Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update).

AIMS: Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline. MATERIALS AND METHODS: We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders. RESULTS: From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions. CONCLUSIONS: These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.

Guidelines on the classification of foot ulcers in people with diabetes (IWGDF 2023 update).

BACKGROUND: This publication represents a scheduled update of the 2019 guidelines of the International Working Group of the Diabetic Foot (IWGDF) addressing the use of systems to classify foot ulcers in people with diabetes in routine clinical practice. The guidelines are based on a systematic review of the available literature that identified 28 classifications addressed in 149 articles and, subsequently, expert opinion using the GRADE methodology. METHODS: First, we have developed a list of classification systems considered as being potentially adequate for use in a clinical setting, through the summary of judgements for diagnostic tests, focussing on the usability, accuracy and reliability of each system to predict ulcer-related complications as well as use of resources. Second, we have determined, following group debate and consensus, which of them should be used in specific clinical scenarios. Following this process, in a person with diabetes and a foot ulcer we recommend: (a) for communication among healthcare professionals: to use the SINBAD (Site, Ischaemia, Bacterial infection, Area and Depth) system (first option) or consider using WIfI (Wound, Ischaemia, foot Infection) system (alternative option, when the required equipment and level of expertise is available and it is considered feasible) and in each case the individual variables that compose the systems should be described rather than a total score; (b) for predicting the outcome of an ulcer in a specific individual: no existing system could be recommended; (c) for characterising a person with an infected ulcer: the use of the IDSA/IWGDF classification (first option) or consider using the WIfI system (alternative option, when the required equipment and level of expertise is available and it is considered as feasible); (d) for characterising a person with peripheral artery disease: consider using the WIfI system as a means to stratify healing likelihood and amputation risk; (e) for the audit of outcome(s) of populations: the use of the SINBAD score. CONCLUSIONS: For all recommendations made using GRADE, the certainty of evidence was judged, at best, as being low. Nevertheless, based on the rational application of current data this approach allowed the proposal of recommendations, which are likely to have clinical utility.

Classification of foot ulcers in people with diabetes: A systematic review.

BACKGROUND: Classification and scoring systems can help both clinical management and audit the outcomes of routine care. AIM: This study aimed to assess published systems used to characterise ulcers in people with diabetes to determine which should be recommended to (a) aid communication between health professionals, (b) predict clinical outcome of individual ulcers, (c) characterise people with infection and/or peripheral arterial disease, and (d) audit to compare outcomes in different populations. This systematic review is part of the process of developing the 2023 guidelines to classify foot ulcers from the International Working Group on Diabetic Foot. METHODS: We searched PubMed, Scopus and Web of Science for articles published up to December 2021 which evaluated the association, accuracy or reliability of systems used to classify ulcers in people with diabetes. Published classifications had to have been validated in populations of >80% of people with diabetes and a foot ulcer. RESULTS: We found 28 systems addressed in 149 studies. Overall, the certainty of the evidence for each classification was low or very low, with 19 (68%) of the classifications being assessed by ≤ 3 studies. The most frequently validated system was the one from Meggitt-Wagner, but the articles validating this system focused mainly on the association between the different grades and amputation. Clinical outcomes were not standardized but included ulcer-free survival, ulcer healing, hospitalisation, limb amputation, mortality, and cost. CONCLUSION: Despite the limitations, this systematic review provided sufficient evidence to support recommendations on the use of six particular systems in specific clinical scenarios.

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: A systematic review.

BACKGROUND: It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design. AIMS: Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only. MATERIALS AND METHODS: For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality. RESULTS: The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence. CONCLUSION: Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.

The value of loss of protective pain sensation in predicting a first ulceration of the foot in people with diabetes.

AIM: To determine both the risk of first ever ulcer (FEU) and its time to onset in a population which had loss of protective sensation (LOPS) in the foot either with or without loss of protective pain (LOPP). METHODS: People with diabetes and LOPS without history of FEU presenting in a specialist clinic were included. LOPP was diagnosed by reduced vibration perception and pain perception by using a pinprick simulator. Participants were followed by routine foot checks, phone interview or by letter until the occurrence of a FEU, death or the end of observation period. Survival functions in LOPP strata were compared by log rank test. The hazard ratio (HR) of an FEU in people with compared to people without LOPP was estimated using Cox regression. Time to first ulcer was estimated using the framework of an accelerated failure time (AFT) model. RESULTS: One hundred and thirty participants were followed up for a median of 48.3 months. Pain perception was lost in 55.4%. Eighteen people with LOPP developed a FEU (25.0%) as opposed to six (10.3%) of those with no LOPP (p = 0.02). Age-sex-adjusted HR for FEU was 3.0 (p = 0.02) for people with compared to people without LOPP. Age-sex-adjusted time to FEU for people with LOPP was approximately half (p = 0.03) than people without LOPP. CONCLUSIONS: It is suggested that estimation of LOPP is included in routine practice because of its high predictive value for a FEU.

Impact of case-mix adjustment on observed variation in the healing of diabetic foot ulcers at 12 weeks using data from the National Diabetes Foot Care Audit of England and Wales: A cohort study.

AIM: This cohort study investigates the extent to which variation in ulcer healing between services can be explained by demographic and clinical characteristics. METHODS: The National Diabetes Foot Care Audit collated data on people with diabetic foot ulcers presenting to specialist services in England and Wales between July 2014 and March 2018. Logistic regression models were created to describe associations between risk factors and a person being alive and ulcer-free 12 weeks from presentation, and to investigate whether variation between 120 participating services persisted after risk factor adjustment. RESULTS: Of 27,030 people with valid outcome data, 12,925 (47.8%) were alive and ulcer-free at 12 weeks, 13,745 (50.9%) had an unhealed ulcer and 360 had died (1.3%). Factors associated with worse outcome were male sex, more severe ulcers, history of cardiac or renal disease and a longer time between first presentation to a non-specialist healthcare professional and first expert assessment. After adjustment for these factors, four services (3.3%) were more than 3SD above and seven services (5.8%) were more than 3SD below the national mean for proportions that were alive and ulcer-free at follow-up. CONCLUSIONS/INTERPRETATIONS: Variation in the healing of diabetic foot ulcers between specialist services in England and Wales persisted after adjusting for demographic characteristics, ulcer severity, smoking, body mass index and co-morbidities. We conclude that other factors contribute to variation in healing of diabetic foot ulcers and include the time to specialist assessment.

Which diagnostic tests in everyday clinical practice are (not) useful in the management of diabetic foot disease?

This commentary reviews the use of a small number of tests used in the routine management of foot disease in diabetes. The aim is to consider some of the evidence underlying the use of these tests and the difficulties that can be encountered in interpretation. All tests have their limitations and it is important for these to be understood by the clinicians who request them. There are few test results which are categorically diagnostic in the field of the diabetic foot and the majority merely provide supporting evidence for a diagnosis that is either less or more strongly suspected on other grounds.

Guidelines on the classification of diabetic foot ulcers (IWGDF 2019).

The International Working Group on the Diabetic Foot (IWGDF) has been publishing evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This publication represents a new guideline addressing the use of classifications of diabetic foot ulcers in routine clinical practice and reviews those which have been published. We only consider systems of classification used for active diabetic foot ulcers and do not include those that might be used to define risk of future ulceration. The guidelines are based on a review of the available literature and on expert opinion leading to the identification of eight key factors judged to contribute most to clinical outcomes. Classifications are graded on the number of key factors included as well as on internal and external validation and the use for which a classification is intended. Key factors judged to contribute to the scoring of classifications are of three types: patient related (end-stage renal failure), limb-related (peripheral artery disease and loss of protective sensation), and ulcer-related (area, depth, site, single, or multiple and infection). Particular systems considered for each of the following five clinical situations: (a) communication among health professionals, (b) predicting the outcome of an individual ulcer, (c) as an aid to clinical decision-making for an individual case, (d) assessment of a wound, with/without infection, and peripheral artery disease (assessment of perfusion and potential benefit from revascularisation), and (d) audit of outcome in local, regional, or national populations. We recommend: (a) for communication among health professionals the use of the SINBAD system (that includes Site, Ischaemia, Neuropathy, Bacterial Infection and Depth); (b) no existing classification for predicting outcome of an individual ulcer; (c) the Infectious Diseases Society of America/IWGDF (IDSA/IWGDF) classification for assessment of infection; (d) the WIfI (Wound, Ischemia, and foot Infection) system for the assessment of perfusion and the likely benefit of revascularisation; and (e) the SINBAD classification for the audit of outcome of populations.

Diabetic foot ulcer classifications: A critical review.

Classification and scoring systems can help both clinical management and audit outcomes of routine care. The aim of this study was to assess published systems of diabetic foot ulcers (DFUs) to determine which should be recommended for a given clinical purpose. Published classifications had to have been validated in populations of > 75% people with diabetes and a foot ulcer. Each study was assessed for internal and external validity and reliability. Eight key factors associated with failure to heal were identified from large clinical series and each classification was scored on the number of these key factors included. Classifications were then arranged according to their proposed purpose into one or more of four groups: (a) aid communication between health professionals, (b) predict clinical outcome of individual ulcers, (c) aid clinical management decision making for an individual case, and (d) audit to compare outcome in different populations. Thirty-seven classification systems were identified of which 18 were excluded for not being validated in a population of >75% DFUs. The included 19 classifications had different purposes and were derived from different populations. Only six were developed in multicentre studies, just 13 were externally validated, and very few had evaluated reliability.Classifications varied in the number (4 - 30), and definition of individual items and the diagnostic tools required. Clinical outcomes were not standardized but included ulcer-free survival, ulcer healing, hospitalization, limb amputation, mortality, and cost. Despite the limitations, there was sufficient evidence to make recommendations on the use of particular classifications for the indications listed above.

Rat bite as a cause of diabetic foot ulcer in sub-Saharan Africa.

There have been relatively few reports of foot ulcers in diabetes resulting from rat bite. The findings were derived from people attending a single specialist service in Dar es Salaam for diabetic foot ulcers (DFUs) between 1 January 1999 and 31 December 2016. Details from people presenting for the first time with an ulcer judged to be caused by rat bite were compared with those with from other causes of foot ulcer. There were 426 first recorded foot ulcer episodes (in 179 people) judged to be caused by rat bite. The affected population was significantly younger (mean 55.9 vs 57.5 years, P = .037) and had a lower body mass index (26.5 vs 27.9, P = .008) than controls with other types of foot ulcer. They also presented significantly sooner (7.8 vs 18.2 days, P < .001) and were more likely to heal (85.8 vs 5.5%, P < .001), even though there was also a trend towards an increased risk of death (9.1% vs 5.3%, P = .032). Rat bite is an uncommon cause of DFU, but is not rare. Although the incidence of ulcer healing is higher than in a general foot ulcer population, the incidence of death is also higher.

Amputation-free survival in 17,353 people at high risk for foot ulceration in diabetes: a national observational study.

AIMS/HYPOTHESIS: Our aim was to investigate amputation-free survival in people at high risk for foot ulceration in diabetes ('high-risk foot'), and to compare different subcategories of high-risk foot. METHODS: Overall, 17,353 people with diabetes and high-risk foot from January 2008 to December 2011 were identified from the Scotland-wide diabetes register (Scottish Care Information-Diabetes: N = 247,278). Participants were followed-up for up to 2 years from baseline and were categorised into three groups: (1) those with no previous ulcer, (2) those with an active ulcer or (3) those with a healed previous ulcer. Participants with prior minor or major amputation were excluded. Accelerated failure time models were used to compare amputation-free survival up to 2 years between the three exposure groups. RESULTS: The 2 year amputation-free survival rate in all people with diabetes with high-risk foot was 84.5%. In this study group, 270 people (10.0%) had an amputation and 2424 (90.0%) died during the 2 year follow-up period. People who had active and healed previous ulcers at baseline had significantly lower 2 year amputation-free survival compared with those who had no previous ulcer (both p < 0.0001). The percentage of people who died within 2 years for those with healed ulcer, active ulcer or no baseline ulcer was 22.8%, 16% and 12.1%, respectively. CONCLUSIONS/INTERPRETATION: In people judged to be at high risk of foot ulceration, the risk of death was up to nine times the risk of amputation. Death rates were higher for people with diabetes who had healed ulcers than for those with active ulcers. However, people with active ulcers had the highest risk of amputation.

Osteomyelitis of the foot: non-surgical management, SPECT/CT scanning and minimising the duration of antibiotic use.

In a paper in this issue of Diabetologia (DOI: https://doi.org/10.1007/s00125-017-4417-x ), Vouillarmet and colleagues have explored the use of single-photon emission computed tomography (SPECT)/computed tomography (CT) to define remission during non-surgical management of osteomyelitis of the foot. Their experience in a non-controlled observational study of 45 individuals was that a negative white blood cell-SPECT/CT scan is a reliable marker of remission, while a positive scan at the end of antibiotic treatment may be relatively useful in the prediction of future short- to medium-term relapse. These findings and conclusions are discussed in the light of current uncertainties relating to the diagnosis of bone infection and the lack of any tested measure that can be used to indicate either its presence or its persistence. In this respect, it is concluded that the value of this approach, and in which population, remains to be clearly established.

Using image J to document healing in ulcers of the foot in diabetes.

The aim of the study was to assess the reliability of measuring the cross-sectional area of diabetic foot ulcers using Image J software. The inter- and intra-rater reliability of ulcer area measures were assessed using digital images of acetate tracings of ulcers of the foot affecting 31 participants in an off-loading randomised trial. Observations were made independently by five specialist podiatrists, one of whom was experienced in the use of Image J software and educated the other four in a single session. The mean (±SD) of the mean cross-sectional areas of the 31 ulcers determined independently by the five observers was 1386·7 (±22·7) mm2 . The correlation between all pairs of observers was >0·99 (P < 0·001). There was no significant difference overall between the five observers (ANOVA F1.538; P = 0·165) and no difference between any two (paired samples test t = -0·787-1·396; P ≥ 0·088). The correlation between the areas determined by two observers on two occasions separated by not less than 1 week was very high (0·997 and 0·999; P < 0·001 and <0·001, respectively). The inter- and intra-reliability of the Image J software is very high, with no evidence of a difference either between or within observers. This technique should be considered for both research and clinical use in order to document changes in ulcer area.

Causes, prevention, and management of diabetes-related foot ulcers.

In this Review, we aim to complement the 2023 update of the guidelines of the International Working Group on the Diabetic Foot. We highlight the complexity of the pathological processes that underlie diabetes-related foot ulceration (DFU) and draw attention to the potential implications for clinical management and outcome. Variation observed in the incidence and outcome of DFUs in different communities might result from differences in study populations and the accessibility of care. Comparing differences in incidence, management, and outcome of DFUs in different communities is an essential component of the quality of disease care. Additionally, these comparisons can also highlight the relationship between DFU incidence, management, and outcome and the structure of local clinical services and the availability of staff with the necessary skills. The clinical outcome is, however, also dependent on the availability of multidisciplinary care and the ability of people with DFUs to gain access to that care.

Who was first to diagnose and report neuropathic arthropathy of the foot and ankle: Jean-Martin Charcot or Herbert William Page?

In November 1883, Jean-Martin Charcot and Charles Féré reported on bone and joint disease of the foot in cases of tabes dorsalis, and referred to the condition as 'pied tabétique'--a disabling neuropathic osteoarthropathy that we usually now refer to as the Charcot foot. Charcot had originally described neuropathic osteoarthropathy in more proximal joints in 1868, and in his 1883 paper with Féré stated that involvement of the short bones and small joints of the foot had not yet been described. They emphasised in the paper that one of their cases was the first ever observed, two years earlier, in 1881. It is relevant, however, that it was in this same year that involvement of the foot by tabetic arthropathy was presented to the International Medical Congress in London by an English surgeon, Herbert William Page. We believe that Page was the first to diagnose and to report a case of tabetic neuropathic osteoarthropathy in which the bones of the foot and ankle were involved. He was also the first to propose a link between the tabetic foot and disease of the peripheral nerves, as opposed to the central nervous system.

Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS).

BACKGROUND: Diabetes-related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD).There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes.Review questions;1. What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes?2. Can the data from each study be adjusted for a consistent set of adjustment factors?3. Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics? METHODS: MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained.We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using "study" as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable. DISCUSSION: This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines.