Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis: A Randomized Controlled Trial.

Background: MIV-711 is a novel selective cathepsin K inhibitor with beneficial effects on bone and cartilage in preclinical osteoarthritis models. Objective: To evaluate the efficacy, safety, and tolerability of MIV-711 in participants with symptomatic, radiographic knee osteoarthritis. Design: 26-week randomized, double-blind, placebo-controlled phase 2a study with a 26-week open-label safety extension substudy. (EudraCT: 2015-003230-26 and 2016-001096-73). Setting: Six European sites. Participants: 244 participants with primary knee osteoarthritis, Kellgren-Lawrence grade 2 or 3, and pain score of 4 to 10 on a numerical rating scale (NRS). Intervention: MIV-711, 100 (n = 82) or 200 (n = 81) mg daily, or matched placebo (n = 77). Participants (46 who initially received 200 mg/d and 4 who received placebo) received 200 mg of MIV-711 daily during the extension substudy. Measurements: The primary outcome was change in NRS pain score. The key secondary outcome was change in bone area on magnetic resonance imaging (MRI). Other secondary end points included cartilage thickness on quantitative MRI and type I and II collagen C-telopeptide biomarkers. Outcomes were assessed over 26 weeks. Results: Changes in NRS pain scores with MIV-711 were not statistically significant (placebo, -1.4; MIV-711, 100 mg/d, -1.7; MIV-711, 200 mg/d, -1.5). MIV-711 significantly reduced medial femoral bone area progression (P = 0.002 for 100 mg/d and 0.004 for 200 mg/d) and medial femoral cartilage thinning (P = 0.023 for 100 mg/d and 0.125 for 200 mg/d) versus placebo and substantially reduced bone and cartilage biomarker levels. Nine serious adverse events occurred in 6 participants (1 in the placebo group, 3 in the 100 mg group, and 2 in the 200 mg group); none were considered to be treatment-related. Limitation: The trial was relatively short. Conclusion: MIV-711 was not more effective than placebo for pain, but it significantly reduced bone and cartilage progression with a reassuring safety profile. This treatment may merit further evaluation as a disease-modifying osteoarthritis drug. Primary Funding Source: Medivir.

Shadowing a foundation-year doctor: a third-year medical student's perspective.

CONTEXT: This paper considers the advantages of shadowing foundation-year doctors (FY1) in the third year of medical school, an opportunity the UK's General Medical Council (UKGMC) recommends to be given to final-year students only. METHOD: Eighteen students spent 1 day each shadowing an FY1, holding their pager and carrying out their duties under direct supervision. Questionnaires, based on UKGMC expectations of an FY1, were completed assessing students' confidence and experience before and after the shifts. The doctors were interviewed. RESULTS: The questionnaire response rate was 72 per cent (13/18). The overall increase in student experiences in good clinical care (p<0.001), maintaining good medical practice--teaching and learning (p=0.002), and recognition and management of the acutely ill (p<0.001), were statistically significant. The increase in student confidence in answering the pager (p<0.001), prioritising jobs (p=0.002), venepuncture (p=0.008), writing drug charts (p=0.031), writing in patient notes (p=0.002) and developing management plans (p=0.002) were statistically significant. Qualitative results yielded an overwhelming opinion from students and doctors that it should be made a compulsory part of the third-year curriculum. The doctors found it increased their knowledge and teaching skills. CONCLUSION: This study has implications for the future of medical training. If incorporated into the third-year curriculum, compulsory shadowing would give students a structured one-to-one learning experience during which to learn clinically relevant skills. By shadowing a doctor so closely, they will also learn first-hand how to interact professionally with patients and other health care workers, a skill difficult to teach at medical school.