Effectiveness and Tolerability of Hyaluronic Acid (HA) for Chronic Wound Healing: A Systematic Review S T U D E N T: AT I K A H S H A H A R U D I N ( M G N 1 3 0 0 0 2 ) S U P E R V I S O R : P R O F. M A D YA D AT I N DR. Z O R I A H A Z I Z
2 Outline Background study Justification of the study Aim & Objectives Methods Results Limitations Conclusions References
3 Background study Chronic wounds defined as wounds that delayed to heal in the normal healing process (Caravaggi, C. et al., 2011). most common types: ulcers Venous ulcer Pressure ulcer Diabetic foot ulcer
4 Hyaluronic Acid (HA) HA is found naturally in skin tissues, eyes, bones, cartilages structures, synovial fluid, tendons and ligaments and connective tissues. Two main characteristics: physicochemical properties biologic functions
5 Justification of study 1. HA is increasingly used, several formulations have been developed 2. No clear evidence on the effectiveness of HA to wound healing 3. Update the previous review
6 Aim To critically assess the current evidences on the effectiveness and tolerability of Hyaluronic Acid (HA) for patients with chronic wounds
7 Objectives 1. Describe the characteristics of randomized controlled trials of HA for the management of patients with chronic wounds 2. Assess efficacy and tolerability of HA for the management of patients with chronic wounds 3. Conduct a risk of bias assessment for all randomized controlled trials included in this review 4. Conduct a meta-analysis if the trials have consistent quantitative outcome measures and pooling of data are appropriate
8 Methods Criteria for considering studies in this review Studies: Participants: Outcomes: All published and unpublished RCTs evaluate effects of HA All age and gender Chronic wounds of any aetiology in any care settings Exclude: studies on corneal, foetal, bone, joint Wound area reduction Number of wounds healed Pain intensity Adverse events
9 Methods Dressings containing HA vs Interventions : Topical preparations of HA vs Dressings without HA Dressings containing other agents Topical preparations containing other agents Placebo/standard treatments (topical) Other topical agents Dressing containing other agents
10 Methods Identification (search terms)+ screening Data collection & extraction Risk of bias assessment Data analysis
11 Results of search terms + selection studies Identification 3381 studies identified through electronic databases searching + 860 studies after duplicates removed 85 studies identified through searching of other sources Screening 860 titles & abstracts screened 810 irrelevant studies were excluded
Results of search terms+ selection 12 studies Eligibility 50 full text papers obtained and assessed for eligibility of inclusion 40 studies excluded Reason for exclusion Non RCTs: 12 Comparison on diff. formulation of HA: 7 Review paper: 4 Different population: 12 No control group: 4 Secondary outcome only: 1 Inclusion 10 studies included in qualitative synthesis 8 studies included in quantitative synthesis
13 Results Characteristics of included studies Study Mostly in European countries Year of study from 1996-2012 Participants Male & Female, Age: >18 875 patients Arterial/venous leg ulcer, diabetic foot ulcer Duration of study Range from 3 weeks to 18 months
Results Characteristics of included studies 14 Interven tion & Control Arterial / venous leg ulcer: HA gauze pad vs normal gauze pad Hyalofill-F vs paraffin gauze Hyaloskin dressing vs OASIS dressing Hydrocolloid + HA dressing vs Hydrocolloid only dressing Ialuset vs DuoDERME HA gauze pad vs Dextranomer paste Hyalofill-F vs Intrasite Gel Ialuset cream vs neutral vehicle cream Diabetic foot ulcer HYAFF11 vs paraffin gauze HYAFF-Hyalograft 3D & laserkin autograft vs paraffin gauze
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Results Graph: Methodological Quality of RCTs 16
17 Results: Primary outcomes Summary of Interventions Effect Outcome Measured Studies included No. of Participants Results of pooled estimate Wound area reduction Number of wounds healed 4 studies Intervention: 225 Control: 220 7 studies Intervention: 390 Control: 384 WMD= -2.00 95% CI= -3.77 to -0.23 P = 0.03 RR=1.14 95% CI= 0.83 to 1.57 P = 0.42
18 Results: Secondary outcomes Summary of Interventions Effect Outcome Measured Studies included No. of Participants Results of pooled estimate Pain intensity 3 studies Intervention: 158 Control: 157 WMD= -9.67 95% CI= -15.20 to -4.15 P = 0.0006 Adverse events 7 studies Intervention: 390 Control: 384 RD= -0.02 95% CI= -0.07to 0.03 P = 0.38
19 Language Restriction BM, English, Chinese Limitations Difficulty in combining outcome effect from various studies Due to different parameter used Essential data could not be calculated High heterogeneity among included studies due to variation in Definitions of healing Duration of treatment Varying quality
20 Conclusions Implications for practice HA is either better or no worse than the comparator Inconclusive evidence to determine the effectiveness and tolerability of HA for chronic wound healing Implications for research High quality evidence regarding the use of HA is still limited, more good quality of RCTs are warranted Use of bias assessment tools & standardized outcome measures is needed among practitioners
21 References 1. Capila I, Sasisekharan R. Methods for Analysis of Hyaluronan and Its Fragments. In: Garg HG, Hales CA, eds. Chemistry and biology of hyaluronan. 1st ed ed: Amsterdam ; Boston : Elsevier, c2004., 2004:21-40. 2. Caravaggi C, Grigoletto F, Scuderi N. Wound Bed Preparation With a Dermal Substitute (Hyalomatrix PA) Facilitates Re-epithelialization and Healing: Results of a Multicenter, Prospective, Observational Study on Complex Chronic Ulcers (The FAST Study). Wounds: A Compendium of Clinical Research & Practice 2011;23(8):228-35 3. Higgins JP, Altman DG. Assessing risk of bias in included studies. In: Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions, 2012:187-235. 4. Lazarus GS, Cooper D, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Wound Repair & Regeneration 1994;2:165-170 5. Voigt J, Driver VR. Hyaluronic acid derivatives and their healing effect on burns, epithelial surgical wounds, and chronic wounds: a systematic review and meta-analysis of randomized controlled trials. Wound Repair And Regeneration: Official Publication Of The Wound Healing Society [And] The European Tissue Repair Society 2012;20(3):317-31 doi: 10.1111/j.1524-475X.2012.00777.x. 6. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Effect Sizes Based on Means. Introduction to Meta- Analysis. United Kingdom: John Wiley & Sons, Ltd, 2009:21-32. 7. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Fixed-Effect Versus Random-Effects Models. Introduction to Meta-Analysis: John Wiley & Sons, Ltd., 2009 1-10. 8. Humbert P, Mikosinki J, Benchikhi H, Allaert FA. Efficacy and safety of a gauze pad containing hyaluronic acid in treatment of leg ulcers of venous or mixed origin: a double-blind, randomised, controlled trial. International wound journal 2012;10(2):159-66 doi: 10.1111/j.1742-481X.2012.00957.x 9. Meaume S, Ourabah Z, Romanelli M, et al. Efficacy and tolerance of a hydrocolloid dressing containing hyaluronic acid for the treatment of leg ulcers of venous or mixed origin. Current medical research and opinion 2008; 24(10).
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