Effectiveness of offloading interventions for people with diabetes-related foot ulcers: A systematic review and meta-analysis.

BACKGROUND: Offloading treatment is crucial to heal diabetes-related foot ulcers (DFU). This systematic review aimed to assess the effectiveness of offloading interventions for people with DFU. METHODS: We searched PubMed, EMBASE, Cochrane databases, and trials registries for all studies relating to offloading interventions in people with DFU to address 14 clinical question comparisons. Outcomes included ulcers healed, plantar pressure, weight-bearing activity, adherence, new lesions, falls, infections, amputations, quality of life, costs, cost-effectiveness, balance, and sustained healing. Included controlled studies were independently assessed for risk of bias and had key data extracted. Meta-analyses were performed when outcome data from studies could be pooled. Evidence statements were developed using the GRADE approach when outcome data existed. RESULTS: From 19,923 studies screened, 194 eligible studies were identified (47 controlled, 147 non-controlled), 35 meta-analyses performed, and 128 evidence statements developed. We found non-removable offloading devices likely increase ulcers healed compared to removable offloading devices (risk ratio [RR] 1.24, 95% CI 1.09-1.41; N = 14, n = 1083), and may increase adherence, cost-effectiveness and decrease infections, but may increase new lesions. Removable knee-high offloading devices may make little difference to ulcers healed compared to removable ankle-high offloading devices (RR 1.00, 0.86-1.16; N = 6, n = 439), but may decrease plantar pressure and adherence. Any offloading device may increase ulcers healed (RR 1.39, 0.89-2.18; N = 5, n = 235) and cost-effectiveness compared to therapeutic footwear and may decrease plantar pressure and infections. Digital flexor tenotomies with offloading devices likely increase ulcers healed (RR 2.43, 1.05-5.59; N = 1, n = 16) and sustained healing compared to devices alone, and may decrease plantar pressure and infections, but may increase new transfer lesions. Achilles tendon lengthening with offloading devices likely increase ulcers healed (RR 1.10, 0.97-1.27; N = 1, n = 64) and sustained healing compared to devices alone, but likely increase new heel ulcers. CONCLUSIONS: Non-removable offloading devices are likely superior to all other offloading interventions to heal most plantar DFU. Digital flexor tenotomies and Achilles tendon lengthening in combination with offloading devices are likely superior for some specific plantar DFU locations. Otherwise, any offloading device is probably superior to therapeutic footwear and other non-surgical offloading interventions to heal most plantar DFU. However, all these interventions have low-to-moderate certainty of evidence supporting their outcomes and more high-quality trials are needed to improve our certainty for the effectiveness of most offloading interventions.

Diabetes-related lower-extremity complications are a leading cause of the global burden of disability.

Globally ~435 million people have diabetes [1], and an estimated 19-34% (~83-148 million people) of those will be expected to develop foot ulcers in their lifetime [2]. Foot ulcers are typically precipitated by other diabetes-related lower-extremity complications, (DRLECs) including peripheral neuropathy and peripheral vascular disease [2,3]. Collectively, DRLECs are a leading cause of infection, hospitalization and amputation outcomes [2-5], yet, these outcomes are readily preventable with evidence-based care [6,7]. This suggests the burden caused by DRLECs is a large, yet reducible, cause of the global burden of disease. This article is protected by copyright. All rights reserved.

Characteristics and clinical assessment of antibiotic delivery by chitosan sponge in the high-risk diabetic foot: a case series.

OBJECTIVE: The local delivery of antimicrobials is attractive for a number of reasons. Chitosan, a biodegradable polysaccharide sponge material, has been proposed as medium to deliver antibiotics directly to wounds. In this report we evaluate the safety and practicality of antimicrobial delivery via chitosan sponge. METHOD: We present the clinical course and systemic absorption characteristics of three cases of people with diabetic foot wounds treated with antibiotic soaked chitosan sponge (Sentrex BioSponge, Bionova Medical, Germantown, TN). The antibiotic sponge was made by reconstituting 1.2g tobramycin or 100mg doxycycline in 10-15ml saline and saturating the sponge with the solution. The sponge was then applied to the wounds. Serum levels of each respective antibiotic were evaluated after application. Additional in vitro studies were conducted evaluating elution of antibiotics from the chitosan sponge at established minimum inhibitory concentrations (MIC) for Staphylococcus aureus over 28 days. RESULTS: No patient experienced adverse local or systemic effects due to the sponge treatment. The measured serum levels applied antibiotics remained far less than established minimums after intravenous therapy. Each patient required further treatment, however local infection or contamination resolved during the course of their hospital stay after the chitosan/antibiotic application. CONCLUSION: The use of antibiotic-impregnated chitosan sponges appears a safe and effective mechanism of local delivery of antimicrobials in wounds. Future studies and clinical trials are ongoing to confirm these results and to guide clinical applications.

Platelet-rich plasma, bilayered acellular matrix grafting and negative pressure wound therapy in diabetic foot infection.

UNLABELLED: Management and treatment of acute severe diabetic foot disease in patients with suboptimal glycaemic control is a critical issue in wound repair. This paper discusses the clinical efficacy of an aggressive surgical intervention combined with targeted use of regenerative medical therapies in limb preservation. Negative pressure wound therapy (NPWT), platelet-rich plasma (PRP), bilayered acellular matrix grafting and split-thickness skin grafting were combined to treat a patient with diabetes, foot necrotising fasciitis and gaseous gangrene. The wound was completely healed. The clinical outcome revealed that a multi-intervention strategy could be effective for large necrotising fasciitis wounds. Early clinical observation, suggests aggresive surgical intervention preserving intact tissue and targeted use of new regenerative technologies can lead to preservation of a limb. DECLARATION OF INTEREST: The authors have received no financial support for the material presented in this study outside of the scope of standard patient care reimbursement. This work was supported by the National Natural Science Foundation of China (NO. 81500596) awarded to Dr Wuquan Deng.

Footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with diabetes: a systematic review.

BACKGROUND: Footwear and offloading techniques are commonly used in clinical practice for preventing and healing of foot ulcers in persons with diabetes. The goal of this systematic review is to assess the medical scientific literature on this topic to better inform clinical practice about effective treatment. METHODS: We searched the medical scientific literature indexed in PubMed, EMBASE, CINAHL, and the Cochrane database for original research studies published since 1 May 2006 related to four groups of interventions: (1) casting; (2) footwear; (3) surgical offloading; and (4) other offloading interventions. Primary outcomes were ulcer prevention, ulcer healing, and pressure reduction. We reviewed both controlled and non-controlled studies. Controlled studies were assessed for methodological quality, and extracted key data was presented in evidence and risk of bias tables. Uncontrolled studies were assessed and summarized on a narrative basis. Outcomes are presented and discussed in conjunction with data from our previous systematic review covering the literature from before 1 May 2006. RESULTS: We included two systematic reviews and meta-analyses, 32 randomized controlled trials, 15 other controlled studies, and another 127 non-controlled studies. Several randomized controlled trials with low risk of bias show the efficacy of therapeutic footwear that demonstrates to relief plantar pressure and is worn by the patient, in the prevention of plantar foot ulcer recurrence. Two meta-analyses show non-removable offloading to be more effective than removable offloading for healing plantar neuropathic forefoot ulcers. Due to the limited number of controlled studies, clear evidence on the efficacy of surgical offloading and felted foam is not yet available. Interestingly, surgical offloading seems more effective in preventing than in healing ulcers. A number of controlled and uncontrolled studies show that plantar pressure can be reduced by several conservative and surgical approaches. CONCLUSIONS: Sufficient evidence of good quality supports the use of non-removable offloading to heal plantar neuropathic forefoot ulcers and therapeutic footwear with demonstrated pressure relief that is worn by the patient to prevent plantar foot ulcer recurrence. The evidence base to support the use of other offloading interventions is still limited and of variable quality. The evidence for the use of interventions to prevent a first foot ulcer or heal ischemic, infected, non-plantar, or proximal foot ulcers is practically non-existent. High-quality controlled studies are needed in these areas.

Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial.

AIMS: Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and ß-hydroxy-ß-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. METHODS: Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and ß-hydroxy-ß-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. RESULTS: Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and ß-hydroxy-ß-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. CONCLUSIONS: While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and ß-hydroxy-ß-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and ß-hydroxy-ß-methylbutyrate in these high-risk subgroups might prove clinically valuable.

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.

The consequences of complacency: managing the effects of unrecognized Charcot feet.

AIMS: Several authors have discussed an early prodromal state of neuroarthropathy (stage 0 Charcot) prior to the development of frank radiographic changes. However, very few reports are available that detail the outcomes of these patients. The purpose of this study was to report on the outcomes of patients with undetected early Charcot neuroarthropathy of the foot. METHODS: Twenty patients, from two health science centres, were diagnosed retrospectively with stage 0 Charcot neuroarthropathy and were managed after referral from outside facilities. We evaluated any complications, including ulcer formation, infection, progression into active Charcot neuroarthropathy and the need for surgical reconstruction. Patients who did not progress to an active Charcot neuroarthropathy (Group I) were compared with those (Group II) who did progress to the destructive phase. RESULTS: The diagnosis of Charcot neuroarthropathy was missed in 19 of 20 patients prior to referral. The average delay in treatment in Group I was 4.1±0.7 weeks compared with 8.7±6.8 weeks in Group II (Mann-Whitney U-test=24.5, n(1) =15, n(2) =7, P<0.05 two-tailed). Sixteen of 22 feet (72%) developed a complication during their treatment course. Group II experienced more complications than Group I (66.7% compared with 14.3%). Overall, eleven of 22 feet (50%) required surgical treatment; however, no patient required an amputation during the follow-up course. CONCLUSIONS: This study reveals that outcomes of stage 0 Charcot neuroarthropathy feet depend on proper recognition and early management. To reduce the rate of future complications for Charcot foot should be the goal of all treatment.

Nutrition, metabolism, and fertility in dairy cows: 3. Amino acids and ovarian function.

Plasma insulin concentrations influence resumption of ovarian activity in postpartum dairy cows, and plasma insulin can be manipulated by changing dietary starch and fat supply. The objective of this experiment was to investigate the role of dietary amino acids in altering peripheral metabolic hormones and ovarian function. Thirty-two cows were fed a standard diet from calving until 40 d in milk (DIM), and then 8 cows were transferred to each of 4 dietary treatments until 70 DIM. The 4 diets were designed to supply either low (diets 1 and 2) or high (diets 3 and 4) levels of metabolizable protein (MP), containing either low (diet 1 and 3) or high (diets 2 and 4) proportions of Leu. Leucine was manipulated with heat-treated lupins and corn gluten meal. Estrus was synchronized at 60 DIM. Between 60 and 70 DIM, energy intake and energy balance were similar among diet groups, although cows receiving high MP containing high Leu had a greater milk yield than other groups (means: 37.8, 37.1, 37.4, 39.4 +/- standard error 0.85 kg/d for diets 1 to 4, respectively). Interactions between MP and Leu were found for insulin, glucagon, and the ratio between them. Insulin was not affected by Leu in diets with low MP but was decreased by greater Leu in diets with high MP (means: 0.37, 0.32, 0.46, 0.39 +/- SE 0.031 ng/mL for diets 1 to 4, respectively). Glucagon was not affected by MP in diets with low Leu but was increased by greater MP in diets with high Leu (means: 92, 81, 88, 95 +/- SE 6.0 pg/mL for diets 1 to 4, respectively). For the low-MP treatments, the insulin-to-glucagon ratio was greater with high Leu; for the high-MP treatments, the insulin-to-glucagon ratio was greater with low Leu (means: 4.28, 5.42, 5.16, 4.22 +/- SE 0.456 for diets 1 to 4, respectively). There was no effect of MP or Leu on ovarian follicle numbers or reproductive hormones. Based on hormonal and ovarian responses, we conclude that altering metabolic hormones through manipulation of amino acid supply and balance is unlikely to have a significant effect on ovarian function in dairy cows.

Outcomes of surgical treatment of diabetic foot osteomyelitis: a series of 185 patients with histopathological confirmation of bone involvement.

AIMS/HYPOTHESIS: We analysed the factors that determine the outcomes of surgical treatment of osteomyelitis of the foot in diabetic patients given early surgical treatment within 12 h of admission and treated with prioritisation of foot-sparing surgery and avoidance of amputation. METHODS: A consecutive series of 185 diabetic patients with foot osteomyelitis and histopathological confirmation of bone involvement were followed until healing, amputation or death. RESULTS: Probing to bone was positive in 175 cases (94.5%) and radiological signs of osteomyelitis were found in 157 cases (84.8%). Staphylococcus aureus was the organism isolated in the majority of cultures (51.3%), and in 35 cases (36.8%) it proved to be methicillin-resistant. The surgical treatment performed included 91 conservative surgical procedures, which were defined as those where no amputation of any part of the foot was undertaken (49.1%). A total of 94 patients received some degree of amputation, consisting of 79 foot-level (minor) amputations (42.4%) and 15 major amputations (8%). Five patients died during the perioperative period (2.7%). Histopathological analysis revealed 94 cases (50.8%) of acute osteomyelitis, 43 cases (23.2%) of chronic osteomyelitis, 45 cases (24.3%) of acute exacerbation of chronic osteomyelitis and three remaining cases (1.6%) designated as 'other'. The risks of failure in the case of conservative surgery were exposed bone, the presence of ischaemia and necrotising soft tissue infection. CONCLUSIONS/INTERPRETATION: Conservative surgery without local or high-level amputation is successful in almost half of the cases of diabetic foot osteomyelitis. Prospective trials should be undertaken to determine the relative roles of conservative surgery versus other approaches.

The effectiveness of footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in diabetes: a systematic review.

BACKGROUND: Footwear and offloading techniques are commonly used in clinical practice for the prevention and treatment of foot ulcers in diabetes, but the evidence base to support this use is not well known. The goal of this review was to systematically assess the literature and to determine the available evidence on the use of footwear and offloading interventions for ulcer prevention, ulcer treatment, and plantar pressure reduction in the diabetic foot. METHODS: A search was made for reports on the effectiveness of footwear and offloading interventions in preventing or healing foot ulcers or reducing plantar foot pressure in diabetic patients published prior to May 2006. Both controlled and uncontrolled studies were included. Assessment of the methodological quality of studies and data extraction was independently performed by two reviewers. Interventions were assigned into four subcategories: casting, footwear, surgical offloading and other offloading techniques. RESULTS: Of 1651 articles identified in the baseline search, 21 controlled studies were selected for grading following full text review. Another 108 uncontrolled and cross-sectional studies were examined. The evidence to support the use of footwear and surgical interventions for the prevention of ulceration is meagre. Evidence was found to support the use of total contact casts and other non-removable modalities for treatment of neuropathic plantar ulcers. More studies are needed to support the use of surgical offloading techniques for ulcer healing. Plantar pressure reduction can be achieved by several modalities including casts, walkers, and therapeutic footwear, but the diversity in methods and materials used limits the comparison of study results. CONCLUSIONS: This systematic review provides support for the use of non-removable devices for healing plantar foot ulcers. Furthermore, more high-quality studies are urgently needed to confirm the promising effects found in both controlled and uncontrolled studies of footwear and offloading interventions designed to prevent ulcers, heal ulcers, or reduce plantar pressure.

A systematic review of the effectiveness 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 uncertainty concerning optimal approaches to management. We have undertaken a systematic review to identify interventions for which there is evidence of effectiveness. A search was made for reports of the effectiveness of interventions assessed in terms of healing, ulcer area or amputation in controlled clinical studies published prior to December 2006. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Selected studies fell into the following categories: sharp debridement and larvae; antiseptics and dressings; chronic wound resection; hyperbaric oxygen (HBO); reduction of tissue oedema; skin grafts; electrical and magnetic stimulation and ultrasound. Heterogeneity of studies prevented pooled analysis of results. Of the 2251 papers identified, 60 were selected for grading following full text review. Some evidence was found to support hydrogels as desloughing agents and to suggest that a systemic (HBO) therapy may be effective. Topical negative pressure (TNP) may promote healing of post-operative wounds, and resection of neuropathic plantar ulcers may be beneficial. More information was needed to confirm the effectiveness and cost-effectiveness of these and other interventions. No data were found to justify the use of any other topically applied product or dressing, including those with antiseptic properties. Further evidence to substantiate the effect of interventions designed to enhance the healing of chronic ulcers is urgently needed. Until such evidence is available from robust trials, there is limited justification for the use of more expensive treatments and dressings.