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Bone & Joint Open
Vol. 3, Issue 11 | Pages 898 - 906
15 Nov 2022
Dakin H Rombach I Dritsaki M Gray A Ball C Lamb SE Nanchahal J

Aims

To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytren’s disease (DD) and the value of further research from an NHS perspective.

Methods

We used data from the Repurposing anti-TNF for Dupuytren’s disease (RIDD) randomized controlled trial of intranodular adalimumab injections in patients with early-stage progressive DD. RIDD found that intranodular adalimumab injections reduced nodule hardness and size in patients with early-stage DD, indicating the potential to control disease progression. A within-trial cost-utility analysis compared four adalimumab injections with no further treatment against standard care alone, taking a 12-month time horizon and using prospective data on EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and resource use from the RIDD trial. We also developed a patient-level simulation model similar to a Markov model to extrapolate trial outcomes over a lifetime using data from the RIDD trial and a literature review. This also evaluated repeated courses of adalimumab each time the nodule reactivated (every three years) in patients who initially responded.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 307 - 307
1 Sep 2005
Harry L Sandison A Paleolog E McCarthy I Pearse M Nanchahal J
Full Access

Introduction and Aims: We have developed a novel murine open tibial fracture model to compare the vascularity of muscle and fasciocutaneous flaps during fracture healing and investigate their role in angiogenesis.

Method: Flaps were emulated by insertion of a piece of sterile, inert material (Polytetrafluoroethylene, PTFE), at the fracture site to exclude either muscle posteriorly (fasciocutaneous flap) or skin and fascia anteriorly (muscle flap). Animals were harvested at days three, five, seven, nine and 14 post-fracture. Immunohistochemistry was performed on specimens, to estimate vascularity using an antibody to factor VIII, which selectively demonstrates vascular endothelium. Vascular densities were determined within the muscle and fasciocutaneous tissues adjacent to the fracture sites. Vascular Endothelial Growth Factor (VEGF) was measured by ELISA in tissue specimens. Immunohistochemistry was performed to qualitatively assess distribution of VEGF.

Results: Significantly greater vascular densities per unit area were observed in fasciocutaneous flaps at all time points compared to muscle flaps (p< 0.0001). VEGF levels peaked at day seven post-fracture, fell at day nine, and increased again at day 14. This time-dependent variation was statistically significant (p< 0.02). However, there was no significant difference between muscle and fasciocutaneous flaps. Maximal staining for VEGF occurred on the deep surface of the flaps adjacent to the fracture site. We found that fasciocutaneous flaps have significantly higher vascular densities compared to muscle flaps during early fracture healing.

Conclusion: Our results contradict the widely held view that muscle flaps are superior. However, there was no significant difference between levels of the pro-angiogenic factor VEGF within the flaps. This would suggest that both flaps are equally effective in supplying the factors necessary for new vessel formation. Our data supports the continuing use of muscle and fasciocutaneous flaps in the clinical setting.