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Evidenced Based Wound Care

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  • Out Patient-Apligraf, slide 6
  • Physical exam
  • It has been shown that both MDs and patients underestimate the mortality associate with PAD, especially in patients wihtout concomitant CAD.
  • Speaker Notes:
  • Use of Advanced Technology in Wound Healing
    Initial healing rates (at 4 weeks) predict overall healing rates
    Initial healing rates of >0.1 cm/wk correlate with healing
    Rapid identification of patients who are unlikely to respond to conventional care will allow for earlier interventions with advanced therapies
  • Apligraf Diabetic Foot Ulcer Value Study:
    Summary (I)
    US Data Survey Study, 21 treatment centers
    83 patients treated with Apligraf, 83 with good wound care
    Apligraf patients had more severe wounds:
    larger in size (21 cm2 vs 11 cm2)
    longer duration (242 vs 156 days)
    more severe on Wagner Scale (2.9 vs 2.5)
    Healing rates comparable (Apligraf 54% vs 63% GWC)
  • Apligraf Diabetic Foot Ulcer Value Study:
    Summary (I)
    US Data Survey Study, 21 treatment centers
    83 patients treated with Apligraf, 83 with good wound care
    Apligraf patients had more severe wounds:
    larger in size (21 cm2 vs 11 cm2)
    longer duration (242 vs 156 days)
    more severe on Wagner Scale (2.9 vs 2.5)
    Healing rates comparable (Apligraf 54% vs 63% GWC)
  • Apligraf Diabetic Foot Ulcer Value Study:
    Summary (I)
    US Data Survey Study, 21 treatment centers
    83 patients treated with Apligraf, 83 with good wound care
    Apligraf patients had more severe wounds:
    larger in size (21 cm2 vs 11 cm2)
    longer duration (242 vs 156 days)
    more severe on Wagner Scale (2.9 vs 2.5)
    Healing rates comparable (Apligraf 54% vs 63% GWC)
  • Efficacy of Apligraf ® in the Treatment of Venous Leg Ulcers
    Apligraf plus compression therapy was more effective in achieving complete wound closure by week 24 (57% vs 40%, P =.022*) than compression therapy alone1
    In patients with ulcers >1 year's duration (n=120), Apligraf plus compression therapy was more than twice as effective in achieving complete wound closure by week 24 (47% vs 19%, P =.002).2 These data compare with 66% vs 73% (Apligraf vs control), P =.434, for patients with ulcers <1 year's duration (n= 120)
  • Efficacy of Apligraf ® In Patients With Venous Leg Ulcers
    >1 Year’s Duration
    In the clinical trial, Apligraf was proven to be beneficial in patients with ulcers of greater than 1 year's duration
    A total of 120 patients had wounds that were of greater than 1 years duration(72 in the Apligraf group, 48 in the active control group). Of those, significantly more patients treated with Apligraf achieved complete wound closure at6 weeks, 8 weeks, 12 weeks, and 6 months than did active control patients (P=.048, P ~ 008, P =.001, and P =.002, respectively)
  • Diabetes affects over 18 million Americans in the U.S. alone, and it’s estimated that over 15% will develop a lower extremity neuropathic ulcer during their lifetime.
    Up to 20% of these patients— 86,000 people each year—will require an amputation, with virtually all amputations being preceded by a non-healing wound. Diabetic ulcers are the most common cause of lower extremity amputation in the U.S.
    These patients are at high risk for second amputation in the two years following the first, and up to 50% will die within three years of surgery.
    These facts make the prevention and management of diabetic neuropathic ulcers a major priority for the healthcare system.
    References:
    3. NIDDK website: Total Prevalence of Diabetes in the United States, All Ages, 2002. http://diabetes.niddk.gov/dm/pubs/statistics/index.htm.
    1. Reiber GE, Boyko EJ, Smith DG. Lower Extremity Foot Ulcers and Amputations in Diabetes. In Diabetes in America, 2nd edition. Bethesda, Md. National Diabetes Data Group, National Institutes of Health, NIDDK, NIH Publication No. 95-1468, 1995.
    4. Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care. 1999;22:382–387.
  • Diabetic Foot Ulcers: The Message Reached >250,000 of Your
    Colleagues in July 2004
    A “Clinical Practice” article appeared in the July issue of New England Journal of Medicine. The Journal reaches greater than 250,000 physicians and has a tremendous impact on clinical practice (based on independent research reports)
    Highlighted through a case presentation, the article discusses the importance of yearly foot exams, with increased monitoring in patients at greater risk (defined as neuropathy, vascular disease, history of ulceration, and foot deformities), based on clinical practice and epidemiologic data this pertains to a majority of patients with diabetes
    Debridement was always a critical step in the management of wound care (data from Steed, et al) and this article reinforces the importance of debridement and pressure reduction
    Ulcers that present with clinical signs of infection should undergo sharp debridement and deep cultures
    Recognizing when wound fail to respond to conventional good wound care is becoming a critical step in the overall management of wounds. Evidence both from a clinical standpoint as well as on a molecular basis supports this time point. Additional research is ongoing in this field as it relates the healing rate and reduction in wound volume over time
  • Mostly Leg p. 10
  • This clinical trial showed that more patients achieved complete closure at 20 weeks in the REGRANEX 0.003% treated group (29/61, 48%), compared to the placebo-treated group (14/57, 25%).
    Reference:
    20. Steed DL, the Diabetic Ulcer Study Group; Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J Vasc Surg 1995;21:71-81.
  • Case Study 6
    Patient was a 60-year-old Caucasian male, suffering from type 1 diabetes mellitus, with peripheral neuropathy.
    The ulcer measured 3.9 cm (length)  1.4 cm (width)  0.5 cm (depth) and had been located on the left medial forefoot since November.
    From May 10, until August 1, a total of 22.5 g of REGRANEX Gel was used over 12 weeks of therapy.
    Patient used an off-loading shoe during treatment. REGRANEX was applied once daily with BID saline-moistened dressing changes.
    Patient had a total of 9 office visits (1 before receiving drug; 8 during therapy).
    The wound was debrided 8 times.
    There has been no recurrence of his ulcer at 36 weeks post-healing (patient continued to use an off-loading shoe).
  • Apligraf ® — Lower Incidence of Osteomyelitis
    Patients receiving Apligraf had a statistically significant (P<.05) lower incidence of osteomyelitis at the study site (2.7% vs 10.4%) compared to the patients treated with conventional therapy at 6 months. (These data compare with 8.9% vs 3.1% respectively at sites other than the study ulcer.)
    All patients were screened at baseline and underwent x-ray evaluation for clinical signs of infection
  • Apligraf ® — Lower Frequency of Amputation
    Apligraf treated patients required significantly fewer amputations/resections of the study limb. (6.3% vs 15.6%) (P<.05) compared to patients treated with conventional therapy at 6 months
  • Frequency of Complete Wound Closure at 12 Weeks
    At the 12-week follow-up, 51% of the bi-layered cell therapy-treated patients achieved complete wound healing compared with 26.3% in the control group (P=0.049, Fisher’s exact test)
  • There is also a significant economic burden associated with diabetic lower extremity ulcers.
    For simple ulcers treated on an outpatient basis, i.e., not requiring intravenous antibiotics or amputation, the average cost per ulcer episode is conservatively estimated at $7,000-$8,000. An infected ulcer needing debridement, hospitalization, and antibiotics cost $17,000-18,000.
    The cost can increase to $45,000 or more, if amputation becomes necessary, excluding the cost of long-term rehabilitation.
    References:
    1. Reiber GE, Boyko EJ, Smith DG. Lower Extremity Foot Ulcers and Amputations in Diabetes. In Diabetes in America, 2nd edition. Bethesda, Md. National Diabetes Data Group, National Institutes of Health, NIDDK, NIH Publication No. 95-1468, 1995.
  • Transcript

    • 1. Evidenced Based Wound CareEvidenced Based Wound Care Robert S. Kirsner, M.D., PhDRobert S. Kirsner, M.D., PhD Department of Dermatology and Cutaneous SurgeryDepartment of Dermatology and Cutaneous Surgery Department of Epidemiology and Public HealthDepartment of Epidemiology and Public Health University of Miami Miller School of MedicineUniversity of Miami Miller School of Medicine Miami, FloridaMiami, Florida
    • 2. University of Miami/University of Miami/ Jackson Memorial Medical CenterJackson Memorial Medical Center
    • 3. How Do We Make Decisions About What toHow Do We Make Decisions About What to Use in a Wound?Use in a Wound? Randomized Controlled Trials are the Gold StandardRandomized Controlled Trials are the Gold Standard
    • 4. What’s The EvidenceWhat’s The Evidence US Preventative Services Task Force. Guide to Clinical Preventative Services. 1996 Gray M, et al. J WOCN 2004;31:53-61 Vacuum Assisted Closure for Pressure Ulcers Silver dressings for pressure ulcers
    • 5. What is Evidence Based Medicine?What is Evidence Based Medicine? The conscientious, explicit and judicious use ofThe conscientious, explicit and judicious use of current best evidence in making decisionscurrent best evidence in making decisions about the care of individual patientsabout the care of individual patients11 This impliesThis implies  An analysis of the strengths and weaknessesAn analysis of the strengths and weaknesses of scientific medical studiesof scientific medical studies  Proper interpretation when communicatingProper interpretation when communicating treatment choices to the patienttreatment choices to the patient 1. Centre for Evidence-Based Medicine1. Centre for Evidence-Based Medicine
    • 6. Why Do We Need EBM?Why Do We Need EBM? A clinical practice deemed effective based onA clinical practice deemed effective based on common sense or experience may, in fact, becommon sense or experience may, in fact, be ineffective, or even harmfulineffective, or even harmful  Improvements may be for reasons otherImprovements may be for reasons other than the interventionthan the intervention – The placebo effectThe placebo effect – Natural resolution of the conditionNatural resolution of the condition  The proper use of available evidenceThe proper use of available evidence should aide (not replace!) clinician trainingshould aide (not replace!) clinician training and experienceand experience
    • 7. What EBM is NotWhat EBM is Not  ‘‘Ivory tower’ medicine confined toIvory tower’ medicine confined to academic and research centersacademic and research centers  Beyond the reach of the averageBeyond the reach of the average practitionerpractitioner  ‘‘Cookbook’ medicineCookbook’ medicine – The use of guidelines and protocols canThe use of guidelines and protocols can simplify the EBM process for the averagesimplify the EBM process for the average practitionerpractitioner  Cost-cutting medicineCost-cutting medicine – The practice of EBM frequently results inThe practice of EBM frequently results in significant cost savings (good medicinesignificant cost savings (good medicine is cost-efficient)is cost-efficient)
    • 8. Components of EBMComponents of EBM  Step 1: Ask a question:Step 1: Ask a question: – Does the use of bioengineered tissue leadDoes the use of bioengineered tissue lead to improved healing in patients with diabeticto improved healing in patients with diabetic foot ulcers?foot ulcers? – What is the treatment for venous ulcers?What is the treatment for venous ulcers? – Is debridement important in chronic woundIs debridement important in chronic wound care?care?
    • 9. Components of EBMComponents of EBM  Step 2: Track down the best evidence to answerStep 2: Track down the best evidence to answer that question using:that question using: – www.pubmed.govwww.pubmed.gov – www.cochrane.orgwww.cochrane.org – www.cebm.netwww.cebm.net – www.ovid.comwww.ovid.com – www.guideline.govwww.guideline.gov – Etc., etc., etc.Etc., etc., etc.
    • 10. Growth Factors With Positive Results in RCTGrowth Factors With Positive Results in RCT Acute WoundsAcute Wounds Donor SitesDonor Sites EGFEGF GHGH Burn WoundsBurn Wounds FGFFGF Punch Biopsy SitesPunch Biopsy Sites PDGFPDGF Chronic WoundsChronic Wounds Venous Leg UlcersVenous Leg Ulcers GM-CSFGM-CSF CGRP+VIPCGRP+VIP Diabetic Foot UlcersDiabetic Foot Ulcers PDGFPDGF EGFEGF NGF (foot ulcers)NGF (foot ulcers)
    • 11. Components of EBMComponents of EBM  Step 3: Critically evaluate the evidence for itsStep 3: Critically evaluate the evidence for its validity, importance, and usefulness in clinicalvalidity, importance, and usefulness in clinical practicepractice  Step 4: Integrate the critical evaluation withStep 4: Integrate the critical evaluation with your clinical expertise and the patient’syour clinical expertise and the patient’s individual problems/needsindividual problems/needs
    • 12. Is Time an Issue?Is Time an Issue? Read Systematic Reviews!Read Systematic Reviews! A systematic review is a summary of the medicalA systematic review is a summary of the medical literature that uses explicit methods to performliterature that uses explicit methods to perform a thorough literature search and criticala thorough literature search and critical appraisal of individual studies.appraisal of individual studies. A meta-analysis may be performed as well. ThisA meta-analysis may be performed as well. This is a systematic review that uses statisticalis a systematic review that uses statistical methods to summarize the results.methods to summarize the results.
    • 13. Cochrane CollaborationCochrane Collaboration  www.cochrane.orgwww.cochrane.org Wounds groupWounds group Summaries for freeSummaries for free Fee for full reportFee for full report
    • 14. EBM: Levels of EvidenceEBM: Levels of Evidence (US Preventive Services Taskforce)(US Preventive Services Taskforce)  Level I: at least oneLevel I: at least one randomized controlled trialrandomized controlled trial  Level II-1: controlled trialsLevel II-1: controlled trials without randomizationwithout randomization  Level II-2:Level II-2: cohort or case-controlcohort or case-control analytic studiesanalytic studies – preferably from more than one center or researchpreferably from more than one center or research groupgroup  Level II-3:Level II-3: multiple time seriesmultiple time series with / withoutwith / without interventionintervention – Includes dramatic results in uncontrolled trialsIncludes dramatic results in uncontrolled trials  Level III:Level III: Opinions of respected authoritiesOpinions of respected authorities based onbased on – Clinical experienceClinical experience – Descriptive studiesDescriptive studies – Reports of expert committeesReports of expert committees
    • 15. Strength ofStrength of EvidenceEvidence (Wound Healing Society)(Wound Healing Society)  Level I: Meta-analysis or at least twoLevel I: Meta-analysis or at least two randomized controlled trials (RCT)randomized controlled trials (RCT)  Level II: At least one RCT and at least oneLevel II: At least one RCT and at least one significant seriessignificant series  Level III: Suggestive data supportingLevel III: Suggestive data supporting principle, but lacking meta-analyses, RCTprinciple, but lacking meta-analyses, RCT or multiple clinical seriesor multiple clinical series
    • 16. Clinical Guidelines and/or AlgorithmsClinical Guidelines and/or Algorithms  Fast, accessible resource for clinicians toFast, accessible resource for clinicians to make patient care decisionsmake patient care decisions  Usually the result of multidisciplinaryUsually the result of multidisciplinary teamworkteamwork  Released by governmental agencies,Released by governmental agencies, professional organizations, universities,professional organizations, universities, individual authorsindividual authors  May vary in regards to strength of scientificMay vary in regards to strength of scientific evidenceevidence Eddy DM. Health Affairs 2005;24:9-17
    • 17.  Wound Healing Society – www.woundheal.org  Association for the Advancement of Wound Care – WWW.AAWCONE.COM Venous UlcersVenous Ulcers Clinical Guidelines and/or AlgorithmsClinical Guidelines and/or Algorithms Summary Algorithm for Venous Ulcer Care with Annotations of Available Evidence  Guidelines for the treatment of venous ulcers Robson et al., Wound Repair Regen. 2006;14:649-62
    • 18. Validation of a Venous Ulcer GuidelineValidation of a Venous Ulcer Guideline  Both UK and US wound care settingsBoth UK and US wound care settings  Retrospective pre-guideline group (n=80 pts)Retrospective pre-guideline group (n=80 pts)  Prospective guideline treated group (n=80 pts)Prospective guideline treated group (n=80 pts) – ABI: pre=8-36% post=93-96%ABI: pre=8-36% post=93-96% – % healed increased% healed increased • 23% to 70% in the US23% to 70% in the US • 40% to 65% in the UK40% to 65% in the UK – Cost decreasedCost decreased • $825 to $113 in the US$825 to $113 in the US • £136 to £78 in the UK£136 to £78 in the UK Better Outcomes and More Cost-EffectiveBetter Outcomes and More Cost-Effective McGuckin, M., et al., Validation of venous leg ulcer guidelines in the United States and UnitedMcGuckin, M., et al., Validation of venous leg ulcer guidelines in the United States and United Kingdom. Am J Surg, 2002. 183(2): p. 132-7.Kingdom. Am J Surg, 2002. 183(2): p. 132-7.
    • 19. Wound Healing Society GuidelinesWound Healing Society Guidelines
    • 20. Diagnosis  Gross arterial disease should be ruled out byGross arterial disease should be ruled out by establishing that pedal pulses are presentestablishing that pedal pulses are present and/or that the ankle brachial index (ABI) isand/or that the ankle brachial index (ABI) is >0.8.>0.8.
    • 21. Mixed Arterial and Venous Ulcer
    • 22. Mixed Arterial and Venous Ulcer
    • 23. 5-year Mortality Rate5-year Mortality Rate 16% 18% 26% 38% 86% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Breast Cancer Hodgkin's Disease PAD Colon and Rectal Cancer Lung Cancer patients,% American Cancer Society Facts and Figures 2000.American Cancer Society Facts and Figures 2000. Kempczinski RF, Bernhard VM. Introduction and general considerations. In: RutherfordKempczinski RF, Bernhard VM. Introduction and general considerations. In: Rutherford RB, ed. Vascular Surgery. 3RB, ed. Vascular Surgery. 3rdrd ed. Philadelphia, PA: WB Saunders; 1989:643-652.ed. Philadelphia, PA: WB Saunders; 1989:643-652.
    • 24. DiagnosisDiagnosis  A biopsy should be obtained in a non healing wound to exclude other causes of ulcers that may mimic venous disease
    • 25. Squamous Cell CarcinomaSquamous Cell Carcinoma
    • 26. Venous Leg Ulcers – TreatmentsVenous Leg Ulcers – Treatments Standard of careStandard of care for VLUs isfor VLUs is multi-layeredmulti-layered compression bandagescompression bandages de Araujo T et al. Ann Intern Med. 2003 ;138):326-34 Valencia IC et al. J Am Acad Dermatol 2001;44:401-21
    • 27. TreatmentTreatment  Compression increases ulcer healing ratesCompression increases ulcer healing rates compared with no compressioncompared with no compression  Multi-layered systems are more effectiveMulti-layered systems are more effective than single-layered systemsthan single-layered systems – Elastic is superior to nonelasticElastic is superior to nonelastic  High compression is more effective thanHigh compression is more effective than low compressionlow compression Cochrane Data Base
    • 28. Nelson EA, et al., J Vasc Surg. 2007;45:134-141. Single Layer vs. Four Layer BandageSingle Layer vs. Four Layer Bandage
    • 29. Healing Ulcers In PracticeHealing Ulcers In Practice 30-60% of venous leg ulcers treated with30-60% of venous leg ulcers treated with multilayered compressionmultilayered compression will heal in 6 monthswill heal in 6 months Br J Surg. 2002;89:40-4. Arch Dermatol 1998;134:293-300Br J Surg. 2002;89:40-4. Arch Dermatol 1998;134:293-300
    • 30. Debridement for VLU
    • 31. Williams, D et al., Wound Rep Regen. 2005; 13:131-137. Debridement Improves HealingDebridement Improves Healing
    • 32. Addressing Bacteria in WoundsAddressing Bacteria in Wounds Pre-TreatmentPre-Treatment 2 Weeks Post-Treatment2 Weeks Post-Treatment
    • 33. Several RCTs showed Cadexomer Iodine plus Compression Speeds Healing Drosou A, Falabella AF, Kirsner RS: Wounds 2003;15:149-166.
    • 34. By week 4, Silver Foam reducedBy week 4, Silver Foam reduced ulcer size by 45% vs. 29% for Controlulcer size by 45% vs. 29% for Control Foam, p = 0.0344Foam, p = 0.0344 Improved healing Relativeulcerarea Weeks Silver Foam Foam Int Wound J 2005;2:64-73
    • 35. Evidenced Based Wound CareEvidenced Based Wound Care Oral AgentsOral Agents PentoxifyllinePentoxifylline AspirinAspirin
    • 36. Relative risk of healing with pentoxifylline compared with placebo (with compression therapy) Jull et al Lancet 2002 Pentoxifylline vs. PlaceboPentoxifylline vs. Placebo
    • 37. Pentoxifylline vs. PlaceboPentoxifylline vs. Placebo Nelson EA, et al., J Vasc Surg. 2007;45:134-141.
    • 38. Pentoxifylline Efficacy (400mg TID)Pentoxifylline Efficacy (400mg TID) Nelson EA, et al., J Vasc Surg. 2007;45:134-141.
    • 39. High Dose PentoxifyllineHigh Dose Pentoxifylline p 0.043≤ Vincent Falanga et al Wound Rep Reg 1999;7:208
    • 40. Predicting HealingPredicting Healing Carnac The MagnificentCarnac The Magnificent
    • 41. Large Ulcers of Long Duration Difficult to HealLarge Ulcers of Long Duration Difficult to Heal >5 cm>5 cm22 -- 1 point1 point >6 months duration>6 months duration -- 1 point1 point Thus a score or 0 to 2 was assigned to each ulcerThus a score or 0 to 2 was assigned to each ulcer In the University of Pennsylvania data setIn the University of Pennsylvania data set 93% of patients healed - score of 093% of patients healed - score of 0 65% of patients healed - score of 165% of patients healed - score of 1 13% of patients healed - score of 213% of patients healed - score of 2 Margolis DJ, Berlin JA, Strom BL: Which venous leg ulcers will heal with limb compression.Margolis DJ, Berlin JA, Strom BL: Which venous leg ulcers will heal with limb compression. Am J Med 2000;109:15-19Am J Med 2000;109:15-19..
    • 42. Falanga V, Moneta G.Falanga V, Moneta G. Vasc Surg.Vasc Surg. 1999; 33:197-210.1999; 33:197-210. Falanga V, Sabolinski ML.Falanga V, Sabolinski ML. Wounds.Wounds. 2000; 12:42A-46A.2000; 12:42A-46A. Sheehan P, et al.Sheehan P, et al. Diabetes CareDiabetes Care. 2003;26(6):1879-1882.. 2003;26(6):1879-1882. Other Predictors of HealingOther Predictors of Healing  Healing rate at 4 weeksHealing rate at 4 weeks predicts overall healing ratepredicts overall healing rate  Initial healing rates of >0.1Initial healing rates of >0.1 cm/wk correlate with healingcm/wk correlate with healing (40-50%)(40-50%)  Rapid identification ofRapid identification of patients who are unlikely topatients who are unlikely to respond to conventional carerespond to conventional care allows for earlierallows for earlier interventions with advancedinterventions with advanced therapiestherapies 0.00.0 2.02.0 4.04.0 6.06.0 8.08.0 10.010.0 12.012.0 4/24/2 4/84/8 4/144/14 4/204/20 4/264/26 5/25/2 5/85/8 Area , cmArea , cm22
    • 43. Advanced Therapy CriteriaAdvanced Therapy Criteria When you switch a patient to more advancedWhen you switch a patient to more advanced therapies, you must ask:therapies, you must ask:  Which patients need this and when toWhich patients need this and when to intervene?intervene?  Which product to use?Which product to use?  What is the evidence for the productWhat is the evidence for the product chosen?chosen? – Level of evidenceLevel of evidence – Strength of evidenceStrength of evidence – Approval typeApproval type – SafetySafety – EfficacyEfficacy
    • 44.  15 randomized controlled trials15 randomized controlled trials  Total N=768 patients in the studiesTotal N=768 patients in the studies  Compression used in 11 trialsCompression used in 11 trials  Treatments:Treatments: – Autologous skin graftAutologous skin graft – Frozen or fresh allograftsFrozen or fresh allografts – Bilayered skin cell therapy (n=345)Bilayered skin cell therapy (n=345) – Dermal cell replacement therapy (n=71)Dermal cell replacement therapy (n=71) – Porcine xenograftPorcine xenograft Best Way to Heal VLUs with Grafts?Best Way to Heal VLUs with Grafts?
    • 45. Jones JE et al Cochrane Database of Systematic Reviews 2007;1:CD001737.pub3 Univ of YorkJones JE et al Cochrane Database of Systematic Reviews 2007;1:CD001737.pub3 Univ of York Meta-AnalysisMeta-Analysis No evidence to indicate STSG is better than Standard ofNo evidence to indicate STSG is better than Standard of CareCare
    • 46. Jones JE et al Cochrane Database of Systematic Reviews 2007;1:CD001737.pub3 Univ of YorkJones JE et al Cochrane Database of Systematic Reviews 2007;1:CD001737.pub3 Univ of York Meta-AnalysisMeta-Analysis Apligraf increases probability of healing compared to Standard of CareApligraf increases probability of healing compared to Standard of Care
    • 47. Cochrane Collaboration A bilayered artificial skin (inA bilayered artificial skin (in conjunction with compressionconjunction with compression bandaging), increases the chance ofbandaging), increases the chance of healing a venous ulcer compared withhealing a venous ulcer compared with compression and a simple dressing.compression and a simple dressing. TreatmentTreatment
    • 48. 6060 4 Weeks4 Weeks PercentofPatientsWithPercentofPatientsWith Ulcers100%ClosedUlcers100%Closed 5050 4040 3030 2020 1010 00 8 Weeks8 Weeks 12 Weeks12 Weeks 24 Weeks24 Weeks Apligraf vs Compression TherapyApligraf vs Compression Therapy Control (n=110)Control (n=110) Apligraf (n=130)Apligraf (n=130) All Patients Achieving 100% ClosureAll Patients Achieving 100% Closure ApligrafApligraf®® in Venous Leg Ulcersin Venous Leg Ulcers PP=.022=.022 4040 5757 By 24 weeksBy 24 weeks PP=.022.=.022. Falanga V, et al.Falanga V, et al. Arch Dermatol.Arch Dermatol. 1998;134:293-300.1998;134:293-300.
    • 49. 6060 4 Weeks4 Weeks %Patientswith%Patientswith ClosedWoundsClosedWounds 5050 4040 3030 2020 1010 00 8 Weeks8 Weeks 12 Weeks12 Weeks 24 Weeks24 Weeks Control (n=48) Apligraf (n=72) Falanga V. Sabolinski M.Falanga V. Sabolinski M. Wound Repair RegenWound Repair Regen. 1999;7:201-207.. 1999;7:201-207. 6 10 10 32 13 40 19 47 P=.008 P=.001 P=.002 ApligrafApligraf®® In VLU of >1 Year DurationIn VLU of >1 Year Duration
    • 50. Care of the Diabetic Foot Ulcer
    • 51. GLOBAL PROJECTIONS FOR THE DIABETESGLOBAL PROJECTIONS FOR THE DIABETES EPIDEMIC: 2003-2025 (millions)EPIDEMIC: 2003-2025 (millions) 25.0 39.7 59% 25.0 39.7 59% 10.4 19.7 88% 10.4 19.7 88% 38.2 44.2 16% 38.2 44.2 16% 1.1 1.7 59% 1.1 1.7 59% 13.6 26.9 98% 13.6 26.9 98% WorldWorld 2003 = 1892003 = 189 millionmillion 2025 = 3242025 = 324 million 81.8 156.1 91% 81.8 156.1 91% 18.2 35.9 97% 18.2 35.9 97%
    • 52. 14-20% patients will require a lower extremity amputation ~ 86,000 leg amputations / year 85% amputations are preceded by a lower extremity ulcer 15% (2.4 million) develop a foot ulcer during their lifetime 18.2 million diabetics (6.3% U.S. population) 798,000 new cases/yr Diabetic Neuropathic Ulcers
    • 53. EBM for Diabetic Foot UlcerEBM for Diabetic Foot Ulcer  All patients with diabetes should have annual footAll patients with diabetes should have annual foot exams (at least)exams (at least)  Greater monitoring in at risk patientsGreater monitoring in at risk patients (neuropathy, vascular, history of(neuropathy, vascular, history of ulceration, foot deformities)ulceration, foot deformities)  Noninfected neuropathic ulcersNoninfected neuropathic ulcers require sharp debridement andrequire sharp debridement and pressure reductionpressure reduction  Ulcers with signs of infection requireUlcers with signs of infection require sharp debridement and deep culturesharp debridement and deep culture  Foot ulcers that are not responding withFoot ulcers that are not responding with appropriate wound care atappropriate wound care at 4 weeks4 weeks, should, should be considered for adjuvant care (growthbe considered for adjuvant care (growth factors, tissue engineered skin) and reassessedfactors, tissue engineered skin) and reassessed Boulton AJM, Kirsner RS, Vileikyte L. N Engl J Med. 2004;351:48-55.
    • 54. Guidelines for the Care of PatientsGuidelines for the Care of Patients with Diabetic Foot Ulcerswith Diabetic Foot Ulcers  Multiple guidelines/algorithms:Multiple guidelines/algorithms: – American Diabetes AssociationAmerican Diabetes Association – American College of Foot and Ankle SurgeonsAmerican College of Foot and Ankle Surgeons – Wound, Ostomy, Continence Nurses SocietyWound, Ostomy, Continence Nurses Society – American Pharmaceutical AssociationAmerican Pharmaceutical Association – American Orthopaedic Foot and Ankle SocietyAmerican Orthopaedic Foot and Ankle Society – International Working Group on the DiabeticInternational Working Group on the Diabetic FootFoot – Infectious Diseases Society of AmericaInfectious Diseases Society of America – Wound Healing SocietyWound Healing Society
    • 55. Protocol for Diabetic Foot Ulcer  Objective evaluation for ischemiaObjective evaluation for ischemia  Rule out osteomyelitisRule out osteomyelitis  Sharp debridementSharp debridement  Moist wound healingMoist wound healing  Off-loadingOff-loading
    • 56. Amputations in Diabetic Foot InfectionsAmputations in Diabetic Foot Infections  Improved outcomes (healing) with decreased ratesImproved outcomes (healing) with decreased rates of major LEA and reduced LOS throughof major LEA and reduced LOS through multidisciplinary team approach and/or Criticalmultidisciplinary team approach and/or Critical PathwayPathway – Gibbons et al Arch Surg 1993 77%Gibbons et al Arch Surg 1993 77% ↓↓ – Larsson et al Diab Med 1995 78%Larsson et al Diab Med 1995 78% ↓↓ – Crane, Werber JFAS 1999 70%Crane, Werber JFAS 1999 70% ↓↓ – Holstein Diabetes Care 1999 ~80%Holstein Diabetes Care 1999 ~80%↓↓ – Driver Diabetes Care 2005Driver Diabetes Care 2005 ~82%~82%↓↓
    • 57. Management Options for Offloading the PatientManagement Options for Offloading the Patient With a Plantar UlcerWith a Plantar Ulcer  Complete bed rest  Wheel chair confinement  Crutches, walker (with protective footwear)
    • 58. Wedge ShoeWedge Shoe Ipos or Darco Wedge ShoeIpos or Darco Wedge Shoe
    • 59. Surgical ShoeSurgical Shoe with Pressure Relief Insolewith Pressure Relief Insole Darco med-surg shoeDarco med-surg shoe with ‘peg assist’ systemwith ‘peg assist’ system
    • 60. Removable Cast Walker /Walking Boot DH Walker –DH Walker – AKA Active Off-loading WalkerAKA Active Off-loading Walker
    • 61. Cost $125 - 350
    • 62. Total Contact CastTotal Contact Cast Custom TCCCustom TCC
    • 63. Total Contact CastTotal Contact Cast ITCC – Instant Total Contact CastITCC – Instant Total Contact Cast
    • 64. 70 60 50 40 30 20 10 0 EasyStepWalker TotalContactCast HalfShoe FeltedFoam PostOpShoe CanvasShoe Wounds 2000; 12(6 Suppl B): 32B Mean Peak Pressure Metatarsal Heads
    • 65. Contraindications  Infection—Wagner Grade 3  Severe arterial disease  Inexperience of clinician applying the cast  Non-compliance  Skin conditions that precludes its use  Contact allergies  Osteomyelitis  Atrophic skin  Blindness  Obesity  Ataxia
    • 66. Understanding and Improving ComplianceUnderstanding and Improving Compliance With Off-loading:With Off-loading:
    • 67. Diabetes Care 24:1019-1022, 2001Diabetes Care 24:1019-1022, 2001 Armstrong et al: Diabetes Care 24:1019-1022, 2001
    • 68. Debridement of Diabetic Foot UlcersDebridement of Diabetic Foot Ulcers
    • 69. Debridement of Diabetic Foot UlcersDebridement of Diabetic Foot Ulcers 5 RCTs of debridement were identified in The5 RCTs of debridement were identified in The Cochrane DatabaseCochrane Database  3 RCTs assessed the effectiveness of a hydrogel3 RCTs assessed the effectiveness of a hydrogel  1 RCT evaluated surgical debridement1 RCT evaluated surgical debridement  1 RCT evaluated larval therapy.1 RCT evaluated larval therapy. Conclusion: Surgical debridement and larvalConclusion: Surgical debridement and larval therapy showed no significant benefit intherapy showed no significant benefit in these small trials. Hydrogel; no significantthese small trials. Hydrogel; no significant evidenceevidence The Cochrane Database of Systematic Reviews 2007 Issue 1
    • 70. Benefit of DebridementBenefit of Debridement Steed DT, et al., 1996
    • 71. Debridement Performance Index  The Scoring System 3 categories: callus, edges & undermining, necrotic tissue Saap & Falanga Wound Rep Reg 2002; 10(6):354-359 Score range (0-2) 0 Debridement needed & not done 1 Debridement needed & done 2 Debridement not needed
    • 72. Debridement Performance IndexDebridement Performance Index 143 patients with diabetic wounds143 patients with diabetic wounds Lower baseline Debridement Performance Index =Lower baseline Debridement Performance Index = lower incidence of wound closure by week 12 (p=0.0276)lower incidence of wound closure by week 12 (p=0.0276) Higher Debridement Performance IndexHigher Debridement Performance Index (3-6) 2.4 times more likely to heal than scores of 0-2(3-6) 2.4 times more likely to heal than scores of 0-2 Saap & Falanga 2002 Wound Rep Regen; 10(6):354-359Saap & Falanga 2002 Wound Rep Regen; 10(6):354-359
    • 73. Debridement to Normal TissueDebridement to Normal Tissue HyperkeratoticHyperkeratotic TissueTissue DebridementDebridement toto this Areathis Area Tomic-Canic, Ayello, Stojadinovic et al (2008) ASWC in press
    • 74. Protocol for Diabetic Foot Ulcer  Objective evaluation for ischemiaObjective evaluation for ischemia  Rule out osteomyelitisRule out osteomyelitis  Sharp debridementSharp debridement  Moist wound healingMoist wound healing  Off-loadingOff-loading
    • 75. Diabetes Care. 1999;22:692-695Diabetes Care. 1999;22:692-695. HEALING OF DIABETIC NEUROPATHIC FOOT ULCERSHEALING OF DIABETIC NEUROPATHIC FOOT ULCERS RECEIVING STANDARD TREATMENT:RECEIVING STANDARD TREATMENT:  A systematic review of the Control groups ofA systematic review of the Control groups of 9 randomized clinical trials9 randomized clinical trials  Endpoints of complete closureEndpoints of complete closure – At 12 weeks: 4 Control groupsAt 12 weeks: 4 Control groups – At 20 weeks: 6 Control groupsAt 20 weeks: 6 Control groups – Complete closure in 24% and 31%, at 12 Weeks and 20 Weeks, respectively Analysis of >26000 Diabetic Neuropathic Foot UlcersAnalysis of >26000 Diabetic Neuropathic Foot Ulcers 30-45% of diabetic foot ulcers heal in a 32 week30-45% of diabetic foot ulcers heal in a 32 week periodperiod Diabetes Care 2001;24:483-8Diabetes Care 2001;24:483-8
    • 76. Wound Healing Trajectories as Predictors of Effectiveness of Therapeutic AgentsWound Healing Trajectories as Predictors of Effectiveness of Therapeutic Agents Robson MC, Hill DP,Robson MC, Hill DP, WoodskeWoodske ME, Steed DL: ArchME, Steed DL: Arch SurgSurg 2000;135:773-777.2000;135:773-777.
    • 77. Protocol for Diabetic Foot Ulcer  Objective evaluation for ischemiaObjective evaluation for ischemia  Rule out osteomyelitisRule out osteomyelitis  Sharp debridementSharp debridement  Moist wound healingMoist wound healing  Off-loadingOff-loading  Adjunctive therapyAdjunctive therapy
    • 78. FDA-Approved Treatments For DFUFDA-Approved Treatments For DFU  Regranex (1997)Regranex (1997) – PDGF-BBPDGF-BB  Apligraf (2000)Apligraf (2000) – Cultured Keratinocytes and Fibroblasts inCultured Keratinocytes and Fibroblasts in collagen matrixcollagen matrix  Dermagraft (2001)Dermagraft (2001) – Fibroblast on Vicryl MeshFibroblast on Vicryl Mesh
    • 79. Steed DL, the Diabetic Ulcer Study Group; Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J Vasc Surg 1995;21:71-81.
    • 80. Regranex Incidence of Complete Healing of DFURegranex Incidence of Complete Healing of DFU at 20 Weeksat 20 Weeks
    • 81. Case
    • 82. Improved Healing With TissueImproved Healing With Tissue Engineered Skin for Diabetic UlcersEngineered Skin for Diabetic Ulcers Apligraf®Apligraf®Dermagraft®Dermagraft® OR healing 1.7xOR healing 1.7x (p=0.044)(p=0.044) Diabetes Care 2003;26:1701-5Diabetes Care 2003;26:1701-5 Diabetes Care 2001;24:290-295.Diabetes Care 2001;24:290-295. OR healing 2.1xOR healing 2.1x (95% CI 1.23-3.74)(95% CI 1.23-3.74)
    • 83. 1818 1414 1010 66 44 22 00 1616 1212 88 PP<.05.<.05. Veves A, et al.Veves A, et al. Diabetes CareDiabetes Care.. 2001;24:290-5.2001;24:290-5. %ofPatients%ofPatients Incidence of Osteomyelitis at the Study Ulcer SiteIncidence of Osteomyelitis at the Study Ulcer Site 10.4%10.4% 2.7%2.7% Lower Incidence of OsteomyelitisLower Incidence of Osteomyelitis Conventional therapy aloneConventional therapy alone (debridement, saline dressings,(debridement, saline dressings, total off-loading) [n=96]total off-loading) [n=96] ApligrafApligraf®® (n=112)(n=112) PP<.05<.05
    • 84. 1818 1414 1010 66 44 22 00 1616 1212 88 PP<.05.<.05. Veves A, et al.Veves A, et al. Diabetes CareDiabetes Care.. 2001;24:290-5.2001;24:290-5. %ofPatients%ofPatients Lower Frequency of AmputationLower Frequency of Amputation Conventional therapy aloneConventional therapy alone (debridement, saline dressings,(debridement, saline dressings, total off-loading) [n=96]total off-loading) [n=96] Apligraf (n=112)Apligraf (n=112) Frequency of Amputation/Resection of the Study LimbFrequency of Amputation/Resection of the Study Limb 15.6%15.6% 6.3%6.3% PP<.05<.05
    • 85. Frequency of Complete Wound Closure at 12 Weeks ApligrafApligraf Standard treatmentStandard treatment 3333 3939 5151 2626 0.0490.049 TreatmentTreatment NN %% ClosedClosed Fisher’sFisher’s Exact TestExact Test (two-tailed)(two-tailed) Edmonds M, et al.Edmonds M, et al. WoundsWounds. 2005:17(3) A43.. 2005:17(3) A43. APLIGRAFAPLIGRAF®® DIABETIC FOOT ULCER EU STUDYDIABETIC FOOT ULCER EU STUDY Phase IV StudiesPhase IV Studies
    • 86. EvidenceEvidence •Patient dataPatient data •Basic, clinical, andBasic, clinical, and epidemiologicalepidemiological researchresearch •Randomized trialsRandomized trials •Systematic reviewsSystematic reviews •Practice GuidelinesPractice Guidelines Patient/ProviderPatient/Provider FactorsFactors •Cultural beliefsCultural beliefs •Personal valuesPersonal values •ExperienceExperience •EducationEducation ConstraintsConstraints •Policies, lawsPolicies, laws •CommunityCommunity standardsstandards •TimeTime •ReimbursementReimbursement ClinicalClinical DecisionDecision Elements of Medical Decision MakingElements of Medical Decision Making Davidoff F. Mt. Sinai J Med 1999;66(2):75-83.
    • 87. Average costAverage cost per ulcer episode:per ulcer episode: Diabetic Neuropathic UlcersDiabetic Neuropathic Ulcers $8,000 $45,000 UncomplicatedUncomplicated woundwound If amputationIf amputation is requiredis required Reiber GE, Boyko EJ, Smith DG. LowerReiber GE, Boyko EJ, Smith DG. Lower Extremity Foot Ulcers and Amputations in Diabetes.Ulcers and Amputations in Diabetes. In Diabetes in America, 2nd edition. Bethesda, Md. National Diabetes Data Group, NationalIn Diabetes in America, 2nd edition. Bethesda, Md. National Diabetes Data Group, National Institutes of Health, NIDDK, NIH Publication No. 95-1468, 1995.Institutes of Health, NIDDK, NIH Publication No. 95-1468, 1995.
    • 88. Evidenced Based Wound CareEvidenced Based Wound Care
    • 89. ConclusionConclusion Evidence based wound care usesEvidence based wound care uses techniques to answer a clinicaltechniques to answer a clinical problem for the betterment ofproblem for the betterment of patient carepatient care
    • 90. University of Miami