RESUMO
GENERAL PURPOSE: To summarize randomized clinical trials addressing patient-centered outcomes of individuals with a venous leg ulcer. 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. Summarize the results of the review of randomized controlled trials addressing patient-centered outcomes of individuals with a venous leg ulcer.2. Identify the limitations of the research analyzed for the review.
To summarize randomized clinical trials addressing patient-centered outcomes of individuals with a venous leg ulcer with a scoping review. Authors searched PubMed using MESH terms for "venous ulcer" AND "randomized" for randomized clinical trials published from January 2002 to October 2021 that explored content-validated patient-centered outcomes for individuals with a clinically diagnosed venous leg ulcer. Authors also searched Cochrane Reviews from inception to April 15, 2022 for additional references using the same MESH terms. Studies in any setting were included if primary or secondary outcomes were venous ulcer-related mobility, pain or analgesic use, healing, infection, quality of life (including odor, social isolation, depression), amputation, or patient-level costs of treatment. Preclinical or nonrandomized clinical studies or those without venous leg ulcers were excluded. Authors tabulated interventions studied, numbers of patients treated per group, risk of delayed ulcer healing, and statistical significance of comparisons of 485 qualifying articles in Google Sheets. Authors graphically represented and tabulated frequencies of studies addressing patient-centered outcomes of individuals with venous ulcers. Studies mainly reported effects of compression, dressings, topical antimicrobials, or systemic therapy on patient healing or pain outcomes. Related ischemia, ultrasonography, or risk factors for delayed healing were not consistently reported, inflating variability of outcomes and decreasing consistency of differences reported. Research is needed on the mobility, amputation risk, infection risk, quality of life, and healthcare costs of patients with venous ulcers. Promising interventions include grafts, exercise, analgesics, electrical modalities, negative pressure, or vascular interventions. Consistently reporting each patient's baseline ischemia and vascular condition would improve relevance.
Assuntos
Úlcera da Perna , Úlcera Varicosa , Humanos , Cicatrização , Úlcera Varicosa/terapia , Úlcera Varicosa/tratamento farmacológico , Recidiva , Assistência Centrada no Paciente , Úlcera da Perna/diagnóstico , Úlcera da Perna/terapiaRESUMO
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.
Assuntos
Educação Continuada , Herpes Zoster/terapia , Assistência Centrada no Paciente/normas , Cicatrização/fisiologia , Herpes Zoster/psicologia , Humanos , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/estatística & dados numéricosRESUMO
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.
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Fármacos Dermatológicos/uso terapêutico , Higiene da Pele/métodos , Cicatrização/fisiologia , Ferimentos e Lesões/terapia , Anti-Infecciosos/uso terapêutico , COVID-19/epidemiologia , Gerenciamento Clínico , HumanosRESUMO
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.
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Enfermeiras e Enfermeiros , Infecção da Ferida Cirúrgica , Estudos de Coortes , Estudos de Viabilidade , Humanos , Internet , Estudos Prospectivos , Reprodutibilidade dos Testes , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
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.
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Técnicas e Procedimentos Diagnósticos/normas , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/normas , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
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.
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Atenção à Saúde/organização & administração , Cicatrização/fisiologia , Infecção dos Ferimentos/prevenção & controle , Ferimentos e Lesões/terapia , Determinação de Ponto Final , Medicina Baseada em Evidências , Humanos , Reprodutibilidade dos Testes , Estados Unidos , United States Food and Drug Administration , Ferimentos e Lesões/microbiologiaRESUMO
Peripheral arterial disease (PAD) impairs patients' quality of life (QOL), walking and ulcer healing, increasing patient pain, costs, and risks of amputation or mortality. A literature appraisal described PAD treatment capacity to improve validated patient-centred outcomes in controlled clinical studies. The PUBMED database was searched from 1 January 1970 to 21 June 2018, for original and derivative controlled clinical trial references addressing MeSH terms for 'ischemia' AND 'leg ulcer'. Non-ischemic ulcer treatment references were excluded. Frequencies of improved (P < .05) outcomes were reported. Eighty-eight studies on 4153 patients were summarized. Walking, pain or QOL improved mainly for interventions administered before PAD became severe. Amputation incidence, pain and ulcer healing were more frequently reported in those with severe PAD. Independent of PAD severity, patients experienced more likely improved walking, QOL, or pain reduction in response to structured walking interventions or those increasing calf muscle activity. Those with more severe PAD were more likely to report amputation reduction, mainly in response to invasive interventions. Those with PAD experienced more consistently improved patient-centred outcomes if they received multidisciplinary PAD management with supervised walking or calf muscle activity, with more likely amputation risk reduced for those with more severe PAD.
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Avaliação de Resultados da Assistência ao Paciente , Doença Arterial Periférica/terapia , Amputação Cirúrgica , Humanos , Úlcera da Perna/terapia , Manejo da Dor , Qualidade de Vida , CaminhadaRESUMO
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.
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Atenção à Saúde/organização & administração , Determinação de Ponto Final , United States Food and Drug Administration/legislação & jurisprudência , Técnicas de Fechamento de Ferimentos , Cicatrização , Infecção dos Ferimentos/prevenção & controle , Ferimentos e Lesões/terapia , Aprovação de Equipamentos , Aprovação de Drogas , Humanos , Medidas de Resultados Relatados pelo Paciente , Estudo de Prova de Conceito , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários , Estados UnidosRESUMO
Structural features of neurons create challenges for effective production and distribution of essential metabolic energy. We investigated how metabolic energy is distributed between cellular compartments in photoreceptors. In avascular retinas, aerobic production of energy occurs only in mitochondria that are located centrally within the photoreceptor. Our findings indicate that metabolic energy flows from these central mitochondria as phosphocreatine toward the photoreceptor's synaptic terminal in darkness. In light, it flows in the opposite direction as ATP toward the outer segment. Consistent with this model, inhibition of creatine kinase in avascular retinas blocks synaptic transmission without influencing outer segment activity. Our findings also reveal how vascularization of neuronal tissue can influence the strategies neurons use for energy management. In vascularized retinas, mitochondria in the synaptic terminals of photoreceptors make neurotransmission less dependent on creatine kinase. Thus, vasculature of the tissue and the intracellular distribution of mitochondria can play key roles in setting the strategy for energy distribution in neurons.
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Escuridão , Metabolismo Energético/fisiologia , Retina/fisiologia , Animais , Creatina Quinase/antagonistas & inibidores , Creatina Quinase/metabolismo , Dinitrofluorbenzeno/farmacologia , Eletrorretinografia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/efeitos da radiação , Glutamatos/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/efeitos da radiação , Modelos Biológicos , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/enzimologia , Terminações Pré-Sinápticas/efeitos da radiação , Inibidores de Proteínas Quinases/farmacologia , Retina/efeitos dos fármacos , Retina/enzimologia , Retina/efeitos da radiação , Células Fotorreceptoras Retinianas Cones/citologia , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Células Fotorreceptoras Retinianas Cones/enzimologia , Células Fotorreceptoras Retinianas Cones/efeitos da radiação , Segmento Externo das Células Fotorreceptoras da Retina/efeitos dos fármacos , Segmento Externo das Células Fotorreceptoras da Retina/metabolismo , Segmento Externo das Células Fotorreceptoras da Retina/efeitos da radiação , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/enzimologia , Vasos Retinianos/efeitos da radiação , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/efeitos da radiação , Urodelos/fisiologiaRESUMO
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.
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Guias de Prática Clínica como Assunto , Melhoria de Qualidade , Úlcera Varicosa/terapia , Cicatrização/fisiologia , Ferimentos e Lesões/terapia , Pesquisa Biomédica , Terapia Combinada , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Cuidados Paliativos/métodos , Úlcera Varicosa/fisiopatologia , Ferimentos e Lesões/fisiopatologiaRESUMO
This randomized, double-blind, placebo-controlled Phase 2 clinical trial explored NorLeu(3)-A(1-7) (DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, noninfected, neuropathic, or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers (n = 172) were screened for nonhealing. Subjects were randomized to receive 4 weeks' once-daily topical treatment with 0.03% DSC127 (n = 26), 0.01% DSC127 (n = 27), or Placebo (n = 24), followed by 20 weeks' standard of care. DSC127 was assessed for safety (including laboratory values and adverse events), primary efficacy (% ulcers completely epithelialized at Week 12), and durability of effect. Baseline, demography, and safety parameters were compared between intent-to-treat groups and were comparable. Dose-response curves for DSC127 effect on % area reduction from baseline at Week 12 (40% placebo; 67% 0.01% DSC127; 80% 0.03% DSC127) and 24 (23% placebo; 53% 0.01% DSC127; 95% 0.03% DSC127) followed a log-linear pattern for both intent-to-treat and per-protocol populations. Covariate analysis compared reduction in ulcer area, depth, and volume from baseline; reductions in the 0.03% DSC127 group were greater at Weeks 12 and 24. Placebo-treated ulcers healed in a median 22 weeks vs. 8.5 weeks for 0.03%DSC127 (p = 0.04). This study provides preliminary evidence that DSC127 is safe and effective in accelerating the healing of diabetic foot ulcers.
Assuntos
Indutores da Angiogênese/farmacologia , Angiotensina II/farmacologia , Pé Diabético/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Cicatrização/efeitos dos fármacos , Administração Tópica , Indutores da Angiogênese/administração & dosagem , Angiotensina II/administração & dosagem , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/patologia , Pé Diabético/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/administração & dosagem , Resultado do TratamentoRESUMO
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. .
RESUMO
RDEB is a genetic skin disorder involving COL7A1, the gene encoding C7, which is a component of the fibers anchoring the epidermis to the dermis. Affected patients (about 1.35 per million persons in the United States) experience lifelong painful itching, blistering, fibrosis, impaired healing, and scarring, with increased likelihood of infection and cancer. RCT involving those affected by RDEB are rare with limited sample sizes due to the low prevalence of this genetic disorder. Treatment with topical or systemic agents has not consistently improved patient outcomes. Therapies focused on replacing C7 using autologous bone marrow or keratinocyte grafts have been difficult, with high complication rates, and have been met with mixed success. Recent HSV-1 vector research4 led to development of HSV-1 vectors capable of transferring the COL7A1 coding sequence to keratinocytes and fibroblasts in vitro and to mice deficient in C7, as well as to RDEB human skin xenografts. This research offered new opportunities for gene therapy for patients with RDEB. In this final Evidence Corner, readers are invited to consider the implications of 2 small RCTs that suggest fruitful avenues for RDEB research and practice. The first study describes a pioneering phase 1 and 2 RCT of topical gene therapy for RDEB. The second study describes a small crossover RCT exploring the effect of topical calcipotriol (VD3) ointment on wound healing and pruritis in patients with RDEB.
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Epidermólise Bolhosa Distrófica , Epidermólise Bolhosa , Humanos , Camundongos , Animais , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Distrófica/terapia , Pele , Queratinócitos/transplante , Epidermólise Bolhosa/terapia , Fibroblastos , Colágeno Tipo VII/genéticaRESUMO
Tranexamic acid (TXA) is a synthetic lysine analog that reduces perioperative blood loss by blocking lysine-binding sites on plasminogen molecules. It has been reported to be effective in limiting blood loss and transfusion needs in various orthopedic surgeries and for pediatric patients at high risk of blood loss. Randomized controlled trials (RCTs) supporting the capacity of TXA to reduce blood loss and improve outcomes associated with various surgical procedures have increased fourfold in the 10 years since Evidence Corner addressed this topic, which highlighted the capacity of locally delivered TXA to reduce blood loss during orthopedic knee surgery and intravenously delivered TXA to reduce blood lost during elective cesarean sections. Research continues to explore whether the ideal method of TXA delivery is local or systemic. One systemic preoperative 10 mg/kg dose of TXA did not improve blood loss, wound healing, or pain-related outcomes associated with ambulatory foot and ankle surgery. However, repeated topical doses of TXA as well as combined systemic and topical doses improved blood loss, inflammation, and nutritional condition following hip arthroplasty. This installment of Evidence Corner reviews 2 recent studies exploring the effects of adding locally delivered TXA to intravenous (IV) systemic TXA during spinal surgery8 and confirming efficacy of a single dose of topical TXA on hip arthroplasty.
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Antifibrinolíticos , Artroplastia de Quadril , Artroplastia do Joelho , Ácido Tranexâmico , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Criança , Feminino , HumanosRESUMO
Venous leg ulcers (VLUs) are caused by compromised flow of venous and lymphatic fluids from the lower leg toward the central circulatory system. They are one of the most common types of chronic wounds, affecting 3% to 5% of those 65 years of age and older.¹ Most VLUs heal within 12 weeks with sustained lower leg compression sufficient to reduce the edema associated with venous insufficiency.² Diagnosing and improving a patient's venous insufficiency and addressing concomitant arterial disease are key elements of VLU management.³ Surgical correction has been effective for superficial venous insufficiency.4 Various topical,5 physical,6 or systemic7 interventions have been studied as adjuncts to compression in efforts to further improve VLU outcomes, with mixed results. This month's Evidence Corner summarizes recent randomized clinical trials (RCTs) documenting healing effects of topical gauze dressings impregnated with hyaluronic acid (HA) or placebo cream8 as an adjunct to patient-appropriate compression or low-level laser radiation as an adjunct to clinically prescribed elastic compression, diet, leg elevation, exercise, and moisture-retentive, absorbent, or microbicidal dressings.8.
Assuntos
Úlcera da Perna , Úlcera Varicosa , Insuficiência Venosa , Bandagens , Humanos , Úlcera Varicosa/tratamento farmacológico , Insuficiência Venosa/terapia , CicatrizaçãoRESUMO
Wound care professionals face complex challenges in their attempts to achieve healing in patients with a diabetic foot ulcer (DFU).1 Peripheral neuropathy limits sensation, which necessitates consistent offloading of the DFU site. Peripheral arterial, venous, or lymphatic circulation disorders must be diagnosed and addressed. Early diagnosis and management of soft tissue or bone infection is required. Chronic kidney disease, glycemic control, and nutritional needs must be addressed along with counterproductive behavior patterns.2 The use of topical hydrocolloid-based hydrogel dressings3 or honey4 on DFUs facilitates moist wound healing and debridement. Randomized controlled trials (RCTs) indicate that carefully controlling all of these factors helps optimize outcomes for individuals with a DFU. Promising phase 2 clinical studies with stringent inclusion criteria and rigorously applied diagnostic and management procedures are rarely replicated in larger phase 3 RCTs with broader inclusion criteria and less rigorously applied DFU management procedures. Narrow RCT inclusion criteria can limit study applicability for the general DFU population. This installment of Evidence Corner reviews 2 RCTs that use different approaches to address these issues. The first RCT reports interim results of a new autologous skin construct applied to Wagner grade 1 DFUs.5 The second compares the effects of standard wound dressings (SWDs) vs negative pressure wound therapy (NPWT) applied to Wagner grade 2, 3, or 4 DFU according to standard protocols during real-world clinical practice in German patients.6.
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Diabetes Mellitus , Pé Diabético , Tratamento de Ferimentos com Pressão Negativa , Bandagens , Desbridamento , Pé Diabético/terapia , Humanos , CicatrizaçãoRESUMO
Ubiquitination of proteins provides a powerful and versatile post-translational signal in the eukaryotic cell. The formation of a thioester bond between ubiquitin (Ub) and the active site of a ubiquitin-conjugating enzyme (E2) is critical for the transfer of Ub to substrates. Assembly of a functional ubiquitin ligase (E3) complex poised for Ub transfer involves recognition and binding of an E2â¼Ub conjugate. Therefore, full characterization of the structure and dynamics of E2â¼Ub conjugates is required for further mechanistic understanding of Ub transfer reactions. Here we present characterization of the dynamic behavior of E2â¼Ub conjugates of two human enzymes, UbcH5câ¼Ub and Ubc13â¼Ub, in solution as determined by nuclear magnetic resonance and small-angle X-ray scattering. Within each conjugate, Ub retains great flexibility with respect to the E2, indicative of highly dynamic species that adopt manifold orientations. The population distribution of Ub conformations is dictated by the identity of the E2: the UbcH5câ¼Ub conjugate populates an array of extended conformations, and the population of Ubc13â¼Ub conjugates favors a closed conformation in which the hydrophobic surface of Ub faces helix 2 of Ubc13. We propose that the varied conformations adopted by Ub represent available binding modes of the E2â¼Ub species and thus provide insight into the diverse E2â¼Ub protein interactome, particularly with regard to interaction with Ub ligases.
Assuntos
Enzimas de Conjugação de Ubiquitina/química , Ubiquitina/química , Cristalografia por Raios X , Humanos , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Estrutura Quaternária de Proteína , Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
Feedback supports learning. No matter how effective medical professionals think they are, evidence of measured patient wound outcomes helps inform their wound care practice, empowering them to improve patient outcomes. Prospective randomized clinical trials (RCTs) proved this principle in relation to healing chronic wounds. Measuring wound healing outcomes and providing caregivers with feedback about the 4-week healing progress increased the percentage of diabetic foot ulcers healed within 20 weeks and venous leg ulcers healed within 24 weeks. Longitudinal research suggests this principle holds true in preventing surgical site infections (SSIs). When individual orthopedic surgeons were provided written feedback about their hand hygiene practices and corresponding SSI rates, surgeon hand hygiene improved and SSI rates in their patients were reduced. This Evidence Corner describes systematic review evidence indicating that feedback given to responsible wound care professionals reduced SSI incidence for patients undergoing orthopedic or trauma surgery3 and abdominal surgery.
Assuntos
Pé Diabético , Úlcera Varicosa , Pé Diabético/cirurgia , Retroalimentação , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , CicatrizaçãoRESUMO
Surgical site infection (SSI) incidence is affected by 3 types of interacting factors: the infecting organisms (eg, number, type, virulence), the local wound environment (eg, foreign matter, aseptic technique, wound dressings), and systemic host defenses (eg, smoking, obesity, diabetes). Cancer or related chemotherapy and other aspects of cancer care may affect host defenses, as evidenced by increased SSI risk following "clean" surgery to remove breast cancer tissue compared with similar "clean" surgeries in patients who do not have cancer. If patient risk factors for development of an SSI are strictly controlled in individuals undergoing breast cancer surgery, the likelihood of the development of an SSI drops sharply, creating the illusion that preoperative antibiotics are not needed. This Evidence Corner, which includes 2 studies, clarifies evidence supporting the use of recognized preoperative antibiotic administration to support host defenses in patients undergoing breast cancer surgery. In the first study, the controversy about wound dressings following cancer surgery is also explored. Some surgeons question whether routine use of gauze dressings promotes the ideal local wound environment after surgical excision of cancerous tissue. Disintegrating gauze strands can act as foreign bodies in wounds, and gauze dressings have been reported to increase SSI incidence in clean surgical wounds. The second study compared healing and SSI incidence of Mohs surgical excisions dressed with either an antibiotic-free, film-forming silicone wound dressing or a triple antibiotic primary dressing following Mohs micrographic or non-Mohs dermatologic surgery. The surprising results reinforce the importance of the local wound environment as a key factor in minimizing SSI in oncologic surgery.
Assuntos
Neoplasias , Infecção da Ferida Cirúrgica , Antibacterianos/uso terapêutico , Bandagens , Humanos , Mastectomia , Neoplasias/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , CicatrizaçãoRESUMO
Activated platelets release a rich broth of growth factors involved in wound healing. One way to deliver activated platelets to wounds is in the form of platelet-rich plasma (PRP) harvested by centrifuging the patient's venous blood after activating the platelets with collagen or calcium chloride and/or autologous thrombin, then delicately removing the supernatant, called platelet-poor plasma (PPP). Platelet-rich plasma is usually injected into the lesion and/or applied topically, then sealed in or over the wound using a moisture-retentive dressing. Platelet-rich plasma (often with PPP) has been applied at different times, depths, and frequencies to chronic and acute wounds using various PRP doses and vehicles to achieve widely differing results. Meta-analyses have reported that PRP improved healing rates of open diabetic foot ulcers and venous ulcers and may reduce pain and surgical site infection (SSI) incidence in open and closed acute surgical wounds. However, inconsistency in study methods and outcome measures limited consistency of pain and SSI results. No consistent effect on healing or deep SSI rates was reported as a result of adding 1 intraoperative dose of PRP in the surgical site before closing elective foot and ankle surgery incisions of 250 patients as compared with 250 similar patients receiving the same procedure without PRP. After decades of research, ideal parameters of PRP delivery and use on each type of wound remain unclear for improving SSI, acute wound pain, and healing outcomes. This installment of the Evidence Corner reviews 2 surgical studies that may provide clues about optimal PRP use. One triple-blind randomized clinical trial (RCT) focused on irrigation of freshly closed carpal ligament surgical incisions with PRP as compared with PPP. Another non-blind RCT explored the effect of injecting PRP into open pilonidal sinus excisions 4 days and 12 days after surgery.