The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

BACKGROUND: Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. METHODS: People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. DISCUSSION: Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013

Alteration of Lymphocytes Subpopulations and Immunoglobulins Levels in Patients with Diabetic Foot Ulcers Infected Particularly by Resistant Pathogens

The aim of our study was to analyse immune abnormalities in patients with chronic infected diabetic foot ulcers (DFUs) especially those infected by resistant microorganisms. Methods. 68 patients treated in our foot clinic for infected chronic DFUs with 34 matched diabetic controls were studied. Patients with infected DFUs were subdivided into two subgroups according to the antibiotic sensitivity of causal pathogen: subgroup S infected by sensitive (n = 50) and subgroup R by resistant pathogens (n = 18). Selected immunological markers were compared between the study groups and subgroups. Results. Patients with infected chronic DFUs had, in comparison with diabetic controls, significantly reduced percentages (p < 0.01) and total numbers of lymphocytes (p < 0.001) involving B lymphocytes (p < 0.01), CD4+ (p < 0.01), and CD8+ T cells (p < 0.01) and their naive and memory effector cells. Higher levels of IgG (p < 0.05) including IgG1 (p < 0.001) and IgG3 (p < 0.05) were found in patients with DFUs compared to diabetic controls. Serum levels of immunoglobulin subclasses IgG2 and IgG3 correlated negatively with metabolic control (p < 0.05). A trend towards an increased frequency of IgG2 deficiency was found in patients with DFUs compared to diabetic controls (22% versus 15%; NS). Subgroup R revealed lower levels of immunoglobulins, especially of IgG4 (p < 0.01) in contrast to patients infected by sensitive bacteria. The innate immunity did not differ significantly between the study groups. Conclusion. Our study showed changes mainly in the adaptive immune system represented by low levels of lymphocyte subpopulations and their memory effector cells, and also changes in humoral immunity in patients with DFUs, even those infected by resistant pathogens, in comparison with diabetic controls

Systematic review of techniques to monitor remission of acute Charcot-neuroarthropathy in people with diabetes

Aim: The management of acute Charcot neuroarthropathy relies on off-loading which is costly and time-consuming. Published studies have used monitoring techniques with unknown diagnostic precision to detect remission. We performed a systematic review of techniques for monitoring response to offloading in acute Charcot neuroarthropathy. Materials and Methods: We included studies of off-loading which evaluated or described monitoring techniques in acute Charcot neuroarthropathy. PubMed, EMBASE, CINAHL and Cochrane databases were searched (January1993-July 2018). We extracted data from papers including study design, setting, population, monitoring techniques and treatment outcomes. We also extracted information on the cost, clinical applicability, sensitivity and specificity, safety and participant acceptability of the monitoring techniques. Results: We screened 1205 titles, 140 abstracts and 45 full-texts, and included 29 studies. All studies were of low quality and at high risk of bias. In seven studies, the primary aim was to evaluate monitoring techniques: three evaluated magnetic resonance imaging, two thermography monitoring, one three-phase bone scanning and one Doppler spectrum analysis. The remaining 22 observational studies reported treatment outcomes and described the monitoring techniques used to assess the Charcot neuroarthropathy. Heterogeneity prevented the pooling of data. Very few studies included data on cost, clinical applicability, sensitivity and specificity, safety and patient acceptability of the monitoring techniques used. Conclusion: Multiple techniques have been used to evaluate remission in acute Charcot neuroathropathy but uncertainty remains about their effectiveness. We recommend further research into the influences of different monitoring techniques on treatment outcomes

Does the point of healthcare contact affect successful diagnosis of diabetic Charcot neuroarthropathy?

Background: Charcot neuroarthropathy (CN) is a lesser-known and commonly misdiagnosed diabetic foot complication. Delays in diagnosis increase the risk of severe long-term foot complications. Aims: To undertake a retrospective audit of patients with active CN, recording the time to diagnosis, misdiagnosis rates, healthcare professional (HCP) and setting type at each contact since symptom onset prior to their referral to a multidisciplinary foot team (MDFT) clinic in a circumscribed part of England. Methods: Clinical notes of 46 consecutive patients attending a MDFT clinic in the East Midlands region of England during a 2-month period, with active CN were assessed. Results: Of the 46 included patients, 22 developed CN while in primary care. These patients had a mean time from symptom onset to confirmed diagnosis of 68 days, with 64% receiving a misdiagnosis. Non-specialist HCPs failed to suspect CN in 85% of contacts compared to 20% in specialist HCPs. Conclusions: Non-specialist HCPs need a greater degree of awareness and understanding of CN to reduce diagnostic delays and misdiagnosis rate

A qualitative study to understand people’s experiences of living with Charcot neuroarthropathy

Aims: Charcot neuroarthropathy (CN) is a complication of neuropathy, in people with diabetes. Treatment requires the prolonged wearing of an offloading device, which can be challenging. The importance of understanding people’s perspectives for promoting their engagement in self-management is well known. However, no such studies have been done in CN. This qualitative study aimed to understand people’s experiences of CN. Methods: Semi-structured interviews with a purposive sample of 14 participants with CN, recruited from a randomised controlled trial. We gathered opinions, thoughts, and the meanings participants attributed to their experiences of CN and its physical, socio-economic, and physiological effects and how this affected their families, and relationships. We analysed the interviews using Inductive Thematic Analysis. Results: Four analytic themes were identified: 1) ‘Trapped at home isolated and missing social life and daily life routines’; 2) ‘Disruption to people’s roles, responsibilities, relationships, and mobility, which people adapted to try and address and manage’; 3) ‘Pain which participants related to the direct or indirect consequences of wearing the cast or boot’; 4) ‘Blame for developing CN, attributed to themselves and healthcare professionals’. Participants described guilt about needing more support, expressing frustration, low mood, and low self-esteem. Conclusion: This study highlights experiential aspects of the previously unrecognised burden of CN. Its physical, social, and emotional impact on participants and their families is substantial and sustained. There is a need to raise clinical awareness of CN and its wider effects

Development of a resource-use measure to capture costs of diabetic foot ulcers to the United Kingdom National Health Service, patients and society

Background:: Diabetic foot ulcers (DFUs) add a significant burden to the lives of people with diabetes in the United Kingdom. They can have a considerable impact on a patient’s daily life, with treatment requiring frequent changes of dressings and clinic attendances. Nurses and other allied health professionals (AHPs) within the community provide most wound care representing the primary cost driver. Aims:: To collaboratively explore key resource use related to the management of DFUs to develop, and pilot, a participant-reported measure to inform economic evaluations. Methods:: A literature search and semi-structured interviews determined health and non-health resource use in management of DFUs. A consensus view of the selected items was established in a modified Delphi study and further tested for acceptability and validity in a pilot study. Results:: Primary care consultations with a podiatrist or orthotist, district nurse visits, out-of-hours and emergency care, scans and investigations, and consumables provided in clinics were rated as the most important resource use items. Conclusions:: This work has informed the development of a measure that captures resource use considered important by the people most affected by DFUs; patients, family members and carers, and the healthcare professionals key to DFU management

Definitions and criteria for diabetic foot disease

Multiple disciplines are involved in the management of diabetic foot disease, and a common vocabulary is essential for clear communication. Based on the systematic reviews of the literature that form the basis of the International Working Group on the Diabetic Foot (IWGDF) Guidelines, the IWGDF has developed a set of definitions and criteria for diabetic foot disease. This document describes these definitions and criteria. We suggest these definitions be used consistently in both clinical practice and research to facilitate clear communication between professionals.</p

Intervention planning for the REDUCE maintenance intervention:a digital intervention to reduce reulceration risk among patients with a history of diabetic foot ulcers

OBJECTIVES: To develop a comprehensive intervention plan for the REDUCE maintenance intervention to support people who have had diabetic foot ulcers (DFUs) to sustain behaviours that reduce reulceration risk.METHODS: Theory-based, evidence-based and person-based approaches to intervention development were used. In phase I of intervention planning, evidence was collated from a scoping review of the literature and qualitative interviews with patients who have had DFUs (n=20). This was used to identify the psychosocial needs and challenges of this population and barriers and facilitators to the intervention's target behaviours: regular foot checking, rapid self-referral in the event of changes in foot health, graded and regular physical activity and emotional management. In phase II, this evidence was combined with expert consultation to develop the intervention plan. Brief 'guiding principles' for shaping intervention development were created. 'Behavioural analysis' and 'logic modelling' were used to map intervention content onto behaviour change theory to comprehensively describe the intervention and its hypothesised mechanisms.RESULTS: Key challenges to the intervention's target behaviours included patients' uncertainty regarding when to self-refer, physical limitations affecting foot checking and physical activity and, for some, difficulties managing negative emotions. Important considerations for the intervention design included a need to increase patients' confidence in making a self-referral and in using the maintenance intervention and a need to acknowledge that some intervention content might be relevant to only some patients (emotional management, physical activity). The behavioural analysis identified the following processes hypothesised to facilitate long-term behaviour maintenance including increasing patients' skills, self-efficacy, knowledge, positive outcome expectancies, sense of personal control, social support and physical opportunity.CONCLUSIONS: This research provides a transparent description of the intervention planning for the REDUCE maintenance intervention. It provides insights into potential barriers and facilitators to the target behaviours and potentially useful behaviour change techniques to use in clinical practice.</p