title: A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers.
abstract: BACKGROUND
  Multiple adjunctive therapies have been proposed to accelerate wound healing in patients with diabetes and foot ulcers. The aim of this systematic review is to summarize the best available evidence supporting the use of hyperbaric oxygen therapy (HBOT), arterial pump devices, and pharmacologic agents (pentoxifylline, cilostazol, and iloprost) in this setting.
  
  
  METHODS
  We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest were complete wound healing and amputation.
  
  
  RESULTS
  We identified 18 interventional studies; of which 9 were randomized, enrolling 1526 patients. The risk of bias in the included studies was moderate. In multiple randomized trials, the addition of HBOT to conventional therapy (wound care and offloading) was associated with increased healing rate (Peto odds ratio, 14.25; 95% confidence interval, 7.08-28.68) and reduced major amputation rate (odds ratio, 0.30; 95% confidence interval, 0.10-0.89), compared with conventional therapy alone. In one small trial, arterial pump devices had a favorable effect on complete healing compared with HBOT and in another small trial compared with placebo devices. Neither iloprost nor pentoxifylline had a significant effect on amputation rate compared with conventional therapy. No comparative studies were identified for cilostazol in diabetic foot ulcers.
  
  
  CONCLUSIONS
  There is low- to moderate-quality evidence supporting the use of HBOT as an adjunctive therapy to enhance diabetic foot ulcer healing and potentially prevent amputation. However, there are only sparse data regarding the efficacy of arterial pump devices and pharmacologic interventions.
authors.affiliation: Evidence-based Practice Center, Mayo Clinic, Rochester, Minn.
authors.forename: Tarig
authors.initials: T
authors.lastname: Elraiyah
authors.affiliation: Second Medical Department, Aristotle University, Thessaloniki, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Tsapas
authors.affiliation: Evidence-based Practice Center, Mayo Clinic, Rochester, Minn; Unidad de Conocimiento y Evidencia, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Prutsky
authors.affiliation: Evidence-based Practice Center, Mayo Clinic, Rochester, Minn; Unidad de Conocimiento y Evidencia, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Domecq
authors.affiliation: Evidence-based Practice Center, Mayo Clinic, Rochester, Minn; Department of Internal Medicine, University of Missouri, Columbia, Mo.
authors.forename: Rim
authors.initials: R
authors.lastname: Hasan
authors.affiliation: Evidence-based Practice Center, Mayo Clinic, Rochester, Minn; Department of Internal Medicine, University of Missouri, Columbia, Mo.
authors.forename: Belal
authors.initials: B
authors.lastname: Firwana
authors.affiliation: Evidence-based Practice Center, Mayo Clinic, Rochester, Minn.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Nabhan
authors.affiliation: Mayo Clinic Libraries, Mayo Clinic, Rochester, Minn.
authors.forename: Larry
authors.initials: L
authors.lastname: Prokop
authors.affiliation: Department of Surgery, Lutheran Medical Center, Brooklyn, NY.
authors.forename: Anil
authors.initials: A
authors.lastname: Hingorani
authors.affiliation: Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, Minn.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Claus
authors.affiliation: Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, Minn.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Steinkraus
authors.affiliation: Evidence-based Practice Center, Mayo Clinic, Rochester, Minn; Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, Minn. Electronic address: murad.mohammad@mayo.edu.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
mesh_terms: D000368:Aged; D000077407:Cilostazol; D017719:Diabetic Foot / Q000188:drug therapy / Q000628:therapy*; D005260:Female; D006801:Humans; D006931:Hyperbaric Oxygenation; D016285:Iloprost / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000627:therapeutic use; D013777:Tetrazoles / Q000627:therapeutic use; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D013777:Tetrazoles; D014665:Vasodilator Agents; D016285:Iloprost; D000077407:Cilostazol; D010431:Pentoxifylline