Alternative Wound Management: Translating Science into Practice.

GENERAL PURPOSE: To present a scoping review of preclinical and clinical trial evidence supporting the efficacy and/or safety of major alternative wound care agents to summarize their effects on validated elements of wound bed preparation and wound management paradigms. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Differentiate the effectiveness of the topical wound care agents included in this review.2. Compare the preventive efficacy of intravenous agents administered to trauma and surgical patients.3. Select the effectiveness of products in this review that are left in place after surgical procedures.4. Identify an oral agent that can be helpful in mitigating the effects of COVID-19.

Effective wound healing is achieved by well-timed host, cell, and environment interactions involving hemostasis, inflammation, formation of repaired dermal structures, and epithelialization, followed by months to years of scar remodeling. Globally, various natural or synthetic agents or dressings are used to optimize wound environments, prolong drug release, aid in fluid absorption, provide favorable healing environments, and act as a mechanical barrier against wound trauma. In this scoping review of evidence from the PubMed and clinicaltrials.gov databases, authors examined clinical study evidence supporting the efficacy and safety of selected phytochemicals, vehicles, polymers, and animal products considered "naturally derived" or "alternative" wound interventions to provide a summary of preclinical evidence. Agents with the most clinical evidence were honey, alginates, polyurethane, gelatin, and dextran. Practice implications are described in the context of the TIMERS clinical paradigm.

Herpes Zoster (Shingles) Patient-Centered Wound Outcomes: A Literature Review.

GENERAL PURPOSE: To present a comprehensive review of patient-centered outcomes of topical or systemic interventions applied to those with shingles or postherpetic neuralgia to inform clinical practice and identify related research needs. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will be able to:1. Explain the importance of early diagnosis and treatment of herpes zoster (HZ).2. Identify interventions that have resulted in documented improvement of validated patient-centered outcomes in patients with HZ or postherpetic neuralgia.3. Recognize the average per patient medical costs of HZ in the US.

One in three people endure herpes zoster (HZ; also known as shingles) during their lifetime, experiencing pain, secondary infections, postherpetic neuralgia, reduced quality of life, and considerable patient costs. These patient burdens remain to be reviewed. To perform a comprehensive review of patient-centered outcomes of topical or systemic interventions applied to those with shingles or postherpetic neuralgia to inform clinical practice and identify related research needs. The PubMed database was searched with supplementary Google Scholar searches for Medical Subject Headings "shingles" or "post-herpetic neuralgia" to find clinical studies documenting validated patient-centered outcomes: pain, secondary infection, healing, function, depression, social isolation, treatment costs, or quality of life. Six representative case studies were examined. Pertinent original and derivative clinical study references were included. Preclinical studies, reviews, or studies of non-HZ conditions were excluded. Two authors tabulated clinical efficacy evidence for interventions affecting patient-centered outcomes. Evidence supported efficacy for systemic antiviral or topical anesthetic interventions improving pain, healing, sleep, vision, or quality of life for those with HZ or postherpetic neuralgia. Patient cases reported improved pain and/or sleep using occlusive dressings. Treatment costs and secondary infections were reported only in cases or cohort studies. Randomized clinical research focused on medications improving patient pain, healing, sleep, or vision outcomes. Research is needed measuring outcomes of adding occlusive dressings to optimal care and effects on secondary infections and treatment costs.

Wound Phototherapy.

Researchers have tested the effects of low-level light therapy (LLLT) using low-power lasers or non-coherent, non-collimated light therapy from light-emitting diodes (LEDs) on wounds for decades, exploring the efficacy of phototherapy treatments for chronic1 and acute2 wounds. Low-level light therapy has received device clearance in the United States for cosmetic improvement of aging or sun-damaged skin, acne, actinic keratoses, non-melanoma skin cancer, improving circulation, and decreasing pain as well as stiffness and muscle spasm. 3 It has been used for dental, dermatologic, neurologic, and chiropractic conditions in Canada, Europe, and Asia for several years.4 There are few adequately powered, double-blind randomized clinical trials (RCTs) carefully evaluating energy dose-response of each color or wavelength of LLLT. Typical ranges of LLLT include infrared light waves (800-1200 nm, penetrating 5-10 mm of tissue), red (630-700 nm, penetrating 2-3 mm), yellow (570-590 nm, penetrating 0.5-2 mm), and blue to ultraviolet (400-170 nm, penetrating ⟨ 1 mm).3 Low-level light therapy is delivered at various power densities (W/cm2), time durations, and duty cycles, accumulating as energy absorbed over time, called fluence (J/cm2). The variety of wound outcomes in response to differing LLLT parameters used to stimulate various aspects, depths, and types of tissue injury can be confusing. In this installment of Evidence Corner, a systematic review5 of LED effects on dermatologic conditions and wounds and a second on LLLT effects on diabetic foot ulcers (DFUs)1 add clarity to LLLT effects on some aspects of wound management.

Reliability and feasibility of registered nurses conducting web-based surgical site infection surveillance in the community: A prospective cohort study.

Surgical site infections increase health care costs, morbidity, and mortality in 2% to 5% of surgical patients. Standardised post-surgical surveillance is rare in community settings, causing under-reporting and under-serving of the documented 60% of surgical site infections occurring following hospital discharge. This study evaluated feasibility and concordance (inter-rater reliability) of paired registered nurses using a web-based surveillance tool (how2trakSSI, based on validated guidelines) to detect surgical site infections for up to 30 days after surgery in a cohort of 101 patients referred to Calea Home Care Clinics in Toronto, Canada, March 2015 to July 2016. After paired registered nurse assessors used the tool-less than 10 minutes apart to measure concordance 5 to 7 days postoperatively, they provided feedback on its usefulness at two teleconference discussion groups September 6 to 7, 2016. Overall concordance between assessors was 0.822, remaining consistently above 0.65 across assessor education level and experience, patient age and weight, and wound area. Assessors documented 39.6% surgical site infection prevalence 5 to 7 days after surgery, confirming clinical need, relevance, reliability, and feasibility of using this web-based tool to standardise community surgical site infection surveillance, noting that it was user-friendly, more efficient to use than traditional paper-based tools and useful as a registry for tracking progress.

Peripheral arterial disease screening and diagnostic practice: A scoping review.

Early reliable, valid screening, diagnosis, and treatment improve peripheral arterial disease outcomes, yet screening and diagnostic practices vary across settings and specialties. A scoping literature review described reliability and validity of peripheral ischaemia diagnosis or screening tools. Clinical studies in the PUBMED database January 1, 1970, to August 13, 2018, were reviewed summarising ranges of reliability and validity of peripheral ischaemia diagnostic and screening tools for patients with non-neuropathic lower leg ischaemia. Peripheral ischaemia screening and diagnostic practices varied in parameters measured such as timing, frequency, setting, ordering clinicians, degree of invasiveness, costs, definitions, and cut-off points informing clinical and referral decisions. Traditional ankle/brachial systolic blood pressure index <0.9 was a reliable, valid lower leg ischaemia screening test to trigger specialist referral for detailed diagnosis. For patients with advanced peripheral ischaemia or calcified arteries, toe-brachial index, claudication, or invasive angiographic imaging techniques that can have complications were reliable, valid screening, and diagnostic tools to inform management decisions. Ankle/brachial index testing is sufficiently reliable and valid for use during routine examinations to improve timing and consistency of peripheral ischaemia screening, triggering prompt specialist referral for more reliable, accurate Doppler, or other diagnosis to inform treatment decisions.

Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 2. Literature survey.

Patients with wounds bear significant clinical, personal, and economic burdens yet complete wound healing is the only United States Food and Drug Administration (FDA) recognized primary clinical trial end point. The overall goal of this project is to work with FDA to expand the list of acceptable primary end points, recognizing that new and innovative treatments, devices, and drugs may not have complete healing as the focus. Part 1 of the project surveyed 628 wound care experts who identified and content-validated 15 end points most relevant to clinical practice and benefitting patients' lives as primary outcomes in clinical trials. Part 2 is focused on critical appraisal of the evidence in the wound care literature supporting FDA criteria to qualify these 15 end points as primary end points in clinical trials. Further research involved systematic review of the literature regarding the most promising end points. Forty volunteer, interdisciplinary, wound healing experts in fields related to the end points compiled evidence from systematic MEDLINE searches and society databases supporting the FDA criteria of reliability, clinical construct validity, capacity to detect concurrent or longitudinal change, and responder analysis. The search revealed 485 references involving over 462,000 subjects supporting FDA-required parameters for all 15 end points More than 50 references supported FDA-required parameters qualifying the following outcomes for use in clinical trials supporting interventions for FDA clearance: Pain reduction, Physical function and ambulation, Infection reduction, Time to heal, and Percent wound area reduction in 4-8 weeks. Among these, only Time to heal is currently recognized by the FDA as a primary wound outcome in clinical trials. These results suggest that wound science is already serving patients and professionals by improving these content-validated outcomes that merit regulatory consideration.

Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory evaluation.

Quality Randomized Clinical Trials of Topical Diabetic Foot Ulcer Healing Agents.

Significance: Diabetic foot ulcers (DFU) significantly add to global economic, social, and clinical burdens. Healing a DFU fast and well limits complications that can lead to lower extremity amputation, morbidity, and mortality. Recent Advances: Many promising topical DFU healing agents have been studied in randomized clinical trials (RCT), but only one, becaplermin, has been cleared for this use by the United States Food and Drug Administration (FDA). Critical Issues: This critical review of DFU topical healing RCTs summarizes issues identified in their design and conduct, highlighting ways to improve study quality so researchers can increase the likelihood of RCT success in propelling effective topical DFU healing agents toward clinical use. Key issues include (1) inadequate sample size, (2) risk of bias, (3) irrelevant or unreported inclusion criteria, (4) substandard outcome measures, (5) unmatched group characteristics that predict nonhealing at baseline, (6) unequal or uncontrolled concurrent interventions or standard of care, (7) heterogeneous subject or DFU samples (8) unblinded allocation, treatment, or outcome measures, or (9) inadequate follow-up for clinical relevance. These can add bias or unexplained variability to RCT outcomes, limiting clinical or statistical significance and accuracy of results. Future Directions: This critical review summarizes ways to overcome these deficiencies to optimize DFU clinical trial design and conduct. It provides a blueprint for future excellence in RCTs testing safety and efficacy of topical DFU healing agents and smoothing the path to their clinical use.

Systematic Reviews and Meta-Analyses - Literature-based Recommendations for Evaluating Strengths, Weaknesses, and Clinical Value.

Good quality systematic reviews (SRs) summarizing best available evidence can help inform clinical decisions, improv- ing patient and wound outcomes. Weak SRs can misinform readers, undermining care decisions and evidence-based practice. To examine the strengths and weaknesses of SRs and meta-analyses and the role of SRs in contemporary evidence-based wound care practice, and using the search terms systematic review, meta-analysis, and evidence-based practice, the authors searched Medline and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for important terminology and recommendations to help clinicians evaluate SRs with meta-analysis. Reputable websites, recent textbooks, and synthesized available literature also were reviewed to describe and summarize SR strengths and weaknesses. After developing a checklist for critically evaluating SR objectives, inclusion/exclusion criteria, study quality, data extraction and synthesis methods, meta-analysis homogeneity, accuracy of results, interpretation, and consistency between significant findings and abstract or conclusions, the checklist was applied to topical wound care SRs identified in Cochrane and MEDLINE searches. Best available evidence included in the SRs from 169 randomized controlled trials on 11,571 patients supporting topical intervention healing effects on burns, surgical sites, and diabetic, venous, or pressure ulcers was summarized and showed SRs and clinical trials can demonstrate different outcomes because the information/data are compiled differently. The results illustrate how evidence insufficient to support firm conclusions may still meet immediate needs to guide carefully considered clinical wound and patient care decisions while encouraging better future science.

NorLeu3-Angiotensin (1-7) [DSC127] as a Therapy for the Healing of Diabetic Foot Ulcers.

Significance: Diabetes is a disorder that is well known to delay wound repair resulting in the formation of colonized chronic wounds. Over their lifetime, diabetic patients have a 25% incidence of foot ulcers (DFUs), which contribute to increased risk of morbidity, including osteomyelitis and amputations, and increased burden to the healthcare system. Recent Advances: The only active product approved for the treatment of diabetic ulcers, Regranex®, is not widely used due to minimal proven efficacy and recent warnings added to the Instructions for Use. A novel topical agent that accelerates healing and increases the proportion of fully healed DFUs, DSC127 [aclerastide; active ingredient, NorLeu3-angiotensin (1-7) (NorLeu3-A(1-7))], is recruiting patients in Phase III clinical trials (NCT01830348 and NCT01849965). NorLeu3-A(1-7) is an analog of the naturally occurring peptide, angiotensin 1-7. The mechanisms of action include induction of progenitor proliferation, accelerated vascularization, collagen deposition, and re-epithelialization. Critical Issues: Current modalities for the treatment of DFUs include strict offloading, bandaging, debridement and, on a limited basis, application of Regranex. Novel potent therapies are needed to combat this significant burden to the diabetic patient and the healthcare system. Future Direction: Preclinical and clinical research shows that DSC127 is highly effective in the closure of diabetic wounds and is superior to Regranex in animal studies. Clinical development of DSC127 as a topical agent for the healing of DFU is underway. Further investigation into the mechanisms by which this product accelerates healing is warranted.

The Association for the Advancement of Wound Care (AAWC) venous and pressure ulcer guidelines.

Guidelines based on best available evidence to support pressure ulcer (PU) or venous ulcer (VU) management decisions can improve outcomes. Historically, such guidelines were consensus-based and differed in content and development methods used. Since 2002, the Association for the Advancement of Wound Care (AAWC) Guideline Task Force has used a systematic approach for developing "guidelines of guidelines" that unify and blend recommendations from relevant published guidelines while meeting Institute of Medicine and Agency for Healthcare Research and Quality standards. In addition to establishing the literature-based strength of each recommendation, guideline clinical relevance is examined using standard content validation procedures. All final recommendations included are clinically relevant and/or supported by the highest level of available evidence, cited with every recommendation. In addition, guideline implementation resources are provided. The most recent AAWC VU and PU guidelines and ongoing efforts for improving their clinical relevance are presented. The guideline development process must be transparent and guidelines must be updated regularly to maintain their relevance. In addition, end-user results and research studies to examine their construct and predictive validity are needed.

An evaluation of the association for the advancement of wound care venous ulcer guideline and recommendations for further research.

OBJECTIVE: The goals of this study were to analyze the 2010 update of the Association for the Advancement of Wound Care (AAWC) Venous Ulcer Guideline (VUG) and examine recommendations with less than A-level evidence to identify important research questions. DATA SOURCES: The AAWC VUG may be found at http://aawconline.org/professional-resources/resources and at the National Guideline Clearinghouse, http://www.guideline.gov. Supporting references for each recommendation, compiled by the AAWC Guideline Task Force from MEDLINE, CINAHL, and EMBASE databases, may be viewed at the first website. STUDY SELECTION: The literature identified in support of the AAWC VUG recommendations with less than A-level evidence was evaluated and is summarized below. DATA EXTRACTION: Questions requiring further research in venous ulcer (VU) care were developed from recommendations having less than A-level support and that fall under the following topics: diagnosis, documentation, prevention, wound care, adjunctive interventions, and palliation. DATA SYNTHESIS: Practitioners lack strong evidence for several generally accepted recommendations of this synthesis of VU guidelines concerning the following: diagnostic or screening validity of varicosities, timing of biopsies for differential diagnosis, clinic visit frequency, criteria for changing VU care plans, and effective VU preventive parameters. Bedside surgical debridement, several biologic interventions, certain types of grafting, and the comparative efficacy of intravascular surgical procedures also require rigorous examination. Adjunctive interventions to be investigated include systemic pain management, topical biophysical treatments, novel devices, pharmaceuticals, timing, methods and procedures for some surgical interventions. CONCLUSIONS: Better evidence for recommendations with less than A-level support may improve the quality and consistency of VU care, reduce costs, and improve resource use.

Using science to advance wound care practice: lessons from the literature.

Wound care professionals can improve clinical, patient-oriented wound outcomes and do so cost-effectively by using scientific evidence to meet patient and wound care goals and needs. A review of the literature was conducted to define evidence-based wound management, describe the potential of science to improve outcomes in wound care, and summarize strategies, tactics, and tools for wound care providers and recipients to utilize science to their mutual benefit. In addition, changes in the availability of randomized and nonrandomized and clinical and preclinical evidence during the past 50 years were examined using MEDLINE database searches of English-language publications, combining the search terms wound, ulcer, or burn limited by the terms randomized or clinical for each decade since 1960. The number of published, nonrandomized wound studies has increased exponentially during the last five decades but, more recently, evidence from randomized controlled trials also has become available. Moreover, while many questions remain unanswered, a substantial number of publications have shown the use of available evidence-based guidelines and wound care strategies improves outcomes of care while saving time and money. The application of science-based wound care in clinical practice is increasing slowly; expensive techniques supported by limited or inconsistent evidence are still in use and add to wound care costs without certainty they improve outcomes. The literature provides compelling evidence that patients with a wide variety of diagnoses benefit when opinion-based care is replaced by clinical wisdom applied on a substrate of best available evidence. Patients with wounds deserve no less.

Benchmarking chronic wound healing outcomes.

UNLABELLED:  Background. Benchmarking chronic wound outcomes (compar- ing outcomes achieved in practice to those reported elsewhere) begins with documenting and summarizing individual and cohort outcomes of one's practice, continues with searching for comparable results, and is completed by improving care if benchmark outcomes exceed one's own. OBJECTIVE: Literature reviewed illustrated this cycle of document- summarize-search-compare outcomes of a recognized healing mea- sure-percent completely healed within ≥ 12 weeks of care. METHODS: MEDLINE and Association for the Advancement of Wound Care (AAWC) Venous and Pressure Ulcer Guidelines and Evidence Table searches identified example healing benchmarks from randomized controlled tri- als (RCTs) with ≥ 100 subjects/group with a diabetic foot ulcer (DU), venous leg ulcer (VU), or pressure ulcer (PU). Graphed benchmarks were compared to outcomes reported for same-etiology cohorts to il- lustrate institutional and patient-level benchmarking. RESULTS: Cohorts in some settings reported results similar to the best RCT results for DU and VU. More adequately powered PU RCTs are needed to provide full- and partial-thickness PU benchmarks. RCTs have strengths and limitations as benchmarking resources. Risk-adjusted analyses would improve benchmarking. CONCLUSION: Documenting and comparing out- comes to published results can support current interventions, highlight opportunities for improvement, or ensure that interventions applied are working to meet individual patient and wound care goals. .