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Symptoms or signs of peripheral artery disease (PAD) can be observed in up to 50% of the patients with a diabetic foot ulcer and is a risk factor for poor healing and amputation. In 2012, a multidisciplinary working group of the International Working Group on the Diabetic Foot published a systematic review on the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. This publication is an update of this review and now includes the results of a systematic search for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980 to June 2014. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 56 articles were eligible for full-text review. There were no randomized controlled trials, but there were four nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1-year limb salvage rates were a median of 85% (interquartile range of 80-90%), and following endovascular revascularization, these rates were 78% (70-89%). At 1-year follow-up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular techniques. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of conservatively treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients., (Copyright © 2015 John Wiley & Sons, Ltd.)

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., (Copyright © 2015 John Wiley & Sons, Ltd.)

Non-invasive tests for the detection of peripheral artery disease (PAD) among individuals with diabetes mellitus are important to estimate the risk of amputation, ulceration, wound healing and the presence of cardiovascular disease, yet there are no consensus recommendations to support a particular diagnostic modality over another and to evaluate the performance of index non-invasive diagnostic tests against reference standard imaging techniques (magnetic resonance angiography, computed tomography angiography, digital subtraction angiography and colour duplex ultrasound) for the detection of PAD among patients with diabetes. Two reviewers independently screened potential studies for inclusion and extracted study data. Eligible studies evaluated an index test for PAD against a reference test. An assessment of methodological quality was performed using the quality assessment for diagnostic accuracy studies instrument. Of the 6629 studies identified, ten met the criteria for inclusion. In these studies, the patients had a median age of 60-74 years and a median duration of diabetes of 9-24 years. Two studies reported exclusively on patients with symptomatic (ulcerated/infected) feet, two on patients with asymptomatic (intact) feet only, and the remaining six on patients both with and without foot ulceration. Ankle brachial index (ABI) was the most widely assessed index test. Overall, the positive likelihood ratio and negative likelihood ratio (NLR) of an ABI threshold <0.9 ranged from 2 to 25 (median 8) and <0.1 to 0.7 (median 0.3), respectively. In patients with neuropathy, the NLR of the ABI was generally higher (two out of three studies), indicating poorer performance, and ranged between 0.3 and 0.5. A toe brachial index <0.75 was associated with a median positive likelihood ratio and NLRs of 3 and ≤ 0.1, respectively, and was less affected by neuropathy in one study. Also, in two separate studies, pulse oximetry used to measure the oxygen saturation of peripheral blood and Doppler wave form analyses had NLRs of 0.2 and <0.1. The reported performance of ABI for the diagnosis of PAD in patients with diabetes mellitus is variable and is adversely affected by the presence of neuropathy. Limited evidence suggests that toe brachial index, pulse oximetry and wave form analysis may be superior to ABI for diagnosing PAD in patients with neuropathy with and without foot ulcers. There were insufficient data to support the adoption of one particular diagnostic modality over another and no comparisons existed with clinical examination. The quality of studies evaluating diagnostic techniques for the detection of PAD in individuals with diabetes is poor. Improved compliance with guidelines for methodological quality is needed in future studies., (Copyright © 2015 John Wiley & Sons, Ltd.)

Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation., (Copyright © 2015 John Wiley & Sons, Ltd.)

Improving ability to predict and prevent diabetic foot ulceration is imperative because of the high personal and financial costs of this complication. We therefore conducted a systematic review in order to identify all studies of factors associated with DFU and assess whether available DFU risk stratification systems incorporate those factors of highest potential value. We performed a search in PubMed for studies published through April 2011 that analysed the association between independent variables and DFU. Articles were selected by two investigators-independently and blind to each other. Divergences were solved by a third investigator. A total of 71 studies were included that evaluated the association between diabetic foot ulceration and more than 100 independent variables. The variables most frequently assessed were age, gender, diabetes duration, BMI, HbA(1c) and neuropathy. Diabetic foot ulceration prevalence varied greatly among studies. The majority of the identified variables were assessed by only two or fewer studies. Diabetic neuropathy, peripheral vascular disease, foot deformity and previous diabetic foot ulceration or lower extremity amputation - which are the most common variables included in risk stratification systems - were consistently associated with diabetic foot ulceration development. Existing diabetic foot ulceration risk stratification systems often include variables shown repeatedly in the literature to be strongly predictive of this outcome. Improvement of these risk classification systems though is impaired because of deficiencies noted, including a great lack of standardization in outcome definition and variable selection and measurement., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Age is associated with both impaired glucose and insulin metabolism. To what extent the age-related changes in insulin resistance (IR) and beta-cell function contribute to the increase in prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) is less known, and this is investigated in this study., Methods: This study included 6610 men and 7664 women of different ethnic groups aged 30-69 years. IR and beta-cell function were examined by the homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis adjusting for body mass index and study., Results: In Chinese men, the ORs (95% CIs) for IFG were 2.69 (1.70, 4.26), 2.51 (1.49, 4.21) and 2.89 (1.68, 4.97), respectively, in age groups of 40-49, 50-59 and 60-69 years compared with 30-39 years (p < 0.001 for trend); the corresponding figures for IGT were 1.73 (1.25, 2.38), 2.54 (1.78, 3.63) and 3.57 (2.46, 5.19) (p < 0.001 for trend). Similar trends for IGT were observed also in Chinese women and other ethnic groups, but not for IFG in Mauritius Indian and Creole men. Adjustment for HOMA-IR and HOMA-B reduced the ORs in all age groups of all ethnicities for both IFG and IGT, but the risk gradient between age groups remained particularly for the IGT., Conclusions: The age-related increase in glucose intolerance may not be fully explained by the defect in HOMA-IR and HOMA-B. As HOMA-IR and HOMA-B are only surrogate measures of insulin sensitivity and insulin secretion, the results need to be further investigated.