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A systematic review and meta-analysis of off-loading methods for diabetic foot ulcers

      Background

      Increased plantar foot pressure is one of several key factors that lead to diabetic foot ulcers. Multiple methods have been proposed to relieve this pressure and thus enhance wound healing and potentially prevent relapse. We aimed in this systematic review to find the best available evidence for off-loading methods.

      Methods

      We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest included complete wound healing, time to complete wound healing, amputation, infection, and relapse rates.

      Results

      We identified 19 interventional studies, of which 13 were randomized controlled trials, including data from 1605 patients with diabetic foot ulcers using an off-loading method. The risk of bias in the included studies was moderate. This analysis demonstrated improved wound healing with total contact casting over removable cast walker, therapeutic shoes, and conventional therapy. There was no advantage of irremovable cast walkers over total contact casting. There was improved healing with half-shoe compared with conventional wound care. Therapeutic shoes and insoles reduced relapse rate in comparison with regular footwear. Data were sparse regarding other off-loading methods.

      Conclusions

      Although based on low-quality evidence (ie, evidence warranting lower certainty), benefits are demonstrated for use of total contact casting and irremovable cast walkers in the treatment of diabetic foot ulcers. Reduced relapse rate is demonstrated with various therapeutic shoes and insoles in comparison with regular footwear.
      The etiology of diabetic foot ulcer is multifactorial; peripheral neuropathy, foot deformity, and trauma are considered the most common factors that contribute to it.
      • Reiber G.E.
      • Vileikyte L.
      • Boyko E.J.
      • del Aguila M.
      • Smith D.G.
      • Lavery L.A.
      • et al.
      Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.
      Other risk factors include but are not limited to peripheral vascular disease, increasing duration of diabetes, past history of foot ulcers or amputation, peripheral edema, and increase in plantar foot pressure.
      • Boulton A.J.
      The diabetic foot: from art to science. The 18th Camillo Golgi lecture.
      Around 50% of diabetic amputations are due to trauma caused by poorly fitting footwear.
      • Reiber G.E.
      • Smith D.G.
      • Wallace C.
      • Sullivan K.
      • Hayes S.
      • Vath C.
      • et al.
      Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial.
      Interventions that relieve the pressure are proposed to enhance wound healing and potentially prevent the relapse of ulcers, thus preventing amputations.
      • Maciejewski M.L.
      • Reiber G.E.
      • Smith D.G.
      • Wallace C.
      • Hayes S.
      • Boyko E.J.
      Effectiveness of diabetic therapeutic footwear in preventing reulceration.
      • Spencer S.
      Pressure relieving interventions for preventing and treating diabetic foot ulcers.
      Several methods are used for off-loading; the most efficient method among them is yet to be known.
      Our aim was to conduct a systematic review to evaluate the quality of the evidence supporting the existing off-loading methods and to estimate the magnitude of benefit and relative efficacy of each one of them.

      Methods

      This systematic review is protocol driven and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

       Eligibility criteria

      Eligible studies were randomized trials and controlled observational studies that enrolled patients with diabetic foot ulcers treated by any off-loading method compared with a different one and reported the outcomes of interest. We were interested in studies that assess the impact of the intervention on patient-important outcomes, such as rate of complete wound healing, time to complete wound healing, amputation, hospitalization, relapse, and infection rates. Studies were included regardless of language, size, or duration of patient follow-up. We excluded articles that were not original studies like review articles, commentaries, and letters. We also excluded uncontrolled studies.

       Study identification

      The search strategy was designed and conducted by an experienced reference librarian (L.J.P.) with input from the study's principle investigator (M.H.M.). A comprehensive search of several databases from each database's earliest inclusive dates to October 2011 was conducted. The databases included Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus. We identified additional candidate studies by review of bibliography of included articles and contact with experts. Controlled vocabulary supplemented with keywords was used to search for the topic: diabetic foot off-loading, limited to randomized and nonrandomized studies. The detailed search strategy is available in the Appendix (online only).

       Data collection

      All relevant abstracts were downloaded into an endnote library and uploaded into an online reference management system (DistillerSR). Reviewers working independently and in duplicate screened the abstracts for eligibility. Disagreements were automatically upgraded to the next level of screening. Full texts of eligible abstracts were retrieved and screened in duplicate. Disagreements at this level were resolved by discussion and consensus. We calculated the inter-reviewer agreement beyond chance (κ) during the full-text screening level. Using a standardized piloted web-based form, reviewers extracted descriptive, methodologic, and outcome data from all eligible studies.
      For each study, we abstracted the following descriptive data: detailed description of baseline characteristics (eg, main demographic characteristics, type and duration of diabetes, size and duration of the ulcer) and interventions received (active or control) for all participants enrolled. We also extracted data for outcomes and assessment of methodologic quality. Extracted data were collated by a third independent reviewer, and inconsistencies were resolved by referring to the full-text article.

       Methodologic quality and risk of bias assessment

      Two reviewers independently assessed the quality of studies included. Nonrandomized studies were evaluated using the Newcastle-Ottawa scale

      Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed September 7, 2015.

      ; we assessed outcome ascertainment, adjustment for confounders, proportion of patients lost to follow-up, and sample selection in each study. Randomized trials were evaluated using the Cochrane risk of bias assessment tool
      • Higgins J.P.T.
      • Altman D.G.
      Assessing risk of bias in included studies. Cochrane handbook for systematic reviews of interventions.
      ; domains assessed included randomization, blinding, allocation concealment, baseline imbalances, loss to follow-up data, and bias due to funding. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods.
      • Murad M.H.
      • Montori V.M.
      • Sidawy A.N.
      • Ascher E.
      • Meissner M.H.
      • Chaikof E.L.
      • et al.
      Guideline methodology of the Society for Vascular Surgery including the experience with the GRADE framework.
      • Murad M.H.
      • Swiglo B.A.
      • Sidawy A.N.
      • Ascher E.
      • Montori V.M.
      Methodology for clinical practice guidelines for the management of arteriovenous access.
      Following this approach, randomized trials are considered to warrant high-quality evidence (ie, high certainty), and observational studies warrant low-quality evidence. Then the evidence grading can be increased (if a large effect is observed) or decreased if other factors are noted, such as studies being at increased risk of bias or imprecise (small with wide confidence intervals [CIs]).

       Statistical analysis

      We pooled relative risk (RR) and 95% CI across included studies using random-effects meta-analysis described by DerSimonian and Laird.
      • DerSimonian R.
      • Laird N.
      Meta-analysis in clinical trials.
      For continuous outcomes, we pooled the weighted mean difference across studies. Between-studies heterogeneity was calculated by I2 statistic, which estimates the proportion of variation in results across studies that is not due to chance.
      • Higgins J.P.
      • Thompson S.G.
      • Deeks J.J.
      • Altman D.G.
      Measuring inconsistency in meta-analyses.
      Meta-analysis was completed using Comprehensive Meta-Analysis (CMA) version 2.2 (Biostat Inc, Englewood, NJ).

       Subgroup analysis and publication bias

      We did not perform any subgroup analyses because of the limited amount of studies that compared each intervention. Evaluation of publication bias was not feasible because of the small number of included studies per comparison.
      • Sterne J.A.
      • Sutton A.J.
      • Ioannidis J.P.
      • Terrin N.
      • Jones D.R.
      • Lau J.
      • et al.
      Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials.

      Results

       Search results and included studies

      The literature search yielded 675 potentially relevant abstracts. We identified 19 interventional studies (13 randomized controlled trials [RCTs] and six controlled observational studies) including data from 1605 patients with diabetic foot ulcers treated with an off-loading method that fulfilled our inclusion criteria and were eligible for data extraction, of which 6 reported sufficient data for meta-analyses (Fig 1). The interventions described included total contact casting (TCC), instant total contact casting (iTCC) or irremovable cast walkers, removable cast walker (RCW), therapeutic shoes and insoles, felted foam, pneumatic walkers, and conventional dressing.
      Figure thumbnail gr1
      Fig 1Flow diagram of how studies were screened and selected. RCTs, Randomized controlled trials.
      Studies in which irremovable casts were used excluded patients with ischemia. The definition of ischemia, however, varied across studies: absent foot pulse or a transcutaneous oxygen pressure (TcPo2) <40 mm Hg
      • Armstrong D.G.
      • Lavery L.A.
      • Wu S.
      • Boulton A.J.M.
      Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial.
      • Armstrong D.G.
      • Nguyen H.C.
      • Lavery L.A.
      • van Schie C.H.
      • Boulton A.J.
      • Harkless L.B.
      Off-loading the diabetic foot wound: a randomized clinical trial [erratum appears in Diabetes Care 2001;24:1509].
      ; ankle-brachial index (ABI) <0.6 or TcPo2 <30 mm Hg
      • Caravaggi C.
      • Faglia E.
      • Giglio R.D.
      • Mantero M.
      • Quarantiello A.
      • Sommariva E.
      • et al.
      Effectiveness and safety of a nonremovable fiberglass off-bearing cast versus a therapeutic shoe in the treatment of neuropathic foot ulcers: a randomized study.
      • Caravaggi C.
      • Sganzaroli A.
      • Fabbi M.
      • Cavaiani P.
      • Pogliaghi I.
      • Ferraresi R.
      • et al.
      Nonwindowed nonremovable fiberglass off-loading cast versus removable pneumatic cast (AircastXP Diabetic Walker) in the treatment of neuropathic noninfected plantar ulcers: a randomized prospective trial.
      ; ABI <0.9 or TcPo2 <50 mm Hg
      • Faglia E.
      • Caravaggi C.
      • Clerici G.
      • Sganzaroli A.
      • Curci V.
      • Vailati W.
      • et al.
      Effectiveness of removable walker cast versus nonremovable fiberglass off-bearing cast in the healing of diabetic plantar foot ulcer: a randomized controlled trial.
      ; absent dorsalis pedis and posterior tibial pulse
      • Katz I.A.
      • Harlan A.
      • Miranda-Palma B.
      • Prieto-Sanchez L.
      • Armstrong D.G.
      • Bowker J.H.
      • et al.
      A randomized trial of two irremovable off-loading devices in the management of plantar neuropathic diabetic foot ulcers.
      ; ABI <0.9
      • Piaggesi A.
      • Macchiarini S.
      • Rizzo L.
      • Palumbo F.
      • Tedeschi A.
      • Nobili L.A.
      • et al.
      An off-the-shelf instant contact casting device for the management of diabetic foot ulcers: a randomized prospective trial versus traditional fiberglass cast.
      ; and clinically critical ischemia or wound with gangrene or necrosis or TcPo2 <20 mm Hg or inability to detect with Doppler a major leg artery or based on angiography.
      • Ha Van G.
      • Siney H.
      • Hartmann-Heurtier A.
      • Jacqueminet S.
      • Greau F.
      • Grimaldi A.
      Nonremovable, windowed, fiberglass cast boot in the treatment of diabetic plantar ulcers: efficacy, safety, and compliance.
      The characteristics of included studies are described in Table I. The adjusted agreement between reviewers (κ) averaged 0.80 as calculated by the online system.
      Table ICharacteristics of included studies
      StudyCountryCare settingNo.Age, years, meanMale, %Patient characteristicsIntervention 1Intervention 2Ulcer area, cm2Follow-up, months
      Armstrong,
      • Armstrong D.G.
      • Nguyen H.C.
      • Lavery L.A.
      • van Schie C.H.
      • Boulton A.J.
      • Harkless L.B.
      Off-loading the diabetic foot wound: a randomized clinical trial [erratum appears in Diabetes Care 2001;24:1509].
      2001
      United StatesNR63NR82.5Diabetes duration: 17 years

      Ulcer duration: 5.2 months

      All patients had clinically significant loss of protective sensation
      TCCRCW1.33
      Armstrong,
      • Armstrong D.G.
      • Lavery L.A.
      • Wu S.
      • Boulton A.J.M.
      Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial.
      2005
      United StatesNR5065.688HbA1c: 8.2%iTCCRCW2.3 ± 1.23 or until wound healing
      Birke,
      • Birke J.A.
      • Pavich M.A.
      • Patout Jr., C.A.
      • Horswell R.
      Comparison of forefoot ulcer healing using alternative off-loading methods in patients with diabetes mellitus.
      2002
      United StatesLouisiana State University Health Sciences Center Diabetes Foot Program705654TCC

      Wagner grade: 2.2

      Ulcer duration: 184 days

      Healing shoe

      Wagner grade: 1.7

      Ulcer duration: 68 days
      TCCAlternative off-loading methods: an accommodative dressing (26 patients), a healing shoe (57 patients), a walking splint (18 patients)Mean, 1.053
      Busch,
      • Busch K.
      • Chantelau E.
      Effectiveness of a new brand of stock ‘diabetic’ shoes to protect against diabetic foot ulcer relapse. A prospective cohort study.
      2003
      GermanyLarge practice of two internists specializing in diabetology926353Diabetes duration: 13 years

      Type 1: 8.7% Type 2: 91.3%
      Customized stock diabetic shoesRegular shoesNA14.1
      Caravaggi,
      • Caravaggi C.
      • Faglia E.
      • Giglio R.D.
      • Mantero M.
      • Quarantiello A.
      • Sommariva E.
      • et al.
      Effectiveness and safety of a nonremovable fiberglass off-bearing cast versus a therapeutic shoe in the treatment of neuropathic foot ulcers: a randomized study.
      2000
      ItalyNR506068Diabetes duration: 17 yearsFiberglass castDiabetic shoe5.11
      Caravaggi,
      • Caravaggi C.
      • Sganzaroli A.
      • Fabbi M.
      • Cavaiani P.
      • Pogliaghi I.
      • Ferraresi R.
      • et al.
      Nonwindowed nonremovable fiberglass off-loading cast versus removable pneumatic cast (AircastXP Diabetic Walker) in the treatment of neuropathic noninfected plantar ulcers: a randomized prospective trial.
      2007
      ItalyDiabetic Foot Department, University Hospital60NRNRNRFiberglass off-loading castAircast pneumatic walkerWalker: 3.4 ± 3.0

      Fiberglass: 3.9 ± 3.4
      3
      Chantelau,
      • Chantelau E.
      • Breuer U.
      • Leisch A.C.
      • Tanudjaja T.
      • Reuter M.
      Outpatient treatment of unilateral diabetic foot ulcers with ‘half shoes’.
      1993
      GermanyUniversity Outpatient Diabetes Foot Clinic485773Diabetes duration: 17 years

      12 patients had prior amputations
      Standard treatment + half-shoeStandard treatmentNRNR
      Faglia,
      • Faglia E.
      • Caravaggi C.
      • Clerici G.
      • Sganzaroli A.
      • Curci V.
      • Vailati W.
      • et al.
      Effectiveness of removable walker cast versus nonremovable fiberglass off-bearing cast in the healing of diabetic plantar foot ulcer: a randomized controlled trial.
      2010
      ItalyTwo centers specializing in diabetic foot management4860.366.7TCC group

      Diabetes duration: 18 years

      HbA1c: 9.1%

      Stabil-D group

      Diabetes duration: 17 years

      HbA1c: 7.5%

      Half of the patients had previous minor amputations
      Nonremovable fiberglass off-bearing cast (TCC group)Walker cast (Stabil-D group)TCC: 1.4 ±1.2

      Stabil-D: 2.2 ± 2.3
      3
      Ganguly,
      • Ganguly S.
      • Chakraborty K.
      • Mandal P.K.
      • Ballav A.
      • Choudhury S.
      • Bagchi S.
      • et al.
      A comparative study between total contact casting and conventional dressings in the non-surgical management of diabetic plantar foot ulcers.
      2008
      IndiaNR58<20 to >7067.3NRTCCSimple dressingNR6
      Ha Van,
      • Ha Van G.
      • Siney H.
      • Hartmann-Heurtier A.
      • Jacqueminet S.
      • Greau F.
      • Grimaldi A.
      Nonremovable, windowed, fiberglass cast boot in the treatment of diabetic plantar ulcers: efficacy, safety, and compliance.
      2003
      FranceDiabetic foot clinic in a teaching hospital936088.5Type 1: 19.3% Type 2: 80.7%

      Diabetes duration: 17 years

      Ulcer duration: 264.5 days

      14.5% of patients had the ulcers for >6 months
      Cast bootOff-loading shoeCast boot: 2.8

      Off-loading shoe: 1.6
      NR
      Katz,
      • Katz I.A.
      • Harlan A.
      • Miranda-Palma B.
      • Prieto-Sanchez L.
      • Armstrong D.G.
      • Bowker J.H.
      • et al.
      A randomized trial of two irremovable off-loading devices in the management of plantar neuropathic diabetic foot ulcers.
      2005
      United StatesReferral clinic dedicated to the treatment of diabetic foot disorders4150.96892.5% of patients had type 2 diabetes

      Diabetes duration: 14 years

      Ulcer duration: 216 days
      RCW with single layer of fiberglass casting material (iTCC)Standard TCCiTCC: 3.1 cm2

      TCC: 2.9 cm2
      3
      Mueller,
      • Mueller M.J.
      • Diamond J.E.
      • Sinacore D.R.
      • Delitto A.
      • Blair 3rd, V.P.
      • Drury D.A.
      • et al.
      Total contact casting in treatment of diabetic plantar ulcers. Controlled clinical trial.
      1989
      United StatesDiabetic Foot Center and Physical Therapy Department at Washington University School of Medicine405570Type 1: 28% Type 2: 72%

      Diabetes duration: 17 years

      Ulcer duration: 160 days
      TCCTDTTCC: 1.8 ± 2.5 TDT: 2.8 ± 3.53
      Nube,
      • Nube V.L.
      • Molyneaux L.
      • Bolton T.
      • Clingan T.
      • Palmer E.
      • Yue D.K.
      The use of felt deflective padding in the management of plantar hallux and forefoot ulcers in patients with diabetes.
      2006
      AustraliaFoot clinic385780-85Diabetes duration: 13 years

      HbA1c: 9.5%

      Ulcer duration: 240 days
      Felt deflective padding on the skinFelt deflective padding in the shoe0.51
      Piaggesi,
      • Piaggesi A.
      • Macchiarini S.
      • Rizzo L.
      • Palumbo F.
      • Tedeschi A.
      • Nobili L.A.
      • et al.
      An off-the-shelf instant contact casting device for the management of diabetic foot ulcers: a randomized prospective trial versus traditional fiberglass cast.
      2007
      ItalySection of Diabetes and Metabolic Diseases, Department of Endocrinology and Metabolism, University Hospital4060.4NRDiabetes duration: 15.5 years

      HbA1c: 7.7%
      TCCOptima Diab walkerA: 3.7 ± 1.6

      B: 3.9 ± 1.8
      3
      Reiber,
      • Reiber G.E.
      • Smith D.G.
      • Wallace C.
      • Sullivan K.
      • Hayes S.
      • Vath C.
      • et al.
      Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial.
      2002
      United StatesTwo Washington State health care organizations400627733% of patients had diabetes >6 years, 11% for 6-24 years, 56% > 25 years (type 1: 7%; type 2: 93%)

      58% of participants were insensate to monofilament

      32% had a moderate foot deformity
      Therapeutic shoes with insertsUsual footwearNA24
      Uccioli,
      • Uccioli L.
      • Faglia E.
      • Monticone G.
      • Favales F.
      • Durola L.
      • Aldeghi A.
      • et al.
      Manufactured shoes in the prevention of diabetic foot ulcers.
      1995
      ItalyTwo teaching hospitals696062.3Type 2: 75%

      Diabetes duration: 17 years
      Therapeutic shoesNontherapeutic shoesNA12
      Van De Weg,
      • Van De Weg F.B.
      • Van Der Windt D.A.
      • Vahl A.C.
      Wound healing: total contact cast vs. custom-made temporary footwear for patients with diabetic foot ulceration.
      2008
      NetherlandsRehabilitation department from two hospitals436278.5Diabetes duration: 12 years

      Ulcer duration: 3-8 weeks
      TCCCustom-made temporary foot wearTCC: 4.2 ± 3.1

      Shoe: 3.0 ± 3.1

      (All the patients but two had grade 2 ulcers)
      4
      Viswanathan,
      • Viswanathan V.
      • Madhavan S.
      • Gnanasundaram S.
      • Gopalakrishna G.
      • Das B.N.
      • Rajasekar S.
      • et al.
      Effectiveness of different types of footwear insoles for the diabetic neuropathic foot: a follow-up study.
      2004
      IndiaNR2415664.73Diabetes duration: 12.3 yearsTherapeutic footwear with different types of insoles: microcellular rubber (100 patients), polyurethane (59 patients), and molded insole (32 patients)Regular footwear with leather board insolesNANR
      Zimny,
      • Zimny S.
      • Meyer M.F.
      • Schatz H.
      • Pfohl M.
      Applied felted foam for plantar pressure relief is an efficient therapy in neuropathic diabetic foot ulcers.
      2002
      GermanyNR616154Type 1: 36% Type 2: 64%

      Diabetes duration: 20 years
      Felted foamConventional therapyFelted foam: 1.1 cm2

      Conventional therapy: 1.19 cm2
      1-14
      HbA1c, Hemoglobin A1c; iTCC, instant total contact casting; NA, not applicable; NR, not reported; RCW, removable cast walker; TCC, total contact casting; TDT, traditional dressing treatment.

       Methodologic quality and risk of bias

      The quality of the included studies ranges from low to moderate. Randomization and allocation concealment were adequately described in only six and four of 13 RCTs, respectively. Blinding was described in only one study, which reported that outcome assessors and data collectors were blinded. Lack of blinding is unlikely to introduce bias for objective outcomes like amputation; however, it could introduce significant bias for subjective or assessor-dependent outcomes, such as complete wound healing. No baseline imbalances were mentioned in any of the studies. The percentage lost to follow-up ranged from 0% to 17%, with five studies reporting no losses.
      The overall methodologic quality of observational studies was moderate. The selection of cohorts of patients was well described in 50% of the studies. Such studies appeared to report on consecutive samples of patients. Thus, selection bias is possible in other studies with inadequate reporting. Moreover, follow-up was adequate, and four studies reported a 100% response rate. Only one of them adjusted for potential confounders. Tables II and III describe the quality of included studies.
      Table IIRisk of bias indicators in randomized trials
      StudyRandomization list prepared in advanceAllocation concealmentBlindingBaseline imbalancesFollow-upAdherence to treatmentLost to follow-up, %Funding
      Armstrong,
      • Armstrong D.G.
      • Nguyen H.C.
      • Lavery L.A.
      • van Schie C.H.
      • Boulton A.J.
      • Harkless L.B.
      Off-loading the diabetic foot wound: a randomized clinical trial [erratum appears in Diabetes Care 2001;24:1509].
      2001
      Computerized randomization scheduleNRNA/NRNoYes, regular clinic visitsNR0Not-for-profit sources
      Armstrong,
      • Armstrong D.G.
      • Lavery L.A.
      • Wu S.
      • Boulton A.J.M.
      Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial.
      2005
      Computerized randomization scheduleYes; method not reportedNA/NRNoYes, regular clinic visitsNR8Not-for-profit sources
      Caravaggi,
      • Caravaggi C.
      • Faglia E.
      • Giglio R.D.
      • Mantero M.
      • Quarantiello A.
      • Sommariva E.
      • et al.
      Effectiveness and safety of a nonremovable fiberglass off-bearing cast versus a therapeutic shoe in the treatment of neuropathic foot ulcers: a randomized study.
      2000
      A table of random numbersAssigned by phoneNA/NRNoYes, regular clinic visitsNR0NR
      Caravaggi,
      • Caravaggi C.
      • Sganzaroli A.
      • Fabbi M.
      • Cavaiani P.
      • Pogliaghi I.
      • Ferraresi R.
      • et al.
      Nonwindowed nonremovable fiberglass off-loading cast versus removable pneumatic cast (AircastXP Diabetic Walker) in the treatment of neuropathic noninfected plantar ulcers: a randomized prospective trial.
      2007
      NRNRNA/NRNoYes, regular clinic visitsYes3NR
      Faglia,
      • Faglia E.
      • Caravaggi C.
      • Clerici G.
      • Sganzaroli A.
      • Curci V.
      • Vailati W.
      • et al.
      Effectiveness of removable walker cast versus nonremovable fiberglass off-bearing cast in the healing of diabetic plantar foot ulcer: a randomized controlled trial.
      2010
      NRRandomization code break envelopesNA/NRNoYes, regular clinic visitsNR6.25Includes for-profit source
      Ganguly,
      • Ganguly S.
      • Chakraborty K.
      • Mandal P.K.
      • Ballav A.
      • Choudhury S.
      • Bagchi S.
      • et al.
      A comparative study between total contact casting and conventional dressings in the non-surgical management of diabetic plantar foot ulcers.
      2008
      NRNRNA/NRNoYes, regular clinic visitsNR5NR
      Katz,
      • Katz I.A.
      • Harlan A.
      • Miranda-Palma B.
      • Prieto-Sanchez L.
      • Armstrong D.G.
      • Bowker J.H.
      • et al.
      A randomized trial of two irremovable off-loading devices in the management of plantar neuropathic diabetic foot ulcers.
      2005
      Random number tableNRNA/NRNoYes, regular clinic visitsNR17Includes for-profit source
      Piaggesi,
      • Piaggesi A.
      • Macchiarini S.
      • Rizzo L.
      • Palumbo F.
      • Tedeschi A.
      • Nobili L.A.
      • et al.
      An off-the-shelf instant contact casting device for the management of diabetic foot ulcers: a randomized prospective trial versus traditional fiberglass cast.
      2007
      NRNRNA/NRNoYes, regular clinic visitsNR0Includes for-profit source
      Reiber,
      • Reiber G.E.
      • Smith D.G.
      • Wallace C.
      • Sullivan K.
      • Hayes S.
      • Vath C.
      • et al.
      Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial.
      2002
      NRNRNA/NRNoYes, regular clinic visitsPatients reported time they used the shoe13.7Not-for-profit sources
      Uccioli,
      • Uccioli L.
      • Faglia E.
      • Monticone G.
      • Favales F.
      • Durola L.
      • Aldeghi A.
      • et al.
      Manufactured shoes in the prevention of diabetic foot ulcers.
      1995
      NRNRNA/NRNoYes, regular clinic visitsNR0Includes for-profit source
      Nube,
      • Nube V.L.
      • Molyneaux L.
      • Bolton T.
      • Clingan T.
      • Palmer E.
      • Yue D.K.
      The use of felt deflective padding in the management of plantar hallux and forefoot ulcers in patients with diabetes.
      2006
      Drawing lotsNRNA/NRNoYes, regular clinic visitsNR15.7Not-for-profit sources
      Van De Weg,
      • Van De Weg F.B.
      • Van Der Windt D.A.
      • Vahl A.C.
      Wound healing: total contact cast vs. custom-made temporary footwear for patients with diabetic foot ulceration.
      2008
      Randomization list prepared in advanceOpaque sealed envelopesYes; outcome assessors, data collectorsNoYes, patients were evaluated at weeks 2, 4, 8, and 16NR11.63Not-for-profit sources
      Zimny,
      • Zimny S.
      • Meyer M.F.
      • Schatz H.
      • Pfohl M.
      Applied felted foam for plantar pressure relief is an efficient therapy in neuropathic diabetic foot ulcers.
      2002
      NRNRNA/NRNoYes, regular clinic visitsNR0NR
      NA, Not applicable; NR, not reported.
      Table IIIMethodologic quality of included observational studies
      StudyRepresentativenessDid the groups come from the same community?Was exposure properly verified?Adjustment for confoundersOutcome assessmentSufficient follow-upSimilarity of outcome assessmentResponse rateFunding
      Birke,
      • Birke J.A.
      • Pavich M.A.
      • Patout Jr., C.A.
      • Horswell R.
      Comparison of forefoot ulcer healing using alternative off-loading methods in patients with diabetes mellitus.
      2002
      Truly representativeYesYesNoYes, similarYesYesResponse rate: 100%NR
      Busch,
      • Busch K.
      • Chantelau E.
      Effectiveness of a new brand of stock ‘diabetic’ shoes to protect against diabetic foot ulcer relapse. A prospective cohort study.
      2003
      Truly representativeYesYesNoYes, similarYesYesResponse rate: 100%Includes for-profit source
      Chantelau,
      • Chantelau E.
      • Breuer U.
      • Leisch A.C.
      • Tanudjaja T.
      • Reuter M.
      Outpatient treatment of unilateral diabetic foot ulcers with ‘half shoes’.
      1993
      NRYesYesYes, they adjusted for sex, age, duration of diabetes, ulcer gradingYes, similarNRYesNRNR
      Ha Van,
      • Ha Van G.
      • Siney H.
      • Hartmann-Heurtier A.
      • Jacqueminet S.
      • Greau F.
      • Grimaldi A.
      Nonremovable, windowed, fiberglass cast boot in the treatment of diabetic plantar ulcers: efficacy, safety, and compliance.
      2003
      Truly representativeYesYesNoYes, similarNRYesResponse rate: 100%NR
      Mueller,
      • Mueller M.J.
      • Diamond J.E.
      • Sinacore D.R.
      • Delitto A.
      • Blair 3rd, V.P.
      • Drury D.A.
      • et al.
      Total contact casting in treatment of diabetic plantar ulcers. Controlled clinical trial.
      1989
      NRYesYesNoYes, similarYesYesNROnly not-for-profit source
      Viswanathan,
      • Viswanathan V.
      • Madhavan S.
      • Gnanasundaram S.
      • Gopalakrishna G.
      • Das B.N.
      • Rajasekar S.
      • et al.
      Effectiveness of different types of footwear insoles for the diabetic neuropathic foot: a follow-up study.
      2004
      NRYesYesNoYes, similarNRYesResponse rate: 100%NR
      NR, Not reported.

       Meta-analysis

       TCC vs RCW

      On the basis of three RCTs,
      • Armstrong D.G.
      • Nguyen H.C.
      • Lavery L.A.
      • van Schie C.H.
      • Boulton A.J.
      • Harkless L.B.
      Off-loading the diabetic foot wound: a randomized clinical trial [erratum appears in Diabetes Care 2001;24:1509].
      • Faglia E.
      • Caravaggi C.
      • Clerici G.
      • Sganzaroli A.
      • Curci V.
      • Vailati W.
      • et al.
      Effectiveness of removable walker cast versus nonremovable fiberglass off-bearing cast in the healing of diabetic plantar foot ulcer: a randomized controlled trial.
      • Ha Van G.
      • Siney H.
      • Hartmann-Heurtier A.
      • Jacqueminet S.
      • Greau F.
      • Grimaldi A.
      Nonremovable, windowed, fiberglass cast boot in the treatment of diabetic plantar ulcers: efficacy, safety, and compliance.
      there was a nonsignificant improvement in healing rate with TCC compared with RCW (RR, 1.15; 95% CI, 0.92-1.45; I2 = 0.00%; Fig 2), with a significant reduction in mean time to complete wound healing for the TCC group (weighted mean difference, −12.36 days; 95% CI, −22.63 to −2.09; P = .018; I2 = 91.36%; Fig 3). Quality of evidence is low, downgraded because of methodologic limitations of the included studies, heterogeneity, and imprecision (wide CIs due to small number of patients).
      Figure thumbnail gr2
      Fig 2Total contact casting (TCC) vs removable cast walker (RCW), complete healing. CI, Confidence interval; RR, relative risk.
      Figure thumbnail gr3
      Fig 3Total contact casting (TCC) vs removable cast walker (RCW), time to heal in days. CI, Confidence interval.

       TCC vs conventional wound therapy

      Pooling of one RCT
      • Ganguly S.
      • Chakraborty K.
      • Mandal P.K.
      • Ballav A.
      • Choudhury S.
      • Bagchi S.
      • et al.
      A comparative study between total contact casting and conventional dressings in the non-surgical management of diabetic plantar foot ulcers.
      and one controlled cohort
      • Mueller M.J.
      • Diamond J.E.
      • Sinacore D.R.
      • Delitto A.
      • Blair 3rd, V.P.
      • Drury D.A.
      • et al.
      Total contact casting in treatment of diabetic plantar ulcers. Controlled clinical trial.
      revealed a nonsignificant improvement in healing rate with TCC compared with conventional wound therapy (RR, 1.76; 95% CI, 0.77-4.02; P = .184; Fig 4). Quality of evidence is low because of methodologic limitations of the included studies and imprecision (wide CIs due to small number of patients).
      Figure thumbnail gr4
      Fig 4Total contact casting (TCC) vs conventional wound care, complete healing. CI, Confidence interval.

       Relapse: Therapeutic shoes and insoles vs regular footwear

      A meta-analysis of two RCTs
      • Reiber G.E.
      • Smith D.G.
      • Wallace C.
      • Sullivan K.
      • Hayes S.
      • Vath C.
      • et al.
      Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial.
      • Uccioli L.
      • Faglia E.
      • Monticone G.
      • Favales F.
      • Durola L.
      • Aldeghi A.
      • et al.
      Manufactured shoes in the prevention of diabetic foot ulcers.
      and two controlled cohorts
      • Busch K.
      • Chantelau E.
      Effectiveness of a new brand of stock ‘diabetic’ shoes to protect against diabetic foot ulcer relapse. A prospective cohort study.
      • Viswanathan V.
      • Madhavan S.
      • Gnanasundaram S.
      • Gopalakrishna G.
      • Das B.N.
      • Rajasekar S.
      • et al.
      Effectiveness of different types of footwear insoles for the diabetic neuropathic foot: a follow-up study.
      showed that therapeutic shoes and insoles significantly reduce ulcer relapse rate compared with regular footwear (RR, 0.34; 95% CI, 0.15-0.79; P = .012; I2 = 85.17%; Fig 5). Quality of evidence is low because of methodologic limitations, imprecision (wide CIs due to small number of patients), and significant heterogeneity in the results.
      Figure thumbnail gr5
      Fig 5Therapeutic shoes and insoles vs regular footwear, relapse. CI, Confidence interval.

       Other comparisons (reported in individual studies)

      Ha Van et al
      • Ha Van G.
      • Siney H.
      • Hartmann-Heurtier A.
      • Jacqueminet S.
      • Greau F.
      • Grimaldi A.
      Nonremovable, windowed, fiberglass cast boot in the treatment of diabetic plantar ulcers: efficacy, safety, and compliance.
      reported a statistically nonsignificant difference in healing rate with nonremovable fiberglass cast boots compared with half-shoe (RR, 1.15; 95% CI, 0.91-1.44; P = .24). However, secondary osteomyelitis was significantly reduced in the cast group compared with the off-loading shoe group (RR, 0.28; 95% CI, 0.08-0.92; P = .035). Osteomyelitis was subjectively defined in this study as a palpable bone in an inflammatory ulcer, radiographic evidence of bone erosions, or joint involvement deep to the ulcer. Quality of evidence is low because of methodologic limitations of the study.
      A controlled cohort by Birke et al
      • Birke J.A.
      • Pavich M.A.
      • Patout Jr., C.A.
      • Horswell R.
      Comparison of forefoot ulcer healing using alternative off-loading methods in patients with diabetes mellitus.
      compared TCC with alternative off-loading methods (an accommodative dressing, a healing shoe, or a walking splint) and reported no difference between healing time in any of the three comparisons, after adjusting for ulcer grade (1, 2, or 3) and width in a stepwise lognormal regression model. Quality of evidence is low because of methodologic limitations of the study.
      One RCT
      • Caravaggi C.
      • Faglia E.
      • Giglio R.D.
      • Mantero M.
      • Quarantiello A.
      • Sommariva E.
      • et al.
      Effectiveness and safety of a nonremovable fiberglass off-bearing cast versus a therapeutic shoe in the treatment of neuropathic foot ulcers: a randomized study.
      compared the healing rate for TCC (fiberglass cast) vs special therapeutic shoe and reported an increased healing rate in favor of TCC (RR, 2.40; 95% CI, 1.01-5.73; P = .048). Quality of evidence is low because of methodologic limitations of the study.
      One RCT compared irremovable cast walkers (iTCC) with RCW.
      • Armstrong D.G.
      • Lavery L.A.
      • Wu S.
      • Boulton A.J.M.
      Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial.
      Investigators constructed iTCC by modifying the RCW (by wrapping the traditional RCW in a layer of cohesive or plaster bandage). They reported an increased healing rate for the iTCC group compared with RCW (RR, 1.59; 95% CI, 1.06-2.40; P = .027). Moreover, there was a shorter healing time for patients treated with iTCC (41.6 ± 18.7 vs 58.0 ± 15.2 days; P = .02).
      • Armstrong D.G.
      • Lavery L.A.
      • Wu S.
      • Boulton A.J.M.
      Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial.
      Quality of evidence is low because of methodologic limitations of the studies and imprecision (wide CIs due to small number of patients).
      One RCT by Katz et al
      • Katz I.A.
      • Harlan A.
      • Miranda-Palma B.
      • Prieto-Sanchez L.
      • Armstrong D.G.
      • Bowker J.H.
      • et al.
      A randomized trial of two irremovable off-loading devices in the management of plantar neuropathic diabetic foot ulcers.
      compared iTCC with standard TCC and reported no difference in the rate of complete healing between the two groups (RR, 1.12; 95% CI, 0.79-1.59; P = .523). Also, there was no difference in amputation rate (RR, 1.05; 95% CI, 0.07-15.68; P = .971). Quality of evidence is low because of methodologic limitations of the study.
      One RCT
      • Zimny S.
      • Meyer M.F.
      • Schatz H.
      • Pfohl M.
      Applied felted foam for plantar pressure relief is an efficient therapy in neuropathic diabetic foot ulcers.
      comparing felted foam vs conventional wound therapy reported no statistically significant difference in the time to complete healing between the two groups (mean of 79.6 vs 83.2 days; P = .61). Quality of evidence is low because of methodologic limitations of the study.
      One observational study by Chantelau et al
      • Chantelau E.
      • Breuer U.
      • Leisch A.C.
      • Tanudjaja T.
      • Reuter M.
      Outpatient treatment of unilateral diabetic foot ulcers with ‘half shoes’.
      evaluated the effect of half-shoe compared with conventional wound care and reported that the number of patients who achieved complete healing was significantly higher in the half-shoe group (RR, 1.63; 95% CI, 1.14-2.32; P = .007). They also reported significant reduction in the hospitalization rate for the half-shoe group compared with the conventional therapy group (RR, 0.09; 95% CI, 0.01-0.69; P = .020). Quality of evidence is low because of methodologic limitations of the study.
      One RCT
      • Caravaggi C.
      • Sganzaroli A.
      • Fabbi M.
      • Cavaiani P.
      • Pogliaghi I.
      • Ferraresi R.
      • et al.
      Nonwindowed nonremovable fiberglass off-loading cast versus removable pneumatic cast (AircastXP Diabetic Walker) in the treatment of neuropathic noninfected plantar ulcers: a randomized prospective trial.
      compared a pneumatic off-loading device with a fiberglass off-loading cast and reported no statistical difference in the healing rates between the two groups (RR, 1.04; 95% CI, 0.81-1.34; P = .738). However, they reported that the Kaplan-Meier curves showed a healing rate of 59.9% per month in the pneumatic device group vs 40.89% in the fiberglass cast group (P < .005), with an average healing time of 71 days in the pneumatic device group and 48 days in the fiberglass cast group. Quality of evidence is low because of methodologic limitations of the study.
      One RCT by Nube et al
      • Nube V.L.
      • Molyneaux L.
      • Bolton T.
      • Clingan T.
      • Palmer E.
      • Yue D.K.
      The use of felt deflective padding in the management of plantar hallux and forefoot ulcers in patients with diabetes.
      compared the application of felt deflective padding on the skin with its application in the shoe and reported that similar healing rates were achieved in both groups (P = .9). Further analysis was not possible because the number of patients who achieved complete healing was not reported separately for the two groups. Quality of evidence is low because of methodologic limitations of the study.

      Discussion

      We conducted a systematic review and meta-analyses to evaluate the comparative effectiveness of different off-loading methods for diabetic foot ulcers. This study demonstrated some advantages for TCC over RCW, therapeutic shoes, and conventional therapy. There was no advantage for iTCC over TCC. Irremovable casts were used in the studies in patients without ischemia. There was improved healing with half-shoe compared with conventional footwear. This study also showed that therapeutic shoes and insoles provided a clear benefit in preventing relapse in comparison with regular footwear. Data were sparse regarding other off-loading methods.
      The quality of comparative effectiveness evidence (ie, the confidence in the estimates) is low, considering the methodologic limitations of the included studies and imprecision (the small sample size and wide CIs). Therefore, future studies may demonstrate different results, particularly if their inclusion criteria are different. In addition, the available data do not allow control for risk factors and other important variables (smoking, ABI, toe-brachial index, diabetes control, renal function, wound depth and area, and vascular supply status), and therefore the association between off-loading method and the outcomes could be confounded in the observational studies and in randomized trials with small size.
      Our results are consistent with earlier evidence synthesis attempts. Cavanagh and Bus
      • Cavanagh P.R.
      • Bus S.A.
      Off-loading the diabetic foot for ulcer prevention and healing.
      demonstrated the benefit of TCC and irremovable walker devices; nevertheless, they did not attempt meta-analysis. Paton et al
      • Paton J.
      • Bruce G.
      • Jones R.
      • Stenhouse E.
      Effectiveness of insoles used for the prevention of ulceration in the neuropathic diabetic foot: a systematic review.
      conducted a systematic review that suggested some benefit of insoles in preventing diabetic ulcers. Maciejewski et al
      • Maciejewski M.L.
      • Reiber G.E.
      • Smith D.G.
      • Wallace C.
      • Hayes S.
      • Boyko E.J.
      Effectiveness of diabetic therapeutic footwear in preventing reulceration.
      described the effect of therapeutic footwear in preventing reulceration. Bus et al
      • Bus S.A.
      • Valk G.D.
      • van Deursen R.W.
      • Armstrong D.G.
      • Caravaggi C.
      • Hlavacek P.
      • et al.
      The effectiveness of footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in diabetes: a systematic review.
      and Spencer
      • Spencer S.
      Pressure relieving interventions for preventing and treating diabetic foot ulcers.
      both highlighted that the evidence supporting the use of the off-loading methods is weak and that further studies need to be conducted, which is consistent with our findings. Our review updated the evidence base and expanded on the previous findings by incorporating any off-loading method.
      The accompanying guideline by the Society for Vascular Surgery will elaborate more on these options and discuss the clinical and practical implications so that both the physician and the patient can select the most favorable method according to the specific clinical scenario, patients' values and preferences, and available resources.

      Conclusions

      Although based on low-quality evidence (ie, evidence warranting lower certainty), benefits are demonstrated for use of TCC and irremovable cast walkers in the treatment of diabetic foot ulcers. Reduced relapse rate is demonstrated with various therapeutic shoes and insoles in comparison with regular footwear.

      Author contributions

      Conception and design: TE, GP, JD, AT, MN, RF, BF, RH, LP, MM
      Analysis and interpretation: TE, MM
      Data collection: TE, GP, JD, AT, MN, RF, BF, RH, LP, MM
      Writing the article: TE, GP, JD, AT, MN, RF, BF, RH, LP, MM
      Critical revision of the article: TE, GP, JD, AT, MN, RF, BF, RH, LP, MM
      Final approval of the article: TE, GP, JD, AT, MN, RF, BF, RH, LP, MM
      Statistical analysis: MM
      Obtained funding: MM
      Overall responsibility: MM

      Appendix (online only).

       Actual search strategy

       Ovid

      Databases: Embase 1988 to 2011 Week 40, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) 1948 to Present, EBM Reviews—Cochrane Central Register of Controlled Trials 4th Quarter 2011, EBM Reviews—Cochrane Database of Systematic Reviews 2005 to October 2011.
      Tabled 1
      #SearchesResults
      1((diabetic or diabetes) adj3 (foot or feet)).mp.14923
      2exp Diabetic Foot/11805
      31 or 214923
      4exp Casts, Surgical/11992
      5(cast or casting or casts).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, ps, rs, nm, ui, tx, ct]69473
      6exp walking aid/2629
      7exp Walkers/3062
      8(offload* or “off-load*”).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, ps, rs, nm, ui, tx, ct]1152
      9walker*.ti.4174
      10exp Orthotic Devices/11121
      11exp shoe/8612
      12(shoe or shoes).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, ps, rs, nm, ui, tx, ct]14229
      13(sandal or sandals).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, ps, rs, nm, ui, tx, ct]314
      14(non-weightbearing or nonweightbearing).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, ps, rs, nm, ui, tx, ct]515
      15“nonweight bearing”.mp.394
      16“non-weight bearing”.mp.1902
      17insole*.mp.1617
      18or/4-17102447
      193 and 181858
      20exp controlled study/3639965
      21exp evidence based medicine/518676
      22evidence-based.mp.175991
      23((control$ or randomized) adj2 (study or studies or trial or trials)).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, ps, rs, nm, ui, tx, ct]4669099
      24meta analysis/87758
      25meta-analys$.mp.139569
      26exp “systematic review”/44105
      27systematic review$.mp.98690
      28exp Guideline/ or exp Practice Guideline/271941
      29guideline$.ti.87215
      30or/20-295188997
      31exp case study/1572995
      32exp Cohort Studies/1330764
      33exp longitudinal study/880349
      34exp retrospective study/628418
      35exp prospective study/532053
      36exp observational study/23108
      37exp comparative study/2198791
      38exp clinical trial/1477518
      39exp evaluation/1088304
      40exp twins/39276
      41exp validation study/28010
      42exp experimental study/ or exp field study/ or exp in vivo study/ or exp panel study/ or exp pilot study/ or exp prevention study/ or exp quasi experimental study/ or exp replication study/ or exp theoretical study/ or exp trend study/6878167
      43((clinical or evaluation or twin or validation or experimental or field or “in vivo” or panel or pilot or prevention or replication or theoretical or trend or comparative or cohort or longitudinal or retrospective or prospective or population or concurrent or incidence or follow-up or observational) adj (study or studies or survey or surveys or analysis or analyses or trial or trials)).mp.6826285
      44(“case study” or “case series” or “clinical series” or “case studies”).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, dv, kw, ps, rs, nm, ui, tx, ct]154865
      45or/31-4412888282
      4619 and (30 or 45)1016
      47from 19 keep 957-1756800
      48limit 47 to (clinical trial or clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or comparative study or controlled clinical trial or guideline or meta analysis or multicenter study or practice guideline or randomized controlled trial or twin study) [Limit not valid in Embase,CDSR; records were retained]170
      4946 or 481016
      50limit 49 to (book or book series or editorial or erratum or letter or note or addresses or autobiography or bibliography or biography or comment or dictionary or directory or interactive tutorial or interview or lectures or legal cases or legislation or news or newspaper article or overall or patient education handout or periodical index or portraits or published erratum or video-audio media or webcasts) [Limit not valid in Embase,Ovid MEDLINE(R),Ovid MEDLINE(R) In-Process,CCTR,CDSR; records were retained]34
      5149 not 50982
      52from 19 keep 1757-1858102
      5351 or 521029
      54remove duplicates from 53654

       Scopus

      • 1
        TITLE-ABS-KEY((diabetes w/3 foot) or (diabetic w/3 foot) or (diabetes w/3 feet) or (diabetic w/3 feet))
      • 2
        TITLE-ABS-KEY(cast or casts or casting or offload* or “off-load*” or orthotic* or shoe* or sandal* or “non-weightbearing” or nonweightbearing or “nonweight bearing” or “non-weight bearing” or insole*)
      • 3
        TITLE(walker or walkers)
      • 4
        TITLE-ABS-KEY( (evidence W/1 based) OR (meta W/1 analys*) OR (systematic* W/2 review*) OR guideline OR (control* W/2 stud*) OR (control* W/2 trial*) OR (randomized W/2 stud*) OR (randomized W/2 trial*))
      • 5
        TITLE-ABS-KEY(“comparative study” OR “comparative survey” OR “comparative analysis” OR “cohort study” OR “cohort survey” OR “cohort analysis” OR “longitudinal study” OR “longitudinal survey” OR “longitudinal analysis” OR “retrospective study” OR “retrospective survey” or “retrospective analysis” OR “prospective study” OR “prospective survey” OR “prospective analysis” OR “population study” OR “population survey” OR “population analysis” OR “concurrent study” OR “concurrent survey” OR “concurrent analysis” or “incidence study” OR “incidence survey” OR “incidence analysis” OR “follow-up study” OR “follow-up survey” OR “follow-up analysis” or “observational study” OR “observational survey” OR “observational analysis” OR “case study” OR “case series” OR “clinical series” OR “case studies” or “clinical study” OR “clinical trial” or “evaluation study” OR “evaluation survey” OR “evaluation analysis” or “twin study” OR “twin survey” OR “twin analysis” or “validation study” OR “validation survey” OR “validation analysis” or “experimental study” OR “experimental analysis” or “field study” OR “field survey” OR “field analysis” or “in vivo study” OR “in vivo analysis” or “panel study” OR “panel survey” OR “panel analysis” or “pilot study” OR “pilot survey” OR “pilot analysis” or “prevention study” OR “prevention survey” OR “prevention analysis” or “replication study” OR “replication analysis” or “theoretical study” OR “theoretical analysis” or “trend study” OR “trend survey” OR “trend analysis”)
      • 6
        1 and (2 or 3) and (4 or 5)
      • 7
        PMID(0*) OR PMID(1*) OR PMID(2*) OR PMID(3*) OR PMID(4*) OR PMID(5*) OR PMID(6*) OR PMID(7*) OR PMID(8*) OR PMID(9*)
      • 8
        6 and not 7
      • 9
        DOCTYPE(le) OR DOCTYPE(ed) OR DOCTYPE(bk) OR DOCTYPE(er) OR DOCTYPE(no) OR DOCTYPE(sh)
      • 10
        8 and not 9

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