A prospective, randomized, controlled clinical study on the effectiveness of a single-use negative pressure wound therapy system, compared to traditional negative pressure wound therapy in the treatment of diabetic ulcers of the lower extremities.

A multicenter, phase 4, randomized, comparative-efficacy study in subjects with lower extremity wounds was carried out to compare wound closure rates, for a single-use negative pressure wound therapy (s-NPWT) versus traditional NPWT (t-NPWT) systems over a 12-week treatment period. From the initial population of patients with diabetic foot ulcers (DFU) and venous leg ulcers (VLU), we analyzed a subgroup of patients with diabetes mellitus and leg and foot ulcers (either DFUs or VLUs in diabetics), termed, the diabetic lower extremity ulcers (DLEU). In the DLEU group, there were 95 patients in intention-to-treat (ITT) and 61 patients in per protocol (PP) populations, respectively. We found a significant difference in favor of s-NPWT over t-NPWT in the confirmed wound closures at 12 weeks both in ITT (p < 0.001) and PP populations (p = 0.017). Significantly higher wound closure rates in s-NPWT group suggest that s-NPWT should be preferred NPWT option for DLEU.

Evidence-Based Review of Antibiofilm Agents for Wound Care.

Significance: Biofilms in vivo are small densely packed aggregations of microbes that are highly resistant to host immune responses and treatment. They attach to each other and to nearby surfaces. Biofilms are difficult to study and identify in a clinical setting as their quantification necessitates the use of advanced microscopy techniques such as confocal laser scanning microscopy. Nonetheless, it is likely that biofilms contribute to the pathophysiology of chronic skin wounds. Reducing, removing, or preventing biofilms is thus a logical approach to help clinicians heal chronic wounds. Recent Advances: Wound care products have demonstrated varying degrees of efficacy in destroying biofilms in in vitro and preclinical models, as well as in some clinical studies. Critical Issues: Controlled studies exploring the beneficial role of biofilm eradication and its relationship to healing in patients with chronic wounds are limited. This review aims to discuss the mode of action and clinical significance of currently available antibiofilm products, including surfactants, dressings, and others, with a focus on levels of evidence for efficacy in disrupting biofilms and ability to improve wound healing outcomes. Future Directions: Few available products have good evidence to support antibiofilm activity and wound healing benefits. Novel therapeutic strategies are on the horizon. More high-quality clinical studies are needed. The development of noninvasive techniques to quantify biofilms will facilitate increased ease of research about biofilms in wounds and how to combat them.

Traditional and advanced therapeutic modalities for wounds in the paediatric population: an evidence-based review.

OBJECTIVE: Children can have non-healing wounds due to a wide range of pathologies, including epidermolysis bullosa (EB), pilonidal disease and Stevens-Johnson syndrome, with some causes being iatrogenic, including extravasation injuries and medical device-related hospital-acquired pressure ulcers. Furthermore, paediatric wounds are vastly different from adult wounds and therefore require a different treatment approach. While there are numerous types of dressings, topical remedies, and matrices with high-tier evidence to support their use in adults, evidence is scarce in the neonatal and paediatric age groups. The purpose of this review is to discuss the basic principles in paediatric wound management, as well as to present new treatment findings published in the literature to date. The benefits and risks of using different types of debridement are discussed in this review. Various topical formulations are also described, including the need to use antibiotics judiciously. METHOD: Databases were searched for relevant sources including Pubmed, Embase, Web of Science and DynaMed. Search terms used included 'wound care', 'wound management', 'paediatrics', 'children', 'skin substitutes', and 'grafts'. Additionally, each treatment and disease entity was searched for relevant sources, including, for example: 'Apligraf', 'dermagraft', 'Manuka honey', 'antibiotic', 'timolol', and 'negative pressure wound therapy' (NPWT). RESULTS: Amniotic membrane living skin equivalent is a cellular matrix that has been reportedly successful in treating paediatrics wounds and is currently under investigation in randomised clinical trials. Helicoll is an acellular matrix, which shows promise in children with recessive dystrophic EB. NPWT may be used as a tool to accelerate wound closure in children; however, caution must be taken due to limited evidence to support its safety and efficacy in the paediatric patient population. Integra has been reported as a useful adjunctive treatment to NPWT as both may act synergistically. Hospitalised children and neonates frequently have pressure ulcers, which is why prevention in this type of wound is paramount. CONCLUSION: Advancements in wound care are rapidly expanding. Various treatments for non-healing wounds in paediatric and neonatal patients have been reported, but high tier evidence in these populations is scarce. We hope to shed light on existing evidence regarding the different therapeutic modalities, from debridement techniques and dressing types to tissue substitutes and topical remedies. There have been promising results in many studies to date, but RCTs involving larger sample sizes are necessary, in order to determine the specific role these innovative agents play in paediatric wounds and to identify true safety and efficacy.

A Cost-Effectiveness Analysis Comparing Single-use and Traditional Negative Pressure Wound Therapy to Treat Chronic Venous and Diabetic Foot Ulcers.

Lower extremity ulcers such as venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs) have a major clinical and economic impact on patients and providers. PURPOSE: The purpose of this economic evaluation was to determine the cost-effectiveness of single-use negative pressure wound therapy (sNPWT) compared with traditional NPWT (tNPWT) for the treatment of VLUs and DFUs in the United States. METHODS: A Markov decision-analytic model was used to compare the incremental cost and ulcer weeks avoided for a time horizon of 12 and 26 weeks using lower extremity ulcer closure rates from a published randomized controlled trial (N = 161) that compared sNPWT with tNPWT. Treatment costs were extracted from a retrospective cost-minimization study of sNPWT and tNPWT from the payer perspective using US national 2016 Medicare claims data inflated to 2018 costs and multiplied by 7 to estimate the weekly costs of treatment for sNPWT and tNPWT. Two (2) arms of the model, tNPWT and sNPWT, were calculated separately for a combination of both VLU and DFU ulcer types. In this model, a hypothetical cohort of patients began in the open ulcer health state, and at the end of each weekly cycle a proportion of the cohort moved into the closed ulcer health state according to a constant transition probability. The costs over the defined timescale were summed to give a total cost of treatment for each arm of the model, and then the difference between the arms was calculated. Effectiveness was calculated by noting the incidence of healing at 12 and 26 weeks and the total number of open ulcer weeks; the incremental effectiveness was calculated as sNPWT effectiveness minus tNPWT effectiveness. Data were extracted to Excel spreadsheets and subjected to one-way sensitivity, scenario (where patients with unhealed ulcers were changed to standard care at 4 or 12 weeks), probabilistic, and threshold analyses. RESULTS: sNPWT was found to provide an expected cost saving of $7756 per patient and an expected reduction of 1.67 open ulcer weeks per patient over 12 weeks and a cost reduction of $15 749 and 5.31 open ulcer weeks over 26 weeks. Probabilistic analysis at 26 weeks showed 99.8% of the simulations resulted in sNPWT dominating tNPWT. Scenario analyses showed that sNPWT remained dominant over tNPWT (cost reductions over 26 weeks of $2536 and $7976 per patient, respectively). CONCLUSION: Using sNPWT for VLUs and DFUs is likely to be more cost-effective than tNPWT from the US payer perspective and may provide an opportunity for policymakers to reduce the economic burden of lower extremity ulcers.

Successful Treatment of Lower Extremity Telangiectasias Using 585-nm Pulsed-Dye Laser at Low Fluence Combined With Optical Coherence Tomography: A Case Report

Background: Significant advances have been made in using lasers and intense pulse light sources to treat common vascular lesions such as telangiectasias. However, the treatment of leg telangiectasia, specifically, is more challenging because it involves the clearing of smaller veins as well as the larger feeding veins. The latest guidelines recommend use of short wavelength pulse-dyed lasers (PDL) as an option to treat telangiectasia cases that are unresponsive to sclerotherapy. Methods: A 29-year-old white woman presented with persistent telangiectasia, with multiple telangiectasias ranging from 1 cm to 20 cm in size involving the dorsal feet and both ankles and legs, which developed 10 years prior, associated with paresthesia. Test spots were treated with a 585-nm pulsed dye laser with various energy settings, and treatment was performed at 5.5 J/cm2 with spot size 10 mm and 0.5ms pulse duration. Results: Near complete clearance was achieved 1 month after the single treatment without adverse effects. Optical coherence tomography (OCT) imaging demonstrated a reduction of cutaneous blood flow after treatment. Discussion: We report successful treatment despite using settings that were previously reported to lack efficacy. This treatment resulted in considerable improvement in aesthetics and symptomatology. Also, OCT confirmed decreased vascular flow and bulging. Conclusion: Our results suggest there is still much to learn about the use of PDL in treating telangiectasias of the lower extremities, and that the ideal parameters warrant further investigation. Moreover, the novel use of OCT in auxiliary imaging for identification of treatment spots, as well as monitoring response at a microvascular level, holds great potential for wider application. J Drugs Dermatol. 2019;18(11):1180-1182.

A prospective, randomized, controlled clinical trial on the efficacy of a single-use negative pressure wound therapy system, compared to traditional negative pressure wound therapy in the treatment of chronic ulcers of the lower extremities.

Multicenter, phase-4, randomized, comparative-efficacy study in patients with VLUs or DFUs comparing for noninferiority the percentage change in target ulcer dimensions (area, depth, and volume) a single-use negative pressure wound therapy (s-NPWT) system versus traditional NPWT (t-NPWT) over a 12-week treatment period or up to confirmed healing. Baseline values were taken at the randomization visit. Randomized by wound type and size, 164 patients with non-infected DFUs and VLUs were included. The ITT population was composed of 161 patients (101 with VLUs, 60 with DFUs) and 115 patients completed follow-up (64 in the s-NPWT group and 51 in the t-NPWT group) (PP population). The average age for all patients was 61.5 years, 36.6% were women, and treatment groups were statistically similar at baseline. Primary endpoint analyses on wound area reduction demonstrated statistically significant reduction in favor of s-NPWT (p = 0.003) for the PP population and for the ITT population (p < 0.001). Changes in wound depth (p = 0.018) and volume (p = 0.013) were also better with s-NPWT. Faster wound closure was observed with s-NPWT (Cox Proportional Hazards ratio (0.493 (0.273, 0.891); p = 0.019) in the ITT population. Wound closure occurred in 45% of patients in the s-NPWT group vs. 22.2% of patients in the t-NPWT group (p = 0.002). Median estimate of the time to wound closure was 77 days for s-NPWT. No estimate could be provided for t-NPWT due to the low number of patients achieving wound closure. Device-related AEs were more frequent in the t-NPWT group (41 AEs from 29 patients) than in the s-NPWT group (16 AEs from 12 patients). The s-NPWT system met noninferiority and achieved statistical superiority vs. t-NPWT in terms of wound progression toward healing over the treatment period. When NPWT is being considered for the management of challenging VLUs and DFUs, s-NPWT should be considered a first choice over other types of NPWT.

Photobiomodulation with non-thermal lasers: Mechanisms of action and therapeutic uses in dermatology and aesthetic medicine.

BACKGROUND: Non-thermal laser therapy in dermatology, is a growing field in medical technology by which therapeutic effects are achieved by exposing tissues to specific wavelengths of light. OBJECTIVES: The purpose of this review was to gain a better understanding of the science behind non-thermal laser and the evidence supporting its use in dermatology. METHODS: A group of dermatologists and surgeons recently convened to review the evidence supporting the use of non-thermal laser for body sculpting, improving the appearance of cellulite, and treating onychomycosis. RESULTS: The use of non-thermal laser for body sculpting is supported by three randomized, double-blind, sham-controlled studies (N = 161), one prospective open-label study (N = 54), and two retrospective studies (N = 775). Non-thermal laser application for improving the appearance of cellulite is supported by one randomized, double-blind, sham-controlled study (N = 38). The use of non-thermal laser for the treatment of onychomycosis is supported by an analysis of three non-randomized, open-label studies demonstrating clinical improvement of nails (N = 292). CONCLUSIONS: Non-thermal laser is steadily moving into mainstream medical practice, such as dermatology. Although present studies have demonstrated the safety and efficacy of non-thermal laser for body sculpting, cellulite reduction and onychomycosis treatment, studies demonstrating the efficacy of non-thermal laser as a stand-alone procedure are still inadequate.

What's new: Management of venous leg ulcers: Treating venous leg ulcers.

Venous leg ulcers account for approximately 70% of all leg ulcers and affect 2.2 million Americans annually. After a comprehensive patient and wound assessment, compression therapy remains the cornerstone of standard care. Adjuvant care with topical or systemic agents is used for wounds that do not heal within 4 weeks. Once healed, long-term compression therapy with stockings or surgical intervention will reduce the incidence of recurrence. This continuing medical education article aims to outline optimal management for patients with venous leg ulcers, highlighting the role of a multidisciplinary team in delivering high quality care.

Chronic wound repair and healing in older adults: current status and future research.

The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi-morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age-associated changes in chronic wound healing.

Diabetic foot ulcers: Part II. Management.

The management of diabetic foot ulcers can be optimized by using an interdisciplinary team approach addressing the correctable risk factors (ie, poor vascular supply, infection control and treatment, and plantar pressure redistribution) along with optimizing local wound care. Dermatologists can initiate diabetic foot care. The first step is recognizing that a loss of skin integrity (ie, a callus, blister, or ulcer) considerably increases the risk of preventable amputations. A holistic approach to wound assessment is required. Early detection and effective management of these ulcers can reduce complications, including preventable amputations and possible mortality.

Diabetic foot ulcers: evaluation and management.

Diabetic foot ulcers (DFUs) are a common complication of diabetes and present a significant health risk to patients, as well as impose a large economic burden. Evaluation for contributory factors that may impact general health or healing, such as hyperglycemia, peripheral artery disease, neuropathy, and nutritional status, is of the utmost importance. Management of DFUs requires involvement of a multidisciplinary team and a standardized approach to patient care. Standard therapy for DFUs includes offloading and debridement. Assessment and control of infection are critical, including determining the severity of the infection, which may drive therapeutic approaches. For recalcitrant ulcers, adjuvant therapies are used to hasten the healing process, and newer therapies are under investigation.

Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial.

Keratinocyte carcinoma (KC) is the most common cancer in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. Topical tretinoin has been used for KC chemoprevention, although this use is unproven. Hence, we conducted the randomized Veterans Affairs Topical Tretinoin Chemoprevention Trial of high-dose topical tretinoin for KC prevention. We randomized 1,131 patients to topical 0.1% tretinoin or a matching vehicle control for 1.5-5.5 years. The primary outcomes were time to development of new basal cell carcinoma (BCC) and new invasive squamous cell carcinoma (SCC) on the face or ears. The effects were not significant (P=0.3 for BCC and P=0.4 for SCC). The proportions of the tretinoin and control groups who developed a BCC at 5 years were 53 and 54% and an invasive SCC at 5 years were 28 and 31%. These differences (95% confidence intervals) were: for BCC, 1.0% (-6.5, 8.6%); for SCC, 3.6% (-3.1, 10.3%). No differences were observed in any cancer-related end points or in actinic keratosis counts. The only quality of life difference was worse symptoms in the tretinoin group at 12 months after randomization. This trial in high-risk patients demonstrates that high-dose topical tretinoin is ineffective at reducing risk of KCs.

Comparison of negative pressure wound therapy with an ultraportable mechanically powered device vs. traditional electrically powered device for the treatment of chronic lower extremity ulcers: a multicenter randomized-controlled trial.

The purpose of this study was to compare the ultraportable mechanically powered Smart Negative Pressure (SNaP(®)) Wound Care System to the traditional electrically powered Vacuum-Assisted Closure (VAC(®)) Therapy System in the treatment of chronic lower extremity wounds. This 12-center randomized-controlled trial of patients with noninfected, nonischemic, nonplantar lower extremity wounds had enrolled 65 patients, as of January 5, 2010, at the time of a planned interim analysis. Subjects were randomly assigned to treatment with either the SNaP(®) or VAC(®) Systems. The trial evaluated treatment for up to 16 weeks or till complete closure was achieved. Fifty-three patients (N=27 SNaP(®), N=26 VAC(®)) completed at least 4 weeks of therapy. Thirty-three patients (N=18 SNaP(®), N=15 VAC(®)) completed the study with either healing or 16 weeks of therapy. At the time of planned interim analysis, no significant differences (p=0.99) in the proportion of subjects healed between the two devices evaluated were found. In addition, the percent wound size reduction between treatment groups was not significantly different at 4, 8, 12, and 16 weeks, with noninferiority analysis at 4 weeks of treatment reaching the p-value <0.05 significance level (*p=0.019). These interim data suggest no difference in wound closure between the SNaP(®) System and the VAC(®) System in the population studied. We look forward to the final analysis results.

New therapies for treatment of diabetic foot ulcers: a review of current clinical trials.

Diabetic foot ulcers are a common problem in clinical practice and one of the most common complications in diabetic patients, often leading to amputation and hospitalization. Although there are a number of options for coadjuvant therapy for diabetic foot ulcers, a considerable number of patients remain unhealed after 12 weeks of treatment and, in general, rates of healing remain low. For these reasons, as well as the rising costs of associated complications of nonhealing diabetic foot ulcers, there is an impetus for the research community to develop more sophisticated ways to manage this condition. We reviewed ongoing clinical trials (clinicaltrials.gov) testing new therapies for foot ulcers and searched the basic science literature for preclinical background of these products. We focused our review on new therapies that include topicals, skin substitutes, bioengineered skin, cellular therapy growth factors, devices, and herbal medications. All of these options are analyzed and presented in this review as promising new options for the treatment of diabetic foot ulcers.

Vitamin D: bone and beyond, rationale and recommendations for supplementation.

Adequate vitamin D status is necessary and beneficial for health, although deficiency plagues much of the world's population. In addition to reducing the risk for bone disease, vitamin D plays a role in reduction of falls, as well as decreases in pain, autoimmune diseases, cancer, heart disease, mortality, and cognitive function. On the basis of this emerging understanding, improving patients' vitamin D status has become an essential aspect of primary care. Although some have suggested increased sun exposure to increase serum vitamin D levels, this has the potential to induce photoaging and skin cancer, especially in patients at risk for these conditions. Vitamin D deficiency and insufficiency can be both corrected and prevented safely through supplementation.