VALUE ANALYSIS BRIEF: Clinical and Economic Evidence Supporting the Value of DERMABOND PRINEO Skin Closure System (22cm) in Hip and Knee Arthroplasty

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1 VALUE ANALYSIS BRIEF: Clinical and Economic Evidence Supporting the Value of DERMABOND PRINEO Skin Closure System (22cm) in Hip and Knee Arthroplasty

2 EXECUTIVE SUMMARY Burden of Wound Closure in Hip and Knee Arthroplasty Wound complications are one of the major sources of morbidity after hip and knee arthroplasty procedures and can prolong inpatient stay or lead to re-admissions. 1 Meta-analyses have reported that the rate of wound dehiscence and infections ranges from 1.3% to 4.8%, and from 3% to 20.9%, respectively. 2,3 Surgical site infections (SSIs) occur in up to 19% and 28% of knee and hip arthroplasties respectively, with Staphylococcus aureus as one of the leading causes. 4 SSIs are associated with a substantial burden, such as extended length of stay, excess mortality, reduced quality of life, increased readmissions, and a 3-fold increase in hospital costs. 4,5 Unmet Need There are several types of wound dressings used as part of wound closure care in hip and knee arthroplasty. 6 However, an important limitation is the need for dressing changes which can be associated with important clinical and economic burden such as pain, healthcare resource professional time, pathogen exposure, and potentially restricted self-care. 6,7 There is a need for a wound closure treatment that provides an ideal healing environment and helps reduce the clinical and economic burden of current care, such as frequent dressing changes, in hip and knee arthroplasty. Clinical Value of the DERMABOND PRINEO System The DERMABOND PRINEO Skin Closure System: The only skin closure device that combines the proven strength, flexibility, and antimicrobial protection of DERMABOND Topical Skin Adhesive with the added support and security of a self-adhering mesh to further facilitate both wound-edge approximation and an optimal healing environment which may be particularly useful in surgeries such as hip and knee arthroplasty. 8,9 Proven 99% effective through 72 hours in vitro against bacteria most commonly associated with SSI, including S. aureus, P. aeruginosa, E. coli, E. faecium, and S. epidermidis (including MRSA and MRSE).* 9,10 Demonstrated strength benefits compared to staples and sutures including: superior strength compared to 4-0 sutures or staples (p<0.01), equivalent strength to a 3-0 suture, and superior skin-holding strength vs. DERMABOND ADVANCED Topical Skin Adhesive with subcuticular sutures Demonstrated tension benefits with the ability to achieve better distribution of tension compared to staples or sutures. 9,14 There are numerous patient benefits associated with the DERMABOND PRINEO System that can help enhance patient satisfaction and comfort including easier self-care, less pain at removal, no need for dressing changes, and the ability to shower immediately after a procedure if directed by their healthcare practitioner. 8-10,15-18 Economic Value of the DERMABOND PRINEO System There are several costly resources associated with wound closure and care in hip and knee arthroplasty such as SSIs, wound care dressings, and outpatient visits. 4,19-21 Wound dressings are typically changed 3 to 5 times in hip and knee arthroplasty. 22,23 This results in an additional burden of increased staff time, potential risk for introducing SSI-causing pathogens to the wound, and material costs. 6,22,23 Evidence demonstrates that in hip and knee arthroplasty, use of a wound dressing that lowers the frequency of dressing changes and wound complications may be cost-effective despite additional upfront costs. 22 Given favorable outcomes observed, as well as the absence of need for wound dressing changes and staples removal, it is anticipated that the DERMABOND PRINEO System may provide important cost savings within hip and knee arthroplasty, particularly in the post-acute care setting. 2 *Clinical significance is unknown

3 WOUND BURDEN Hip and Knee Arthroplasty and Wound Complications The estimated number of annual total hip and knee arthroplasties in the United States is 2.5 million and 4.7 million, respectively. 24 Wound complications are common in hip and knee arthroplasty and can include dehiscence, infection, inflammation, necrosis, abscess, and blistering. 2,3,22 Meta-analyses have reported that the rate of wound dehiscence ranges from 1.3% to 4.8%, and the rate of infection ranges from 3% to 20.9%. 2,3 Factors that affect wound healing and associated complications include: Operative factors (e.g., antibiotic prophylaxis) 25,26 Wound factors (e.g., foreign body) Patient factors (e.g., age, comorbidities, smoking) Infection at the wound site prolongs inflammation and immune response, potentially leading to the wound becoming chronic and non-healing. 33,34 Wound complications are one of the major sources of morbidity after orthopedic procedures and can prolong the inpatient stay or lead to re-admission. 1 Clinical and Economic Burden of Surgical Site Infections Surgical site infections (SSIs) are common in hip and knee arthroplasty, with Staphylococcus aureus as one of the leading causes. 4 Hip arthroplasty (median SSI rate: 2.1%; range: 0.05% to 28%). 4 Knee arthroplasty (median SSI rate: 1.3%; range: 0.05% to 19%). 4 S. aureus accounted for 35% of all orthopaedic surgery SSIs, of which 35.7% were specifically attributed to MRSA infections. 4 Burden of SSIs in Hip and Knee Arthroplasty 4,5 Extended LOS Re-admissions 2 to 3 fold increase in LOS 2 fold increased re-admission rate Surgical site infections are reported to occur in up to 19% and 28% of knee and hip arthroplasties respectively. 4 Mortality Total Costs Patient Experience 1.2% to 56% mortality over 1 year 3 fold increase in hospital costs Decreased quality of life Some factors reported to be predictive for the risk of SSIs in hip and knee arthroplasty include osteoarthritis, diabetes, obesity, increasing age, wound dehiscence, duration of surgery, transfusions, wound drainage, length of stay, and bladder catheter A recent meta-analysis has shown several risk factors to significantly increase the risk of SSI, for example: 35 Diabetes Mellitus: odds ratio = 1.26; (p < 0.001) Prolonged Operative Time: odds ratio = 2.18; (p = 0.001) Obesity (BMI > 40): odds ratio = 3.74; (p < 0.001) Wound Dehiscence: odds ratio = 8.08; (p < 0.001) The odds of a surgical site infection are reported to be 8-fold greater with wound dehiscence. 35 Abbreviations: BMI = body mass index; LOS = length of stay; MRSA = Methicillin-resistant Staphylococcus aureus; MRSE = Methicillin-resistant Staphylococcus epidermidis 3

4 CURRENT TREATMENT Limitations of Sutures, Staples and Wound Dressings Recent studies of sutures and staples in hip and knee arthroplasty suggests that a considerable risk of wound complications remains. Rates of wound complications were reported to range from 3.8% to 19.5% Findings from meta-analyses have reported that wound dehiscence and infection risk is comparable or higher with staples versus sutures.1,3 Application of a wound dressing is necessary for proper wound management. 6 Wound dressings provide mechanical protection, absorb exudate, stop bleeding and help create environment suitable for healing. 6 However: Wound dressings are not intended for wound closure and thus do not have the strength necessary to close wounds. As such, separate wound closure methods are required in addition to the dressing. Controversy exists as to the best method of wound closure after orthopedic procedures such as lower limb joint arthroplasty... 1 Many wound dressings do not have bacterial inhibition properties. 6 An important limitation of several wound dressings is the need for dressing changes, which is associated with important clinical and economic burdens. 6,7 Patient dissatisfaction Increased risk of pain Time-consuming Pathogen exposure Restricted self-care Post-operative care burden UNMET NEED Current methods for wound closure, primarily sutures and staples, with a variety of wound dressings, may not provide an ideal healing environment due to: Need for frequent dressing changes. 6 Variability in patient, as well as caregiver, care. Minimizing postsurgical dressings and dressing changes may reduce risk for infection and allow easier self-care. 6 Several factors are cited as important goals of orthopedic wound closure and include: speed of wound healing, adequate closure, patient satisfaction, low complications, and cosmesis. 1,39 There is a need for a wound closure treatment that provides an ideal healing environment and helps to reduce the clinical and economic burden of current care such as the need for frequent dressing changes. The objective of good wound closure is rapid skin healing and an acceptable cosmetic result while minimizing risk of complications such as wound dehiscence or infection. 1 4

5 CLINICAL VALUE Features of DERMABOND PRINEO System The DERMABOND PRINEO System (22 cm) uses 2 unique components allowing for uncompromising strength and wound healing: 8,9 1. Liquid topical skin adhesive (2-octyl cyanoacrylate) formulation which sets in ~60 seconds when applied to mesh Flexible self-adhesive polyester mesh that accelerates polymerization of liquid adhesive and conforms to body s contours. 8 The dual components make the DERMABOND PRINEO System particularly useful in surgeries such as hip and knee arthroplasty The DERMABOND PRINEO System has proven 99% effective through 72 hours in vitro against bacteria most commonly associated with for SSIs, including S. aureus, P. aeruginosa, E. coli, E. faecium, and S. epidermidis (including MRSA and MRSE).* 9,10 DERMABOND PRINEO System is the only skin closure device to combine a topical skin adhesive with a selfadhering mesh. Clinical Studies of DERMABOND PRINEO System The DERMABOND PRINEO System has been studied in 4 randomized trials with a total of 430 patients evaluated across a variety of surgery types (abdominoplasty, breast, and trauma lacerations). 15,41-43 Comparable wound closure efficacy versus sutures 41,43 Decreased skin closure time by 5.19 to min (breast and abdominoplasty; p<0.0001) 41,43 and procedure time by 13 min (abdominoplasty; p<0.05) 15 relative to sutures. Favorable cosmetic results up to 30 days 42 and up to 1 year 15,41,43 Less pain at removal compared to adhesive strips 15 Low rates of adverse events (e.g., blistering or infection) 15,41-43 DERMABOND PRINEO System has demonstrated favorable cosmesis, closure time, and pain outcomes in randomized trials across a variety of surgery types. 15,41-43 The topical skin adhesive component of DERMABOND PRINEO System has been extensively studied in over 40 RCTs*, with several finding positive outcomes in hip and/or knee arthroplasty Patient Benefits of DERMABOND PRINEO System The DERMABOND PRINEO System (22 cm) design, supported with proven clinical data, contributes to numerous benefits that can help enhance patient comfort and satisfaction including: Easier self-care as post-surgical dressings are not needed (i.e., no dressing changes required). 16,17 Designed to provide microbial barrier protection against organisms commonly responsible for surgical site infections. 9,10 The ability for patients to shower immediately after procedure if directed by their healthcare practitioner. 8 Easy mesh tape removal when wound is sufficiently healed , 41, 43 Less pain at removal vs other wound closure methods Good cosmetic results. 15,41,43 Abbreviations: MRSE = Methicillin-resistant Staphylococcus epidermidis *See appendix for full list of references. *Clinical significance is unknown Patient Benefits with the DERMABOND PRINEO System include: No dressing changes Easy self-care Microbial barrier protection No suture or staple removal Good cosmetic results Can shower immediately Less pain at removal 5

6 CLINICAL VALUE Strength of DERMABOND PRINEO System The DERMABOND PRINEO System (22 cm) has demonstrated the following benefits pertaining to strength: Superior strength compared with 4-0 sutures or staples (p<0.01). 11 Equivalent strength to a 3-0 suture. 12 Superior skin-holding strength vs. DERMABOND ADVANCED Adhesive alone and DERMABOND ADVANCED Adhesive with subcuticular sutures (p<0.05). 13 Mean Max Load (N) prior to 3mm gap (±1mm) Comparative Skin-Holding Strengths DERMABOND PRINEO System has demonstrated statistically significant greater skin holding strength than skin staples or subcuticular suture DERMABOND PRINEO Skin Closure System (22cm) Skin Staples 4-0 Subcuticular Suture Tension load needed to achieve a 3-mm gap in porcine samples close with DERMABOND PRINEO Skin Closure System (22 cm), surgical staples or sutures. Incisions closed with DERMABOND PRINEO Skin Closure System (22 cm) required significantly greater loads to close the 3 mm gap. 48 Study performed ex vivo Tension Distribution of DERMABOND PRINEO System The DERMABOND PRINEO System (22 cm) has demonstrated the following benefits pertaining to tension distribution: Disperses tension gently and evenly across the entire incision area. 9 Better distribution of tension compared with staples or sutures. 14 Visual maps of tension across incisions revealed sutures and staples had high concentration points of tension while DERMABOND PRINEO System had more uniform tension distribution. 14 Key Mapping of tissue movement under 1 lb of tensile load Intact incision line More Tissue Movement Less Tissue Movement Undesired stress concentrations Too much movement near incision 3-0 Suture Skin Staples DERMABOND PRINEO Skin Closure System (22cm) Undesired stress concentrated far from incision 6 In a head-to-head study vs. staples and subcuticular sutures, incised tissue samples were approximated using 3-0 suture, skin staples or DERMABOND PRINEO System (22cm), respectively. Samples were then placed in a device and tensioned mechanically. Digital Image Correlation (DIC) technology was used to map strain (as revealed by tissue movement). Black spacing in mapping image is due to the sensors not being able to capture any readings. Study performed ex vivo

7 ECONOMIC VALUE Opportunity for Cost Savings in Hip and Knee Arthroplasty Several resources and costs are associated with wound closure in hip and knee arthroplasties. Some examples include the following: Resource Wound Closure Devices Wound Dressing Operative Time Hospital Stay* Surgical Site Infection Nursing Time* Physician Office Visit Unit Costs Traditional sutures: $2 to $83 (avg. material costs) 2 Barbed sutures: $24 to $106 (avg. material costs) 2 Staples: $6 to $8 23,45 $1 to $39 20,21 $28 to $103 per minute 2 $2,212 per inpatient day 49 $36,651 per case 4 (range: $11,224 to $88,134) $34.14 per hour 50 $118 per visit 19 There is the potential for cost savings with wound closure methods that reduce resource use, such as frequent dressing changes, nursing care, and length of hospital stay. 6 *National average cost per inpatient day and average cost for registered nurse, costs not specific to hip and knee. Wound dressings are typically changed 3 to 5 times in hip and knee arthroplasty 22,23 Results in the additional burden of increased staff time, potential risk for introducing SSI-causing pathogens to the wound, and material costs. 6,22,23 Evidence demonstrates that in hip and knee arthroplasty, use of a wound dressing that lowers the frequency of dressing changes and wound complications may be cost-effective despite additional upfront costs. 22 A recent study of 250 Medicare beneficiaries with total joint arthroplasty, including hip and knee replacements, reported that post-discharge payments accounted for 36% of the total episode-of-care payments. 51 Resource use in post-acute care, after hip and knee arthroplasty, such as dressing changes or staple removal, remains a top area of focus for optimizing costs for payers. 52 Post-discharge care costs were found to account for over 1/3 of total episode costs in total joint (e.g., hip and knee) arthroplasties. 51 Total Weighted Costs for MS-DRG Categories for Total Joint Arthroplasty* 51 32% 9% 4% 55% Mean index stay payment (facility) Mean index stay payment (professional fees) Mean index postacute care payments Mean readmission payment * Breakdown of procedures by MSRG in the total weighted costs include: MS-DRG 462 (2%), 466 (4%), 467 (19%), 468 (8%), 469 (9%), and 470 (58%) 7

8 ECONOMIC VALUE Current Healthcare Performance Metrics and Wound Closure U.S. healthcare reform goals are to improve quality of care, patient outcomes and satisfaction, and total performance scores (TPS) while reducing hospital acquired conditions (HAC) and episode of care costs Reimbursement implications associated with wound closure care in hip and knee replacement surgery: CMS stopped payment of HACs such as SSIs. 56 CMS will reduce payment to hospitals in top 25% of HAC rates. 56 Readmissions program: penalties for readmissions.55 Value Based Purchasing and potential impact to patient experience. 54 Bundled payment incentivize coordination across care continuum. 51,57 On April 1, 2016, CMS first mandatory bundle for hip and knee replacement was implemented in 67 U.S. regions (~800 hospitals). 53 This program established one price to compensate total joint providers for an entire episode of care, rather than the individual components of care: 53 Providers accountable for quality and cost of care to 90 days Fixed reimbursement amount to be shared among all providers Hospitals to keep costs below $25,565 per episode or face penalty Medicare target episode prices to inform penalties or rewards Bundled payments increasingly used with private insurers Comprehensive Care for Joint Replacement Model On April 1, 2016, CMS first mandatory bundle for hip and knee replacement was implemented for hospitals and doctors in 67 regions of the United States. 53 Current Healthcare Performance Metrics and Wound Closure The DERMABOND PRINEO System has the following advantages that may translate into less healthcare resources and avoided costs: 10 No need for wound dressing changes (i.e., avoided material costs and healthcare professional visits). 8 Antimicrobial protection to potentially help minimize the risk of SSIs. 10 No need for staple or suture removal, potentially avoiding follow-up visits. 8 The advantages with the DERMABOND PRINEO System are particularly important for managing post-acute care costs, which is an important consideration with recent health reform and bundled payments. DERMABOND PRINEO Skin Closure System may provide the potential for cost savings for hip or knee arthroplasty. The clinical and economic burden of wound closure in hip and knee arthroplasty in the U.S. is substantial. With recent healthcare reform, decision-makers will need to consider products that provide the best clinical outcomes while balancing costs. The DERMABOND PRINEO System is a wound closure product that provides uncompromised strength and protection which may help reduce costly healthcare resources, particularly in the post-acute care setting (e.g., dressing changes). 8

9 REFERENCES 1. Smith TO, Sexton D, Mann C, Donell S (2010) Sutures versus staples for skin closure in orthopaedic surgery: meta-analysis. BMJ 340 c Zhang W, Xue D, Yin H, Xie H, Ma H et al. (2016) Barbed versus traditional sutures for wound closure in knee arthroplasty: a systematic review and metaanalysis. Sci Rep Krishnan R, MacNeil SD, Malvankar-Mehta MS (2016) Comparing sutures versus staples for skin closure after orthopaedic surgery: systematic review and meta-analysis. BMJ Open 6 (1): e Patel H, Khoury H, Girgenti D, Welner S, Yu H (2016) Burden of Surgical Site Infections Associated with Arthroplasty and the Contribution of Staphylococcus aureus. Surg Infect (Larchmt) 17 (1): Whitehouse JD, Friedman ND, Kirkland KB, Richardson WJ, Sexton DJ (2002) The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost. 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10 REFERENCES 35. Zhu Y, Zhang F, Chen W, Liu S, Zhang Q et al. (2015) Risk factors for periprosthetic joint infection after total joint arthroplasty: a systematic review and metaanalysis. J Hosp Infect 89 (2): Kunutsor SK, Whitehouse MR, Blom AW, Beswick AD, Team I (2016) Patient-Related Risk Factors for Periprosthetic Joint Infection after Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. PLoS One 11 (3): e Gibbons C, Bruce J, Carpenter J, Wilson AP, Wilson J et al. (2011) Identification of risk factors by systematic review and development of risk-adjusted models for surgical site infection. Health Technol Assess 15 (30): 1-156, iii-iv. 38. Campbell AL, Patrick DA, Jr., Liabaud B, Geller JA (2014) Superficial wound closure complications with barbed sutures following knee arthroplasty. J Arthroplasty 29 (5): Buttaro MA, Quinteros M, Martorell G, Zanotti G, Comba F et al. (2015) Skin staples versus intradermal wound closure following primary hip arthroplasty: a prospective, randomised trial including 231 cases. Hip Int 25 (6): Patel RM, Cayo M, Patel A, Albarillo M, Puri L (2012) Wound complications in joint arthroplasty: comparing traditional and modern methods of skin closure. Orthopedics 35 (5): e Blondeel PN, Richter D, Stoff A, Exner K, Jernbeck J et al. (2014) Evaluation of a new skin closure device in surgical incisions associated with breast procedures. Ann Plast Surg 73 (6): Singer AJ, Chale S, Giardano P, Hocker M, Cairns C et al. (2011) Evaluation of a novel wound closure device: a multicenter randomized controlled trial. Acad Emerg Med 18 (10): Richter D, Stoff A, Ramakrishnan V, Exner K, Jernbeck J et al. (2012) A comparison of a new skin closure device and intradermal sutures in the closure of full-thickness surgical incisions. Plast Reconstr Surg 130 (4): Khan RJ, Fick D, Yao F, Tang K, Hurworth M et al. (2006) A comparison of three methods of wound closure following arthroplasty: a prospective, randomised, controlled trial. J Bone Joint Surg Br 88 (2): Eggers MD, Fang L, Lionberger DR (2011) A comparison of wound closure techniques for total knee arthroplasty. J Arthroplasty 26 (8): e El-Gazzar Y, Smith DC, Kim SJ, Hirsh DM, Blum Y et al. (2013) The use of dermabond(r) as an adjunct to wound closure after total knee arthroplasty: examining immediate post-operative wound drainage. J Arthroplasty 28 (4): Siddiqui M, Bidaye A, Baird E, Abu-Rajab R, Stark A et al. (2016) Wound dressing following primary total hip arthroplasty: a prospective randomised controlled trial. J Wound Care 25 (1): 40, Lo IK, Burkhart SS, Chan KC, Athanasiou K (2004) Arthroscopic knots: determining the optimal balance of loop security and knot security. Arthroscopy 20 (5): The Henry J Kaiser Family Foundation (Web Page) Hospital Adjusted Expenses per Inpatient Day. Updated Available online at: Accessed: May 12, United States Department of Labor: Bureau of Labor Statistics (2015). Occupational Employment and Wages, May 2015: Registered Nurses. Available online at: Accessed: May 18, Bozic KJ, Ward L, Vail TP, Maze M (2014) Bundled payments in total joint arthroplasty: targeting opportunities for quality improvement and cost reduction. Clin Orthop Relat Res 472 (1): Pasquale MK, Louder AM, Cheung RY, Reiners AT, Mardekian J et al. (2015) Healthcare Utilization and Costs of Knee or Hip Replacements versus Pain- Relief Injections. Am Health Drug Benefits 8 (7): Forbes (Web Page) Medicare s Bundled Fees Hit Knee, Hip Replacements. Updated Available online at: brucejapsen/2016/04/01/starting-today-medicares-bundled-fees-hit-hospitals-hard/#2e68bda315e4. Accessed: May 18, The Advisory Board Company (Web Page) Hospital Value-Based Purchasing. Updated Available online at: Accessed: June 27, The Advisory Board Company (Web Page) Hospital Readmissions Reduction Program. Updated June 27, Available online at: com/research/health-care-industry-committee/members/resources/cheat-sheets/readmissions. Accessed: June 27, The Advisory Board Company (Web Page) Hospital-Acquired Condition Reduction Program. Updated Available online at: research/health-care-industry-committee/members/resources/cheat-sheets/hac-reduction-program. Accessed: June 27, Froimson MI, Rana A, White RE, Jr., Marshall A, Schutzer SF et al. (2013) Bundled payments for care improvement initiative: the next evolution of payment formulations: AAHKS Bundled Payment Task Force. J Arthroplasty 28 (8 Suppl):

11 APPENDIX 1. Amin M, Glynn F, Timon C. Randomized trial of tissue adhesive vs staples in thyroidectomy integrating patient satisfaction and Manchester score. Otolaryngol Head Neck Surg. 2009;140(5): Blondeel, PNV, Murphy JW, Debrosse D, Nix III JC, Puls LE, Theodore N, Coulthard P. Closure of long surgical incisions with a new formulation of 2-octylcyanoacrylate tissue adhesive versus commercially available methods. Am J Surg. 2004;188(3): Brown JK, Campbell BT, Drongowski RA, Alderman AK, Geiger JD, Teitelbaum DH, Quinn J, Coran AG, Hirschl RB. A prospective, randomized comparison of skin adhesive and subcuticular suture for closure of pediatric hernia incisions: cost and cosmetic considerations. J Pediatr Surg. 2009;44(7): Bruns TB, Robinson BS, Smith RJ, Kile DL, Davis TP, Sullivan KM, Quinn JV. A new tissue adhesive for laceration repair in children. J Pediatr. 1998;132(6): Carleo C, Singer AJ, Thode HC Jr. Effect of frequent water immersion on the rate of tissue adhesive sloughing: a randomized study. CJEM. 2005;7(6): Chen K, Klapper AS, Voige H, Del Priore G. A randomized, controlled study comparing two standardized closure methods of laparoscopic port sites. JSLS. 2010;14(3): Eymann R, Kiefer M. Glue instead of stitches: a minor change of the operative technique with a serious impact on the shunt infection rate. Acta Neurochir Suppl. 2010;106: Gennari R, Rotmensz N, Ballardini B, Scevola S, Perego E, Zanini V, Costa A. A prospective, randomized, controlled clinical trial of tissue adhesive (2-octylcyanoacrylate) versus standard wound closure in breast surgery. Surgery. 2004;136(3): Greene D, Koch RJ, Goode RL. Efficacy of octyl-2-cyanoacrylate tissue glue in blepharoplasty. A prospective controlled study of wound-healing characteristics. 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