ABSTRACTThe iron overload disorder hemochromatosis is primarily caused by the homozygous HFE p.C282Y variant, but the scale of excess related musculoskeletal morbidity is uncertain. We estimated hemochromatosis‐genotype associations with clinically diagnosed musculoskeletal outcomes and joint replacement surgeries in the UK Biobank community cohort. A total of 451,143 European ancestry participants (40 to 70 years at baseline) were followed in hospital records (mean 11.5‐years). Cox proportional hazards models estimated HFE p.C282Y and p.H63D associations with incident outcomes. Male p.C282Y homozygotes (n = 1294) had increased incidence of osteoarthritis (n = 52, hazard ratio [HR]: 2.12 [95% confidence interval, CI: 1.61 to 2.80]; p = 8.8 × 10−8), hip replacement (n = 88, HR: 1.84 [95% CI: 1.49 to 2.27]; p = 1.6 × 10−8), knee replacement (n = 61, HR: 1.54 [95% CI: 1.20 to 1.98]; p = 8.4 × 10−4), and ankle and shoulder replacement, compared to males with no HFE mutations. Cumulative incidence analysis, using Kaplan–Meier lifetable probabilities demonstrated 10.4% of male homozygotes were projected to develop osteoarthritis and 15.5% to have hip replacements by age 75, versus 5.0% and 8.7% respectively without mutations. Male p.C282Y homozygotes also had increased incidence of femoral fractures (n = 15, HR: 1.72 [95% CI: 1.03 to 2.87]; p = 0.04) and osteoporosis (n = 21, HR: 1.71 [95% CI: 1.11 to 2.64]; p = 0.02), although the latter association was limited to those with liver fibrosis/cirrhosis diagnoses. Female p.C282Y homozygotes had increased incidence of osteoarthritis only (n = 57, HR: 1.46, [95% CI: 1.12 to 1.89]; p = 0.01). Male p.C282Y/p.H63D compound heterozygotes experienced a modest increased risk of hip replacements (n = 234, HR: 1.17 [95% CI: 1.02 to 1.33], p = 0.02), but this did not pass multiple testing corrections. In this large community cohort, the p.C282Y homozygote genotype was associated with substantial excess musculoskeletal morbidity in males. Wider HFE genotype testing may be justified, including in orthopedic clinics serving higher HFE variant prevalence populations. © 2023 the Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Diagnostic imaging services are essential to the diagnosis pathway for many patients arriving at hospital emergency departments with a suspected fracture. Commonly, these patients need to be seen again by a doctor or emergency nurse practitioner after an X-ray image has been taken in order to finalise the diagnosis and determine the next stage in the patients’ pathway. Here, significant waiting times can accrue for these follow-up consultations after radiographic imaging although the vast majority of patients are discharged. Research evidence from pilot studies suggests that patients with minor appendicular injuries could be safely discharged by a suitably qualified radiographer directly after imaging thereby avoiding queues for repeated consultation. In this study, we model patient pathways through an emergency department (ED) at a hospital in the South West of England using process mapping, interviews with ED staff and discrete event simulation (DES). The DES model allowed us to compare the current practice at the hospital with scenarios using radiographer-led discharge of patients directly after imaging and assess the reduction in patients’ length of stay in ED. We also quantified trade-offs between the provision of radiographer-led discharge and its effects, i.e. reduction in waiting times and ED workload. Finally, we discuss how this decision support tool can be used to support understanding for patients and members of staff.