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Dressings for treating foot ulcers in people with diabetes: an overview of systematic reviews

  1. Jo C Dumville*,
  2. Susan O'Meara,
  3. Sally EM Bell-Syer

Editorial Group: Cochrane Wounds Group

Published Online: 30 APR 2013

DOI: 10.1002/14651858.CD010471


How to Cite

Dumville JC, O'Meara S, Bell-Syer SEM. Dressings for treating foot ulcers in people with diabetes: an overview of systematic reviews (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD010471. DOI: 10.1002/14651858.CD010471.

Author Information

  1. University of York, Department of Health Sciences, York, UK

*Jo C Dumville, Department of Health Sciences, University of York, York, YO10 5DD, UK. jd34@york.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 30 APR 2013

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

Also see Glossary (Appendix 1).

 

Description of the condition

Diabetes mellitus (DM) (high glucose levels in the blood) is a common condition that affects 1.8 million people in the UK (approximately 3% of the population) and 24 million in the US. Incidence of DM is projected to increase rapidly over the next 25 years (WHO 2005). Global projections suggest that the worldwide prevalence of DM could rise to 4.4% in 2030, which would mean that approximately 366 million people would be affected (Wild 2004).

Success in treating DM has improved the life expectancy of patients. However, the increased prevalence of DM, coupled with the extended time people now live with the disease, has led to increased numbers of DM-related complications, such as neuropathy (nerve damage) and peripheral arterial disease (PAD).

Both PAD and neuropathy are risk factors for the development of chronic foot ulceration in people with DM (Pecoraro 1990; Reiber 1999). PAD and neuropathy can occur separately (ischaemic foot and neuropathic foot), or in combination (in the neuroischaemic foot). Foot ulceration is reported to affect 15% or more of the diabetic population at some time in their lives (Reiber 1996; Singh 2005). Estimates from UK surveys indicate that around 1% to 4% of people with DM have foot ulcers at any given time (Abbott 2002; Kumar 1994). In 2008, the prevalence of having at least one foot ulcer was 8% amongst people with DM receiving US Medicare (Margolis 2011).

An ulcer forms as a result of damage to the epidermis (skin) and subsequent loss of underlying tissue. Specifically, the International Consensus on the Diabetic Foot defines a foot ulcer as a wound that extends through the full thickness of the skin below the level of the ankle (Apelqvist 2000a). This is irrespective of duration (although some definitions of chronic ulceration require a duration of six weeks or more), and the ulcer can extend to muscle, tendon and bone. Foot ulcers in people with DM can be graded for severity using a number of systems. The Wagner wound classification system was one of the first described, and has, historically, been widely used, although it is now rarely used in clinical practice. The system assesses ulcer depth and the presence of osteomyelitis (bone infection) or gangrene and grades them as: grade 0 (pre- or post-ulcerative lesion); grade 1 (partial/full-thickness ulcer); grade 2 (probing to tendon or capsule); grade 3 (deep with osteitis (bone inflammation)); grade 4 (partial foot gangrene); and grade 5 (whole foot gangrene) (Wagner 1981). Newer grading systems, such as the PEDIS system (Schaper 2004), the University of Texas Wound Classification System and SINBAD (Ince 2008; Oyibo 2001), have been developed, with variable validation (Karthikesalingam 2010).

Foot ulcers in people with DM impact seriously on health-related quality of life (Nabuurs-Franssen 2005; Ribu 2006), and treating people with DM and foot ulcers incurs costs to the health system - not only for dressings applied, but also for staff (for podiatry, nurses, doctors), tests and investigations, antibiotics and specialist footwear. Twelve years ago the cost of diabetic foot ulceration to the UK National Health Service was believed to be about GBP 12.9 million annually (Lewis 2013); this figure will have increased significantly since. Also, the economic impact is high in terms of the personal costs to patients and carers, and includes costs associated with lost work time and productivity while the patient is non-weight bearing (taking weight off the affected foot), or hospitalised. As many as 85% of foot-related amputations are preceded by ulceration (Apelqvist 2000b; Pecoraro 1990).

In terms of ulcer healing, a meta-analysis of trials in which people with neuropathic foot ulcers received good wound care reported that 24% of ulcers attained complete healing by 12 weeks and 31% by 20 weeks (Margolis 1999). Reasons for delayed healing might include: infection (especially osteomyelitis), co-morbidities and the size and depth of ulcer at presentation. Even when ulcers do heal, the risk of ulcer recurrence is high. Pound 2005 reported that 62% of ulcer patients (n = 231) became ulcer-free at some stage over a 31-month observation period. However, 40% of the ulcer-free group went on to develop a new or recurrent ulcer after a median period of 126 days. The ulcer recurrence rate over five years can be as high as 70% (Dorresteijn 2010; Van Gils 1999). Failure of ulcers to heal may result in amputation, and people with DM have a 10 to 20-fold higher risk of losing a lower limb, or part of a lower limb, due to non-traumatic amputation than those without DM (Morris 1998; Wrobel 2001).

 

Description of the interventions

The treatment of foot ulcers in people with DM comprises several strategies, some of which may be used concurrently. These include: pressure relief (i.e. off-loading - taking weight off the affected foot); wearing special footwear, or shoe inserts, designed to redistribute load on the surface of the foot; removal of dead cellular material from the surface of the wound (debridement or desloughing); infection control; and the use of wound dressings. Other general treatment strategies include: patient education (e.g. in relation to foot care, or other aspects of self-management); optimisation of blood glucose control; correction (where possible) of arterial insufficiency, for example with arterial reconstruction surgery; and other surgical interventions such as debridement, drainage of pus and amputation.

Dressings are widely used in wound care, both to protect the wound and to promote healing. Classification of a dressing normally depends on the key material used. Several attributes of an ideal wound dressing have been described (BNF 2010), including:

  • the ability of the dressing to absorb and contain exudate without leakage or strike-through;
  • lack of particulate contaminants left in the wound by the dressing;
  • thermal insulation;
  • impermeability to water and bacteria;
  • avoidance of wound trauma on dressing removal;
  • frequency with which the dressing needs to be changed (less frequent dressing changes seen as positive);
  • provision of pain relief; and
  • comfort.

There is a vast choice of dressings available to treat chronic wounds like foot ulcers in people with DM. For ease of comparison this review has categorised dressings according to the British National Formulary 2010 (BNF 2010), which is freely available via the Internet. We will use "generic" names where possible, also providing UK trade names and manufacturers, where these are available, to allow cross reference with the BNF. However, it is important to note that the way dressings are categorised, as well as dressing names, manufacturers and distributors of dressings may vary from country to country, so these are provided as a guide only. A description of all categories of dressings is given below:

 

1. Basic wound contact dressings

 

Low-adherence dressings and wound contact materials

Low-adherence dressings and wound contact materials usually consist of cotton pads that are placed directly in contact with the wound. These can be non-medicated (e.g. paraffin gauze dressing), or medicated (e.g. containing povidone iodine or chlorhexidine). Examples include paraffin gauze dressing, BP 1993 and Xeroform® (Covidien) dressing (a non-adherent petrolatum blend with 3% bismuth tribromophenate on fine mesh gauze).

 

Absorbent dressings

Absorbent dressings are applied directly to the wound, and may be used as secondary absorbent layers in the management of heavily exuding wounds. Examples include Primapore® (Smith & Nephew), Mepore® (Mölnlycke) and absorbent cotton gauze (BP 1988).

 

2. Advanced wound dressings

 

Alginate dressings

Alginate dressings are highly absorbent and come in the form of calcium alginate or calcium sodium alginate, which can be combined with collagen. Alginates form a gel when in contact with the wound surface; this can be lifted off when the dressing is removed, or rinsed away with sterile saline. Bonding the alginate to a secondary viscose pad increases absorbency. Examples include: Curasorb (Covidien), SeaSorb (Coloplast) and Sorbsan (Unomedical).

 

Hydrogel dressings

Hydrogel dressings consist of cross-linked insoluable polymers (i.e. starch or carboxymethylcellulose) and up to 96% water. These dressings are designed to absorb wound exudate, or rehydrate a wound, depending on the wound moisture levels. They are supplied in flat sheets, as an amorphous hydrogel, or as beads. Examples include: ActiformCool® (Activa) and Aquaflo® (Covidien).

 

Films (permeable film and membrane dressings)

Films (permeable film and membrane dressings) are permeable to water vapour and oxygen, but not to water or micro-organisms. Examples include Tegaderm® (3M) and Opsite® (Smith & Nephew).

 

Soft polymer dressings

Soft polymer dressings are composed of a soft silicone polymer held in a non-adherent layer, and are moderately absorbent. Examples include: Mepitel® (Mölnlycke) and Urgotul® (Urgo).

 

Hydrocolloid dressings

Hydrocolloid dressings are occlusive and usually composed of a hydrocolloid matrix bonded onto a vapour-permeable film or foam backing. When in contact with the wound surface this matrix forms a gel to provide a moist environment for the wound. Examples include: Granuflex® (ConvaTec) and NU DERM® (Systagenix). Fibrous alternatives have been developed that resemble alginates and are not occlusive, but which are more absorbant than standard hydrocolloid dressings, for example, Aquacel® (ConvaTec).

 

Foam dressings

Foam dressings contain hydrophilic polyurethane foam and are designed to absorb wound exudate and maintain a moist wound surface. These are available in a variety of versions: some include additional absorbent materials, such as viscose and acrylate fibres or particles of superabsorbent polyacrylate, while others are silicone-coated for non-traumatic removal. Examples include: Allevyn® (Smith & Nephew), Biatain® (Coloplast) and Tegaderm® (3M).

 

Capillary-action dressings

Capillary-action dressings consist of an absorbent core of hydrophilic fibres held between two low-adherent contact layers. Examples include: Advadraw® (Advancis) and Vacutx® (Protex).

 

Odour-absorbent dressings

Odour-absorbent dressings contain charcoal and are used to absorb wound odour. Often these types of wound dressings are used in conjunction with a secondary dressing to improve absorbency. An example of an odour-absorbent dressing is CarboFLEX® (ConvaTec).

 

3. Anti-microbial dressings

 

Honey-impregnated dressings

Honey-impregnated dressings contain medical-grade honey, which is proposed to have antimicrobial and anti-inflammatory properties and can be used for acute or chronic wounds. Examples include: Medihoney® (Medihoney) and Activon Tulle® (Advancis).

 

Iodine-impregnated dressings

Iodine-impregnated dressings release free iodine when exposed to wound exudate. The free iodine is thought to act as a wound antiseptic. Examples include Iodoflex® (Smith & Nephew) and Iodozyme® (Insense).

 

Silver-impregnated dressings

Silver-impregnated dressings are used to treat infected wounds, as silver ions are thought to have antimicrobial properties. Silver versions of most dressing types are available (e.g. silver foam, silver hydrocolloid, etc). Examples include: Acticoat® (Smith & Nephew) and Urgosorb Silver® (Urgo).

 

Other antimicrobial dressings

Other antimicrobial dressings are composed of a dressing impregnated with an ointment thought to have antimicrobial properties. Examples include: chlorhexidine gauze dressing (Smith & Nephew), Cutimed Sorbact® (BSN Medical), and dressing impregnated with the anti-microbial polyhexamethylene biguanide (PHMB).

 

4. Specialist dressings

 

Protease-modulating matrix dressings

Protease-modulating matrix dressings alter the activity of proteolytic (protein-digesting) enzymes in chronic wounds. Examples include: Promogran® (Systagenix) and Sorbion® (H & R).

It is difficult to make an evidence-informed decision of the best treatment regimen for patients, given the diversity of dressings available to clinicians (including variation within each type listed above). In a UK survey performed to determine treatments used for debriding diabetic foot ulcers, a wide range of treatments was reported (Smith 2003), and it is possible that a similar scenario is true for choice of dressing. A survey of Diabetes Specialist Nurses found that low/non-adherent dressings, hydrocolloids and alginate dressings were the most popular for all wound types, despite a paucity of evidence for any of these dressing types (Fiskin 1996). However, several new, heavily-promoted, types of dressing have become available in recent years. Some dressings now have a 'active' ingredients, such as silver, that are promoted as options to reduce infection, and thus possibly promote healing. As increasingly sophisticated technology is applied to wound care, practitioners need to know how effective these - often expensive - dressings are compared with more traditional dressings.

 

How the intervention might work

Animal experiments conducted over 40 years ago suggested that acute wounds heal more quickly when their surface is kept moist, rather than left to dry and scab (Winter 1963). A moist environment is thought to provide optimal conditions for the cells involved in the healing process, as well as allowing autolytic debridement (disposal of dead cells by the body), which is thought to be an important part of the healing pathway (Cardinal 2009). The desire to maintain a moist wound environment is a key driver for the use of wound dressings. Different wound dressings vary in their levels of absorbency, so a very wet wound can be treated with an absorbent dressing (such as an alginate dressing) that draws excess moisture away from the wound in order to avoid skin damage, whilst a drier wound can be treated with a more occlusive dressing to maintain a moist environment.

 

Why it is important to do this overview

Foot ulcers in people with DM are a prevalent and serious global issue. Treatment with dressings forms a key part of the treatment pathway when caring for such ulcers: there are many types of dressings that can be used, and these vary considerably in cost. Guidelines for the treatment of foot ulcers in people with DM maintain that clinical judgement should be used to select a moist wound dressing (e.g. Steed 2006). Yet, it can be challenging to make clinical decisions in the light of so many dressing options.

Given the number of dressing types available, the potential volume of data available was considered to be too great for a single Cochrane review of dressings for foot ulcers in people with DM, although such reviews had previously been published. A now out of date UK Health Technology Assessment review of wound dressings included 10 trials (O'Meara 2000). Nine of these trials investigated a dressing, or topical treatment, for healing foot ulcers in people with DM. The review did not find any evidence to suggest that one dressing type was more, or less, effective in terms of treating diabetic foot ulcers. The methodological quality of trials was poor and all were small. Only one comparison was repeated in more than one trial. Another systematic review, also out of date (Mason 1999), reported similar findings. More recently a systematic review was published on the effectiveness of interventions to enhance the healing of chronic ulcers of the foot (search date December 2006) (Hinchliffe 2008). This included only eight trials that looked at dressings (as well as further non-randomised studies), and, again, did not identify any evidence that one dressing type was superior to another in terms of promoting ulcer healing. It is important to note that the review was very broad in its outlook, looking at other non-dressing interventions, and that since its publication more than six years-worth of new literature has become available.

There are several Cochrane reviews that examine the effects of different dressing types on the healing of foot ulcers in people with DM. However, there is a need to draw together all existing review evidence regarding the effectiveness of dressings for the treatment of this condition and to present these data to decision makers.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

To summarise all randomised controlled trials (RCTs) regarding the effectiveness of dressings to heal foot ulcers in people with diabetes mellitus (DM).

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

The conduct of this overview will be guided by the recommendations of The Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

 

Criteria for considering reviews for inclusion

 

Types of studies

We will include:

  1. Cochrane systematic reviews of RCTs of any dressing type (as defined in type of intervention) in the treatment of foot ulcers in people with DM.*
  2. Non-Cochrane systematic reviews of RCTs of any dressing type in the treatment of foot ulcers in people with DM. However, to be included a non-Cochrane systematic review must be deemed to have employed a systematic approach including a detailed search strategy, have included only RCTs, have clear study selection criteria, and have assessed methodological features of the included studies.*
  3. Mixed treatment comparison meta-analyses. Mixed treatment comparison meta-analyses are only eligible for inclusion in this overview when undertaken as part of/as a result of a systematic review including RCTs.*

*If reviews have included other studies as well as RCTs (e.g. controlled clinical trials) they will be investigated to see whether RCTs are presented separately within the analysis (for example as a sensitivity analysis). If so, these RCT data will be included; if not, the review will be excluded. If reviews have a wider participant inclusion criterion than foot ulcers (e.g. post-operative foot wounds resulting from amputation), the presentation of included studies will be investigated and a decision made regarding inclusion of the review. Inclusion would only be possible if data on foot ulcers were presented separately. Recent primary RCTs not yet included in retrieved reviews will not be included until they have been incorporated into a suitable review.

 

Types of participants

People of any age with either Type 1 or Type 2 DM who have a foot ulcer.

 

Types of interventions

We will include dressing treatments, classified according to the BNF classification (BNF 2010), into four broad sub-groups ( Table 1). However, this list is not exhaustive, and, given the international perspective of this overview, we plan to include reviews of dressings that may not fall into the subgroups specified by the BNF. However, dressings that contain living cells (skin-substitute dressings) will not be included in this review as we consider these to be a separate class of treatment. Additionally, if a review focuses on an intervention type that can be applied as a dressing, or a topical application (i.e. silver), we will consider only those sections of the review that fulfil our inclusion criteria and address the dressing treatment. We will only consider dressings compared with a different dressing or no dressing, we will not include comparisons of dressings with adjunct therapies (e.g. hyperbaric oxygen, negative pressure wound therapy, etc).

 

Types of outcomes

 

Primary outcomes

 
Complete wound healing

Trialists measure and report wound healing in many different ways that include: time to complete wound healing, the proportion of wounds healed during follow-up, and rates of change of wound size. For this review we will regard reviews that report one or more of the following as providing the best measures of outcome in terms of relevance and rigour:

  • Time to wound healing within a specific time period correctly analysed using survival, time-to-event, approaches - ideally with adjustment for relevant co-variates such as baseline size. We will assume that the period of time in which healing could occur was the duration of the trial, unless otherwise stated.
  • Number of wounds completely healed during follow-up (frequency of complete healing), with healing being defined by the study authors.
  • Change (and rate of change) in wound size, when adjusted for baseline size, ideally analysed using multi-level modelling or (multiple) linear regression.

We note that since wound healing is a subjective outcome it can be at high risk of measurement bias when outcome assessment is not blinded.

We will extract, but not discuss further, mean or median time to healing without time-to-event analysis (i.e. a review has presented time to healing as a continuous measure without accounting for censoring), and change, or rate of change, in wound size measures without further between-group analysis that includes adjustment for baseline size, or that uses limited analytical approaches (e.g. based on only two measures: first measure and last measure).

 

Secondary outcomes  

Only useful summary data as defined below will be extracted and reported for secondary outcomes.

  • Participant health-related quality of life/health status (measured using a standardised generic questionnaire such as EQ-5D, SF-36, SF-12 or SF-6 (Dolan 1995; Ware 2001), or wound-specific questionnaires such as the Cardiff wound impact schedule (Price 2004), at noted time points. We will not include ad hoc measures of quality of life that are likely not to be validated, and will not be common to multiple trials. Ideally reports will summarise data collected at multiple time points using an approach such as the area under the curve method or multi-level modelling. Where health-related quality of life data are presented for several time points only (with no summary measure), we will record only data from the time point specified as the primary outcome, or, where this is not clear, the last time point. Finally, we will note the method of data collection, and comment on potential risk of measurement and performance bias.
  • Other adverse events including infection and pain (measured using survey/questionnaire/data capture process or visual analogue scale) where a clear methodology for the collection of adverse event data has been provided. Adverse event data will only be summarised when it is clear that the participant (or wound) is the denominator. That is, data are presented so that the number of events per participant are known (or an overview of this, e.g. number of participants with one or more event). Conversely, where the potential for multiple count data per participant cannot be assessed, data will not be considered further. Finally, we will note the method of data collection, and comment on the potential risk of measurement and performance bias.
  • Resource use (including measurements of resource use such as number of dressing changes, nurse visits, length of hospital stay and re-operation/intervention).
  • Wound recurrence.
  • Dressing performance.

 

Search methods for identification of reviews

For this overview we will search the following electronic databases to identify both Cochrane and non-Cochrane systematic reviews and reports of mixed treatment comparisons:

  • The Cochrane Library (Latest issue);
  • Ovid MEDLINE (1946 to present);
  • Ovid EMBASE (1974 to present);

We will use the following provisional search strategy to identify Cochrane and non-Cochrane systematic reviews in The Cochrane Library (which includes the Database of Abstracts of Reviews of Effects (DARE), a repository of structured, critical summaries of published systematic reviews):

#1 MeSH descriptor: [Occlusive Dressings] explode all trees435
#2 MeSH descriptor: [Bandages, Hydrocolloid] explode all trees143
#3 MeSH descriptor: [Biological Dressings] explode all trees61
#4 MeSH descriptor: [Alginates] explode all trees170
#5 MeSH descriptor: [Hydrogels] explode all trees211
#6 MeSH descriptor: [Silver] explode all trees152
#7 MeSH descriptor: [Silver Sulfadiazine] explode all trees132
#8 MeSH descriptor: [Honey] explode all trees80
#9 (dressing* or hydrocolloid* or alginate* or hydrogel* or "foam" or "bead" or "film" or "films" or tulle or gauze or non-adherent or "non adherent" or silver or honey or matrix):ti,ab,kw 9012
#10 {or #1-#9} 9012
#11 MeSH descriptor: [Foot Ulcer] explode all trees437
#12 MeSH descriptor: [Diabetic Foot] explode all trees390
#13 (diabet* near/3 ulcer*):ti,ab,kw 524
#14 (diabet* near/3 (foot or feet)):ti,ab,kw 814
#15 (diabet* near/3 wound*):ti,ab,kw 119
#16 (diabet* near/3 amputat*):ti,ab,kw 53
#17 {or #11-#16} 958
#18 #10 and #17 177

This overview will examine any non-Cochrane reviews that include relevant RCTs that are not already included in any eligible Cochrane review. To identify such reviews we will use the search strategy designed by the Centre for Reviews and Dissemination, York, UK (http://www.york.ac.uk/inst/crd/) to identify the systematic reviews summarised in DARE. This provisional strategy is shown in Appendix 2 and will be used to identify non-Cochrane systematic reviews in Ovid MEDLINE, particularly those systematic reviews not yet indexed on DARE. We have also developed a provisional search strategy intended to identify reports of mixed treatment comparison meta-analysis in Ovid MEDLINE (Appendix 3). Both Ovid MEDLINE search strategies will be adapted for Ovid EMBASE.

We will handsearch the Cochrane Wounds Group list of reviews to ensure that all relevant reviews have been identified. During the conduct of this overview the Cochrane Reviews we include may be updated, consequently we propose to conduct this search several times during the review process to ensure that the most up-to-date review versions are included. Where we are aware that a review update is in process, but not complete, we will record this in our overview, and plan an up-date in the next six months. Review protocols will not be included, but will be monitored for publication of the corresponding full review. Relevant review authors will also be contacted for information, if necessary.

Searches will not be restricted by language, date of publication or study setting.

 

Data collection and analysis

 

Selection of reviews

Two overview authors will screen review titles and abstracts to identify potentially relevant inclusions.The full text of all potentially relevant sources will then be screened by the same two overview authors for inclusion into the overview. Any disagreements will be resolved through discussion with a third overview author.

 

Data extraction and management

Data will be extracted into a pre-defined and piloted data extraction form to ensure consistent data capture from each review. Data will be extracted independently by two overview authors, with a third acting as arbitrator where required. For each included review we intend to extract the following data:

  • study identification, authors' details;
  • review objectives;
  • search strategies, including search dates;
  • study inclusion and exclusion criteria;
  • included settings;
  • included populations;
  • all relevant comparisons;
  • the number of relevant included RCTs;
  • outcomes reported and details of reported outcome values;
  • method and results of risk of bias/quality assessment.

Where a comparison is included in more than one review, its details will be recorded multiple times; as it is relevant to each review in which it is contained. If any information from a review is unclear or missing, we will access the published reports of the individual trials. We do not plan to contact trial authors for details of missing data, but rather assume that reviewers have done all they can to retrieve the data. We will enter data into Review Manager software (RevMan 2011).

 

Assessment of methodological quality of included reviews

As discussed in the Cochrane Handbook (Shea 2007), two overview authors will independently assess the methodological quality of included reviews using the 'assessment of multiple systematic reviews' (AMSTAR) instrument (Shea 2007), which is composed of the following 11 criteria:

  • Was an a priori design provided?
  • Was there duplicate study selection and data extraction?
  • Was a comprehensive literature search performed?
  • Was the status of publication (i.e. grey literature) used as an inclusion criterion?
  • Was a list of studies (included and excluded) provided?
  • Were the characteristics of the included studies provided?
  • Was the scientific quality of the included studies assessed and documented?
  • Was the scientific quality of the included studies used appropriately in formulating conclusions?
  • Were the methods used to combine the findings of studies appropriate?
  • Was the likelihood of publication bias assessed?
  • Was the conflict of interest stated?

The response to each criterion can be yes (clearly done), in which case the criterion will be given a score of 1; no (clearly not done); can't answer, or not applicable, based on the published review report. A review with an AMSTAR score of 8 to 11 will be rated as one of high quality; 4 to 7 will equate to medium quality, and 3 or lower will equate to low quality (Shea 2007).

 

Quality of evidence in included reviews

Independently, two overview authors will assess overall quality of the evidence for each included comparison and outcome within a 'Summary of findings' table using the GRADE approach (Atkins 2004). The GRADE approach specifies four levels of quality:

  • High quality for randomised trials; or double-upgraded observational studies.
  • Moderate quality for downgraded randomised trials; or upgraded observational studies.
  • Low quality for double-downgraded randomised trials; or observational studies.
  • Very low quality for triple-downgraded randomised trials; or downgraded observational studies; or case series/case reports.

Authors could downgrade randomised trial evidence by one or two levels depending on the presence of five factors:

  • Serious (-1) or very serious (-2) limitation to study quality.
  • Important inconsistency (-1).
  • Some (-1), or major (-2), uncertainty about directness.
  • Imprecise or sparse data (-1).
  • High probability of reporting bias (-1).

 

Data synthesis

There are a number of different dressings for the treatment of foot ulcers in people with DM. To maximise value to the reader at this stage we plan to present a summary of current evidence for all available comparisons, taking account of any instances of overlap of evidence between reviews. Firstly each unique direct comparison for which relative treatment effect data are available will be reported (e.g. gauze versus foam; foam versus alginate, etc) with any relevant indirect comparison data also summarised - by outcome, where required. Subsequently, where availability of mixed treatment comparison meta-analysis data results in comparisons informed only by indirect data, these will be summarised briefly. The totality of evidence for each comparison will be considered, and summary of effect estimates reported, mostly likely as a narrative review. Thus, within each comparison, review data will be presented in the following order:

  1. Pairways analyses by source.
  2. Further evidence synthesis source (i.e. mixed treatment comparison meta-analysis).
  3. Final summary of comparison evidence.

Where applicable, we will aim to convert relevant summaries to the risk ratio (RR) or hazard ratio (HR) although we will be limited by the statistical information available in each included review. It is important to note that we are not planning to undertake re-analysis of any data (beyond conversion of data).

In terms of presenting data, each individual included review, or mixed treatment comparison meta-analysis, will be summarised using a Characteristics of included reviews table. We then plan to present a summary overview of outcome data (by comparison) across reviews. We anticipate the application of forest plots and 'Summary of findings' tables to help present data. As this is a relatively new process, we acknowledge that aspects of this data synthesis approach may change as the work progresses.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

The authors would like to thank the peer referees (Lorne Becker, Tianjing Li, David Margolis, Denise Thomson and Janet Wale) for their comments to improve the protocol and to the copy editor Elizabeth Royle.

 
CRG Funding Acknowledgement:

The National Institute for Health Research (NIHR) is the largest single funder of the Cochrane Wounds Group.  

 
Disclaimer: 

The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Appendix 1. Glossary


Alginate

 
Substance derived from algic acid, derived from seaweed, used in making dressings for wounds

DebridementThe removal of foreign material and dead or damaged tissue from a wound

Diabetes MellitusA metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. The two most common forms are Type 1 and Type 2 diabetes mellitus. Other, less common, forms also exist

Dressing*A therapeutic or protective material applied to a wound

Gangrene*Death and decay of body tissue, often occurring in a limb, caused by insufficient blood supply and usually following injury or disease

HydrocolloidDressing that reacts with wound exudate to maintain the moisture at the surface of a wound

HydrogelWater based jelly-like substance, which can be used for the same purpose as hydrocolloid dressings

InsulinHormone secreted by the pancreas in response to blood glucose levels. It is involved in regulating blood glucose levels and promotes fuel storage within the body

IschaemicDeficient blood supply to any part of the body

Ischaemic ulcerArea of skin loss (see ulcer, arterial ulcer) resulting from deficient blood supply

Neuropathy*A disease or abnormality of the nervous system

Occlusive dressing*A dressing that prevents air from reaching a wound or lesion and that retains moisture, heat, body fluids, and medication

Osteitis*Inflammation of bone

OsteomyelitisInflammation in the marrow of a bone, can occur as a complication of infected diabetic foot ulcers

PeripheralOutlying: for example: peripheral neuropathy affects the nerves in the outlying parts of the body; and peripheral vascular disease is disease of the small blood vessels close to the surface of the skin

Ulcer in people with diabetesAn area of skin loss resulting from poor blood supply and/or reduced nerve function in the lower limb caused by diabetes mellitus



Definitions taken from Cochrane Wounds Group Glossary unless marked * when taken from The Free Medical Dictionary (http://medical-dictionary.thefreedictionary.com).

 

Appendix 2. Search strategy to identify non-Cochrane systematic reviews in Ovid MEDLINE

1 exp Occlusive Dressings/ (3359)
2 exp Bandages, Hydrocolloid/ (563)
3 exp Biological Dressings/ (1122)
4 exp Alginates/ (6361)
5 exp Hydrogels/ (8384)
6 exp Silver/ (12518)
7 exp Silver Sulfadiazine/ (737)
8 exp Honey/ (2047)
9 (dressing* or hydrocolloid* or alginate* or hydrogel* or foam or bead or film* or tulle or gauze or non-adherent or non adherent or silver or honey or matrix).tw. (340728)
10 or/1-9 (349782)
11 exp Foot Ulcer/ (6231)
12 exp Diabetic Foot/ (5195)
13 (diabet* adj3 ulcer*).tw. (2360)
14 (diabet* adj3 (foot or feet)).tw. (4521)
15 (diabet* adj3 wound*).tw. (1194)
16 (diabet* adj3 amputat*).tw. (599)
17 or/11-16 (8927)
18 10 and 17 (657)
19 systematic* review*.tw. (36034)
20 meta-analysis as topic/ (12359)
21 (meta-analytic* or meta-analysis or metanalysis or metaanalysis or meta analysis or meta-synthesis or metasynthesis or meta synthesis or meta-regression or metaregression or meta regression).tw. (37831)
22 (synthes* adj3 literature).tw. (1042)
23 (synthes* adj3 evidence).tw. (2912)
24 (integrative review or data synthesis).tw. (6729)
25 (research synthesis or narrative synthesis).tw. (437)
26 (systematic study or systematic studies).tw. (5597)
27 (systematic comparison* or systematic overview*).tw. (1409)
28 ((evidence based or comprehensive or critical or quantitative or structured) adj review).tw. (15809)
29 (realist adj (review or synthesis)).tw. (33)
30 or/19-29 (100139)
31 review.pt. (1734481)
32 (medline or pubmed or embase or cinahl or psyc?lit or psyc?info).ab. (58238)
33 ((literature or database* or bibliographic or electronic or computeri?ed or internet) adj3 search*).tw. (39600)
34 (electronic adj3 database*).tw. (6818)
35 included studies.ab. (4054)
36 (inclusion adj3 studies).ab. (4224)
37 ((inclusion or selection or predefined or predetermined) adj criteria).ab. (39033)
38 (assess* adj3 (quality or validity)).ab. (31366)
39 (select* adj3 (study or studies)).ab. (29761)
40 (data adj3 extract*).ab. (21026)
41 extracted data.ab. (4781)
42 (data adj3 abstraction).ab. (615)
43 published intervention*.ab. (83)
44 ((study or studies) adj2 evaluat*).ab. (83681)
45 (intervention* adj2 evaluat*).ab. (4705)
46 (confidence interval* or heterogeneity or pooled or pooling or odds ratio*).ab. (319533)
47 (Jadad or coding).ab. (101847)
48 or/32-47 (631785)
49 31 and 48 (93486)
50 review.ti. (209748)
51 48 and 50 (30178)
52 (review* adj4 (papers or trials or studies or evidence or intervention* or evaluation*)).tw. (78981)
53 30 or 49 or 51 or 52 (213228)
54 letter.pt. (758034)
55 editorial.pt. (307072)
56 comment.pt. (484716)
57 or/54-56 (1152182)
58 53 not 57 (207741)
59 exp animals/ not humans/ (3749650)
60 58 not 59 (199437)
61 18 and 60 (42)

 

Appendix 3. Search strategy to identify reports of mixed treatment comparisons in Ovid MEDLINE

1 exp Occlusive Dressings/ (3359)
2 exp Bandages, Hydrocolloid/ (563)
3 exp Biological Dressings/ (1122)
4 exp Alginates/ (6361)
5 exp Hydrogels/ (8384)
6 exp Silver/ (12518)
7 exp Silver Sulfadiazine/ (737)
8 exp Honey/ (2047)
9 (dressing* or hydrocolloid* or alginate* or hydrogel* or foam or bead or film*1 or tulle or gauze or non-adherent or non adherent or silver or honey or matrix).tw. (340728)
10 or/1-9 (349782)
11 exp Foot Ulcer/ (6231)
12 exp Diabetic Foot/ (5195)
13 (diabet* adj3 ulcer*).tw. (2360)
14 (diabet* adj3 (foot or feet)).tw. (4521)
15 (diabet* adj3 wound*).tw. (1194)
16 (diabet* adj3 amputat*).tw. (599)
17 or/11-16 (8927)
18 10 and 17 (657)
19 exp *Comparative Effectiveness Research/ (557)
20 exp "Outcome Assessment (Health Care)"/mt, sn [Methods, Statistics & Numerical Data] (8453)
21 exp Randomized Controlled Trials as Topic/ (83097)
22 exp Meta-Analysis as Topic/ (12359)
23 exp *Treatment Outcome/ (4605)
24 (mixed treatment comparison* or indirect treatment comparison* or indirect comparison*).tw. (628)
25 (network meta-analysis or multiple treatments meta-analysis or evidence synthesis).tw. (1002)
26 or/19-25 (105754)
27 19 and 26 (557)

 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

Jo Dumville: conceived and developed the protocol and co-ordinated its development, completed the first draft of the protocol, made an intellectual contribution, approved the final version prior to submission.
Susan O'Meara: conceived and developed the protocol and co-ordinated its development, completed the first draft of the protocol, made an intellectual contribution, approved the final version prior to submission.
Sally Bell-Syer: conceived and developed the protocol and co-ordinated its development, completed the first draft of the protocol, made an intellectual contribution, approved the final version prior to submission.

 

Contributions of editorial base:

Nicky Cullum: edited the protocol; advised on methodology, interpretation and protocol content.
Joan Webster Editor: approved the final protocol prior to submission.
Ruth Foxlee: designed the search strategy and edited the search methods section.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

Jo Dumville and Susan O'Meara received funding from the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme. This study presents independent research commissioned by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0407-10428). The views expressed in this review are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Internal sources

  • Department of Health Sciences, University of York, UK.

 

External sources

  • NIHR/Department of Health (England), (Cochrane Wounds Group), UK.

References

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Acknowledgements
  7. Appendices
  8. Contributions of authors
  9. Declarations of interest
  10. Sources of support
  11. Additional references
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