{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:25:27Z","timestamp":1790886327008,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T00:00:00Z","timestamp":1450828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Wound Journal"],"published-print":{"date-parts":[[2016,4]]},"abstract":"Abstract<\/jats:title>\n \n Advanced therapies such as bioengineered skin substitutes (\n BSS<\/jats:styled-content>\n ) and dehydrated human amnion\/chorion membrane (\n dHACM<\/jats:styled-content>\n ) have been shown to promote healing of chronic diabetic ulcers. An interim analysis of data from 60 patients enrolled in a prospective, randomised, controlled, parallel group, multi\u2010centre clinical trial showed that\n dHACM<\/jats:styled-content>\n (\n EpiFix<\/jats:styled-content>\n \u00ae,\n MiMedx<\/jats:styled-content>\n Group Inc., Marietta,\n GA<\/jats:styled-content>\n ) is superior to standard wound care (\n SWC<\/jats:styled-content>\n ) and\n BSS<\/jats:styled-content>\n (Apligraf\u00ae, Organogenesis, Inc., Canton,\n MA<\/jats:styled-content>\n ) in achieving complete wound closure within 4\u20136 weeks. Rates and time to closure at a longer time interval and factors influencing outcomes remained unassessed; therefore, the study was continued in order to achieve at least 100 patients. With the larger cohort, we compare clinical outcomes at 12 weeks in 100 patients with chronic lower extremity diabetic ulcers treated with weekly applications of Apligraf (\n n<\/jats:italic>\n = 33),\n EpiFix<\/jats:styled-content>\n (\n n<\/jats:italic>\n = 32) or\n SWC<\/jats:styled-content>\n (\n n<\/jats:italic>\n = 35) with collagen\u2010alginate dressing as controls. A Cox regression was performed to analyse the time to heal within 12 weeks, adjusting for all significant covariates. A Kaplan\u2013Meier analysis was conducted to compare time\u2010to\u2010heal within 12 weeks for the three treatment groups. Clinical characteristics were well matched across study groups. The proportion of wounds achieving complete closure within the 12\u2010week study period were 73% (24\/33), 97% (31\/32), and 51% (18\/35) for Apligraf,\n EpiFix<\/jats:styled-content>\n and\n SWC<\/jats:styled-content>\n , respectively (adjusted\n P<\/jats:italic>\n = 0\u00b700019). Subjects treated with\n EpiFix<\/jats:styled-content>\n had a very significant higher probability of their wounds healing [hazard ratio (\n HR<\/jats:styled-content>\n : 5\u00b766; adjusted\n P<\/jats:italic>\n : 1\u00b73 x 10\n \u22127<\/jats:sup>\n ] compared to\n SWC<\/jats:styled-content>\n alone. No difference in probability of healing was observed for the Apligraf and\n SWC<\/jats:styled-content>\n groups. Patients treated with Apligraf were less likely to heal than those treated with\n EpiFix<\/jats:styled-content>\n [\n HR<\/jats:styled-content>\n : 0\u00b730; 95% confidence interval\n (CI)<\/jats:styled-content>\n : 0\u00b717\u20130\u00b754; unadjusted\n P<\/jats:italic>\n : 5\u00b78 x 10\n \u22125<\/jats:sup>\n ]. Increased wound size and presence of hypertension were significant factors that influenced healing. Mean time\u2010to\u2010heal within 12 weeks was 47\u00b79 days (95%\n CI<\/jats:styled-content>\n : 38\u00b72\u201357\u00b77) with Apligraf, 23\u00b76 days (95%\n CI<\/jats:styled-content>\n : 17\u00b70\u201330\u00b72) with\n EpiFix<\/jats:styled-content>\n group and 57\u00b74 days (95%\n CI<\/jats:styled-content>\n : 48\u00b72\u201366\u00b76) with the\n SWC<\/jats:styled-content>\n alone group (adjusted\n P<\/jats:italic>\n = 3\u00b72 x 10\n \u22127<\/jats:sup>\n ). Median number of grafts used per healed wound were six (range 1\u201313) and 2\u00b75 (range 1\u201312) for the Apligraf and\n EpiFix<\/jats:styled-content>\n groups, respectively. Median graft cost was $8918 (range $1,486\u201319,323) per healed wound for the Apligraf group and $1,517 (range $434\u201325,710) per healed wound in the EpiFix group (\n P<\/jats:italic>\n \u2009<\u20090\u00b70001). These results provide further evidence of the clinical and resource utilisation superiority of\n EpiFix<\/jats:styled-content>\n compared to Apligraf for the treatment of lower extremity diabetic wounds.\n <\/jats:p>","DOI":"10.1111\/iwj.12566","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T03:38:42Z","timestamp":1450841922000},"page":"272-282","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":167,"title":["Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a prospective, randomised, controlled, multi\u2010centre comparative study examining clinical efficacy and cost"],"prefix":"10.1111","volume":"13","author":[{"given":"Charles M","family":"Zelen","sequence":"first","affiliation":[{"name":"Professional Education and Research Institute Roanoke VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E","family":"Serena","sequence":"additional","affiliation":[{"name":"Serena Group Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5167-4679","authenticated-orcid":false,"given":"Lisa","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Wound Recovery Center Kent Hospital Warwick RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam","family":"Le","sequence":"additional","affiliation":[{"name":"St. John Wound Care Tulsa OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa J","family":"Carter","sequence":"additional","affiliation":[{"name":"Strategic Solutions, Inc. Cody WY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Keller","sequence":"additional","affiliation":[{"name":"Shenandoah Lower Extremity Research Troutville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W","family":"Li","sequence":"additional","affiliation":[{"name":"The Angiogenesis Foundation Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,23]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0270"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-9021"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4801.2005.00085.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2625"},{"key":"e_1_2_5_6_1","first-page":"197","article-title":"Wound percent area reduction and making decisions about utilizing advanced therapies","volume":"29","author":"Snyder R","year":"2010","journal-title":"Podiatry Manage"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2006.00176.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-8422(02)00018-6"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASW.0000288217.83128.f3"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.324.7330.160"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13169-8"},{"key":"e_1_2_5_12_1","first-page":"55","volume-title":"Implementing comparative effectiveness research: priorities, methods and impact","author":"Pearson S","year":"2009"},{"key":"e_1_2_5_13_1","unstructured":"HoC TranK HuxM SibbaldG CampbellK. 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