Efficacy of a 3D Electrospun Synthetic Polymer Matrix on Hard-to-Heal Wounds.

INTRODUCTION: The aim of this study was to evaluate the efficacy of a 3D electrospun synthetic polymer matrix (3DESPM) on hard-to-heal wounds. MATERIALS AND METHODS: This prospective case series took place at four sites. The primary endpoints were the percentage area reduction (PAR) in wound area at four and eight weeks. Secondary endpoints included time to heal (Kaplan-Meier analysis) and the proportion of healed wounds at 12 weeks. After applying 3DESPM, the physician applied sterile saline, as appropriate, to adhere the matrix to the wound bed and facilitate the polymer degradation process. A nonadherent dressing, a secondary dressing, and additional bandages (as needed) were then applied. The physician left the product on the wound until complete degradation was observed, as appropriate, and reapplied, as appropriate. Combination advanced therapies were applied, per physician discretion. RESULTS: Thirty-eight patients (mean age: 64.3 years [SD: 17.6]) with 50 wounds (35 chronic, 70%) participated. The mean number of comorbidities per patient was 4.4 (2.3). All wounds received 3DESPM; 12 wounds (24%) received combination therapies; and 38 wounds (76%) completed the study. The mean (SD) PAR at four and eight weeks was 67.6% (38%) and 80% (35%), respectively. Thirty-three wounds (66%) healed at 12 weeks. The Kaplan-Meier mean time to heal for all wounds was 49.0 days (95% confidence interval: 41.3-56.7). CONCLUSIONS: In a complex patient population with severe comorbidities and heterogeneous wounds, 3DESPM appeared to accelerate the stalled healing process to contribute to wound closure. Further investigation of 3DESPM on a larger patient population and in a controlled setting is pending.

Guidelines for the use of topical oxygen therapy in the treatment of hard-to-heal wounds based on a Delphi consensus.

A growing body of evidence supports the use of topical oxygen therapy (TOT) in the treatment of diabetic foot ulcers (DFUs). In addition, anecdotal evidence suggests that topical oxygen may be effective in the treatment of other wound types. In May 2021, experts in the field of wound healing from across the US assembled in New Orleans for the inaugural Leaders in Wound Healing conference. In an interactive session dedicated to TOT, several physicians presented and debated the evidence for TOT. Experts in the audience also shared their experiences in treating patients with TOT. The consensus of the experts recommended the use of TOT in DFUs and supported payer reimbursement for the modality. However, they stressed the need for a guidance document on the use of TOT in patients with hard-to-heal wounds. Following the conference, a Delphi method was employed to establish consensus guidelines for prescribing TOT. A multidisciplinary panel of 24 wound experts (15 wound specialists, six vascular surgeons, one plastic surgeon, one critical care provider and one PhD researcher) participated in two rounds of questionnaires. The Delphi survey questions focused on the indications for topical oxygen, when to prescribe the therapy, pretreatment work-up, visit frequency and length of therapy. A clinical workflow algorithm was also included as part of the Delphi. After two rounds, the Delphi participants were able to reach consensus of >77% on when to prescribe topical oxygen, the wound types that may benefit from the therapy, pretreatment wound preparation and work-up and length of therapy. The goal of the guidelines is to standardise the use of topical oxygen and inform further research efforts.

Podiatrist care and outcomes for patients with diabetes and foot ulcer.

We examined whether outcomes of care (amputation and hospitalisation) among patients with diabetes and foot ulcer differ between those who received pre-ulcer care from podiatrists and those who did not. Adult patients with diabetes and a diagnosis of a diabetic foot ulcer were found in the MarketScan Databases, 2005-2008. Multivariate Cox proportional hazard models estimated the hazard of amputation and hospitalisation. Logistic regression estimated the likelihood of these events. Propensity score weighting and regression adjustment were used to adjust for potentially different characteristics of patients who did and did not receive podiatric care. The sample included 27 545 patients aged greater than 65+ years (Medicare-eligible patients with employer-sponsored supplemental insurance) and 20 208 patients aged lesser than 65 years (non Medicare-eligible commercially insured patients). Care by podiatrists in the year prior to a diabetic foot ulcer was associated with a lower hazard of lower extremity amputation, major amputation and hospitalisations in both non Medicare-eligible commercially insured and Medicare-eligible patient populations. Systematic differences between patients with diabetes and foot ulcer, receiving and not receiving care from podiatrists were also observed; specifically, patients with diabetes receiving care from podiatrists tend to be older and sicker.

Expandable dehydrated human umbilical cord allograft for the management of nonhealing lower extremity wounds in patients with diabetes: a case series.

Advanced wound treatments are derived primarily from human placental membranes or animal tissue sources and composed of cellular and acellular dermal substitutes. The use of advanced wound treatments is practitioner directed and individualized to the wound characteristics. A multidisciplinary approach to wound closure is necessary, including the use of advanced treatments (eg, human umbilical cord derivatives) to achieve durable resolution of hard-to-heal wounds. In this case series, DHUC was used as an alternative to amniotic and amnion/chorion allografts for closure of a deep heel ulcer and a wound of the plantar aspect of the foot. The allografts were applied after wound closure had stalled with previous treatment attempts, which demonstrates use of DHUC in a staged approach to wound bed preparation and closure. The thickness and durability of DHUC allowed it to be used more like a skin graft for deep wounds. The meshed product can be expanded to provide a cost-effective solution to cover larger wound surfaces. It can be applied in an outpatient setting, thus avoiding more invasive and costly procedures (eg, split-thickness skin grafts). The use of umbilical allografts in the current report resulted in closure of stalled wounds and avoided hospitalization, thus reducing overall costs.

Total Dystrophic Onychomycosis Successfully Treated with Efinaconazole Topical Solution in Times of Coronavirus Disease of 2019: A Case Study.

Toenail onychomycosis is a common condition that is equally challenging for podiatrists and patients. This case study documents a 26-year-old woman with bilateral total dystrophic onychomycosis of at least 5 years' duration. She had previously failed to respond to treatment with ciclopirox nail lacquer 8% and, despite hiding her condition with nail polish, was suffering from embarrassment, distress, and low self-esteem. At initial consultation, 100% of both great toenails was affected. After discussion of all treatment options, the patient opted for topical efinaconazole 10% solution, once daily for 48 weeks. Significant improvement was noted at the first (4-week) assessment period. This improvement was maintained through each subsequent virtual consultation, and complete cure was seen at a 30-week follow-up visit. To the author's knowledge, this is the first published report on the use of efinaconazole in total dystrophic onychomycosis. It suggests that the product may be effective in patients with even the most severe and treatment-recalcitrant disease, who are unwilling or unable to tolerate systemic antifungal therapy.

Reduced Hospitalizations and Amputations in Patients with Diabetic Foot Ulcers Treated with Cyclical Pressurized Topical Wound Oxygen Therapy: Real-World Outcomes.

Background: This study sought to examine the real-world impact of multimodality cyclical-pressure topical wound oxygen therapy (TWO2) on hospitalizations and amputations in patients with diabetic foot ulcer (DFU) compared with patients without TWO2. Methods: We conducted a retrospective review of deidentified patient medical records at 2 U.S. Veterans Affairs hospitals between January 2012 and January 2020. DFU patients were assigned to TWO2 or NO TWO2 cohorts based on their treatment records. Patients received appropriate standard of care and may have received other advanced wound treatments, including skin substitutes, negative pressure wound therapy, and growth factors. Primary study outcomes were patients requiring hospitalization and/or amputation within 360 days of initial wound documentation. Findings: Among unmatched cohorts of 202 patients with DFU (91 TWO2, 111 NO TWO2), 6.6% and 12.1% of TWO2 patients had hospitalizations and amputations, respectively, compared with 54.1% and 41.4% of NO TWO2 patients within 360 days (p < 0.0001, p < 0.0001), representing 88% and 71% reductions. Among propensity score-matched cohorts of 140 DFU patients (70 TWO2, 70 NO TWO2), compared with NO TWO2, 82% fewer TWO2 patients were hospitalized (7.1% vs. 40.0%, p < 0.0001) and 73% fewer TWO2 patients had amputations (8.6% vs. 31.4%, p = 0.0007). Logistic regression among matched cohorts demonstrated nearly ninefold and fivefold higher risk of hospitalization and amputation, respectively, for NO TWO2 versus TWO2. Interpretation: This retrospective cohort study demonstrates that treating patients with DFU with TWO2 is associated with significant reductions in hospitalizations and amputations in the real-world setting.

A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study.

OBJECTIVE: Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone. RESEARCH DESIGN AND METHODS: Patients with diabetes and chronic DFUs were randomized (double-blind) to either active TWO2 therapy or sham control therapy-both in addition to optimal SOC. The primary outcome was the percentage of ulcers in each group achieving 100% healing at 12 weeks. A group sequential design was used for the study with three predetermined analyses and hard stopping rules once 73, 146, and ultimately 220 patients completed the 12-week treatment phase. RESULTS: At the first analysis point, the active TWO2 arm was found to be superior to the sham arm, with a closure rate of 41.7% compared with 13.5%. This difference in outcome produced an odds ratio (OR) of 4.57 (97.8% CI 1.19, 17.57), P = 0.010. After adjustment for University of Texas Classification (UTC) ulcer grade, the OR increased to 6.00 (97.8% CI 1.44, 24.93), P = 0.004. Cox proportional hazards modeling, also after adjustment for UTC grade, demonstrated >4.5 times the likelihood to heal DFUs over 12 weeks compared with the sham arm with a hazard ratio of 4.66 (97.8% CI 1.36, 15.98), P = 0.004. At 12 months postenrollment, 56% of active arm ulcers were closed compared with 27% of the sham arm ulcers (P = 0.013). CONCLUSIONS: This sham-controlled, double-blind randomized controlled trial demonstrates that, at both 12 weeks and 12 months, adjunctive cyclical pressurized TWO2 therapy was superior in healing chronic DFUs compared with optimal SOC alone.

The Importance of Wound Care Researchers and Manufactures Working with Medical Associations When Bringing New Products to the Marketplace.

Every day products and their accompanying procedures are delivered to the marketplace and touted to aid physicians and other qualified health care professionals (QHPs) in taking care of patients who have chronic wounds. Some of these products/procedures have been developed with the patient in mind and with a serious regulatory and reimbursement strategy, and other products/procedures make physicians, other QHPs, and payers scratch their heads about the true purpose of the product/procedure. Researchers and developers often only focus on gaining Food and Drug Administration (FDA) clearance and often plunge into the marketplace unaware of the reimbursement stumbling blocks that can prevent the expected market acceptance. Researchers and developers should simultaneously plan for FDA clearance and reimbursement from the product's inception. If a product/procedure requires a new procedure code, researchers and manufacturers should seek the help and guidance of professional medical associations to navigate the Current Procedural Terminology (CPT®; CPT is a registered trademark of the American Medical Association), to make available useful new products/procedures for appropriate patients and to adequately reimburse the physician and other QHPs.

Use of Dehydrated Human Amnion/Chorion Membrane Allografts in More Than 100 Patients with Six Major Types of Refractory Nonhealing Wounds.

BACKGROUND: Biochemical properties of the amniotic membrane help modulate inflammation and enhance soft-tissue healing. In controlled trials, the efficacy of dehydrated human amnion/chorion membrane (dHACM) allografts has been established. Our purpose is to describe our experience with using dHACM to treat nonhealing wounds of various etiologies. METHODS: We conducted a retrospective review of deidentified data from 117 consecutive patients treated in an outpatient clinic with dHACM allografts with wounds of various etiologies over 2 years. The decision to use advanced wound-care treatments is based on rate of healing observed after initiation of standard wound care and patient risk factors. Eligibility for treatments such as amniotic membrane allografts includes wounds without 50% reduction after 4 weeks, or earlier in patients deemed to be at high risk for nonhealing or with a history of chronic wounds. In micronized or sheet formulation, dHACM is applied to the wound weekly after sharp/mechanical debridement as necessary, and wound-care practices appropriate for wound type and location are continued. RESULTS: Thirty-four percent of allograft recipients had diabetic foot ulcers, 25% had venous leg ulcers, 20% had surgical wounds, 14% had pressure ulcers, 6% had ischemic wounds, and 2% had traumatic wounds. Complete healing occurred in 91.1% of treated patients, with a mean ± SD number of weekly applications per healed wound of 5.1 ± 4.2. CONCLUSIONS: In addition to wounds of diabetic origin, dHACM can significantly expedite healing in refractory wounds of varying etiologies.

Third-party reimbursement for lower-extremity wound care.

This article describes the treatment of lower-extremity wounds, specifically foot and ankle ulcerations, in the context of reimbursement for treatments rendered. Therefore, such issues as standard of care, documentation, classification of foot wounds, coding, and reimbursement are discussed.

The economic value of specialized lower-extremity medical care by podiatric physicians in the treatment of diabetic foot ulcers.

BACKGROUND: We sought to examine the economic value of specialized lower-extremity medical care by podiatric physicians in the treatment of diabetic foot ulcers by evaluating cost outcomes for patients with diabetic foot ulcer who did and did not receive care from a podiatric physician in the year before the onset of a foot ulcer. METHODS: We analyzed the economic value among commercially insured patients and Medicare-eligible patients with employer-sponsored supplemental medical benefits using the MarketScan Databases. The analysis consisted of two parts. In part I, we examined cost or savings per patient associated with care by podiatric physicians using propensity score matching and regression techniques; in part II, we extrapolated cost or savings to populations. RESULTS: Matched and regression-adjusted results indicated that patients who visited a podiatric physician had $13,474 lower costs in commercial plans and $3,624 lower costs in Medicare plans during 2-year follow-up (P < .01 for both). A positive net present value of increasing the share of patients at risk for diabetic foot ulcer by 1% was found, with a range of $1.2 to $17.7 million for employer-sponsored plans and $1.0 to $12.7 million for Medicare plans. CONCLUSIONS: These findings suggest that podiatric medical care can reduce the disease and economic burdens of diabetes.