IntroductionPerianal fistulising Crohn’s disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.Methods and analysisPatients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18–80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate.Ethics and disseminationResults will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.
Purpose To compare the biomechanical characteristics between diaphyseal and metaphyseal ulnar-shortening osteotomy with respect to (1) maximal shortening achieved at each osteotomy site and (2) force required to achieve shortening at each site. Methods Nine fresh frozen cadaveric upper extremities were affixed through the proximal ulna to a wooden surgical board. A metaphyseal 20-mm bone wedge was resected from the distal ulna and sequential shortening was performed. A load cell was attached to a distal post that was clamped to the surgical board and used to measure the force required for each sequential 5-mm of shortening until maximal shortening was achieved. The resected bone was reinserted, and plate fixation was used to restore normal anatomy. A 20-mm diaphyseal osteotomy was performed, and force measurements were recorded in the same manner with (1) interosseous membrane intact, (2) central band released, and (3) extensive interosseous membrane and muscular attachments released. Results Metaphyseal osteotomy allowed greater maximal shortening than diaphyseal osteotomy with the interosseous membrane intact and with central band release but similar shortening when extensive interosseous membrane and muscle release was performed. Force at maximal shortening was similar between metaphyseal and diaphyseal osteotomy. Sequential soft tissue release at the diaphysis allowed for increased shortening with slightly decreased shortening force with sequential release. Conclusion Metaphyseal ulnar osteotomy allows greater maximal shortening but requires similar force compared with diaphyseal osteotomy. Sequential release of the interosseous membrane permits increased shortening at the diaphysis but requires extensive soft tissue release. Clinical Relevance Both sites of osteotomy can achieve sufficient shortening to decompress the ulnocarpal joint for most cases of ulnar impaction syndrome. The greater shortening from metaphyseal ulnar osteotomy may be reserved for severe cases of shortening, especially after distal radius malunion or in the setting of distal radius growth arrest in the pediatric population. Level of Evidence This is a Level V, basic science study.
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