Neuropathic Diabetic Foot Ulcers Research Articles

Treatment of diabetic foot ulcers with dehydrated amniotic membrane allograft: a prospective case series.

A diabetic foot ulcer (DFU) is one of the many potential complications associated with diabetes. If not effectively and rapidly treated, DFUs can result in lower extremity amputations. This prospective case series aimed to assess the effectiveness of a dehydrated amniotic-derived tissue allograft (DAMA), with regards to time to wound closure and total number of applications. Patients were recruited with a neuropathic non-healing DFU(s) despite standard care for at least 4 weeks before the study. The number of DAMA applications and time between applications was based on the physician's judgment. For the majority of patients (n=13/14), offloading, usually total contact casting (TCC), was used in conjunction with DAMA. Wounds were assessed, measured, and photographed every 1-2 weeks. Cases included 14 patients (11 men, 3 women; mean age 56.7±9.1 years) with 15 non-healing neuropathic DFUs with a mean baseline wound area of 6.5±11.6cm2 (median: 2.2cm2; range: 0.1-44.2cm2) and mean volume of 4.3±10.9cm3 (median: 0.3cm3; range: 0-39.8cm3). All patients in this series achieved complete wound closure within a median time of 5 weeks (range: 1-14 weeks). Wound area was reduced by a median of 58.3% at week 1 and 74.1% at week 3, and volume by a median of 62.8% at week 1, 97.4% at week 3 and by a median of 100% at week 5 and all time points thereafter. Patients received a median of 2 DAMA applications (range: 1-11). In those that required more than 1 application (n=12), DAMA was applied at intervals of 1 week (n=3) or ≥2 weeks (n=9). Smaller wounds (areas <2.2cm2) closed rapidly (<1 month, 1-2 applications), whereas larger wounds (>2.2cm2) required >2 weekly/biweekly applications. The use of DAMA, particularly when coupled with TCC, led to wound closure of DFUs in all patients in this case series, including complex patients with DFUs of ≥1 year in duration, lack of prior response to conservative treatment measures, area >10cm2 and/or multiple comorbidities. Prospective randomised trials would help to elucidate the precise role of DAMA in these encouraging results. Derma Sciences, Inc. (Princeton, NJ) funded editorial support services.

A Pilot Study to Evaluate the Efficacy of Class IV Lasers on Nonhealing Neuroischemic Diabetic Foot Ulcers in Patients With Type 2 Diabetes

Diabetic foot ulcers (DFUs) represent a disabling complication of diabetes that has a devastating impact on the quality of life and predict lower-limb amputation and premature mortality (1). Despite best practice, 30–40% of DFUs do not heal within 12–20 weeks (2). Novel therapeutic agents have been tested in clinical trials, and it has been estimated that ∼30–50% of patients with neuropathic DFUs receiving these new treatments have healed by 12–20 weeks (3). Laser therapy, delivered with devices emitting one or two wavelengths, has been reported as an adjunctive procedure that promotes the healing of chronic diabetic wounds by increasing the blood flow and the release of growth factors and by reducing the inflammation (4). In this pilot study, we have been the first to investigate the efficacy of an advanced class IV …

Illustration of Cost Saving Implications of Lower Extremity Nerve Decompression to Prevent Recurrence of Diabetic Foot Ulceration.

The US diabetic foot ulcer (DFU) incidence is 3-4% of 22.3 million diagnosed diabetes cases plus 6.3 million undiagnosed, 858 000 cases total. Risk of recurrence after healing is 30% annually. Lower extremity multiple nerve decompression (ND) surgery reduces neuropathic DFU (nDFU) recurrence risk by >80%. Cost effectiveness of hypothetical ND implementation to minimize nDFU recurrence is compared to the current $6.171 billion annual nDFU expense. A literature review identified best estimates of annual incidence, recurrence risk, medical management expense, and noneconomic costs for DFU. Illustrative cost/benefit calculations were performed assuming widespread application of bilateral ND after wound healing to the nDFU problem, using Center for Medicare Services mean expense data of $1143/case for unilateral lower extremity ND. Calculations use conservative, evidence-based cost figures, which are contemporary (2012) or adjusted for inflation. Widespread adoption of ND after nDFU healing could reduce annual DFU occurrences by at least 21% in the third year and 24% by year 5, representing calculated cost savings of $1.296 billion (year 3) to $1.481 billion (year 5). This scenario proffers significant expense reduction and societal benefit, and represents a minimum 1.9× return on the investment cost for surgical treatment. Further large cost savings would require reductions in initial DFU incidence, which ND might achieve by selective application to advanced diabetic sensorimotor polyneuropathy (DSPN). By minimizing the contribution of recurrences to yearly nDFU incidence, ND has potential to reduce by nearly $1 billion the annual cost of DFU treatment in the United States.

Cost-effectiveness of clostridial collagenase ointment on wound closure in patients with diabetic foot ulcers: economic analysis of results from a multicenter, randomized, open-label trial.

BackgroundApproximately 10%–15% of people with diabetes develop at least one foot ulcer during their lifetime. Treatment of diabetic foot ulcers (DFUs) represents a significant economic burden. Enzymatic debridement with clostridial collagenase ointment (CCO) can be used to remove necrotic tissue from wounds. This study examined the impact of CCO as an effective adjunct therapy to serial sharp debridement (SSD) and assessed the cost-effectiveness of CCO compared with standard DFU treatments over 1 year.MethodsAdults 18 years or older with a diagnosis of type 1 or type 2 diabetes who had a neuropathic DFU were enrolled in a 12-week, randomized, open-label trial. Patients were randomly assigned to either treatment with CCO + SSD or to investigator-selected supportive care + SSD (Control). A 3-state Markov model with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of healed-wound weeks and the expected DFU cost per patient. The 3 states included unhealed, healed, and death. Results were extrapolated to 1 year to estimate the number of healed-wound weeks per treatment and the average cost to achieve epithelialization. The perspective of the analysis was that of the payer, specifically, the third party payer.ResultsThe study sample included 55 patients (28 in CCO group; 27 Control). The majority were men (74.5%) with a mean age of 57.9 years. Projected healing rates were greater for the CCO + SSD group compared to Control (89% vs. 80%, respectively). The expected number of epithelialized weeks accumulated over 1 year was 25% greater in the CCO + SSD group than for Control (35 vs. 28 weeks, respectively). Over a 1-year time horizon, the expected cost per DFU was greater in the Control group than the CCO group ($2,376 vs. $2,099, respectively). The estimated cost per ulcer-free week was 40% higher for Control ($85/closed-wound week) than for CCO + SSD ($61/closed-wound week).ConclusionsCCO + SSD therapy is a cost-effective method of debridement in the management of patients with DFUs, providing better outcomes at a lower cost. Further high quality trials are needed to confirm this finding.Trial registrationThis study was registered at ClinicalTrials.gov as NCT01408277.Electronic supplementary materialThe online version of this article (doi:10.1186/s13047-015-0065-x) contains supplementary material, which is available to authorized users.

Clinical and Economic Assessment of Diabetic Foot Ulcer Debridement with Collagenase: Results of a Randomized Controlled Study

BackgroundDespite significant advances, the treatment of diabetic foot ulcers (DFUs) remains a major therapeutic challenge for clinicians, surgeons, and other health care professionals. There is an urgent need for new strategies with clinically effective interventions to treat DFUs to reduce the burden of care in an efficient and cost-effective way. ObjectiveThis randomized trial evaluated and compared the clinical effectiveness, tolerability, and costs of clostridial collagenase ointment (CCO) debridement to that of debridement using saline moistened gauze (SMG) and selective sharp debridement for the treatment of DFUs. MethodsRandomized, controlled, parallel group, multicenter, open-label, 12-week study of 48 patients with neuropathic DFUs randomized to 4 weeks of treatment with either CCO or SMG after baseline surgical debridement. The primary end point was the condition of the ulcer bed at the end of treatment as measured using a standardized wound assessment tool. Secondary end points were the percentage of reduction in wound area and therapeutic response rates. Adverse events were monitored for the tolerability analysis. In addition, a comparative cost-effectiveness analysis was performed from the perspective of the Centers for Medicare and Medicaid Services as a payer. ResultsBoth the CCO and SMG groups had significantly improved wound assessment scores after 4 weeks of treatment (CCO, −2.5, P = 0.007; SMG, −3.4, P = 0.006). Only CCO treatment resulted in a statistically significant decrease from baseline in the mean wound area at the end of treatment (P = 0.0164) and at the end of follow-up (P = 0.012). In addition, the CCO group exhibited a significantly better response rate at the end of follow-up compared with the SMG group (0.92 vs 0.75, P < 0.05). Reported adverse events were similar between the 2 treatment groups. None of the reported adverse events were considered to be related to treatment. The economic analysis indicated that the direct mean costs per responder in the physician office setting of care were $832 versus $1042 for the CCO group versus the SMG group, whereas the direct mean costs per responder in the hospital outpatient department setting were $1607 versus $1980. ConclusionsCCO treatment provides equivalent debridement of DFUs similar to SMG while fostering better progress toward healing as measured by decreasing wound area over time and improved response rates at the end of follow-up. In addition, CCO yields a more favorable cost-effectiveness ratio in both the physician office and hospital outpatient department settings of care. ClinicalTrials.gov identifier: NCT01056198.

US Skin Disease Assessment: Ulcer and Wound Care

Chronic ulcers are a growing cause of patient morbidity and contribute significantly to the cost of health care in the United States. The most common etiologies of chronic ulcers include venous leg ulcers (VLUs), pressure ulcers (PrUs), diabetic neuropathic foot ulcers (DFUs), and leg ulcers of arterial insufficiency. Chronic wounds account for an estimated $6 to $15 billion annually in US health care costs; however, it is difficult to get accurate measurements on this, because these patients are often seen in a variety of settings or simply fail to access the health care system.

A Prospective Study of the PUSH Tool in Diabetic Foot Ulcers

The purpose of this study was to examine the predictive validity of Pressure Ulcer Scale for Healing (PUSH; v. 3.0) in monitoring healing of neuropathic foot ulcers in patients with diabetes mellitus. This is a 13-week descriptive, prospective study describing the trajectory of change over time and the time-to-heal associated with PUSH scores. The study monitored a convenience sample of 18 subjects with Wagner 2 or greater neuropathic, nonischemic ulcers on the plantar surface of the foot, which healed completely over a 13-week follow-up period. Every 2 weeks, the study ulcers were evaluated via PUSH. Healing was defined as complete reepithelialization. PUSH scores were modeled using a piecewise linear regression. PUSH values decreased significantly (P < .0001) at a rate of 0.6656 per week, until 2 weeks before healing, and then decreased significantly (P < .0001) at a rate of 2.2496 per week for the last 2 weeks of healing. Conversely, the time-to-heal (in weeks) increased significantly (P < .0001), at a rate of 0.6412 per each unit increase in PUSH for PUSH values of 4 or less, and then significantly (P < .0001) increased at a rate of 1.072 for PUSH values greater than 5. In predicting time-to-heal, the subitem of length × width alone (R = 0.81) is comparable to the total PUSH score (R = 0.76). Individually, exudate (R = 0.36) and tissue type (R = 0.42) are not nearly as useful as length × width. Our findings indicate that PUSH scores significantly decrease over time in healing neuropathic diabetic foot ulcers (DFUs) that have no arterial etiologic component. Findings also suggest that total PUSH scores predict time-to-heal for DFU. We showed that a DFU with a PUSH score of 10 would be expected to heal in 8.8 weeks (95% CI: 7.4-10.2) and a DFU with a PUSH score of 4 in 2.6 weeks (95% CI: 1.88-3.25). Finally, measurements of size alone predict healing time for neuropathic DFU. This finding could greatly simplify clinical assessments.

Vascular Endothelial Growth Factor Delivery via Gene Therapy for Diabetic Wounds: First Steps

Nonhealing wounds are a major complication of diabetes. Diabetic foot ulcerations (DFUs) affect 12–15% of patients with diabetes mellitus during their lifetime (Reiber et al., 1995). As a result, DFUs impair quality of life, cause significant morbidity, and account for 20% of all diabetes-related hospital admissions. A majority of neuropathic DFUs fail to heal even after 5 months of therapy, and foot ulcers precede 85% of nontraumatic amputations in patients with diabetes, indicating a need for better therapy (Margolis et al., 1999).

Diabetic foot ulcer burden may be modified by high‐dose atorvastatin: A 6‐month randomized controlled pilot trial

Diabetic foot ulcers (DFUs) are common complications of diabetes mellitus (DM), with a complex pathogenesis. Treatment is difficult and no single treatment with measurable clinical impact is available. In the present clinical pilot trial, we investigated whether statins could be of use against some of the pathogenic factors in DFUs. Thirteen diabetic patients (10 men; 11 with Type 2 DM; mean age 64 years; mean duration of DM 18 years) with neuropathic DFUs <4 months were randomized to treatment with either 10 mg (six patients; six ulcers) or 80 mg (seven patients; nine ulcers) atorvastatin for 6 months in addition to conventional DFU care (i.e. prompt debridement, DFU pressure relief, and management of any underlying infection). There were no significant differences in background factors (i.e. HbA1c 8.9%, micro- and macrovascular complications, concomitant medications) or DFU characteristics (duration, surface area, grading) between the two groups. All ulcers in the group receiving 10 mg atorvastatin healed, compared with six of nine ulcers in the group receiving 80 mg atorvastatin (NS). However, two previously healed DFUs recurred and six new DFUs developed in the low-dose group compared with none and one, respectively, in the high-dose group (P = 0.048). There was a significant decrease in C-reactive protein (-1.5 mg/L; P = 0.044) and a non-significant trend towards beneficial effects on lipids and the ankle-arm blood pressure index in the high-dose compared with the low-dose group. We observed a possible beneficial effect of 6-months high-dose atorvastatin on DFUs, which should be tested in appropriately sized prospective studies.

034 The Effectiveness of Topical Becaplermin for the Treatment of Diabetic Neuropathic Foot Ulcer

The goal of this study was to specifically estimate the effectiveness of Becaplermin, which is recombinant human platelet derived growth factor (rhPDGF). This was the first FDA-approved growth factor therapy for the treatment of diabetic neuropathic foot ulcer (DNFU). The previously published pivotal trials have shown that those who used rhPDGF were about 35%(i.e., a relative risk (RR) of about 1.35) more likely to heal by the 20th week of care. In our study treatment effectiveness was estimated in a retrospective cohort study, controlling for treatment selection bias using propensity scores derived from logistic regression. The cohort that we studied were patients with a DNFU treated at a Curative Health Services-affiliated wound care center between 1998–2004. We noted 25,098 individuals with a DNFU and overall about 10% received rhPDGF. We were able to successfully create a propensity score model such that the distributions of patient age and gender, wound duration, wound area, wound grade, treating center, and wound location were evenly balanced between those who received rhPDGF and those who did not. The RR for a wound to heal after treatment with rhPDGF as compared to standard care after 20 weeks of care at a wound care center was 1.33 (1.28, 1.38). With respect to amputation, the RR for having an amputation after receiving rhPDGF was 0.86 (0.77, 0.97). In conclusion, rhPDGF is more effective than standard therapy in both helping a wound to heal and preventing amputation. The effectiveness of rhPDGF with respect to getting a wound to heal is similar “in this real-world setting” as the efficacy estimates from the previously published randomized controlled trials. Acknowledgments: Funding for this study was provided by Ethicon to the Trustees of the University of Pennsylvania.

Technical Notes and Tips: Excision of Metatarsal Bone and Metatarso-Phalangeal (MTP) Joint in Neuropathic Diabetic Foot Ulcer

Technical Notes and Tips: Excision of Metatarsal Bone and Metatarso-Phalangeal (MTP) Joint in Neuropathic Diabetic Foot Ulcer

Effectiveness of recombinant human platelet‐derived growth factor for the treatment of diabetic neuropathic foot ulcers

The goal of this study was to estimate the effectiveness in actual clinical practice of recombinant human platelet-derived growth factor (rhPDGF) for the treatment of diabetic neuropathic foot ulcer (DNFU). Previously published pivotal trials have shown that by the 20th week of care 35 percent more ulcers healed in the group randomized to receive rhPDGF than those who did not receive rhPDGF (i.e., a relative risk [RR] of about 1.35). This represents an estimate of the efficacy of rhPDGF under the tightly controlled conditions of randomized clinical trials. Treatment effectiveness under standard clinical practice was estimated in a retrospective cohort study, controlling for treatment selection bias using propensity scores. We noted 24,898 individuals with a DNFU, of whom 9.6 percent received rhPDGF. We successfully created a propensity score model that evenly balanced many wound characteristics between those who received rhPDGF and those who did not. We created five groups, which varied from those least likely to receive rhPDGF to those most likely to receive rhPDGF. The RR, controlling for the propensity, to receive rhPDGF for a healed wound after treatment with rhPDGF as compared with standard care was 1.32 (1.22, 1.38). With respect to amputation, the RR for undergoing amputation after receiving rhPDGF was 0.65 (0.54, 0.78) as compared with those who did not receive rhPDGF. Within the limitations of our study, rhPDGF is more effective than standard therapy in both helping a wound to heal and preventing amputation, and its effect is similar to the efficacy estimates from previously published randomized controlled trials.

018 Healing Rate for Diabetic Neuropathic Foot Ulcer

The goal of this study was to benchmark by year the likelihood that an individual with a diabetic neuropathic foot ulcer (DNFU) will heal. We observed these rates over a more than 10 year period (1988–2000). For this study, we designed a cohort study within the multi‐center Curative Health System wound care network of diabetics who have DNFU and whether they healed by the 20th week of care stratified by calendar year.In total, we evaluated 27, 193 individuals with a DNFU. For, example, between 1988 and 1990 approximately 66% of patients did not heal. By 1999 this percentage had decreased to 49%. Most of the change in improvement occurred before 1998. We noted that the change in the rate of failure to heal was very closely associated with an increase over time in the proportion of patients seen with wounds identified as prognostically favorable as determined by a previously published prognostic model (i.e., individuals with wounds ≤ 2 cm2, wound less ≤2 months old, and wound of grade less ≤ 2). Among those most likely to heal, the likelihood of failing to heal went from 62% in 1990 to 32% in 2000. Therefore, the overall decrease in likelihood that a patient with a DNFU would not heal is not just due to the enrollment of less severe cases. There was, however, no real improvement in the likelihood that those with wounds that were unlikely to heal over time and fewer patients with these wounds sought care over time.In conclusion, those with a DFFU seeking care are more likely to heal today than 10 years ago. This improvement is related to the fact that individuals are seeking care when their wounds are most easily treated and these wounds are now more likely to heal. Unfortunately, those with the most severe wounds are not anymore likely to heal today than they were 10 years ago.

Diabetic Neuropathic Foot Ulcers: Predicting Healing

Foot ulcers are a common complication of diabetes, especially in persons with neuropathy or arterial insufficiency. Standard therapy consists of debridement, moist dressings, and use of a protective device (e.g., special footgear, crutches) to reduce trauma to the wound. To develop a model for predicting which ulcers are unlikely …