Efficacy and cost-effectiveness of Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial).

INTRODUCTION: Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months. METHODS AND ANALYSIS: The Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat. ETHICS AND DISSEMINATION: This protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897.

Validity of European position paper on rhinosinusitis disease control assessment and modifications in chronic rhinosinusitis.

OBJECTIVES: To develop a chronic rhinosinusitis (CRS) disease control staging system that predicts patient and physician opinion. This involved exploring the predictive capacity of the proposed European Position Paper on Rhinosinusitis (EPOS) 2012 staging system and other potential scoring systems based on patient symptoms and objective criteria. STUDY DESIGN: Prospective study. SETTING: Tertiary hospitals. SUBJECTS AND METHODS: Adults CRS patients undergoing sinus surgery were prospectively enrolled from a tertiary clinic. The Sino-Nasal Outcome Test 22, endoscopy score, and systemic medication were recorded at 6 and 12 months. A physician and patient report of their condition as either "controlled,""partly controlled," or "uncontrolled" was also recorded. Ordinal regression was used for modeling a staging system. The EPOS criteria and various combinations were assessed. Kappa agreements between the staging systems and patient/physician reports were analyzed. RESULTS: One hundred six patients were assessed. Nasal obstruction (P = .02), endoscopic mucosal inflammation (P < .001), and thick and/or purulent discharge (P = .01) associated with progress reports. A modified staging system of Nasal Obstruction, Systemic medication used, and Endoscopic inflammation (NOSE) was selected on predictive strengths. The EPOS and NOSE had significant agreement with physician's (k = 0.29, P < .01, and k = 0.45, P < .01) and patient's report (k = 0.18, P = .01, and k = 0.32, P < .01). CONCLUSIONS: The disease control assessment by EPOS has slight agreement with patients and a physician. A simpler NOSE system using nasal obstruction, mucosa, and discharge is proposed.

Multilevel latent variable models for global health-related quality of life assessment.

Quality of life (QOL) assessment is a key component of many clinical studies and frequently requires the use of single global summary measures that capture the overall balance of findings from a potentially wide-ranging assessment of QOL issues. We propose and evaluate an irregular multilevel latent variable model suitable for use as a global summary tool for health-related QOL assessments. The proposed model is a multiple indicator and multiple cause style of model with a two-level latent variable structure. We approach the modeling from a general multilevel modeling perspective, using a combination of random and nonrandom cluster types to accommodate the mixture of issues commonly evaluated in health-related QOL assessments--overall perceptions of QOL and health, along with specific psychological, physical, social, and functional issues. Using clinical trial data, we evaluate the merits and application of this approach in detail, both for mean global QOL and for change from baseline. We show that the proposed model generally performs well in comparing global patterns of treatment effect and provides more precise and reliable estimates than several common alternatives such as selecting from or averaging observed global item measures. A variety of computational methods could be used for estimation. We derived a closed-form expression for the marginal likelihood that can be used to obtain maximum likelihood parameter estimates when normality assumptions are reasonable. Our approach is useful for QOL evaluations aimed at pharmacoeconomic or individual clinical decision making and in obtaining summary QOL measures for use in quality-adjusted survival analyses.