Self-regulation training for people with knee osteoarthritis: a protocol for a feasibility randomised control trial (MiNT trial).

Introduction: Knee osteoarthritis (OA) is a chronic secondary musculoskeletal pain condition resulting in disability, reduced quality of life, and high societal costs. Pain associated with knee OA is linked to increased sensitivity in sensory, cognitive, and emotional areas of the brain. Self-regulation training targeting brain functioning related to pain experience could reduce pain and its associated disability. Self-regulatory treatments such as mindfulness meditation (MM) and electroencephalography neurofeedback (EEG-NF) training improve clinical outcomes in people with knee OA. A feasibility clinical trial can address factors that could inform the design of the full trial investigating the effectiveness of self-regulation training programmes in people with knee OA. This clinical trial will evaluate the feasibility, safety, acceptability, experience and perceptions of the self-regulatory training programmes. Methods: The proposed feasibility trial is based on a double-blind (outcome assessor and investigators), three-arm (MM usual care, EEG-NF + usual care and usual care control group) randomised controlled parallel clinical trial. Participants with knee OA will be recruited from the community and healthcare practices. A research assistant (RA) will administer both interventions (20-min sessions, four sessions each week, and 12 sessions over three successive weeks). Feasibility measures (participant recruitment rate, adherence to interventions, retention rate), safety, and acceptability of interventions will be recorded. An RA blinded to the group allocation will record secondary outcomes at baseline, immediately post-intervention (4th week), and 3 months post-intervention. The quantitative outcome measures will be descriptively summarised. The qualitative interviews will evaluate the participants' experiences and perceptions regarding various aspects of the trial, which includes identifying the barriers and facilitators in participating in the trial, evaluating their opinions on the research procedures, such as their preferences for the study site, and determining the level of acceptability of the interventions as potential clinical treatments for managing knee OA. Maori participant perceptions of how assessment and training practices could be acceptable to a Maori worldview will be explored. The interviews will be audio-recorded and analysed thematically. Discussion: This trial will provide evidence on the feasibility, safety, and acceptability of the MM and EEG-NF training in people with knee OA, thus informing the design of a full randomised clinical control trial.

A pilot investigation of reliability and validity of balance and gait assessments using telehealth with healthy older adults.

BACKGROUND: The use of telehealth has increased since the COVID-19 pandemic; however, the lack of reliable and valid tools to measure balance and gait remotely makes assessing these outcomes difficult. Thus, we investigated whether balance and gait measures used in clinical practice are reliable and valid when assessed remotely through telehealth. METHOD: In this pilot study, we investigated 15 healthy older adults who performed validated tests: Timed Up and Go simple, dual cognitive and motor tasks; Berg Balance Scale; Functional Gait Assessment and Dynamic Gait Index. The tests were assessed on two dates: (i) face-to-face, (ii) and remotely, via videoconference between 7 and 14 days after the initial assessment. Participants also undertook the Physiological Profile Assessment (PPA) to assess their risk of falling. Reliability was measured using intraclass correlation (ICC) two-way mixed with absolute agreement to contrast the score of the assessments undertaken face-to-face and remotely in real-time and recorded. We also assessed inter-rater reliability. Criterion validity was measured using Pearson correlation between the tests that were undertaken remotely and PPA. RESULTS: All tests showed good reliability between face-to-face and real-time telehealth (ICC = 0.79-0.87) and face-to-face and recorded telehealth (ICC = 0.78-0.88) assessments and good to excellent inter-rater reliability (ICC = 0.80-1.00). Correlation between the tests and PPA were significantly (p < 0.05) moderate for real-time (r = -0.68-0.64) and recorded (r = -0.69-0.71) telehealth assessments. CONCLUSIONS: The good reliability between face-to-face and remote measurements together with moderate validity of these measures to assess fall risk suggest that health professionals could use these measures to evaluate the balance and gait of healthy older adults remotely.

Characterization and Validation of Arg286 Residue of IL-1RAcP as a Potential Drug Target for Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis and the fastest growing cause of chronic disability in the world. Formation of the ternary IL-1ß /IL-1R1/IL-1RAcP protein complex and its downstream signaling has been implicated in osteoarthritis pathology. Current OA therapeutic approaches target either the cytokine IL-1ß or the primary receptor IL-1RI but do not exploit the potential of the secondary receptor IL-1RAcP. Our previous work implicated the Arg286 residue of IL-1RAcP as a key mediator of complex formation. Molecular modeling confirmed Arg286 as a high-energy mediator of the ternary IL-1ß complex architecture and interaction network. Anti-IL-1RAcP monoclonal antibodies (mAb) targeting the Arg286 residue were created and were shown to effectively reduce the influx of inflammatory cells to damaged joints in a mouse model of osteoarthritis. Inhibitory peptides based on the native sequence of IL-1RAcP were prepared and examined for efficacy at disrupting the complex formation. The most potent peptide inhibitor had an IC50 value of 304 pM in a pull-down model of complex formation, and reduced IL-1ß signaling in a cell model by 90% at 2 µM. Overall, therapies that target the Arg286 region surface of IL-1RAcP, and disrupt subsequent interactions with subunits, have the potential to serve as next generation treatments for osteoarthritis.