VALUE ANALYSIS BRIEF:

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

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 as a microbial barrier against bacteria most commonly associated with SSI, including S. aureus, P. aeruginosa, E. coli, E. faecium, and S. epidermidis.*,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.**,11-13

− 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.

*Clinical significance is unknown **Study performed ex vivo

2

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)26-28

− Patient factors (e.g., age, comorbidities, smoking)29-32

• Infection at the wound site prolongs inflammation and immune response, potentially leading to the wound becoming chronic and non-healing.33,34

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

• 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.35-37

• 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)

Abbreviations: BMI = body mass index; LOS = length of stay; MRSA = Methicillin-resistant Staphylococcus aureus; MRSE = Methicillin-resistant Staphylococcus epidermidis

“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

Surgical site infections are reported to occur in up to 19% and 28% of knee and hip arthroplasties respectively.4

The odds of a surgical site infection are reported to be 8-fold greater with wound dehiscence.35

Burden of SSIs in Hip and Knee Arthroplasty4,5

Extended LOS

Re-admissions

Mortality

Total Costs

Patient Experience

2 to 3 fold increase in LOS

2 fold increased re-admission rate

1.2% to 56% mortality over 1 year

3 fold increase in hospital costs

Decreased quality of life

3

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%.38-40

• 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.

− 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 − Pathogen exposure

− Increased risk of pain − Restricted self-care

− Time-consuming − Post-operative care burden

• 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.

“Controversy exists as to the best method of wound closure after orthopedic procedures such as lower limb joint arthroplasty...”1

“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

UNMET NEED

4

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

1. Liquid topical skin adhesive (2-octyl cyanoacrylate) formulation which sets in ~60 seconds when applied to mesh.8

2. Flexible self-adhesive polyester mesh that initiates 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 as a microbial barrier against bacteria most commonly associated with SSIs, including S. aureus, P. aeruginosa, E. coli, E. faecium, and S. epidermidis 9,10

• Demonstrated in vitro inhibition of MRSA and MRSE. **

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 sutures41,43

− Decreased skin closure time by 5.19 to 13.66 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 days42 and up to 1 year15,41,43

− Less pain at removal compared to adhesive strips15

− Low rates of adverse events (e.g., blistering or infection)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.44-47

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.18

− Less pain at removal vs other wound closure methods15, 41, 43

− Good cosmetic results.15,41,43

Abbreviations: MRSE = Methicillin-resistant Staphylococcus epidermidis *See appendix for full list of references. **Clinical significance is unknown

DERMABOND™ PRINEO™ System is the only skin closure device to combine a topical skin adhesive with a self-adhering mesh.

DERMABOND™ PRINEO™ System has demonstrated favorable cosmesis, closure time, and pain outcomes in randomized trials across a variety of surgery types.15,41-43

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

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

Tension Distribution of DERMABOND™ PRINEO™ System• The DERMABOND™ PRINEO™ System (22 cm) has demonstrated the

following benefits pertaining to tension distribution:

− Distributes 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

DERMABOND™ PRINEO™ System has demonstrated statistically significant greater skin holding strength than skin staples or subcuticular suture.11

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

Comparative Skin-Holding Strengths11

150

100

50

0

Mea

n M

ax L

oad

(N)

prio

r to

3mm

gap

(±1m

m)

DERMABOND™ PRINEO™Skin Closure System (22cm)

Skin Staples 4-0 SubcuticularSuture

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

166.5

112.498.7

Mapping of tissue movement under 1 lb of tensile load

3-0 Suture

Intactincision line

Skin Staples

More Tissue Movement

Less Tissue Movement

DERMABOND PRINEOSkin Closure System (22cm)

Undesired stress concentrations

Key

Too much movement near incision

Undesired stress concentrated far from incision

6

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:

*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 arthroplasty22,23

− 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

* 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%)

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

“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

Resource

Wound Closure Devices

Wound Dressing

Operative Time

Hospital Stay*

Surgical Site Infection

Nursing Time*

Physician Office Visit

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 minute2

$2,212 per inpatient day49

$36,651 per case4 (range: $11,224 to $88,134)

$34.14 per hour50

$118 per visit19

Unit Costs

Total Weighted Costs for MS-DRG Categories for Total Joint Arthroplasty*51

Mean index stay payment (facility)

Mean index stay payment (professional fees)

Mean index postacute care payments

Mean readmission payment

55%

32%

9%

4%

7

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.54-57

• 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

− Hospitals must manage total bundle cost to meet price established by CMS

− Hospitals will also be rated on 2 quality metrics (complication rate and patient

satisfaction) which will affect net payment reconciliation amount

− Medicare target episode prices to inform penalties or rewards

− Bundled payments increasingly used with private insurers

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

− The microbial barrier addresses some of the risk factors for 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.

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

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 strength and protection which may help reduce costly healthcare resources, particularly in the post-acute care setting (e.g., dressing changes).

8

REFERENCES

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3. 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): e009257.

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6. Chowdhry M, Chen AF (2015) Wound dressings for primary and revision total joint arthroplasty. Ann Transl Med 3 (18): 268.

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9

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55. The Advisory Board Company (Web Page) Hospital Readmissions Reduction Program. Updated June 27, 2016. Available online at: https://www.advisory.com/research/health-care-industry-committee/members/resources/cheat-sheets/readmissions. Accessed: June 27, 2016.

56. The Advisory Board Company (Web Page) Hospital-Acquired Condition Reduction Program. Updated Available online at: https://www.advisory.com/research/health-care-industry-committee/members/resources/cheat-sheets/hac-reduction-program. Accessed: June 27, 2016.

57. 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): 157-165.

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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):703-8.

2. 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):307-313.

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):1418-1422.

4. 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):1067-1070.5. 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):391-395.6. 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):391-394.7. 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;106:87-89.8. 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):593-599.9. Greene D, Koch RJ, Goode RL. Efficacy of octyl-2-cyanoacrylate tissue glue in blepharoplasty. A prospective controlled study of wound-healing characteristics. Arch

Facial Plast Surg. 1999;1(4):292-296.10. Handschel JG, Depprich RA, Dirksen D, Runte C, Zimmermann A, Kübler NR. A prospective comparison of octyl-2- cyanoacrylate and suture in standardized facial

wounds. Int J Oral Maxillofac Surg. 2006;35(4):318-323.11. Holger JS, Wandersee SC, Hale DB. Cosmetic outcomes of facial lacerations repaired with tissue-adhesive, absorbable, and nonabsorbable sutures. Am J Emerg Med.

2004;22(4):254-257.12. Hollander JE, Singer AJ. Application of tissue adhesives: rapid attainment of proficiency. Acad Emerg Med. 1998;5(10):1012-101713. Jallali N, Haji A, Watson CJ. A prospective randomized trial comparing 2-octyl cyanoacrylate to conventional suturing in closure of laparoscopic cholecystectomy

incisions. J Laparoendosc Adv Surg Tech A. 2004;14(4):209-211.14. Khan RJ, Fick D, Yao F, Tang K, Hurworth M, Nivbrant B, Wood D. A comparison of three methods of wound closure following arthroplasty: A prospective, randomised,

controlled trial. J Bone Joint Surg Br. 2006;88(2):238-242.15. Krishnamoorthy B, Najam O, Khan UA, Waterworth P, Fildes JE, Yonan N. Randomized Prospective Study Comparing Conventional Subcuticular Skin Closure With

Dermabond Skin Glue After Saphenous Vein Harvesting. Ann Thorac Surg. 2009;88(5):1445-1449.16. Maartense S, Bemelman WA, Dunker MS, de Lint C, Pierik EG, Busch OR, Gouma DJ. Randomized study of the effectiveness of closing laparoscopic trocar wounds

with octylcyanoacrylate, adhesive papertape or poliglecaprone. Br J Surg. 2002;89(11):1370-1375.17. Man SY, Wong EM, Ng YC, Lau PF, Chan MS, Lopez V, Mak PS, Graham CA, Rainer TH. Cost-Consequence Analysis Comparing 2-Octyl Cyanoacrylate Tissue Adhesive

and Suture for Closure of Simple Lacerations: A Randomized Controlled Trial. Ann Emerg Med. 2009;53(2):189-197.18. Matin SF. Prospective randomized trial of skin adhesive versus sutures for closure of 217 laparoscopic port-site incisions. J Am Coll Surg. 2003;196(6):845-853.19. Mattick A, Clegg G, Beattie T, Ahmad T. A randomised, controlled trial comparing a tissue adhesive (2-octylcyanoacrylate) with adhesive strips (Steristrips) for paediatric

laceration repair. Emerg Med J. 2002;19(5):405-407.20. Mota R, Costa F, Amaral A, Oliveira F, Santos CC, Ayres-De-Campos D. Skin adhesive versus subcuticular suture for perineal skin repair after episiotomy - A randomized

controlled trial. Acta Obstet Gynecol Scand. 2009;88(6):660-666.21. Nipshagen MD, Hage JJ, Beekman WH. Use of 2-octyl-cyanoacrylate skin adhesive (dermabond) for wound closure following reduction mammaplasty: A prospective,

randomized intervention study. Plast Reconstr Surg. 2008;122(1):10-18.22. Ong CC, Jacobsen AS, Joseph VT. Comparing wound closure using tissue glue versus subcuticular suture for pediatric surgical incisions: A prospective, randomised

trial. Pediatr Surg Int. 2002;18(5-6):553-555.23. Ong J, Ho KS, Chew MH, Eu KW. Prospective randomised study to evaluate the use of DERMABOND ProPen (2- octylcyanoacrylate) in the closure of abdominal

wounds versus closure with skin staples in patients undergoing elective colectomy. Int J Colorectal Dis. 2010;25(7):899-905.24. Osmond MH, Quinn JV, Sutcliffe T, Jarmuske M, Klassen TP. A randomized, clinical trial comparing butylcyanoacrylate with octylcyanoacrylate in the management of

selected pediatric facial lacerations. Acad Emerg Med. 1999;6(3):171-177.25. Pronio A., Di Filippo A., Narilli P., Caporillli D., Vestri A., Ciamberlano B., Pelle F., Montesani C. Closure of cutaneous incision after thyroid surgery: A comparison between

metal clips and cutaneous octyl-2-cyanoacrylate adhesive. A prospective randomized clinical trial. Eur J Plast Surg. 2011;34(2):103-110.26. Quinn J, Wells G, Sutcliffe T, Jarmuske M, Maw J, Stiell I, Johns P. A randomized trial comparing octylcyanoacrylate tissue adhesive and sutures in the management

of lacerations. JAMA. 1997;277(19):1527-1530.27. Ridgway DM, Mahmood F, Moore L, Bramley D, Moore PJ. A blinded, randomised, controlled trial of stapled versus tissue glue closure of neck surgery incisions. Ann R

Coll Surg Engl. 2007;89(3):242-246.28. Romero P, Frongia G, Wingerter S, Holland-Cunz S. Prospective, randomized, controlled trial comparing a tissue adhesive (Dermabond) with adhesive strips (Steri-

Strips™) for the closure of laparoscopic trocar wounds in children. Eur J Pediatr Surg. 2011;21(3):159-162.29. Sebesta MJ, Bishoff JT. Octylcyanoacrylate skin closure in laparoscopy. JSLS. 2004;8(1):9-14.30. Shamiyeh A, Schrenk P, Stelzer T, Wayand WU. Prospective randomized blind controlled trial comparing sutures, tape, and octylcyanoacrylate tissue adhesive for skin

closure after phlebectomy. Dermatol Surg. 2001;27(10):877-880.31. Singer AJ, Giordano P, Fitch JL, Gulla J, Ryker D, Chale S. Evaluation of a new high-viscosity octylcyanoacrylate tissue adhesive for laceration repair: a randomized,

clinical trial. Acad Emerg Med. 2003;10(10):1134-1137.32. Singer AJ, Hollander JE, Valentine SM, Turque TW, McCuskey CF, Quinn JV. Prospective, randomized, controlled trial of tissue adhesive (2- octylcyanoacrylate) vs

standard wound closure techniques for laceration repair. Acad Emerg Med. 1998;5(2):94-99.33. Singer AJ, Quinn JV, Clark RE, Hollander JE. Closure of lacerations and incisions with octylcyanoacrylate: a multicenter randomized controlled trial. Surgery.

2002;131(3):270-276.34. Sniezek PJ, Walling HW, DeBloom JR 3rd, Messingham MJ, VanBeek MJ, Kreiter CD, Whitaker DC, Arpey CJ. A randomized controlled trial of high-viscosity 2-octyl

cyanoacrylate tissue adhesive versus sutures in repairing facial wounds following Mohs micrographic surgery. Dermatol Surg. 2007;33(8):966-971.35. Strauss EJ, Weil WM, Jordan C, Paksima N. A Prospective, Randomized, Controlled Trial of 2-Octylcyanoacrylate Versus Suture Repair for Nail Bed Injuries. J Hand

Surg Am. 2008;33(2):250-253.36. Sun J, Chen Q-M, Zhang M, Shi C-R. Octylcyanoacrylate versus absorbable suture in the repair of skin wound in children. Chinese J Clin Rehabilitation. 2005;19:26-2937. Switzer EF, Dinsmore RC, North JH Jr. Subcuticular closure versus dermabond: A prospective randomized trial. Am Surg. 2003;69(5):434-436.38. Tierney EP, Moy RL, Kouba DJ. Rapid absorbing gut suture versus 2-octylethylcyanoacrylate tissue adhesive in the epidermal closure of linear repairs. J Drugs Dermatol.

2009;8(2):115-119.39. Toriumi DM, O’Grady K, Desai D, Bagal A. Use of octyl-2-cyanoacrylate for skin closure in facial plastic surgery. Plast Reconstr Surg. 1998;102(6):2209-2219.40. Zempsky WT, Parrotti D, Grem C, Nichols J. Randomized controlled comparison of cosmetic outcomes of simple facial lacerations closed with Steri-Strip™ Skin

Closures or Dermabond tissue adhesive. Pediatr Emerg Care. 2004;20(8):519-524.

11

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