound in the management of venous leg ulcers. Health Technol Assess. 2011;15:1–192.

    Article  CAS  Google Scholar 

  41. Pham B, Harrison MB, Chen MH, Carley ME. Cost-effectiveness of compression technologies for evidence-informed leg ulcer care: results from the Canadian Bandaging Trial. BMC Health Serv Res. 2012;12:346–53.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Schonfeld WH, Villa KF, Fastenau JM, Mazonson PD, Falanga V. An economic assessment of Apligraf (Graftskin) for the treatment of hard-to-heal venous leg ulcers. Wound Repair Regen. 2000;8:251–7.

    Article  CAS  PubMed  Google Scholar 

  43. Simon DA, Freak L, Kinsella A, Walsh J, Lane C, Groarke L, et al. Community leg ulcer clinics: a comparative study in two health authorities. BMJ. 1996;312:1648–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Carr L, Phillips Z, Posnett J. Comparative cost-effectiveness of four-layer bandaging in the treatment of venous leg ulceration. J Wound Care. 1999;8:243–8.

    Article  CAS  PubMed  Google Scholar 

  45. Guest JF, Nagy E, Sladkevicius E, Vowden P, Price P. Modelling the relative cost-effectiveness of amelogenin in non-healing venous leg ulcers. J Wound Care. 2009;18:216.

    Article  CAS  PubMed  Google Scholar 

  46. Dumville JC, Worthy G, Soares MO, Bland JM, Cullum N, Dowson C, et al. VenUS II: a randomised controlled trial of larval therapy in the management of leg ulcers. Health Technol Assess. 2009;13:1–182.

    Article  CAS  PubMed  Google Scholar 

  47. Ohlsson P, Larsson K, Lindholm C, Moller M. A cost-effectiveness study of leg ulcer treatment in primary care. Comparison of saline-gauze and hydrocolloid treatment in a prospective, randomized study. Scand J Prim Health Care. 1994;14:295–9.

    Article  Google Scholar 

  48. Abidia A, Laden G, Kuhan G, Johnson BF, Wilkinson AR, Renwick PM, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg. 2003;25:513–8.

    Article  CAS  PubMed  Google Scholar 

  49. Apelqvist J, Ragnarson TG. Cavity foot ulcers in diabetic patients: a comparative study of cadexomer iodine ointment and standard treatment. An economic analysis alongside a clinical trial. Acta Derm Venereol. 1996;76:231–5.

    CAS  PubMed  Google Scholar 

  50. Edmonds M, Gough A, Solovera J, Standaert B. Filgrastim in the treatment of infected diabetic foot ulcers. Retrospective cost analysis of a phase II randomised clinical trial. Clin Drug Investig. 1999;17:275–86.

    Article  Google Scholar 

  51. Guo S, Counte MA, Gillespie KN, Schmitz H. Cost-effectiveness of adjunctive hyperbaric oxygen in the treatment of diabetic ulcers. Int J Technol Assess Health Care. 2003;19:731–7.

    Article  PubMed  Google Scholar 

  52. Habacher W, Rakovac I, Gorzer E, Haas W, Gfrerer RJ, Wach P, et al. A model to analyse costs and benefit of intensified diabetic foot care in Austria. Eur J Vasc Endovasc Surg. 2007;13:906–12.

    Google Scholar 

  53. Horswell RL, Birke JA, Patout Jr CA. A staged management diabetes foot program versus standard care: a 1-year cost and utilization comparison in a state public hospital system. Arch Phys Med Rehabil. 2003;84:1743–6.

    Article  PubMed  Google Scholar 

  54. Jansen JP, Kumar R, Carmeli Y. Accounting for the development of antibacterial resistance in the cost effectiveness of ertapenem versus piperacillintazobactam in the treatment of diabetic foot infections in the UK. Pharmacoeconomics. 2009;27:1045–56.

    Article  PubMed  Google Scholar 

  55. Jeffcoate WJ, Price PE, Phillips CJ, Game FL, Mudge E, Davies S, et al. Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes. Health Technol Assess. 2009;13:1–86.

    Article  CAS  PubMed  Google Scholar 

  56. McKinnon PS, Paladino JA, Grayson ML, Gibbons GW, Karchmer AW. Cost-effectiveness of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients. Clin Infect Dis. 1997;24:57–63.

    Article  CAS  PubMed  Google Scholar 

  57. Persson U, Willis M, Odegaard K, Apelqvist J. The cost-effectiveness of treating diabetic lower extremity ulcers with becaplermin (Regranex): a core model with an application using Swedish cost data. Value Health. 2000;3:39–46.

    Article  PubMed  Google Scholar 

  58. Piaggesi A, Macchiarini S, Rizzo L, Palumbo F, Tedeschi A, Nobili LA, et al. An off-the-shelf instant contact casting device for the management of diabetic foot ulcers: a randomized prospective trial versus traditional fiberglass cast. Diabetes Care. 2007;30:586–90.

    Article  PubMed  Google Scholar 

  59. Redekop WK, McDonnel J, Verboom P, Lovas K, Kalo Z. The cost-effectiveness of Apligraf treatment of diabetic foot ulcers. Pharmacoeconomics. 2003;21:1171–83.

    Article  PubMed  Google Scholar 

  60. Allenet B, Paree F, Lebrun T, Carr L, Posnett J, Martinin J, et al. Cost-effectiveness modelling of Dermagraft for the treatment of diabetic foot ulcers in the French context. Diabetes Metab. 2000;26:125–32.

    CAS  PubMed  Google Scholar 

  61. Ghatnekar O, Willis M, Persson U. Cost-effectiveness of treating deep diabetic foot ulcers with Promogram in four European countries. J Wound Care. 2002;11:70–4.

    Article  CAS  PubMed  Google Scholar 

  62. Ghatnekar O, Persson U, Willis M, Odegaard K. Cost effectiveness of becaplermin in the treatment of diabetic foot ulcers in four European countries. Pharmacoeconomics. 2001;19:767–78.

    Article  CAS  PubMed  Google Scholar 

  63. Hailey D, Jacobs P, Perry DC, Chuck A, Morrison A, Boudreau R. Adjunctive hyperbaric oxygen therapy for diabetic foot ulcer: an economic analysis. Canadian Agency for Drugs and Technologies in Health. 2007;75:1–19.

    Google Scholar 

  64. Branom R, Rappl LM. Constant force technology versus low-air-loss therapy in the treatment of pressure ulcers. Ostomy Wound Manage. 2001;47:38–46.

    CAS  PubMed  Google Scholar 

  65. Burgos A, Gimenez J, Moreno E, Lamberto E, Utrera M, Urraca EM, et al. Cost, efficacy, efficiency and tolerability of collagenase ointment versus hydrocolloid occlusive dressing in the treatment of pressure ulcers. A comparative, randomised, multicentre study. Clin Drug Investig. 2000;19:357–65.

    Article  Google Scholar 

  66. Chang KW, Alsagoff S, Ong KT, Sim PH. Pressure ulcers–randomised controlled trial comparing hydrocolloid and saline gauze dressings. Med J Malaysia. 1998;53:428–31.

    CAS  PubMed  Google Scholar 

  67. Chuangsuwanich A, Charnsanti O, Lohsiriwat V, Kangwanpoom C, Thong-In N. The efficacy of silver mesh dressing compared with silver sulfadiazine cream for the treatment of pressure ulcers. J Med Assoc Thai. 2011;94:559–65.

    PubMed  Google Scholar 

  68. Ferrell BA, Keeler E, Siu AL, Ahn SH, Osterweil D. Cost-effectiveness of low-air-loss beds for treatment of pressure ulcers. J Gerontol A Biol Sci Med Sci. 1995;50:M141–6.

    Article  CAS  PubMed  Google Scholar 

  69. Foglia E, Restelli U, Napoletano AM, Coclite D, Porazzi E, Bonfanti M, et al. Pressure ulcers management: an economic evaluation. J Prev Med Hyg. 2012;53:30–6.

    CAS  PubMed  Google Scholar 

  70. Graumlich JF, Blough LS, McLaughlin RG, Milbrandt JC, Calderon CL, Agha SA, et al. Healing pressure ulcers with collagen or hydrocolloid: a randomized, controlled trial. J Am Geriatr Soc. 2003;51:147–54.

    Article  PubMed  Google Scholar 

  71. Muller E, van Leen MW, Bergemann R. Economic evaluation of collagenase-containing ointment and hydrocolloid dressing in the treatment of pressure ulcers. Pharmacoeconomics. 2001;19:1209–16.

    Article  CAS  PubMed  Google Scholar 

  72. Narayanan S, Van Vleet J, Strunk B, Ross RN, Gray M. Comparison of pressure ulcer treatments in long-term care facilities: clinical outcomes and impact on cost. J Wound Ostomy Continence Nurs. 2005;32:163–70.

    Article  PubMed  Google Scholar 

  73. Payne WG, Posnett J, Alvarez O, Brown-Etris M, Jameson G, Wolcott R, et al. A prospective, randomized clinical trial to assess the cost-effectiveness of a modern foam dressing versus a traditional saline gauze dressing in the treatment of stage II pressure ulcers. Ostomy Wound Manage. 2009;55:50–5.

    PubMed  Google Scholar 

  74. Robson MC, Hill DP, Smith PD, Wang X, Meyer-Siegler K, Ko F, et al. Sequential cytokine therapy for pressure ulcers: clinical and mechanistic response. Ann Surg. 2000;231:600–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Sanada H, Nakagami G, Mizokami Y, Minami Y, Yamamoto A, Oe M, et al. Evaluating the effect of the new incentive system for high-risk pressure ulcer patients on wound healing and cost-effectiveness: a cohort study. Int J Nurs Stud. 2010;47:279–86.

    Article  PubMed  Google Scholar 

  76. Xakellis GC, Chrischilles EA. Hydrocolloid versus saline-gauze dressings in treating pressure ulcers: a cost-effectiveness analysis. Arch Phys Med Rehabil. 1992;73:463–9.

    CAS  PubMed  Google Scholar 

  77. Sebern MD. Pressure ulcer management in home health care: efficacy and cost effectiveness of moisture vapor permeable dressing. Arch Phys Med Rehabil. 1986;67:726–9.

    Article  CAS  PubMed  Google Scholar 

  78. Bale S, Hagelstein S, Banks V, Harding KG. Costs of dressings in the community. J Wound Care. 1998;7:327–30.

    CAS  PubMed  Google Scholar 

  79. Terry M, Halstead LS, O’Hare P, Gaskill C, Ho PS, Obecny J, et al. Feasibility study of home care wound management using telemedicine. Adv Skin Wound Care. 2009;22:358–64.

    Article  PubMed  Google Scholar 

  80. Vu T, Harris A, Duncan G, Sussman G. Cost-effectiveness of multidisciplinary wound care in nursing homes: a pseudo-randomized pragmatic cluster trial. Fam Pract. 2007;24:372–9.

    Article  PubMed  Google Scholar 

  81. Sebern MD. Cost and efficacy of pressure ulcer management in a metropolitan visiting nurse association. Decubitus. 1989;2:58–9.

    CAS  PubMed  Google Scholar 

  82. Chuck AW, Hailey D, Jacobs P, Perry DC. Cost-effectiveness and budget impact of adjunctive hyperbaric oxygen therapy for diabetic foot ulcers. Int J Technol Assess Health Care. 2008;24:178–83.

    Article  PubMed  Google Scholar 

  83. Iglesias C, Nelson EA, Cullum NA, Torgerson DJ, VenUS Team. VenUS I: a randomised controlled trial of two types of bandage for treating venous leg ulcers. Health Technol Assess. 2004;8:iii. 1-105.

  84. International Conference on Harmonisation (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use. Guidance E9: Statistical Principles for Clinical Trials. Rockville, MD: ICH; 1998.

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Acknowledgements

We thank the Toronto Central Local Health Integrated Network (TC LHIN) for their generous funding. ACT is funded by Canadian Institutes for Health Research/Drug Safety and Effectiveness Network (CIHR/DSEN) New Investigator Award in Knowledge Synthesis. SES is funded by a CIHR Tier 1 Research Chair in Knowledge Translation. We thank Dr. James Mahoney and Chris Shumway from the TC LHIN who provided invaluable feedback on our original report. We thank Laure Perrier for conducting the literature searches, and Afshin Vafaei, Alana Harrington, Charlotte Wilson, and John Ivory for screening articles. We also thank Inthuja Selvaratnam and Wasifa Zarin for formatting the report and references, and Judy Tran for obtaining the full-text articles.

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Authors and Affiliations

  1. Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada

    Andrea C Tricco, Elise Cogo, Wanrudee Isaranuwatchai, Paul A Khan, Geetha Sanmugalingham, Jesmin Antony, Jeffrey S Hoch & Sharon E Straus

  2. Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada

    Andrea C Tricco

  3. Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto, ON, M5T 3M7, Canada

    Wanrudee Isaranuwatchai & Jeffrey S Hoch

  4. Department of Geriatric Medicine, University of Toronto, 200 Elizabeth Street, Suite RFE 3-805, Toronto, ON, M5G 2C4, Canada

    Sharon E Straus

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Correspondence to Sharon E Straus.

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Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

ACT conceived the study, helped obtain funding for the study, screened articles, analyzed the data, interpreted the results, and wrote the manuscript. EC coordinated the study, peer reviewed the MEDLINE search, screened articles, abstracted data, appraised quality, cleaned the data, converted the costs, analyzed the data, generated tables, interpreted the results, and helped write the manuscript. WI abstracted data, appraised quality, and edited the manuscript. PAK screened articles, abstracted data, scanned reference lists, and edited the manuscript. GS screened articles, abstracted data, appraised quality, and edited the manuscript. JA helped coordinate the review, screened articles, and edited the manuscript. JSH provided economic guidance and edited the manuscript. SES conceived and designed the study, obtained the funding, interpreted the results, and edited the manuscript. All authors read and approved the final manuscript.

Additional files

Additional file 1:

Wound care protocol. Outlines the protocol used in the systematic review.

Additional file 2:

MEDLINE search strategy. Lists MEDLINE search terms.

Additional file 3:

Classification of wound care interventions. Lists the wound care interventions in each classification.

Additional file 4:

Drummond’s 10-item checklist tool used for cost-effectiveness analyses quality appraisal. Provides the descriptions of the 10 items in Drummond’s 10-item checklist tool.

Additional file 5:

Cost-effectiveness analysis methodological quality appraisal results. Lists the quality appraisal results for the 59 included cost-effectiveness analyses.

Additional file 6:

Cost-effectiveness analyses sensitivity analysis, uncertainty of results and incremental variabilities. Outlines the sensitivity analyses, level of uncertainty, and incremental variabilities for the cost-effectiveness analyses results.

Additional file 7:

Summary of the less costly and more effective interventions for studies with a Drummond score ≥8. Lists 42 cost-effectiveness studies with a Drummond score ≥8.

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Tricco, A.C., Cogo, E., Isaranuwatchai, W. et al. A systematic review of cost-effectiveness analyses of complex wound interventions reveals optimal treatments for specific wound types. BMC Med 13, 90 (2015). https://doi.org/10.1186/s12916-015-0326-3

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Keywords

BMC Medicine

ISSN: 1741-7015

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