BackgroundAnnual foot risk assessment of people with diabetes is recommended in national and international clinical guidelines. At present, these are consensus based and use only a proportion of the available evidence.ObjectivesWe undertook a systematic review of individual patient data (IPD) to identify the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes.Data sourcesStudies were identified from searches of MEDLINE and EMBASE.Review methodsThe electronic search strategies for MEDLINE and EMBASE databases created during an aggregate systematic review of predictive factors for foot ulceration in diabetes were updated and rerun to January 2013. One reviewer applied the IPD review eligibility criteria to the full-text articles of the studies identified in our literature search and also to all studies excluded from our aggregate systematic review to ensure that we did not miss eligible IPD. A second reviewer applied the eligibility criteria to a 10% random sample of the abstract search yield to check that no relevant material was missed. This review includes exposure variables (risk factors) only from individuals who were free of foot ulceration at the time of study entry and who had a diagnosis of diabetes mellitus (either type 1 or type 2). The outcome variable was incident ulceration.ResultsOur search identified 16 cohort studies and we obtained anonymised IPD for 10. These data were collected from more than 16,000 people with diabetes worldwide and reanalysed by us. One data set was kept for independent validation. The data sets contributing IPD covered a range of temporal, geographical and clinical settings. We therefore selected random-effects meta-analysis, which assumes not that all the estimates from each study are estimates of the same underlying true value, but rather that the estimates belong to the same distribution. We selected candidate variables for meta-analysis using specific criteria. After univariate meta-analyses, the most clinically important predictors were identified by an international steering committee for inclusion in the primary, multivariable meta-analysis. Age, sex, duration of diabetes, monofilaments and pulses were considered most prognostically important. Meta-analyses based on data from the entire IPD population found that an inability to feel a 10-g monofilament [odds ratio (OR) 3.184, 95% confidence interval (CI) 2.654 to 3.82], at least one absent pedal pulse (OR 1.968, 95% CI 1.624 to 2.386), a longer duration of a diagnosis of diabetes (OR 1.024, 95% CI 1.011 to 1.036) and a previous history of ulceration (OR 6.589, 95% CI 2.488 to 17.45) were all predictive of risk. Female sex was protective (OR 0.743, 95% CI 0.598 to 0.922).LimitationsIt was not possible to perform a meta-analysis using a one-step approach because we were unable to procure copies of one of the data sets and instead accessed data via Safe Haven.ConclusionsThe findings from this review identify risk assessment procedures that can reliably inform national and international diabetes clinical guideline foot risk assessment procedures. The evidence from a large sample of patients in worldwide settings show that the use of a 10-g monofilament or one absent pedal pulse will identify those at moderate or intermediate risk of foot ulceration, and a history of foot ulcers or lower-extremity amputation is sufficient to identify those at high risk. We propose the development of a clinical prediction rule (CPR) from our existing model using the following predictor variables: insensitivity to a 10-g monofilament, absent pedal pulses and a history of ulceration or lower-extremities amputations. This CPR could replace the many tests, signs and symptoms that patients currently have measured using equipment that is either costly or difficult to use.Study registrationThis study is registered as PROSPERO CRD42011001841.FundingThe National Institute for Health Research Health Technology Assessment programme.

Clinical guidelines recommend that all patients with diabetes should be screened annually to establish their risk of foot ulceration. The aim of this systematic review was to quantify the predictive value of diagnostic tests, physical signs and elements from the patient's history in relation to diabetic foot ulcers. Observational studies were identified from: electronic databases (MEDLINE, EMBASE and CINAHL); bibliographies of studies meeting the inclusion criteria; review articles and clinical guidelines; direct contact with authors. Published reports of cohort and case-control studies were considered for inclusion. Pooled estimates were calculated from absolute numbers as weighted mean differences, standard mean differences or odds ratios. Adjusted odds ratios from published reports were also extracted. We identified five case-control and 11 cohort studies. The incidence of foot ulcers ranged from 8% to 17% in the cohort studies, with varying lengths of follow-up. Diagnostic tests and physical signs that detect peripheral neuropathy (biothesiometry, monofilaments and absent ankle reflexes), and those that detect excessive plantar pressure (peak plantar pressure and joint deformity) were all significantly associated with future diabetic foot ulceration. However, there was a paucity of evidence concerning the predictive value of symptoms and signs. Further research is needed to establish the independent factors associated with diabetic foot ulceration, particularly elements from a patient's history and physical examination.

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