A third of diabetic foot ulcer patients are wrongly diagnosed with bone infection, leading to months of unnecessary antibiotics. Diabetes affects 4.5 million UK adults, and one in four will develop a foot ulcer. When infection spreads to the bone—osteomyelitis—current diagnosis relies on clinical signs, which over-diagnose 30% of patients. This exposes them to prolonged antibiotics, raising risks of antimicrobial resistance and hospital-acquired infections. The gold-standard test, a bone biopsy, is rarely used because doctors disagree on whether to sample through the wound or through healthy skin. This fellowship will compare both biopsy methods in 192 patients to determine which gives the most accurate microbiology and histology results. Using that gold standard, the researcher will then develop a diagnostic prediction model—combining blood markers, X-rays, and clinical features—to rule out osteomyelitis without invasive biopsy in most patients. If successful, the model could spare thousands of patients unnecessary antibiotics each year, cut NHS costs (currently £1 billion annually for diabetic foot ulcers), and reduce the spread of drug-resistant infections. The model will be validated against a Dutch dataset before a planned phase III trial.
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Diabetes affects 4.5million UK adults, of whom 25% will develop a diabetic foot ulcer (DFU). DFU treatment costs the NHS £1billion annually. 20% of DFUs will develop osteomyelitis (DFO) by contiguous spread of infection from the ulcer, with detrimental outcomes. Guidelines suggest bone biopsy to aid diagnosis and target antibiotic management, but the proposed route (through-the-wound versus remote biopsy) is discrepant. Current diagnosis is based on clinical features, leading to over-diagnosis in 30% of patients, unnecessary and prolonged antibiotics, associated risk of antimicrobial resistance and health-care associated infections. The aims of this fellowship are to: Describe the current clinical standard for diagnosis of DFO. Quantify the concordance of 'though-the-wound' and 'remote' bone biopsies for microbiology and histology to identify a gold-standard diagnostic test for DFO. Using the gold-standard test, develop and validate a diagnostic prediction model to improve diagnostic and therapeutic yield compared to current clinical standard. Workpackage 1 I will conduct a 3-centre observational prospective cohort of patients presenting with DFUs. All new patients (~4550) will be invited to enter the cohort requiring minimal data collection for most. Amongst these patients will be a subgroup with high-risk features for DFO. Additional data in these patients will be collected in 3 phases: Phase 1 (225 patients; 6 months): To define current clinical standard for diagnosis of DFO, data on diagnostic criteria, antibiotic utilisation, clinical outcomes to 52-weeks and if consenting, quality-of-life and health resource utilisation will be collected. Phase 2 (192 patients; 18 months): To identify gold-standard bone biopsy technique, patients providing second-level consent will have remote and through-the-wound bone trephine biopsies (Workpackage 1b). Outcomes: histology; presence and number of pathogens; estimated concordance and diagnostic yield; complications; clinical outcomes as for Phase 1. Biochemical markers and X-ray will be performed in all patients. Phase 3 (450 patients; 18 months): To develop a diagnostic prediction model for DFO, patients will be investigated using optimal bone biopsy technique, biochemical markers and X-rays. Clinical outcomes are as for Phase 1. Workpackage 2 A national audit of healthcare professionals managing DFO to ensure cohort centre practice as determined in WP1 Phase 1 is reflective of national practice, and to identify information clinicians require of a new diagnostic pathway to maximise NHS adoption. Workpackage 3 Using data from WP1 Phase 2 and 3, a diagnostic prediction model for DFO using clinical, biochemical and X-ray criteria against a gold-standard of optimised bone biopsy will be modelled (642 patients) and validated internally. External validation will use a Dutch dataset. Clinical- and cost-effectiveness will be compared to current practice. I have involved patients in the development of this Fellowship. Five Leeds DFU PPI group members felt this was an important question, and that the proposed design encouraged patient engagement. Two participants will fulfil Fellowship project management roles. The project will be delivered over 60 months. Results will be disseminated in peer review journals, national/international conferences, and will inform national/international guidelines. The Fellowship will inform design of a Phase III cluster-randomised trial comparing the diagnostic model with standard practice.
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