***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
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    Input: OBJECTIVE Determine the cost-effectiveness of extracellular matrix ( ECM ) relative to human fibroblast-derived dermal substitute ( HFDS ) on  diabetic foot ulcer ( DFU ) wound closure .  METHOD Outcomes data were obtained from a 12-week , r and omised , clinical trial of adults aged 18 years or older diagnosed with type 1 or type 2 diabetes with a DFU . Patients were treated with either ECM or HFDS treatment . A two-state Markov model ( healed and unhealed ) with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of closed-wound weeks and the expected DFU cost per patient . Results were recorded over 12 weeks to estimate the number of closed-wound weeks per treatment and the average cost to achieve epithelialisation ( primary outcome ) . The perspective of the analysis was that of the payer , specifically the Centers for Medicare and Medicaid Services . No cost discounting was performed because of the short duration of the study . RESULTS The study consisted of 26 patients , with 13 in each group . In the ECM group , 10 wounds closed ( 77 % ) , with an average closure time of 36 days ; 11 wounds closed in the HFDS group ( 85 % ) , with an average closure time of 41 days . There was no significant difference between these results ( p=0.73 ) . Over 12 weeks , the expected cost per DFU was $ 2522 ( £ 1634 ) for ECM and $ 3889 ( £ 2524 ) for HFDS . Patients treated with HFDS  incurred total treatment costs that were approximately 54 % higher than those treated with ECM . Sensitivity analyses revealed that the total cost of care for two applications of HFDS was more costly than eight applications of ECM by approximately $ 500 ( £ 325 ) . CONCLUSION In patients with DFU  , ECM yielded similar clinical outcomes to HFDS but at a lower cost . Health-care providers should consider ECM as a cost-saving alternative to HFDS . DECLARATION OF INTEREST A.M. Gilligan , and C.R. Waycaster , are employees of Smith & Nephew Inc .. This study was funded by Smith & Nephew Inc .. A.L. L and sman , reports no conflicts of interest An estimated 25 % of all people with diabetes may experience a foot ulcer in their lifetime , which may lead to serious complications including infection and amputation . A prospect i ve , multicenter , r and omized , controlled clinical trial was conducted to compare an in vitro-engineered , human fibroblast-derived dermal skin ( HFDS ) substitute and a biologically active cryopreserved human skin allograft ( HSA ) to determine the relative number of diabetic foot ulcers ( DFUs ) healed ( 100 % epithelialization without any drainage ) and the number of grafts required by week 12 . Secondary variables included the proportion of healed patients at weeks 16 and 20 , time to healing during the study , and wound size progression .  The 23 eligible participants ( 11 r and omized to the HSA , 12 to the HFDS group ) were recruited from two hospital-based outpatient wound care centers . Baseline patient ( body mass index , age , gender , race , type and duration of diabetes , presence of neuropathy and /or peripheral arterial disease , tobacco use ) and wound characteristics ( size and duration ) were recorded , and follow-up visits occurred every week for up to 20 weeks . Descriptive and multivariate regression analyses were used to compare wound outcomes . At baseline , no statistically significant differences between patients and wounds were observed . At week 12 , seven ( 63.6 % ) patients in the HSA and four ( 33.3 % ) in the HFDS group were healed ( P = 0.0498 ) . At the end of the 20-week evaluation period , 90.91 % of HSA versus 66.67 % of HFDS were healed ( P = 0.4282 ) . Among the subset of wounds that healed during the first 12 weeks of treatment , an average of 4.36 ( range 2 - 7 ) HSA grafts were applied versus 8.92 ( range 6 - 12 ) in the HFDS subset ( P < 0.0001 , SE 0.77584 ) . Time to healing in the HSA group was significantly shorter ( 8.9 weeks ) than in the HFDS group ( 12.5 weeks ) ( log-rank test , P = 0.0323 ) . The results of this study are similar to previous outcomes reported using these treatment modalities and suggest that , after 12 weeks of care , DFUs managed with HSA are approximately twice as likely to heal as DFUs managed with HFDS with approximately half the number of grafts required . Research confirming these results with a larger sample size and in patients with different types of wounds is warranted OBJECTIVE To test the safety , efficacy , and immunological impact of a cultured allogeneic human skin equivalent ( HSE ) in the treatment of venous ulcers . DESIGN Prospect i ve , r and omized study . SETTING Multicenter study in the outpatient setting . INTERVENTION Each patient with a venous ulcer received either compression therapy alone or compression therapy and treatment with HSE . The patients were evaluated for  HSE safety , complete ( 100 % ) ulcer healing , time to wound closure , wound recurrence , and immune response to the HSE .  OUTCOME The study was completed as planned in 293 r and omized patients . RESULTS Treatment with HSE was more effective than compression therapy in the percentage of patients healed by 6 months ( 63 % vs 49 % ; P=.02 , Fisher exact test , 2-tailed ) and the median time to complete wound closure ( 61 days vs 181 days ; P=.003 , log-rank test ) . Treatment with HSE was superior to compression therapy in healing larger ( > 1000 mm2 ; P=.02 ) and deeper ulcers ( P=.003 ) and ulcers of more than 6 months ' duration ( P=.001 ) . Occurrence of adverse events was similar in both groups . No symptoms or signs of rejection occurred in response to treatment with HSE , and no  HSE-specific immune responses were detected in vitro to bovine collagen or to alloantigens expressed on keratinocytes or fibroblasts . CONCLUSIONS Treatment with HSE healed venous ulcers more rapidly and in more patients than compression therapy alone . There was no clinical or laboratory evidence of rejection or sensitization in response to HSE application . These data suggest that HSE represents a significant advance in the treatment of venous ulcers , particularly those that are difficult to heal A prospect i ve , multicenter , r and omized , controlled 12-week study was undertaken to evaluate the effectiveness of a human fibroblast-derived dermis for treating foot ulcers in the diabetic patient . This report summarizes the findings from one center . Following a 2-week screening period , patients were r and omized to either human fibroblast-derived dermis ( HFDD ) ( Dermagraft ) plus saline-moistened gauze or to the control group ( CT ) of saline-moistened gauze alone . Effectiveness end points were : 1 ) wound closure by week 12 , 2 ) time to wound closure , and 3 ) percent wound closure by week 12 . Safety was assessed by review of adverse events and laboratory findings . Patients r and omized to HFDD received an application at day 0 and up to seven additional treatments . All patients in each group received shoes with custom-molded inserts and were seen weekly . The study population was comprised of 28 patients ( 14 HFDD/14 CT ) with chronic ulcers ( > 6 weeks ' duration at time of screening ) . By week 12 , significantly more chronic ulcers healed in the HFDD group than in the CT group ( 71.4 % versus 14.3 % , p = .003 ) . Healed HFDD patients achieved wound closure significantly faster than CT patients ( p = .004 ) . Patients treated with HFDD showed a statistically significant higher percent of wound closure by week 12 than did CT patients ( p = .002 ) . The percent of patients who experienced an infection involving their study wound was less in the HFDD group than in the CT group . It was concluded that HFDD is a safe and effective treatment for chronic foot ulcers in diabetic patients Our purpose was to compare healing characteristics of diabetic foot ulcers treated with  dehydrated human amniotic membrane allografts ( EpiFix ® , MiMedx , Kennesaw , GA ) versus st and ard of care . An IRB-approved , prospect i ve , r and omised , single-centre clinical trial was performed . Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion . Patients were r and omised to receive st and ard care alone or st and ard care with the addition of EpiFix . Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated . In the st and ard care group ( n = 12 ) and the EpiFix group ( n = 13 ) wounds reduced in size by a mean of 32·0 % ± 47·3 % versus 97·1 % ± 7·0 % ( P < 0·001 ) after 4 weeks , whereas at 6 weeks wounds were reduced by −1·8 % ± 70·3 % versus 98·4 % ± 5·8 % ( P < 0·001 ) , st and ard care versus EpiFix , respectively . After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77 % and 92 % , respectively , whereas st and ard care healed 0 % and 8 % of the wounds ( P < 0·001 ) , respectively . Patients  treated with EpiFix  achieved superior healing rates  over st and ard treatment alone . These results show that using EpiFix in addition to st and ard care is efficacious for wound healing OBJECTIVE We assessed in a r and omized prospect i ve trial the effectiveness of Graftskin , a living skin equivalent , in treating noninfected nonischemic chronic plantar diabetic foot ulcers . RESEARCH DESIGN AND METHODS In 24 centers in the U.S. , 208 patients were r and omly assigned to ulcer treatment either with Graftskin ( 112 patients ) or saline-moistened gauze ( 96 patients , control group ) .  St and ard state-of-the-art adjunctive therapy , which included extensive surgical debridement and adequate foot off-loading , was provided in both groups . Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks ( maximum of five applications ) or earlier if complete healing occurred . The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit . RESULTS At the 12-week follow-up visit , 63 ( 56 % ) Graftskin-treated patients achieved complete wound healing compared with 36 ( 38 % ) in the control group ( P = 0.0042 ) . The Kaplan-Meier median time to complete closure was 65 days for Graftskin , significantly lower than the 90 days observed in the control group ( P = 0.0026 ) . The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 ( 95 % CI 1.23 - 3.74 ) . The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations , both of which were less frequent in the Graftskin group . CONCLUSIONS Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects . Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available st and ard of care OBJECTIVE To evaluate the clinical efficacy and safety of HYAFF 11-based autologous dermal and epidermal grafts in the management of diabetic foot ulcers . RESEARCH DESIGN AND METHODS A total of 79 patients with diabetic dorsal ( n = 37 ) or plantar ( n = 42 ) ulcers were r and omized to either the control group with nonadherent paraffin gauze ( n = 36 ) or the treatment group with autologous tissue-engineered grafts ( n = 43 ) . Weekly assessment , aggressive debridement , wound infection control , and adequate pressure relief ( fiberglass off-loading cast for plantar ulcers ) were provided in both groups . Complete wound healing was assessed within 11 weeks . Safety was monitored by adverse events . RESULTS Complete ulcer healing was achieved in 65.3 % of the treatment group and 49.6 % of the control group ( P = 0.191 ) . The Kaplan-Meier mean time to closure was 57 and 77 days , respectively , for the treatment versus control groups . Plantar foot ulcer healing was 55 % and 50 % in the treatment and control groups , respectively . Dorsal foot ulcer healing was significantly different , with 67 % in the treatment group and 31 % in the control group ( P = 0.049 ) . The mean healing time in the dorsal treatment group was 63 days , and the odds ratio for dorsal ulcer healing compared with the control group was 4. 
    Output:
    
Based on the studies included in this review , the overall therapeutic effect of skin grafts and tissue replacements used in conjunction with st and ard care shows an increase in the healing rate of foot ulcers and slightly fewer amputations in people with diabetes compared with st and ard care alone .