The cost of diabetic foot ulcers and amputations to the National Health Service in England.

AIM: To estimate the healthcare costs of diabetic foot disease in England. METHODS: Patient-level data sets at a national and local level, and evidence from clinical studies, were used to estimate the annual cost of health care for foot ulceration and amputation in people with diabetes in England in 2014-2015. RESULTS: The cost of health care for ulceration and amputation in diabetes in 2014-2015 is estimated at between £837 million and £962 million; 0.8% to 0.9% of the National Health Service (NHS) budget for England. More than 90% of expenditure was related to ulceration, and 60% was for care in community, outpatient and primary settings. For inpatients, multiple regression analysis suggested that ulceration was associated with a length of stay 8.04 days longer (95% confidence interval 7.65 to 8.42) than that for diabetes admissions without ulceration. CONCLUSIONS: Diabetic foot care accounts for a substantial proportion of healthcare expenditure in England, more than the combined cost of breast, prostate and lung cancers. Much of this expenditure arises through prolonged and severe ulceration. If the NHS were to reduce the prevalence of diabetic foot ulcers in England by one-third, the gross annual saving would be more than £250 million. Diabetic foot ulceration is a large and growing problem globally, and it is likely that there is potential to improve outcomes and reduce expenditure in many countries.

Interventions in the management of infection in the foot in diabetes: a systematic review.

The expert panel on diabetic foot infection (DFI) of the International Working Group on the Diabetic Foot conducted a systematic review seeking all published reports relating to any type of treatment for infection of the foot in persons with diabetes published as of 30 June 2014. This review, conducted with both PubMed and EMBASE, was used to update an earlier one undertaken on 30 June 2010 using the same search string. Eligible publications included those that had outcome measures reported for both a treated and a control population that were managed either at the same time, or as part of a before-and-after case design. We did not include studies that contained only information related to definition or diagnosis, but not treatment, of DFI. The current search identified just seven new articles meeting our criteria that were published since the 33 identified with the previous search, making a total of 40 articles from the world literature. The identified articles included 37 randomised controlled trials (RCTs) and three cohort studies with concurrent controls, and included studies on the use of surgical procedures, topical antiseptics, negative pressure wound therapy and hyperbaric oxygen. Among the studies were 15 RCTs that compared outcomes of treatment with new antibiotic preparations compared with a conventional therapy in the management of skin and soft tissue infection. In addition, 10 RCTs and 1 cohort study compared different treatments for osteomyelitis in the diabetic foot. Results of comparisons of different antibiotic regimens generally demonstrated that newly introduced antibiotic regimens appeared to be as effective as conventional therapy (and also more cost-effective in one study), but one study failed to demonstrate non-inferiority of a new antibiotic compared with that of a standard agent. Overall, the available literature was both limited in both the number of studies and the quality of their design. Thus, our systematic review revealed little evidence upon which to make recommendations for treatment of DFIs. There is a great need for further well-designed trials that will provide robust data upon which to make decisions about the most appropriate treatment of both skin and soft tissue infection and osteomyelitis in diabetic patients.

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

The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post-operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality.

Evaluation of the effect of nurse education on patient-reported foot checks and foot care behaviour of people with diabetes receiving haemodialysis.

AIMS: To assess whether a programme of nurse education increased the frequency with which nurses conducted foot checks on people with diabetes undergoing haemodialysis and to evaluate whether this influenced self-reported foot care behaviour. METHODS: A non-randomized stepped-wedge design was used to evaluate a nurse education programme implemented in four UK National Health Service dialysis units. People with diabetes undergoing haemodialysis were invited to complete a questionnaire on the frequency of foot examination by health professionals, on the presence of foot problems and on their own foot care behaviour, using the Nottingham Assessment of Functional Foot-care (NAFF). An education session for nurses, including procedures for foot examination, was conducted sequentially in each of four haemodialysis units. The questionnaire was repeated at 2-monthly intervals. RESULTS: The education session resulted in a significant increase in the reported number of foot examinations by nurses (P = 0.007). There was also a significant improvement in reported foot care behaviour (P < 0.001), but this occurred between the first and second 2-monthly assessments and was unrelated to the timing of the intervention. CONCLUSIONS: A single education session can improve the routine checking of the feet of people with diabetes undergoing haemodialysis. The administration of the Nottingham Assessment of Functional Foot-care questionnaire was associated with improved self-reported foot care behaviour, reflecting greater awareness of risk in this population.

Use of HSI to measure oxygen saturation in the lower limb and its correlation with healing of foot ulcers in diabetes.

AIM: To explore the use of hyperspectral imaging (HSI) to predict healing of diabetic foot ulcers in patients with diabetes. METHODS: We used a HSI technique that incorporated novel software to account for tissue scattering of light, and was validated using blood samples of varying oxygen saturation assessed by blood gas analysis. HSI was then performed on a population newly presenting with diabetic foot ulcers to a specialist clinic, and associations were sought with healing at 12 and 24 weeks. RESULTS: The correlation between the results of HSI and blood gas analysis was strong (r = 0.994). A total of 43 patients (mean ± sd age 62.7 ± 12.2 years; 31 men, 12 women; 37 with Type 2 diabetes, six with Type 1 diabetes) with foot ulcers were included in the prospective clinical study and underwent HSI within 16 days of presentation. In all, 26 ulcers healed within 12 weeks and 28 within 24 weeks. There was a negative association between tissue oxygenation assessed by HSI at baseline and healing by 12 weeks (P = 0.009), and this was observed in both infected and non-infected ulcers. There was a significant positive correlation between oxygenation assessed by HSI and time to healing (P = 0.03). No correlations were observed at 24 weeks. CONCLUSIONS: These findings suggest that HSI may predict healing in routine practice. The fact that the correlation between HSI and healing was negative could be explained by HSI being a measure of oxygenation of haemoglobin and there may be an inverse relationship between this and the oxygenation of extravascular tissue in people with neuropathy and/or microvascular disease.

Charcot foot syndrome.

Charcot foot syndrome is an uncommon complication of diabetes but is potentially devastating in its consequences. Outcome is made worse by widespread professional ignorance leading to delayed diagnosis, but it is also hampered by lack of understanding of its causes and lack of treatments with proven effectiveness, other than offloading. There remains a desperate need for studies into its causes as well as comparative audit and trials designed to determine the best treatment for this difficult condition. Such work can probably only be effectively carried out through the establishment of multicentre networks. Nevertheless, improved understanding in recent years of the likely role of inflammatory pathways has raised awareness of the multiple ways in which the effects of neuropathy may be manifest in the development of the Charcot foot. This awareness is also leading to the realization that similar processes may conceivably contribute to the refractoriness of other foot diseases in diabetes, including both chronic unhealing ulcers and osteomyelitis.

Cost of diabetic foot disease to the National Health Service in England.

AIM: To estimate the annual cost of diabetic foot care in a universal healthcare system. METHODS: National datasets and economic modelling were used to estimate the cost of diabetic foot disease to the National Health Service in England in 2010-2011. The cost of hospital admissions specific to foot disease or amputation was estimated from Hospital Episode Statistics and national tariffs. Multivariate regression analysis was used to estimate the impact of foot disease on length of stay in admissions that were not specific to foot disease or amputation. Costs in other areas were estimated from published studies and data from individual hospitals. RESULTS: The cost of diabetic foot care in 2010-2011 is estimated at £580 m, almost 0.6% of National Health Service expenditure in England. We estimate that more than half this sum (£307 m) was spent on care for ulceration in primary and community settings. Of hospital admissions with recorded diabetes, 8.8% included ulcer care or amputation. Regression analysis suggests that foot disease was associated with a 2.51-fold (95% CI 2.43-2.59) increase in length of stay.The cost of inpatient ulcer care is estimated at £219 m, and that of amputation care at £55 m. CONCLUSIONS: The cost of diabetic foot disease is substantial. Ignorance of the cost of current care may hinder commissioning of effective services for prevention and management in both community and secondary care.

Variation in the recorded incidence of amputation of the lower limb in England.

AIMS/HYPOTHESIS: The study aimed to explore the variation in recorded incidence of lower limb amputation in England. METHODS: The incidences of amputations in adults with and without diabetes were determined from hospital episode statistics over 3 years to 31 March 2010 and compared between the 151 Primary Care Trusts (PCTs) in England. RESULTS: There were 34,109 amputations, including 16,693 (48.9%) in people with diabetes. The incidence was 2.51 per 1,000 person-years in people with diabetes and 0.11 per 1,000 person-years in people without (relative diabetes risk 23.3). Incidence varied eightfold across PCTs in people both with diabetes (range 0.64-5.25 per 1,000 person-years) and without (0.03-0.24 per 1,000 person-years). Amputations in people with diabetes varied tenfold--both major (range 0.22-2.20 per 1,000 person-years) and minor (range 0.30-3.25 per 1,000 person-years). The incidences of minor and major amputations were positively correlated both in those with (r = 0.537, p < 0.0005) and without (r = 0.611, p < 0.0005) diabetes. Incidences of amputations were also correlated between people with and without diabetes (total amputations r = 0.433, p < 0.0005; major amputations r = 0.528, p < 0.0005). There was a negative correlation between the incidence of amputation and estimated prevalence of ethnic Asians. No association was found between the PCT incidence of either total amputations and general population prevalence of social deprivation (r = -0.138, p = 0.092) or smoking (r = 0.137, p = 0.096). CONCLUSIONS/INTERPRETATION: Variation in amputation incidence occurs across England. Because of the similarity in amputation variation between people with and without diabetes the variation may reflect generic differences in local healthcare delivery, although racial factors may also contribute.

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

The outcome of management of diabetic foot ulcers is poor, and there is continuing uncertainty concerning optimal approaches to management. It was for these reasons that in 2006 the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing undertook a systematic review of the evidence to inform protocols for routine care and to highlight areas which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between December 2006 and June 2010. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae and hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; hyperbaric oxygen therapy (HBOT); compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound; other systemic therapies which did not fit in the above categories. Heterogeneity of studies prevented pooled analysis of results. Of the 1322 papers identified, 43 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic review, but the conclusion is similar: that with the exception of HBOT and, possibly, negative pressure wound therapy, there is little published evidence to justify the use of newer therapies. This echoes the conclusion of a recent Cochrane review and the systematic review undertaken by the National Institute for Health and Clinical Excellence Guidelines Committee in the UK. Analysis of evidence presents considerable difficulties in this field particularly as controlled studies are few and the majority are of poor methodological quality.

A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot.

The International Working Group on the Diabetic Foot expert panel on infection conducted a systematic review of the published evidence relating to treatment of foot infection in diabetes. Our search of the literature published prior to August 2010 identified 7517 articles, 29 of which fulfilled predefined criteria for detailed data extraction. Four additional eligible papers were identified from other sources. Of the total of 33 studies, 29 were randomized controlled trials, and four were cohort studies. Among 12 studies comparing different antibiotic regimens in the management of skin and soft-tissue infection, none reported a better response with any particular regimen. Of seven studies that compared antibiotic regimens in patients with infection involving both soft tissue and bone, one reported a better clinical outcome in those treated with cefoxitin compared with ampicillin/sulbactam, but the others reported no differences between treatment regimens. In two health economic analyses, there was a small saving using one regimen versus another. No published data support the superiority of any particular route of delivery of systemic antibiotics or clarify the optimal duration of antibiotic therapy in either soft-tissue infection or osteomyelitis. In one non-randomized cohort study, the outcome of treatment of osteomyelitis was better when the antibiotic choice was based on culture of bone specimens as opposed to wound swabs, but this study was not randomized, and the results may have been affected by confounding factors. Results from two studies suggested that early surgical intervention was associated with a significant reduction in major amputation, but the methodological quality of both was low. In two studies, the use of superoxidized water was associated with a better outcome than soap or povidone iodine, but both had a high risk of bias. Studies using granulocyte-colony stimulating factor reported mixed results. There was no improvement in infection outcomes associated with hyperbaric oxygen therapy. No benefit has been reported with any other intervention, and, overall, there are currently no trial data to justify the adoption of any particular therapeutic approach in diabetic patients with infection of either soft tissue or bone of the foot.

Expert opinion on the management of infections in the diabetic foot.

This update of the International Working Group on the Diabetic Foot incorporates some information from a related review of diabetic foot osteomyelitis (DFO) and a systematic review of the management of infection of the diabetic foot. The pathophysiology of these infections is now well understood, and there is a validated system for classifying the severity of infections based on their clinical findings. Diagnosing osteomyelitis remains difficult, but several recent publications have clarified the role of clinical, laboratory and imaging tests. Magnetic resonance imaging has emerged as the most accurate means of diagnosing bone infection, but bone biopsy for culture and histopathology remains the criterion standard. Determining the organisms responsible for a diabetic foot infection via culture of appropriately collected tissue specimens enables clinicians to make optimal antibiotic choices based on culture and sensitivity results. In addition to culture-directed antibiotic therapy, most infections require some surgical intervention, ranging from minor debridement to major resection, amputation or revascularization. Clinicians must also provide proper wound care to ensure healing of the wound. Various adjunctive therapies may benefit some patients, but the data supporting them are weak. If properly treated, most diabetic foot infections can be cured. Providers practising in developing countries, and their patients, face especially challenging situations.

Audit of acute Charcot's disease in the UK: the CDUK study.

AIMS/HYPOTHESIS: We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study. METHODS: Clinicians managing cases of acute Charcot foot in the UK and Ireland between June 2005 and February 2007 were invited to register anonymised details on a secure website. RESULTS: A total of 288 cases (age 57.0 ± 11.3 years [mean ± SD]; 71.2% male) were registered from 76 centres. Of these, 36% of patients recalled an episode of relevant trauma in the preceding 6 months, while 12% had had surgery to the affected foot. In 101 (35%) cases, ulceration was present at registration and 20% of these had osteomyelitis. Non-removable off-loading devices were used at presentation in 35.4% of cases, with removable off-loading used in 50%. Data on resolution were available for 219 patients. The median time to resolution was 9 months in patients whose initial management included the use of non-removable off-loading, compared with 12 months in the remainder (p = 0.001). Bisphosphonates were administered intravenously in 25.4% and orally in 19.4% of cases. The median time to resolution in patients who received bisphosphonates was 12 months and was longer than in those who did not (10 months, p = 0.005). CONCLUSIONS/INTERPRETATION: The median time to resolution was longer than in earlier series. Although limited by being observational and non-randomised, these data suggest that the use of non-removable off-loading at presentation may shorten the time to resolution. They provide no evidence to indicate that the use of bisphosphonates is beneficial.

Stratification of foot risk predicts the incidence of new foot disease, but do we yet know that the adoption of routine screening reduces it?

The evidence to justify classifications of foot risk is derived from a number of large cross-sectional and prospective studies, and is very strong: it is possible to identify clinical features of the individual patient that are linked to the relative risk of future ulceration. The presence of peripheral arterial disease, neuropathy or deformity will increase the risk modestly, while any combination of these will increase it more and the risk is highest in those with a history of previous foot disease or surgery. If foot risk classification is linked to the increased adoption of preventive strategies of proven effectiveness, the incidence of new foot disease will fall. Foot risk classification should therefore become a routine part of diabetes care.

Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes.

OBJECTIVES: To determine the comparative effectiveness and cost-effectiveness of three dressing products, N-A, Inadine and Aquacel, for patients with diabetic foot ulcers, as well as the feasibility and consequences of less frequent dressing changes by health-care professionals. DESIGN: A multicentre, prospective, observer-blinded, parallel group, randomised controlled trial, with three arms. SETTING: Established expert multidisciplinary clinics for the management of diabetic foot ulcers across the UK. PARTICIPANTS: Patients over age 18 with type 1 or type 2 diabetes with a chronic (present for at least 6 weeks) full-thickness foot ulcer (on or below the malleoli) not penetrating to tendon, periosteum or bone, and with a cross-sectional area between 25 and 2500 mm(2). INTERVENTIONS: Participants were randomised 1:1:1 to treatment with one of N-A (a non-adherent, knitted, viscose filament gauze), Inadine (an iodine-impregnated dressing), both traditional dressings, or Aquacel, a newer product. MAIN OUTCOME MEASURES: The primary outcome measure was the number of ulcers healed in each group at week 24. Secondary measures included time to healing, new ulcerations, major and minor amputations, and episodes of secondary infection. RESULTS: A total of 317 patients were randomised. After 88 withdrawals, 229 remained evaluable. A greater proportion of smaller (25-100 mm(2) ulcers healed within the specified time (48.3% versus 37.3%; p = 0.048). There was, however, no difference between the three dressings in terms of percentage healed by 24 weeks, or in the mean time to healing, whether analysed on the basis of intention to treat (Inadine 44.4%, N-A 38.7%, Aquacel 44.7%; not significant) or per protocol (Inadine 55.2%, N-A 59.4%, Aquacel 63.0%; not significant). There was no difference in the quality of healing, as reflected in the incidence of recurrence within 12 weeks. Likewise, there was no difference in the incidence of adverse events, although a greater proportion of those randomised to the non-adherent dressings were withdrawn from the study (34.9% versus 29.1% Aquacel and 19.4% Inadine; p = 0.038). The only statistically significant difference found in the health economic analysis was the cost associated with the provision of dressings (mean cost per patient: N-A 14.85 pounds, Inadine 17.48 pounds, Aquacel 43.60 pounds). The higher cost of Aquacel was not offset by the fewer dressings required. There was no difference in measures of either generic or condition-specific measures of quality of life. However, there was a significant difference in the change in pain associated with dressing changes between the first and second visits, with least pain reported by those receiving non-adherent dressings (p = 0.012). There was no difference in the costs of professional time, and this may relate to the number of dressing changes undertaken by non-professionals. Fifty-one per cent of all participants had at least one dressing change undertaken by themselves or a non-professional carer, although this ranged from 22% to 82% between the different centres. CONCLUSIONS: As there was no difference in effectiveness, there is no reason why the least costly of the three dressings could not be used more widely across the UK National Health Service, thus generating potentially substantial savings. The option of involving patients and non-professional carers in changing dressings needs to be assessed more formally and could be associated with further significant reductions in health-care costs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78366977.

Medial arterial calcification in diabetes and its relationship to neuropathy.

Calcification of the media of arterial walls is common in diabetes and is particularly associated with distal symmetrical neuropathy. Arterial calcification also complicates chronic kidney disease and is an independent risk factor for cardiovascular and all-cause mortality. The term calcification is not strictly accurate because the morphological changes incorporate those of new bone formation, i.e. ossification. The processes are complex, but are closely related to those involved in bone homeostasis, and it is relevant that calcification of the arterial wall and osteopenia often co-exist. One particular factor linked to the development of arterial calcification is distal symmetrical neuropathy; indeed, it has been suggested that neuropathy explains the distal distribution of arterial calcification in diabetes. It has also been suggested that the link with neuropathy results from loss of neuropeptides, such as calcitonin gene-related peptide, which are inherently protective. The association between distal symmetrical neuropathy and calcification of the arterial wall highlights the fact that neuropathy may be an independent risk factor for cardiovascular mortality.

A proof-of-concept study of the effectiveness of a removable device for offloading in patients with neuropathic ulceration of the foot: the Ransart boot.

AIM: To undertake a proof-of-concept study to determine whether a removable offloading device (the Ransart boot) for the management of diabetic foot ulcers (DFU) was as effective as reports of non-removable devices. RESEARCH DESIGN AND METHODS: This observational study used the Ransart boot for patients with DFU, in seven specialist centres. If a patient had two or more ulcers, one was selected as the index ulcer. Ulcers were classified by the University of Texas (UT) system. RESULTS: There were 135 patients (mean age 60.3 +/- 11.4 years); 96 (71.1%) male. Median ulcer duration at presentation was 90 [interquartile range (IQR) 30-1825] days. Seven were lost to follow-up, seven developed other major illnesses and four died; outcomes were documented in the remaining 117. Eighty-two (70.1% of 117) healed, after a median (IQR) 60 (43-99) days, while 22 (18.8%) ulcers were resolved by amputation (one major). The remaining 13 (11.1%) patients were judged non-compliant. There was a close correlation between ulcer classification at baseline and both time to healing (P < 0.001 chi(2)-test) and amputation (P < 0.001; Spearman's rank correlation coefficient). There was a positive correlation between ulcer duration at presentation and time to healing (P < 0.02), UT class (P < 0.01), glycated haemoglobin (P < 0.02) and amputation (P < 0.04). CONCLUSIONS: Time to healing and incidence of amputation were comparable with those previously reported for non-removable devices. Given that a removable device is much more acceptable to the patient, the effectiveness, cost and acceptability of the removable devices, such as the Ransart boot, need to be compared with a non-removable device in a randomized trial. Diabet. Med. 26, 778-782 (2009).