Economic benefit of a novel dual-mode ambulatory compression device for treatment of chronic venous leg ulcers in a randomized clinical trial.

BACKGROUND: Limb compression is a key component of protocols used to heal venous leg ulcers (VLUs). A novel ambulatory pneumatic compression device was tested in comparison with multilayered bandage (MLB) compression systems for the treatment of VLUs in a prospective randomized clinical trial. METHODS: Patients with VLUs measuring 1.5 to 50 cm2 with duration of 1 to 24 months were randomized to treatment with a pneumatic compression device, the ACTitouch adaptive compression therapy (ACT) system (Tactile Medical, Minneapolis, Minn), or MLB. The ACT group patients were seen in the clinic at weeks 1, 2, 4, 6, 9, 12, and 16 or until wounds healed; the MLB group was seen weekly for bandage and dressing changes for 16 weeks or until wounds healed. All other aspects of VLU care were standardized between the two groups. The primary study objective was to compare the VLU percentage area reduction at 16 weeks in the ACT group compared with the MLB group. RESULTS: There were 56 patients randomized to treatment with ACT (n = 26) or MLB (n = 30). In the ACT group, five patients exited because of skin or wound problems related to the ACT device and five withdrew because of the inconvenience of using the device. Therefore, the trial was halted before full randomization so improvements to the ACT device could be made. Data collected on 42 patients who were able to tolerate treatment for the 16-week study period (per protocol group) showed that both groups experienced similar rates of wound healing. In the per protocol population, the percentage area size reduction was greater for the ACT group compared with the MLB group (83.8% vs 70.5%, respectively), whereas no significant differences were noted in the percentage of wounds that healed by 16 weeks (60.0% vs 63.0%, respectively). CONCLUSIONS: In this truncated clinical trial, a novel dual-mode ambulatory compression device, when tolerated, achieved wound healing results similar to those with MLB for chronic VLUs. The device requires modifications to improve the patient's comfort and ease of use. However, this mode of therapy appears to have promise for improving the cost-effectiveness of treatment for chronic VLUs.

A Prospective, Randomized, Multicenter, Controlled Evaluation of the Use of Dehydrated Amniotic Membrane Allograft Compared to Standard of Care for the Closure of Chronic Diabetic Foot Ulcer.

UNLABELLED: Delayed closure of foot ulcers is a primary factor leading to lower extremity amputation in patients with diabetes, creating great demand for products or therapies to accelerate the rate of wound closure in this population. This study (ClinicalTrials.gov Identifier: NCT02209051) was designed to evaluate dehydrated amniotic membrane allograft (DAMA) (AMNIOEXCEL, Derma Sciences Inc, Princeton, NJ) plus standard of care (SOC) compared to SOC alone for the closure of chronic diabetic foot ulcers (DFUs). MATERIALS AND METHODS: This prospective, open-label, randomized, parallel group trial was implemented at 8 clinical sites in the United States. Eligibility criteria included adults with type 1 or type 2 diabetes mellitus who have 1 or more ulcers with a Wagner classification of grade 1 or superficial 2 measuring between 1 cm2 and 25 cm2 in area, presenting for more than 1 month with no signs of infection/osteomyelitis; ABI > 0.7; HbA1c Less than 12%; and serum creatinine less than 3.0 mg/dL. Eligible subjects were randomized (1:1) to receive either SOC alone (n = 14) or DAMA+SOC (n = 15) until wound closure or 6 weeks, whichever occurred first. The endpoint was the proportion of subjects with complete wound closure (defined as complete reepithelialization without drainage or need for dressings). RESULTS: Thirty-five percent of subjects in the DAMA+SOC cohort achieved complete wound closure at or before week 6, compared with 0% of the SOC alone cohort (intent-to-treat population, P = 0.017). There was a more robust response noted in the per protocol population, with 45.5% of subjects in the DAMA+SOC cohort achieving complete wound closure, while 0% of SOC-alone subjects achieved complete closure (P = 0.0083). No treatment-related adverse events were reported. CONCLUSION: The results suggest DAMA is safe and effective in the management of DFUs, but additional research is needed.

Limb salvage using advanced technologies: a case report.

Patients with severe acute and chronic lower extremity wounds often present a significant challenge in terms of limb salvage. In addition to control of infection, assuring adequate perfusion and providing standard wound care, advanced modalities are often required to facilitate final wound closure. We herein present a case study on a diabetic patient with gangrene and necrotising soft-tissue infection who underwent a forefoot pedal amputation to control the sepsis. Despite his non invasive vascular studies demonstrating poor healing potential at this level, he was not deemed suitable for revascularisation by our vascular surgeons and ankle-level amputation was recommended. Nonetheless, over a 5-month period using multiple advanced wound care therapies, wound closure was ultimately achieved.

Clinical and economic assessment of diabetic foot ulcer debridement with collagenase: results of a randomized controlled study.

BACKGROUND: Despite 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. OBJECTIVE: This 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. METHODS: Randomized, 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. RESULTS: Both 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. CONCLUSIONS: CCO 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.

Heparin-induced thrombocytopenia in the setting of perioperative bridging for podiatric surgery: a case report.

Heparin is an anticoagulant commonly used to treat and prevent deep venous thrombosis. Heparin-induced thrombocytopenia and possible thrombosis are serious complications associated with its use. This can occasionally complicate treatment of patients undergoing podiatric surgery. Heparin-induced thrombocytopenia is often not immediately recognized and is underreported in podiatric medicine literature. The goal of this case report is to highlight the multiple risk factors associated with the development of heparin-induced thrombocytopenia and to aid with early recognition, understanding of pathogenesis, and treatment options.

Prevalence of equinus in diabetic versus nondiabetic patients.

BACKGROUND: There are no conclusive data to support the contention that diabetic patients have an increased frequency of ankle equinus compared with their nondiabetic counterparts. Additionally, a presumed contributing cause of foot ulceration is ankle joint equinus. Therefore, we sought to determine whether persons with diabetes have a higher prevalence of ankle joint equinus than do nondiabetic persons. METHODS: A prospective pilot survey of 102 outpatients (43 diabetic and 59 nondiabetic) was conducted. Demographic and historical data were obtained. Each patient underwent a standard lower-extremity examination, including the use of a biplane goniometer to measure ankle joint range of motion. RESULTS: Equinus, defined as ankle dorsiflexion measured at 0° or less, was found in 24.5% of the overall population. In the diabetes cohort, 16 of 43 patients (37.2%) were affected compared with 9 of 59 nondiabetic participants (15.3%) (P = .011). There was a threefold risk of equinus in the diabetic population (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.28-8.44; P < .013). The equinus group had a history of ulceration in 52.0% compared with 20.8% of the nonequinus group (P = .003). Equinus, therefore, imparted a fourfold risk of ulceration (OR, 4.13; 95% CI, 1.58-10.77; P < .004). We also found a 2.8 times risk of equinus in patients with peripheral neuropathy (OR, 2.8; 95% CI, 1.11-7.09; P < .029). CONCLUSIONS: Equinus may be more prevalent in diabetic patients than previously reported. Although we cannot prove causality, we found a significant association between equinus and ulceration.

Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers.

We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GAM501) compared with Standard of Care (SOC) in patients with 1.5-10.0 cm(2) chronic diabetic neuropathic foot ulcers that healed <30% during Run-in. Wound size was assessed by planimetry of acetate tracings and photographs in 124 patients. Comparison of data sets revealed that acetate tracings frequently overestimated areas at some sites. For per-protocol analysis, 113 patients qualified using acetate tracings but only 82 qualified using photographs. Prior animal studies suggested that collagen alone would have little effect on healing and would serve as a negative control. Surprisingly trends for increased incidence of complete closure were observed for both GAM501 (41%) and FCG (45%) vs. Standard of Care (31%). By photographic data, Standard of Care had no significant effect on change in wound radius (mm/week) from during Run-in to Week 1 (-0.06 ± 0.32 to 0.78 ± 1.53, p=ns) but both FCG (-0.08 ± 0.61 to 1.97 ± 1.77, p<0.002) and GAM501 (-0.02 ± 0.58 to 1.46 ± 1.37, p<0.002) significantly increased healing rates that gradually declined over subsequent weeks. Both GAM501 and FCG appeared to be safe and well tolerated, and alternate dosing schedules hold promise to improve overall complete wound closure in adequately powered trials.

A case history of multimodal therapy in healing a complicated diabetic foot wound: negative pressure, dermal replacement and pulsed radio frequency energy therapies.

Advanced multimodal therapies are being used with increasing frequency in the management of difficult or complex wounds. Although the primary goal remains to expedite complete healing, secondary goals include avoidance of superimposed infection, repeated hospitalisations and subsequent amputations. We describe a case involving a limb- and life-threatening necrotising infection in a diabetic patient in which we successfully applied negative pressure wound therapy, dermal replacement therapy and pulsed radio frequency energy to achieve definitive healing. Further study is warranted to elucidate the most effective combinations of such therapies to promote healing of similarly complex wounds.

Treatment of nonhealing diabetic foot ulcers with a platelet-derived growth factor gene-activated matrix (GAM501): results of a phase 1/2 trial.

The results from a Phase 1/2 study of a replication-defective adenovirus encoding human platelet-derived growth factor (PDGF)-B formulated in a bovine collagen (Ad-5PDGF-B; 2.6% collagen; GAM501) gel for nonhealing neuropathic diabetic foot ulcers is reported. The primary objectives of the study were to evaluate the safety, maximum-tolerated dose, and preliminary biological activity of GAM501. Fifteen patients enrolled into the study with chronic, nonhealing ulcers received either a single administration of GAM501 at one of three dose levels, or up to four administrations of GAM501 at 1-week intervals. All patients received standard of care treatment including debridement and were required to wear an off-loading shoe. GAM501 was found to be safe and well tolerated with no evidence of systemic or local toxicity at all doses so no maximum-tolerated dose was reached. Serum antibody titers to platelet-derived growth factor-B homodimer and collagen were negative and adenoviral DNA was not detected in the blood. In the 12 patients that completed the study, ulcer closure was observed by Month 3 in 10 patients, seven of whom received a single application of GAM501. In conclusion, GAM501 did not appear to have any toxicity at doses that showed biological activity. GAM501 holds promise as a potentially effective treatment for nonhealing diabetic foot ulcers.

Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study.

This 12-week, prospective, randomised, controlled multi-centre study compared the proportion of healed diabetic foot ulcers and mean healing time between patients receiving acellular matrix (AM) (study group) and standard of care (control group) therapies. Eighty-six patients were randomised into study (47 patients) and control (39 patients) groups. No significant differences in demographics or pre-treatment ulcer data were calculated. Complete healing and mean healing time were 69.6% and 5.7 weeks, respectively, for the study group and 46.2% and 6.8 weeks, respectively, for the control group. The proportion of healed ulcers between the groups was statistically significant (P = 0.0289), with odds of healing in the study group 2.7 times higher than in the control group. Kaplan-Meier survivorship analysis for time to complete healing at 12 weeks showed a significantly higher non healing rate (P = 0.015) for the control group (53.9%) compared with the study group (30.4%). After adjusting for ulcer size at presentation, which was a statistically significant covariate (P = 0.0194), a statistically significant difference in non healing rate between groups was calculated (P = 0.0233), with odds of healing 2.0 times higher in the study versus control group. This study supports the use of single-application AM therapy as an effective treatment of diabetic, neuropathic ulcers.

Cell proliferation induction: healing chronic wounds through low-energy pulsed radiofrequency.

Chronic lower extremity wounds are a major source of morbidity and health care expenditure across the world. In the last decade, numerous advanced modalities have become available that can help expedite wound healing when standard wound care modalities are unsuccessful. In this case report, the authors present their early experience with one such modality that uses pulsed radiofrequency energy to initiate cell proliferation induction in chronic lower extremity wounds of different etiologies that had failed to respond to standard therapy.