Putting Evidence into Practice: Using evidence-based strategies to improve wound care practice Linda Cowan, PhD, ARNP, FNP-BC, CWS Research Health Scientist,

Putting Evidence into Practice: Using evidence-based strategies to improve wound care practice Linda Cowan, PhD, ARNP, FNP-BC, CWS Research Health Scientist, Research Service, Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System Gainesville, Florida Associate Professor, UF College of Nursing Gainesville, Florida

Financial Disclosures: Research projects funded by: Veterans Administration Biomonde Healthpoint Celleration Medline Hollister Employed by or Consultant for: University of Florida College of Nursing WHS Consultants, Inc. CEUFAST, Inc.

Objectives Describe Evidence Based Practice processes vs. practices Identify key differences between EBP, PI/QI, and Research tools Discuss ways to appraise and apply research evidence to clinical practice Review examples of wound related research evidence (venous leg ulcers, biofilm, pressure ulcers)

Value of Evidence in Clinical Care

When clinicians have access to information, it changes their patient care management decisions: In 1998, Dr. David Sackett, using an "evidence cart" on rounds, reported using information searches to answer 71 clinical questions: 37 (52%) Evidence confirmed the management decision, 18 (25%) Evidence lead to a new therapy or diagnostic test 16 (23%) Evidence corrected (changed) the previous plan.

What is Evidence-Based Practice? EBP is a problem solving approach to clinical practice that integrates the conscientious use of best evidence in combination with a clinicians expertise as well as patient preferences and values to make decisions about the type of care that is provided.

Types of Clinical Evidence External Evidence: Generated from rigorous research Important question: Does the evidence generated by rigorous research still hold true when translated to the real world? Internal Evidence: Generated from outcomes management; practice-based evidence (PI/QI/QA) projects Other Sources: Text books, expert opinion, professional organizations

Getting Started: The Five As* Ask good clinical question Acquire best evidence Enough evidence to answer question? Appraise that evidence (level/strength) Is evidence strong? Apply Does evidence support practice change? Can practice change be implemented? Assess/Re-assess How did practice change impact outcomes? *Modified from Duke Universitys The Five As of the Evidence Cycle available at: http://eno.duhs.duke.edu/sites/eno.duhs.duke.edu/files/public/guides/evidencecycle.pdf http://eno.duhs.duke.edu/sites/eno.duhs.duke.edu/files/public/guides/evidencecycle.pdf

Ask Acquire Appraise Apply Assess & Reassess Patient dilemma Process of evidence-based practice Evidence alone does not decide add clinical experience and pt. values! Hierarchy of evidence Richardson, 2007; http://www.cebm.net/?o=1021 Act

Accessed from: Titler, M.G., Kleiber, C., Steelman, V.J., Rakel, B.A., Budreau, G., Everett, L.Q., Buckwalter, K.C., Tripp-Reimer, T., & Goode C. (2001).The Iowa Model of Evidence-Based Practice to Promote Quality Care. Critical Care Nursing Clinics of North America, 13(4), 497- 509. (Used with permission).

EBP ResearchQI / PI Evidence Summary & Recommendation Evidence Based Generates External Evidence Generates Internal Evidence Evidence Utilization Toolboxes: Rules and Tools

ALL PI/QI, Research, & Evidence Summaries start with: Asking a question Acquiring the Evidence Appraising /evaluating the Evidence (critical appraisal) Determining how the evidence may be Applied to the question we have asked...

Asking a Searchable Question: USING PICO Population/problem Intervention (if there is one) or E = exposure Comparison (if there is one) Outcome of interest PICOT (T=Time span)

THERAPY QUESTION: Jean is a 55 y/o woman who quite often crosses the Atlantic to visit her elderly mother. She tends to get swollen legs on these flights and is worried about her risk of developing deep vein thrombosis (DVT), because she has read quite a bit about this in the newspaper lately. She asks you if she should wear elastic stockings on her next trip to reduce her risk of this. Glasziou et al, 2007

USING PICO Population/problem = passengers on long-haul flights Intervention = wearing elastic compression stockings Comparison = no elastic stockings Outcome = development of DVT

After you ask the question, then what? Asking a question Acquiring the Best Evidence Appraising /evaluating the Evidence (critical appraisal) Determining how the evidence may be Applied to the question we have asked... Great Resource: Glasziou, 2007. How do we nurture Evidence-Based Practice? http://www.cebm.net/?o=1021http://www.cebm.net/?o=1021

Using PICO to Help Search 1. Underline the key terms 2. Number the order of importance from 1 to 4 3. Think of alternate spellings, synonyms, & Truncations 1 2 3 Population/problem = passengers on long-haul flights Intervention = wearing elastic compression stockings Comparator/control = no elastic stockings Outcome = development of DVT 4 Glasziou, 2007; http://www.cebm.net/?o=1021

Computerized decision support systems linking patient needs to best evidence Specialized documentation software NICE (www.nice.org.uk/guidance/)www.nice.org.uk/guidance/ Integrates best evidence from synthesis to provide comprehensive options and Guidelines Clinical Evidence (www.clinicalevidence.com)www.clinicalevidence.com PIER (http://pier.acponline.org/index.html)http://pier.acponline.org/index.html Up-to-Date (www.uptodate.com)www.uptodate.com Guidelines (www.guidelines.gov)www.guidelines.gov Systematic reviews (SRs) and Meta Analyses Bmjupdates+ (http://bmjupdates.com)http://bmjupdates.com Cochrane Library Worldviews on evidence-based Nursing http://www.blackwell-synergy.com/loi/wvn http://www.blackwell-synergy.com/loi/wvn PubMed Clinical Queries (http://www.ncbi.nlm.nih.gov/entrez/query/static/clinic al.shtml)http://www.ncbi.nlm.nih.gov/entrez/query/static/clinic al.shtml Succinct descriptions of an individual study or an SR ACP Journal Club (www.acpjc.org)www.acpjc.org EBM (www.evidence-basedmedicine.com)www.evidence-basedmedicine.com EBN (http://ebn.bmj.com/)http://ebn.bmj.com/ Original research articlesBmjupdates+ PubMed Clinical Queries

After you acquire the evidence, then what? Asking a question Acquiring the Best Evidence Appraising /evaluating the Evidence (critical appraisal) Determine how evidence can be applied

Critical Appraisal Tools & Skills Systematic Reviews/Meta Analyses CEBM (www.cebm.net) has free CAT tools to usewww.cebm.net Common questions Is the question of the research or SR clearly stated? Does the SR answer the specific question you asked? Is the info current? Is it likely relevant articles/studies were missed? Are results applicable to your population of interest? Were appropriate methods used in research or SR? Large enough samples? Valid/reliable tools? Homogeneous results vs. heterogeneous results Meaningful results? Levels of evidence and strength of recommendations?

Clinical Pearls about Evaluating Research Evidence Know where to look in articles Gehlbachs book: Interpreting Medical Literature 2006 Read methodology section first (not abstract) Sample large enough? Sample size power analysis reported? Appropriate study design for clinical question? Outcome measures described adequately; valid, reliable? Is enough detail given so that study could be reproduced? Abstract: Research question/population same as yours? Methods: Sampling techniques? Robust methods? Results: Believable and can be applied to your situation?

Know about some Crud detectors Heterogeneity of Meta-analysis results? Quick look at stem and leaf plots Odds ratio: measure of relative risk 95% Confidence Intervals Should never contain 1 0.2 0.4 0.6 0.8 1.0 3.0 5.0 7.0 Study1 T(25/152) C(2/160) Study2 T(2/16) C(1/15) Study3 T(35/200) C(3/185) Combined T(80/368) C(6/360) (Combined sample n= 728) -----X---- OR 0.6(95%CI 0.4-0.8) -----X--- OR 1.0(95%CI 0.8-1.5) --X OR 0.5(95%CI 0.4-0.6) -X- OR 0.5 (95%CI 0.5-0.6)

After you appraise the evidence, then what? Asking a question Acquiring the Best Evidence Appraising /evaluating the Evidence (critical appraisal) Determining how evidence may be Applied.. Is there sufficient evidence to suggest a recommendation for practice change? or Are PI or research methods/tools needed?

Remember our Toolboxes? ResearchQI / PI Evidence Summary Evidence Based Generates External Evidence Generates Internal Evidence Evidence User

Evidence Summaries Ask Acquire High level (current) evidence Look for syntheses / summaries / guidelines Systematic reviews/meta-analyses Appraise Workgroup summarizes appraised evidence Critical appraisal tools (CATs) AGREE for Guidelines Apply Make recommendations for applying to practice Policy/procedure need to be changed/updated? Practice need to be changed? Present report to change facilitators

Evidence Summary & Recommendations Examples Ear irrigation in ambulatory care With what device, how much solution, what solution? Acute urinary retention presenting to ER Should you clamp Foley catheter every 500cc? CAUTI question for admissions with Foleys Should you change Foley if admitted w/existing Foley?

Utilizing the PI/QI Toolbox ResearchQI / PI Evidence Summary Evidence Based Generates External Evidence Generates Internal Evidence

Quality Improvement (QI) Process Improvement (PI) A process by which individuals work together to improve systems and processes with the intention to improve outcomes (unit/facility/organization specific) A data driven systematic approach to improving care (typically with a local or organizational focus) Utilizes the PDCA (PDSA), Systems Redesign, Lean Six Sigma (or similar) framework/methods PI/QI language Newhouse, 2007

Common PI/QI/QA Language Plan-Do-Check-Act (PDCA/PDSA) Improve Project, change activity Systems / Processes Satisfaction Local/unit specific Work flow / work around Barriers / Facilitators Reduce time/cost Collect and evaluate data Lessons learned Information found (outcomes): Not generally a risk to pts, not generalizable (no intent to publish) If any of these are potential issues, will need IRB review PI/QI approach often in response to national mandates, quality indicators, skills competency & educational needs

PI/QI Examples CHF teach back method for discharge instructions Reduced re-admissions CABG/Valve replacement clinical pathway Improved interdisciplinary communication, care consistency, patient communication Pharmacy Lock Box Eliminating unnecessary RN visits

Research What if there is not enough evidence to answer the clinical question (evidence summary) or support an improvement activity (PI/QI)?

Utilizing the Research Toolbox ResearchQI / PI Evidence Summaries Evidence Based Generates External Evidence

RESEARCH Research is a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge Theory building / testing Federal regulatory definitions available in document 38 CFR 16.102(d) http://www.gpo.gov/fdsys/pkg/CFR-2004- title38-vol1/pdf/CFR-2004-title38-vol1-sec16-103.pdfhttp://www.gpo.gov/fdsys/pkg/CFR-2004- title38-vol1/pdf/CFR-2004-title38-vol1-sec16-103.pdf

Common Research Language Generate new knowledge Investigate / research / study Testing / trial / develop / theory / hypothesis Randomize / random allocation Intervention / experiment / experimental Sample / Sampling / Controls / Cases Inclusion criteria/exclusion criteria Informed consent / subjects / n=x Retrospective chart review / prospective design Cohort / case controls / comparison group

Research vs. Non-Research Activity If you are not sure, consider: Is anything outside of usual care being done/proposed? Any potential risk to patient, pts info, corporate info? What kind of data? How will data be collected, stored, reported? Is there a goal to generalize/publish/present this data? IF YES even if it is being done as a PI project/activity, IRB and human subject protection review will be necessary. Each Federal agency may have their own additional layers of approvals: All VA Research must be reviewed by the IRB and VA Privacy officer, Information security officer, safety committee and R & D Committees before research can begin!

Typical Research Proposals Writing the proposal Be specific about methods, who will: Have access to data, use the data, where will data be stored (VA server!) etc. Typical components of proposals for UF IRB follow something like this: Project Title and List of Investigators Project Abstract Background & Significance Specific Aims Research Plan (Sample, Inclusion/Exclusion criteria, Methods of data collection, Variables, Methods of data analysis, Project Management Plan, Dissemination Plan, Budget, Timeline) Possible Discomforts and Risks and Possible Benefits (Human Subjects protection, data safety monitoring plan) Conflict of Interest of investigators References

Wound Research Team Members Qingping Yang, MS Randal Wolcott, MD, CWS Joyce Stechmiller, PhD, ARNP, FAAN Gregory Schultz, PhD Priscilla Phillips, PhD Daniel Gibson, PhD Micah Flores, PhD Cyndi Garvan, PhD Briana Foerman, BS Joshua Yarrow, PhD Linda Cowan, PhD, ARNP, CWS

Purpose of Evidence Syntheses Provides reports of body of evidence on important clinical practice topics relevant to patients and these reports help: Develop clinical policies informed by evidence, Implement effective services to improve patient outcomes Support clinical practice guidelines and performance measures, and Guide the direction for future research to address gaps in clinical knowledge

National Evidence Example Advanced Wound Care Therapies for Non- Healing Diabetic, Venous, and Arterial Ulcers: A Systematic Review Completed November 2012, Published May 2013 Full-length report available on ESP website: http://www.hsrd.research.va.gov/publications/es p/reports.cfm http://www.hsrd.research.va.gov/publications/es p/reports.cfm MEDLINE Search 1995 through August 2012 plus hand-search of references lists in eligible trials and recent systematic reviews

SR Review and Appraisal Team: Leads: Neal Foman & Nancy Greer (Minneapolis VA) Co-Authors/Collaborators Timothy J. Wilt, MD, MPH James Dorrian, MD Roderick MacDonald, MS Patrick Fitzgerald, MPH Indulis Rutks, BS Expert Panel/Reviewers Jeffrey Robbins, DPM Leonard Pogach, MD James Wrobel, DPM, MS Clifford Buckley, MD Lucille Beck, PhD Margaret Cary, MD Roya Mirmiran, DPM David Margolis, MD, PhD

Specific Purpose of This Review Evaluate published, RCTs of efficacy & harms of advanced wound care therapies compared to either usual care or other advanced therapy Therapies Reviewed: Collagen Platelet-derived growth factors (PDGF); Negative pressure wound therapy (NPWT); Biological dressings (BD); Platelet-rich plasma (PRP); Electromagnetic therapy (EMT); Biological skin equivalents (BSE); Silver products; Oxygen therapies (hyperbaric [HBOT], topical, ozone); Keratinocytes; Intermittent pneumatic compression (IPC)

Inclusion/exclusion Randomized, controlled trials enrolling human subjects age 18 and over and published in English language Non-healing, lower extremity, diabetic, venous, or arterial ulcers (excluded acute wounds, surgical wounds, or pressure ulcers) Included only studies reporting percentage of ulcers healed at study completion or time to complete ulcer healing as an outcome

VA Evidence-based Synthesis Program (ESP) 2012 Literature Search Flow 1,230 Titles and Abstracts 1,053 Excluded 177 Full Text Review 130 Excluded 21 from Hand Search Final: 68 Articles (64 Trials) Diabetic: 35 trials ; Venous: 20 trials; Arterial: 1 trial Other: 8 trials

Outcomes Examined Main Outcomes: Proportion of ulcers healed at study completion Time to complete ulcer healing Patient global assessment Return to daily activities Secondary Outcomes: Ulcer infection Pain Amputation Quality of life Revascularization surgery All-cause mortality Ulcer recurrence Adverse events Time to recurrence

Major Findings Our systematic review of randomized controlled trials found discouragingly LOW strength of evidence regarding the effectiveness of advanced wound care therapies for treatment of lower extremity ulcers

Limitations of many of the reviewed studies: - Narrow patient population, i.e. limited enrollment - Many of the trials were industry sponsored - Definitions of chronic ulcers vary widely - Few studies were of long duration - Advanced therapies compared only to standard therapies in majority of studies - Methodological quality of studies was fair or poor - Dont know how effective standard care was prior to entering trials

Future Studies Needed: That will compare advanced therapies to each other To examine microvascular disease to more clearly distinguish diabetic from arterial ulcers On advanced wound care therapies in patients with strictly arterial disease Several organizations have outlined overall methodological standards for future research of wound healing therapies

Comparative Effectiveness SR: Treatments for VLU Systematic Review: benefits & harms of advanced wound dressings on wound healing, mortality, quality of life, pain, condition of wound bed, and adverse events for patients with chronic VLU compared with compression alone Valle et al. (Johns Hopkins University) Literature reviewed: Jan 1980 thru July 2012 10,676 total studies initially reviewed Only 37 met criteria (3,990 patients) 0.34% of studies available

Limited evidence on comparative effectiveness and safety in this comprehensive systematic review. Of thousands of citations reviewed, just 38 met criteria. Five studies generated moderate levels of evidence from which conclusions were drawn on CVU healing. Poor quality of study design and heterogeneity among studies limited ability to draw meaningful conclusions related to QOL, pain, condition of the wound bed, and most adverse events. Improved healing rates were observed in trials that evaluated allogeneic bilayered cultured human skin equivalent, Apligraf. Three times more rapid healing of CVUs than compression alone, especially for recalcitrant ulcers that were present for over 1 year. However, no added benefit was seen in recurrence rates.

Cadexomer iodine provided a significant advantage in wound healing rates in one trial Silver-impregnated dressings and Manuka honey did not significantly affect healing rates of CVUs. More studies are needed to further explore the role of antimicrobial dressings in management of CVUs. Hydrocolloid dressings do not appear more effective than compression alone in healing the chronic venous leg ulcers. However, all hydrocolloids are not exactly the same, and the lack of standardization in water vapor transmission rates among hydrocolloid dressings could potentially affect wound healing. Low strength of evidence on hydrocolloids indicates cannot rule out possibility of a benefit, but better studies would be needed to show a benefit.

Conclusions A few AWDs may be helpful in improving wound healing, but other important effectiveness and safety outcomes are still understudied for these AWDs. Our findings do not imply that AWDs have no merit in the treatment of the CVU. Rather, they indicate that there is insufficient data to support such claims, and re-evaluation of the standards for conducting research on AWDs for CVUs is imperative. We speculate that because many wound dressings are classified as medical devices, the existing evidence is partly a response to the less rigorous standards set forth by the Food and Drug Administration for medical devices.

Antibiofilm Strategies

Evidence Biofilms in chronic wounds Dowd, James, Wolcott Biofilm Research Wound Research at University of Florida and North Florida/South Georgia VA: Pigskin explant biofilm model Topical antimicrobial agents Non-contact non thermal US Larval debridement therapy (LDT or MDT)

Cadexomer iodine P. Phillips, Q. Yang, E. Sampson, G. Schultz. Effects of Antimicrobial Agents on an In Vitro Biofilm Model of Skin Wounds, Advances Wound Care, 1: 299-304, 2010.

Non-contact non-thermal ultrasound 3 day mature PA biofilm before US 3 day mature PA biofilm after US Bacteria rods

Value of medicinal larvae (maggots) or Larval Debridement Therapy (LDT) as an anti-biofilm strategy

Results L. Cowan, J. Stechmiller, P. Phillips, Q.P. Yang and G. Schultz. Chronic Wounds, Biofilms and Use of Medicinal Larvae, Ulcers, Article ID 487024, 7 pages; http://dx.doi.org/10.1155/2013/487024, 2013.http://dx.doi.org/10.1155/2013/487024

Before Larval Debridement SA35556 3 day mature biofilm culture on pig skin explant

After Larval Debridement SA35556 biofilm culture 24 hours after LDT

Before Larval Debridement PA01 (3 day mature biofilm culture on pig skin explant)

After Larval Debridement PA01 biofilm culture 24 hours after LDT

Evidence for larval therapy Enzymatic secretions Antimicrobial secretions Effective debridement of necrotic tissue Not disruptive of healthy tissue No known bacterial resistance

Innovation: Biofilm Detector Dye Cowan, L., Schultz, G., Gibson, D., Yang, Q., Proof of concept in vitro studies completed April 2014 Using dental plaque dye to stain biofilm for clinical visualization Visualization of biofilm allows more effective treatment (removal of biofilm) and treatment monitoring

Photo of non-inoculated pigskin explants (free of biofilm) Exposed for 10 seconds to one concentration of dental biofilm dye and then rinsed vigorously x 1 with 5 ml sterile water

This experiment demonstrated proof of concept that the dental dye does not significantly stain pigskin tissue, but did stain biofilm material. These results support the proposed research to test a similar dye in an open wound on a living rat model where living tissue and wound fluid with other proteins are present.

Future directions Effective wound bed preparation T-I-M-E* principles in practice Anti-biofilm strategies Including Larval Debridement Therapy (LDT) Biofilm Detector Dye Animal studies and human studies Targeted multiple factor approach Combination therapies: disruption or removal of biofilm (such as LDT) + antimicrobials Human RCT in progress: LDT vs. bedside sharp debridement against biofilm Schultz, G & Dowsett, C. (2012). Wound bed preparation revisited. Wounds International, 3(1). Available at: http://www.woundsinternational.com/practice-development/wound-bed-preparation-revisited/page-2 )http://www.woundsinternational.com/practice-development/wound-bed-preparation-revisited/page-2

PU Treatment

PU Treatments AHRQ: Pressure Ulcer Treatment Strategies: Comparative Effectiveness Review Number 90 (May 8, 2013). Interprofessional team of expert authors. Contains 488 pages. http://effectivehealthcare.ahrq.gov/search-for- guides-reviews-and- reports/?pageaction=displayproduct&productID=14 91 http://effectivehealthcare.ahrq.gov/search-for- guides-reviews-and- reports/?pageaction=displayproduct&productID=14 91

Articles published between January 1, 1985, and October 17, 2012 Identified from searches of: MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCOhost),EBM Reviews (Ovid), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Health Technology Assessment. Additional studies identified by searching reference lists from included studies & systematic reviews of pressure ulcer treatments. Gray literature, including unpublished data, abstracts, dissertations, and individual product packets from manufacturers, also reviewed.

Evidence for Tx Moderate Low Air-fluidized beds Alternating pressure beds Protein-containing nutritional supplements Hydrocolloid compared to foam Radiant heat compared with other dressings (stage III-IV ulcers) Electrical stimulation NPWT Low air loss beds vs. foam Vitamin C Platelet derived growth factor Topical collagen compared to hydrocolloid or standard care Therapeutic ultrasound Electromagnetic therapy Light therapy Laser therapy Hydrotherapy

Insufficient Evidence Alternating pressure chair cushions Zinc Comparison of different wound dressings Debriding enzymes compared with dressings or other topical therapies (few studies) Topical phenytoin Biological agents (macrophage suspension, etc.) Surgical closure *Maggot studies were also listed here because only 3 poor quality studies were reviewed (but didnt have our results published yet!)

Summary Maggots are our friends PU prevention starts with education and appropriate risk assessment Preventive interventions should be Evidence-Based and will likely never replace attentive care & repositioning PU treatments should be evidence-based and patient need specific (wound characteristics & comorbidities) More research needed to determine when specific interventions are likely to succeed or fail.

Documents

Putting Evidence into Practice: Using evidence-based strategies to improve wound care practice Linda Cowan, PhD, ARNP, FNP-BC, CWS Research Health Scientist,