Factors Associated With Healing of Diabetes-Related Foot Ulcers: Observations From a Large Prospective Real-World Cohort

Diabetes-related foot ulcers (DFUs) affect around 20 million people annually and are a leading cause of the global disability burden (1). DFUs are complex to treat, take months to heal, result in poorer quality of life, and place patients at high risk of hospitalization and amputation. Thus, understanding the influence that different factors have on healing of DFUs is vital. Various demographic, comorbidity, limb, ulcer, and treatment-related factors associated with healing of DFUs have been identified from cohorts attending mostly metropolitan tertiary centers (2–4). However, very few studies have prospectively investigated the influence that these and other factors have on healing in more real-world DFU cohorts attending geographically diverse secondary and tertiary centers. Therefore, we aimed to investigate the influence of 34 factors on healing in a large real-world DFU cohort. We prospectively examined 4,832 consecutive patients with DFU(s) that presented for their first visit to 1 of 65 secondary or tertiary diabetic foot services, across 15 of 17 regions in Queensland (Australia), between July 2011 and December 2017. A DFU was defined as a full-thickness wound below the ankle on a person with diabetes. For DFU clinical and research purposes, foot-related health professionals using the Queensland High Risk Foot Form (QHRFF) directly examined each patient clinically at their first (and subsequent) visit for 4 demographic, 9 comorbidity, 6 limb, 3 ulcer, and 12 treatment factors (5). For those with multiple DFUs, we used the most severe score for each factor and the combined ulcer size from all DFUs (5). Factors from the first visit were used as the baseline. Subsequent visit examinations determined if the DFU(s) healed, defined as complete epithelialization of all DFUs without amputation, death, or recurrence within 1 month. The QHRFF is valid and reliable for the direct capture of these factors by the foot-related health professionals that were trained with a QHRFF manual (5). DFUs healed within 3 and 12 months were the primary outcomes, as different factors have been reported to influence shortand longer-term healing (2–4). All factors were analyzed at a univariable level, with those achieving P < 0.1 entered into multivariable logistic regression models to examine factors independently associated with each outcome. Before analysis, we excluded 123 patients lost to follow-up after baseline visit, excluded factors with >25% missing data, and used multiple imputation for factors with <25% missing data. All analyses were performed using Stata/SE version 16.1 (StataCorp, TX, USA). Of 4,709 included patients (median age 63 years [interquartile range 54–72], 69.5% male, 91.0% with type 2 diabetes, 10.5% Indigenous Australians), 1,956 (41.5%) healed within 3 months and 3,012 (64.0%) within 12 months. After entering 18 factors into the multivariable models (Fig. 1), 7 were negatively associated with DFU healing within both 3 and 12 months, including younger age (<50 years), geographical remoteness, smoking, peripheral arterial disease, large ulcer sizes, deep ulcers,