1. 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

2. 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.

3. 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)

4. Value of Evidence in Clinical Care

5. 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.

6. 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 clinician’s expertise as well as patient preferences and values to make decisions about the type of care that is provided.

7. 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

8. Getting Started: The Five A’s*
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 University’s “The Five A’s of the Evidence Cycle” available at:

9. Process of “evidence-based practice”
Patient
dilemma
Assess & Reassess
Ask
Acquire
Process of
“evidence-based
practice”
Act
Appraise
Hierarchy
of evidence
Evidence alone does not
decide – add clinical experience and pt. values!
Apply
Richardson, 2007;

10. 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),
(Used with permission).

11. Evidence Summary & Recommendation
Toolboxes:
Rules and
Tools
EBP
Research
QI / PI
Evidence Summary & Recommendation
Generates External Evidence
Generates Internal Evidence
Evidence Utilization
Evidence Based

12. 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. . .

13. 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)

14. 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

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

16. 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, How do we nurture Evidence-Based Practice?

17. Using PICO to Help Search1
Population/problem = passengers on long-haul flights
Intervention = wearing elastic compression stockings
Comparator/control = no elastic stockings
Outcome = development of DVT 3 4 2
Underline the key terms
Number the order of importance from 1 to 4
Think of alternate spellings, synonyms, & Truncations
Glasziou, 2007;

18. Computerized decision support systems linking patient needs to best evidence
Specialized documentation software
NICE (
Integrates best evidence from synthesis to provide comprehensive options and Guidelines
Clinical Evidence (
PIER (
Up-to-Date (
Guidelines (
Systematic reviews (SRs) and Meta Analyses
Bmjupdates+ (
Cochrane Library
Worldviews on evidence-based Nursing
PubMed Clinical Queries (
Succinct descriptions of an individual study or an SR
ACP Journal Club (
EBM (
EBN (
Original research articles
Bmjupdates+
PubMed Clinical Queries

19. 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…

20. Critical Appraisal Tools & Skills
Systematic Reviews/Meta Analyses
CEBM ( has free CAT tools to use
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?

21. Clinical Pearls about Evaluating Research Evidence
Know where to look in articles
Gehlbach’s 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?

22. 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”
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 )
-----X--- OR 1.0(95%CI )
--X— OR 0.5(95%CI )
-X- OR 0.5 (95%CI )

23. 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?

24. Remember our Toolboxes?
Research
QI / PI
Evidence Summary
Generates Internal Evidence
Generates External Evidence
Evidence User
Evidence Based

25. Evidence Summaries Ask Acquire Appraise Apply
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

26. 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?

27. Utilizing the PI/QI Toolbox
Research
QI / PI
Evidence Summary
Generates External Evidence
Generates Internal Evidence
Evidence Based

28. 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

29. 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

30. 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

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

32. Utilizing the Research Toolbox
QI / PI
Evidence Summaries
Generates
External Evidence
Evidence Based

33. 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 (d)

34. 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

35. 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, pt’s 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!

36. 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

37. 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

38. 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

39. 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:
p/reports.cfm
MEDLINE Search – 1995 through August plus hand-search of references lists in eligible trials and recent systematic reviews

40. 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

41. 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)

42. 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

43. 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

44. 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

45. 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”

46. 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
- Don’t know how effective standard care was prior to entering trials

47. 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

48. 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

50. 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.

51. 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.

52. 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.”

53. Antibiofilm Strategies

54. Evidence Biofilms in chronic wounds Biofilm Research
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)

55. 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: , 2010.

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

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

58. Results
L. Cowan, J. Stechmiller, P. Phillips, Q.P. Yang and G. Schultz.  Chronic Wounds, Biofilms and Use of Medicinal Larvae, Ulcers, Article ID , 7 pages;

59. Before Larval Debridement
SA day mature biofilm culture on pig skin explant

60. After Larval Debridement
SA35556 biofilm culture 24 hours after LDT

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

62. After Larval Debridement
PA01 biofilm culture 24 hours after LDT

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

64. 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

65. 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

66. 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.

67. 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: )

68. PU Treatment

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

70. 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.

71. 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

72. 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 didn’t have our results published yet!)

73. 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.