Development of the Tardivo Algorithm to Predict Amputation Risk of Diabetic Foot

Diabetes is a chronic disease that affects almost 19% of the elderly population in Brazil and similar percentages around the world. Amputation of lower limbs in diabetic patients who present foot complications is a common occurrence with a significant reduction of life quality, and heavy costs on the health system. Unfortunately, there is no easy protocol to define the conditions that should be considered to proceed to amputation. The main objective of the present study is to create a simple prognostic score to evaluate the diabetic foot, which is called Tardivo Algorithm. Calculation of the score is based on three main factors: Wagner classification, signs of peripheral arterial disease (PAD), which is evaluated by using Peripheral Arterial Disease Classification, and the location of ulcers. The final score is obtained by multiplying the value of the individual factors. Patients with good peripheral vascularization received a value of 1, while clinical signs of ischemia received a value of 2 (PAD 2). Ulcer location was defined as forefoot, midfoot and hind foot. The conservative treatment used in patients with scores below 12 was based on a recently developed Photodynamic Therapy (PDT) protocol. 85.5% of these patients presented a good outcome and avoided amputation. The results showed that scores 12 or higher represented a significantly higher probability of amputation (Odds ratio and logistic regression-IC 95%, 12.2–1886.5). The Tardivo algorithm is a simple prognostic score for the diabetic foot, easily accessible by physicians. It helps to determine the amputation risk and the best treatment, whether it is conservative or surgical management.     

In vitro glycation of a tissue-engineered wound healing model to mimic diabetic ulcers

Diabetic foot ulcers are a major complication of diabetes that occurs following minor trauma. Diabetes-induced hyperglycemia is a leading factor inducing ulcer formation and manifests notably through the accumulation of advanced glycation end-products (AGEs) such as N-carboxymethyl-lysin. AGEs have a negative impact on angiogenesis, innervation, and reepithelialization causing minor wounds to evolve into chronic ulcers which increases the risks of lower limb amputation. However, the impact of AGEs on wound healing is difficult to model (both in vitro on cells, and in vivo in animals) because it involves a long-term toxic effect. We have developed a tissue-engineered wound healing model made of human keratinocytes, fibroblasts, and endothelial cells cultured in a collagen sponge biomaterial. To mimic the deleterious effects induced by glycation on skin wound healing, the model was treated with 300 µM of glyoxal for 15 days to promote AGEs formation. Glyoxal treatment induced carboxymethyl-lysin accumulation and delayed wound closure in the skin mimicking diabetic ulcers. Moreover, this effect was reversed by the addition of aminoguanidine, an inhibitor of AGEs formation. This in vitro diabetic wound healing model could be a great tool for the screening of new molecules to improve the treatment of diabetic ulcers by preventing glycation.     

Smart Diabetic Socks: Embedded device for diabetic foot prevention

ObjectivesMost foot ulcers are the consequence of a trauma (repetitive high stress, ill-fitting footwear, or an object inside the shoe) associated to diabetes. They are often followed by amputation and shorten life expectancy. This paper describes the prototype of the Smart Diabetic Socks that has been developed in the context of the French ANR TecSan project. The objective is to prevent pressure foot ulcers for diabetic persons.Material and methodsA fully wireless, customizable and washable “smart sock” has been designed. It is made of a textile which fibers are knitted in a way they provide measurements of the pressure exerted under and all around the foot in real-life conditions. This device is coupled with a subject-specific Finite Element foot model that simulates the internal strains within the soft tissues of the foot.ResultsA number of derived stress indicators can be computed based on that analysis, such as the accumulated stress dose, high internal strains or peak pressures near bony prominences during gait. In case of risks for pressure ulcer, an alert is sent to the person and/or to the clinician. A watch, a smart-phone or a distant laptop can be used for providing such alert.     

The amputation and survival of patients with diabetic foot based on establishment of prediction model

ObjectiveThe objective of this paper is to study the establishment of predictive models and the amputation and survival of patients with diabetic foot.MethodsA total of 200 inpatients with diabetic foot were selected as the research subject in this study. The amputation and survival status of diabetic foot patients were followed up by telephone. The relevant indicators were screened by cluster analysis. The predictive model was established respectively based on proportional hazard regression analysis, back propagation neural network (BPNN) and BPNN based on genetic algorithm optimization, and the reliability of the three prediction models (PM) was evaluated and compared.ResultsThe risk factors for amputation were severe ulcer disease, glycosylated hemoglobin and low-density lipoprotein cholesterol. The risk factors for death were cerebrovascular disease, severe ulcer disease and peripheral arterial disease. In case that the outcome was amputation, the PM of BPNN and the PM of BPNN based on genetic algorithm optimization have obviously higher AUC (area under the receiver operating characteristic curve) than the PM of proportional hazard regression analysis, and the difference was statistically significant (P < 0.05). Among the three PMs, the PM based on BPNN had the highest AUC, sensitivity and specificity (SAS). In case that the outcome was death, the PM of BPNN and the PM of BPNN based on genetic algorithm optimization had almost the same AUC, and were obviously higher than the PM based on proportional hazard regression analysis. The difference was statistically significant (P < 0.05). The PM based on BPNN and the BPNN based on genetic algorithm optimization had higher SAS than the PM based on COX regression analysis.ConclusionThe PM of BPNN and BPNN based on genetic algorithm optimization have better prediction effect than the PM based on proportional hazard regression analysis. It can be used for amputation and survival analysis of diabetic foot patients.     

Mathematical Model of Hyperbaric Oxygen Therapy Applied to Chronic Diabetic Wounds

The failure of certain wounds to heal (including diabetic foot ulcers) is a significant socioeconomic issue for countries worldwide. There is much debate about the best way to treat these wounds and one approach that is shrouded with controversy is hyperbaric oxygen therapy (HBOT), a technique that can reduce the risk of amputation in diabetic patients.     

Regression modeling of semicompeting risks data

Semicompeting risks data are often encountered in clinical trials with intermediate endpoints subject to dependent censoring from informative dropout. Unlike with competing risks data, dropout may not be dependently censored by the intermediate event. There has recently been increased attention to these data, in particular inferences about the marginal distribution of the intermediate event without covariates. In this article, we incorporate covariates and formulate their effects on the survival function of the intermediate event via a functional regression model. To accommodate informative censoring, a time-dependent copula model is proposed in the observable region of the data which is more flexible than standard parametric copula models for the dependence between the events. The model permits estimation of the marginal distribution under weaker assumptions than in previous work on competing risks data. New nonparametric estimators for the marginal and dependence models are derived from nonlinear estimating equations and are shown to be uniformly consistent and to converge weakly to Gaussian processes. Graphical model checking techniques are presented for the assumed models. Nonparametric tests are developed accordingly, as are inferences for parametric submodels for the time-varying covariate effects and copula parameters. A novel time-varying sensitivity analysis is developed using the estimation procedures. Simulations and an AIDS data analysis demonstrate the practical utility of the methodology.     

Metformin Induces Cell Cycle Arrest,Reduced Proliferation,Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients

BackgroundSeveral epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation.ResultsMetformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin.ConclusionsMetformin treatment reduces cell proliferation and reduces wound healing in an animal model and affects clinical outcomes in diabetic foot ulcer patients. Chronic use of this drug should be further investigated to provide evidence of their security in association with DFU.     

Clinical application of fresh fibroblast allografts for the treatment of diabetic foot ulcers: a pilot study

Diabetic foot ulcers often pose a difficult problem for health care professionals because of the defects associated with fibroblast functioning. Although there has been much interest recently in the use of topical growth factors for the treatment of diabetic foot ulcers, the effects are generally not very dramatic. Cryopreserved fibroblast implants, which are able to adjust to a wound's environment and provide the desired growth factors and other substances that may be lacking in a chronic wound, represent an exciting development and a major advance. These products may well provide growth factors in the right concentration and in the right sequence, something that has proved difficult to achieve with the topical application of recombinant growth factors. However, cell activities are impaired by cryopreservation. The purpose of this study was to assess the effects of fresh human allogeneic fibroblast grafting for the treatment of diabetic foot ulcers. Eight patients with diabetic foot ulcers ranging from 6 to 17 weeks in duration were treated. The size of the wounds ranged from 2.0 to 6.0 cm2, with three patients exhibiting exposed bones. A history of diabetic foot ulcers was present in five patients. Human dermal fibroblasts from healthy teenagers were cultured in Dulbecco's modified Eagle medium/Ham's F-12 supplemented with 10% autologous serum. The cultured cells were applied over the wounds immediately after debridement; fibrin was used as a cell carrier. A dressing was then applied with Tegaderm and kept moist until healing was complete. The progress and time for complete wound closure and patient satisfaction were assessed, with follow-up time ranging from 6 to 18 months. Complete wound healing occurred in all patients. Eleven to 21 days were needed for complete reepithelization of the wound, and no clinical or laboratory abnormalities were noted. Patient satisfaction was also very positive. In this study, the use of fresh human fibroblast allografts was found to be a safe and effective treatment for diabetic foot ulcers.     

Method of healing diabetic forefoot ulcers.

Six diabetic patients with neuropathic ulceration of the sole of the foot (seven feet, eight ulcers) were treated by the application of a below knee walking plaster with a rubber rocker. All the ulcers healed with this treatment, greatly reducing the usual period of hospital inpatient stay. After healing, study of the forces acting on the sole of the foot showed that these ulcers occur at the site of maximal horizontal shear force and confirmed that they occur at the site of maximal vertical force. This treatment is highly effective for neuropathic ulcers of the sole not affecting bone or complicated by deep sepsis. There may be a high rate of recurrence, however, reflecting inadequacy of methods of protecting damaged neuropathic feet.     

Parametric survival models for interval-censored data with time-dependent covariates

We present a parametric family of regression models for interval-censored event-time (survival) data that accomodates both fixed (e.g. baseline) and time-dependent covariates. The model employs a three-parameter family of survival distributions that includes the Weibull, negative binomial, and log-logistic distributions as special cases, and can be applied to data with left, right, interval, or non-censored event times. Standard methods, such as Newton-Raphson, can be employed to estimate the model and the resulting estimates have an asymptotically normal distribution about the true values with a covariance matrix that is consistently estimated by the information function. The deviance function is described to assess model fit and a robust sandwich estimate of the covariance may also be employed to provide asymptotically robust inferences when the model assumptions do not apply. Spline functions may also be employed to allow for non-linear covariates. The model is applied to data from a long-term study of type 1 diabetes to describe the effects of longitudinal measures of glycemia (HbA1c) over time (the time-dependent covariate) on the risk of progression of diabetic retinopathy (eye disease), an interval-censored event-time outcome.     

Single-stage surgical treatment of noninfected diabetic foot ulcers

A retrospective study was undertaken to evaluate a single-stage approach in the treatment of noninfected, chronic, well-perfused diabetic foot wounds. This single-stage approach consisted of total excision of the ulcer with broad exposure, correction of the underlying osseous deformity, and immediate primary closure using a local random flap. Four hundred cases of pedal ulcers were analyzed by chart review. Of those, 67 cases underwent a single-stage surgical treatment and were analyzed for length of hospital stay, postoperative complications, time to heal, recurrence of the ulcer, and postprocedure ambulatory status. The age of the ulcers before surgery was 12 +/- 12 months (mean +/- SD), with a range of 1 to 60. The median perioperative hospital stay was 5 +/- 7.6 days. All patients were followed until the wounds were healed or to amputation. The median total time to heal was 30.8 +/- 40 days. Ninety-seven percent of the wounds healed. The recurrence rate of ulceration was 10.4 percent (seven of 67), over a time span of up to 6 years. All but one patient returned to previous levels of ambulation, and many patients had improved levels of ambulation. The single-stage approach eliminated the need for additional surgical procedures, with their associated costs and risks. In addition, healing times were significantly reduced, resulting in decreased hospital stays and subsequent costs and providing the patient with an expedient return to footwear so that bipedal function could be restored. Most importantly, by addressing the underlying bony pathologic findings, the recurrence rates were also drastically reduced.     

Heparin-induced Extracorporal LDL precipitation (H.E.L.P) in diabetic foot syndrome - preventive and regenerative potential?

Peripheral arterial disease is more aggressive in concomitant diabetes posing an increased risk for critical limb ischemia and subsequent limb loss. The majority of therapies available are not effective to prevent amputation in patients with severe disease. The current observational study reports the effect of the heparin-induced extracorporal LDL-precipitation (H.E.L.P.) as a novel therapeutic approach in patients with severe diabetic foot syndrome. Seventeen diabetic patients with septic foot lesions recruited from the diabetic outpatient clinic underwent H.E.L.P. apheresis regularly until fibrinogen levels were stabilized at 3 g/l or infection was controllable as evidenced by alleviation of necrosis. Patients were subsequently followed up for 2 to 73 months. Fibrinogen levels were reduced by 68% after H.E.L.P. treatment. No severe complications were noted. Necrosis could be confined in sixteen patients. Minor amputations were indicated in twelve patients. Three patients underwent major amputations of the lower limb and two patients received surgical reconstruction. In conclusion, H.E.L.P. apheresis may offer an alternative therapeutic option to diabetic patients with critically ischemic feet and appears to have a beneficial major/minor amputation ratio.     

Human α defensins promote the expression of the inflammatory cytokine interleukin‐8 under high‐glucose conditions: Novel insights into the poor healing of diabetic foot ulcers

Sustained infection and chronic inflammation are the most common features and complex mechanisms of diabetic foot disease. In this study, we examined the expression and functional roles of human endogenous α defensins in diabetic foot ulcer. The expression levels of human α defensins HNP1, HNP3, and HNP4 were significantly higher in the wound center than the edge of diabetic foot ulcers. And the inflammatory cytokine interleukin IL‐8 (IL‐8) was also highly expressed in wound exudates. In human foreskin fibroblasts, these human α defensins were found only slightly to affect IL‐8 expression directly. hemoglobin A1C (HbA1c) is the main clinical indicator of diabetic foot disease. Advanced glycation end products of bovine serum albumin (AGE‐BSA), as HbA1c analogue, was found to promote IL‐8 expression. Human α defensins, in the presence of AGE‐BSA, further significantly promoted IL‐8 expression. These findings showed that human α defensins aggravated the inflammatory response in diabetic foot ulcers patients, providing new insights in to the poor healing of diabetic foot ulcers.     

Topical hyperbaric oxygen and low energy laser therapy for chronic diabetic foot ulcers resistant to conventional treatment

Chronic foot ulcers are common in long-standing diabetes, may herald severe complications and are often resistant to therapy. To evaluate the effects of adjunctive topical hyperbaric oxygen treatment (THBO) and low energy laser (LEL) irradiation on ulcer healing, a 100 consecutive patients with chronic diabetic foot ulcers (DFU) refractory to 4.5 +/- 1.2 months of comprehensive treatment, were enrolled in a prospective open study. While conventional treatment was continued as necessary, THBO was administered by pumping 100 percent oxygen into a disposable sealed polythylene hyperbaric chamber (150 min x 2 to 3/wk at up to 1.04 atm). Helium-neon LEL irradiation was given concurrently using a Unilaser Scan Unit at 4 J/cm2 for 20 min. Some patients continued THBO at home or their treatment was confined to THBO at home. Patients were monitored every two weeks revealing 81 percent cure after 25 +/- 13 treatments over 3.2 +/- 1.7 months. On follow-up (median 18 months), only 3/81 (4 percent) had reulceration, which responded to THBO/LEL retreatment. Nonresponders had significantly lower ankle brachial indices (ABI) than patients whose ulcers were healed (0.55 vs. 0.78, p < 0.01) and ultimately required amputation. Patient compliance was full and no adverse events occurred. In conclusion, although the study was open and uncontrolled, an 81 percent healing of DFU in patients who previously did not respond to a comprehensive treatment program, constitutes an intriguing preliminary result. Thus, THBO/LEL therapy may be a safe, simple, and inexpensive early adjunctive treatment for patients with chronic diabetic foot ulcers. Our findings should prompt its evaluation by large randomized controlled trials.     

Diabetic foot infections: fate of the contralateral foot

Following an initial report urging conservative management of severe diabetic foot infections, the authors have managed 45 patients with a minimum 3-year follow-up. By using standard principles for soft-tissue infection, 78 percent of the patients healed minor amputation sites and maintained biped ambulation following the initial foot involvement. Only 22 percent required a major amputation at the time of the initial foot involvement. The 45 patients were followed and 22 (or 49 percent) developed a severe infection involving the contralateral foot within 18 months. Although 15 of the 22 patients developing contralateral infection (or 33 percent of the total series) required some type of amputation on the contralateral foot, the conservative approach allowed 64 percent of the patients with severe infections in both feet to maintain biped ambulation. This included 40 percent of the patients who required amputation of some portion of both feet.     

Tool for Rapid & Easy Identification of High Risk Diabetic Foot: Validation & Clinical Pilot of the Simplified 60 Second Diabetic Foot Screening Tool

Background

Most diabetic foot amputations are caused by ulcers on the skin of the foot i.e. diabetic foot ulcers. Early identification of patients at high risk for diabetic foot ulcers is crucial. The ‘Simplified 60-Second Diabetic Foot Screening Tool’ has been designed to rapidly detect high risk diabetic feet, allowing for timely identification and referral of patients needing treatment. This study aimed to determine the clinical performance and inter-rater reliability of ‘Simplified 60 Second Diabetic Foot Screening Tool’ in order to evaluate its applicability for routine screening.

Methods and Findings

The tool was independently tested by n=12 assessors with n=18 Guyanese patients with diabetes. Inter-rater reliability was assessed by calculating Cronbach’s alpha for each of the assessment items. A minimum value of 0.60 was considered acceptable. Reliability scores of the screening tool assessment items were: ‘monofilament test’ 0.98; ‘active ulcer’ 0.97; ‘previous amputation’ 0.97; ‘previous ulcer’ 0.97; ‘fixed ankle’ 0.91; ‘deformity’ 0.87; ‘callus’ 0.87; ‘absent pulses’ 0.87; ‘fixed toe’ 0.80; ‘blisters’ 0.77; ‘ingrown nail’ 0.72; and ‘fissures’ 0.55. The item ‘stiffness in the toe or ankle’ was removed as it was observed in only 1.3% of patients. The item ‘fissures’ was also removed due to low inter-rater reliability. Clinical performance was assessed via a pilot study utilizing the screening tool on n=1,266 patients in an acute care setting in Georgetown, Guyana. In total, 48% of patients either had existing diabetic foot ulcers or were found to be at high risk for developing ulcers.

Conclusions

Clinicians in low and middle income countries such as Guyana can use the Simplified 60-Second Diabetic Screening Tool to facilitate early detection and appropriate treatment of diabetic foot ulcers. Implementation of this screening tool has the potential to decrease diabetes related disability and mortality.     

Off-loading the diabetic foot for ulcer prevention and healing

Retrospective and prospective studies have shown that elevated plantar pressure is a causative factor in the development of many plantar ulcers in diabetic patients and that ulceration is often a precursor of lower-extremity amputation. Herein, we review the evidence that relieving areas of elevated plantar pressure (off-loading) can prevent and heal plantar ulceration.There is no consensus in the literature concerning the role of off-loading through footwear in the primary or secondary prevention of ulcers. This is likely due to the diversity of intervention and control conditions tested, the lack of information about off-loading efficacy of the footwear used, and the absence of a target pressure threshold for off-loading. Uncomplicated plantar ulcers should heal in 6 to 8 weeks with adequate off-loading. Total-contact casts and other nonremovable devices are most effective because they eliminate the problem of nonadherence to recommendations for using a removable device. Conventional or standard therapeutic footwear is not effective in ulcer healing. Recent US and European surveys show that there is a large discrepancy between guidelines and clinical practice in off-loading diabetic foot ulcers. Many clinics continue to use methods that are known to be ineffective or that have not been proved to be effective while ignoring methods that have demonstrated efficacy.A variety of strategies are proposed to address this situation, notably the adoption and implementation of recently established international guidelines, which are evidence based and specific, by professional societies in the United States and Europe. Such an approach would improve the often poor current expectations for healing diabetic plantar ulcers.     

Expression of natural antimicrobial peptide beta-defensin-2 and Langerhans cell accumulation in epidermis from human non-healing leg ulcers

Chronic wounds like venous calf and diabetic foot ulcers are frequently contaminated and colonized by bacteria and it remains unclear whether there is sufficient expression of defensins and recruitment of epidermal Langerhans cells in the margin of ulcer compared to normal skin. The aim of this study was to examine immunohistochemically the expression of beta-defensin-2 (hBD2), GM-CSF, VEGF growth factors and accumulation of CD1a+ Langerhans cells (LC) in epidermis from chronic skin ulcers and to compare it to normal skin from the corresponding areas. Studies were carried out in 10 patients with diabetic foot, 10 patients with varicous ulcers of the calf and 10 patients undergoing orthopedic surgery (normal skin for control). Biopsy specimens were immunostained using specific primary antibodies, LSAB+ kit based on biotin-avidin-peroxidase complex technique and DAB chromogen. Results were expressed as a mean staining intensity. Statistical analysis of staining showed significantly higher staining of hBD2 in both normal and ulcerated epidermis from foot sole skin compared to calf skin (normal and ulcerated, p < 0.05). Chronic ulcers showed the same expression of hBD2 as normal skin. There was significantly lower accumulation of CD1a+ LC in normal epidermis from foot sole skin compared to normal calf skin (p<0.05). Accumulation of CD1a+ LC and GM-CSF upregulation at the border area of diabetic foot ulcer and reduction of LC concentration at the margin of venous calf ulcer compared to normal skin were observed. It seems that normal calf and sole epidermis is, unlike in the mechanisms of innate immunity, influenced by the different keratinocyte turnover and bacterial flora colonizing these regions. Insufficient upregulation of hBD2 in both diabetic foot and venous calf ulcers may suggest the pathological role of this protein in the chronicity of ulcers.     

干细胞治疗糖尿病足的实验研究进展

糖尿病足是指因糖尿病血管病变和（或）神经病变及感染等综合因素,导致I陵性进行性波及肢体大、中、微血管,引起足部疼痛、皮肤深溃疡或肢体坏疽的一种病变,是糖尿病的严重并发症之一。临床治疗非常棘手,难以取得令人满意的疗效,最终导致截肢甚至危及病患生命。因此,临床上迫切需要找到创伤小、易接受、疗效好的新的治疗方法。干细胞具有高度增殖和分化成为体内各种细胞的潜能,其可塑性强,为糖尿病足的治疗带来新前景,目前是国内外学者研究的热点之一。该文就干细胞移植治疗糖尿病足的实验研究进展作一综述。     

A Diabetic Emergency One Million Feet Long: Disparities and Burdens of Illness among Diabetic Foot Ulcer Cases within Emergency Departments in the United States, 2006–2010

Objectives

To evaluate the magnitude and impact of diabetic foot ulcers (DFUs) in emergency department (ED) settings from 2006–2010 in the United States (US).

Methods

This cross-sectional study utilized Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) National Emergency Department Sample (NEDS) discharge records of ED cases among persons ≥18 years with any-listed diagnosis of DFUs. Multivariable analyses were conducted for clinical outcomes of patient disposition from the ED and economic outcomes of charges and lengths of stay based upon patient demographic and socioeconomic factors, hospital characteristics, and comorbid disease states.

Results

Overall, 1,019,861 cases of diabetic foot complications presented to EDs in the US from 2006–2010, comprising 1.9% of the 54.2 million total diabetes cases. The mean patient age was 62.5 years and 59.4% were men. The national bill was $1.9 billion per year in the ED and $8.78 billion per year (US$ 2014) including inpatient charges among the 81.2% of cases that were admitted. Clinical outcomes included mortality in 2.0%, sepsis in 9.6% of cases and amputation in 10.5% (major-minor amputation ratio of 0.46). Multivariable analyses found that those residing in non-urban locations were associated with +51.3%, +14.9%, and +41.4% higher odds of major amputation, minor amputation, and inpatient death, respectively (p<0.05). Medicaid beneficiaries incurred +21.1% and +25.1% higher odds for major or minor amputations, respectively, than Medicare patients (p<0.05). Persons within the lowest income quartile regions were associated with a +38.5% higher odds of major amputation (p<0.05) versus the highest income regions.

Conclusion

Diabetic foot complications exact a substantial clinical and economic toll in acute care settings, particularly among the rural and working poor. Clear opportunities exist to reduce costs and improve outcomes for this systematically-neglected condition by establishing effective practice paradigms for screening, prevention, and coordinated care.