Ruben C Hoogeveen, Johannes AN Dorresteijn, Didi MW Kriegsman, Gerlof D Valk

Ulceration of the feet, which can lead to the amputation of feet and legs, is a major problem for people with diabetes mellitus, and can cause substantial economic burden. Single preventive strategies have not been shown to reduce the incidence of foot ulceration to a significant extent. Therefore, in clinical practice, preventive interventions directed at patients, healthcare providers and/or the structure of health care are often combined (complex interventions). To assess the effectiveness of complex interventions in the prevention of foot ulcers in people with diabetes mellitus compared with single interventions, usual care or alternative complex interventions. A complex intervention is defined as an integrated care approach, combining two or more prevention strategies on at least two different levels of care: the patient, the healthcare provider and/or the structure of health care. For the second update we searched the Cochrane Wounds Group Specialised Register (searched 22 May 2015), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2015, Issue 4), The Health Technology Assessment Database (HTA) (The Cochrane Library 2015, Issue 4), The NHS Economic Evaluation Database (NHS EED) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (1946 to 22 May 2015), Ovid MEDLINE (In-Process & Other Non-Indexed Citations 21 May, 2015), Ovid EMBASE (1974 to 21 May, 2015) and EBSCO CINAHL (1982 to 22 May, 2015). Prospective randomised controlled trials (RCTs) which compared the effectiveness of combinations of preventive strategies, not solely patient education, for the prevention of foot ulcers in people with diabetes mellitus, with single interventions, usual care or alternative complex interventions. Two review authors were assigned to independently select studies, to extract study data and to assess risk of bias of included studies, using predefined criteria. Only six RCTs met the criteria for inclusion. The study characteristics differed substantially in terms of healthcare settings, the nature of the interventions studied and outcome measures reported. In three studies that compared the effect of an education-centred complex intervention with usual care or written instructions, only little evidence of benefit was found. Three studies compared the effect of more intensive and comprehensive complex interventions with usual care. One study found a significant and cost-effective reduction, one of lower extremity amputations (RR 0.30, 95% CI 0.31 to 0.71). One other study found a significant reduction of both amputation and foot ulcers. The last study reported improvement of patients' self care behaviour. All six included RCTs were at high risk of bias, with hardly any of the predefined quality assessment criteria met. There is no high-quality research evidence evaluating complex interventions for preventing diabetic foot ulceration and insufficient evidence of benefit.