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Objective: Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain, but rapid absorption into systemic circulation may limit efficacy and produce untoward effects. We compared the pharmacokinetics (PK) of IA triamcinolone acetonide (TA) delivered as an extended-release, microsphere-based formulation (FX006) vs a crystalline suspension (TAcs) in knee OA patients.Method: This Phase 2 open-label study sequentially enrolled 81 patients who received a single IA injection of FX006 (5 mL, 32 mg delivered dose, N = 63) or TAcs (1 mL, 40 mg, N = 18). Synovial fluid (SF) aspiration was attempted in each patient at baseline and one post-IA-injection visit (FX006: Week 1, Week 6, Week 12, Week 16 or Week 20; TAcs: Week 6). Blood was collected at baseline and multiple post-injection times. TA concentrations (validated LC-MS/MS, geometric means (GMs)), PK (non-compartmental analysis models), and adverse events (AEs) were assessed.Results: SF TA concentrations following FX006 were quantifiable through Week 12 (pg/mL: 231,328.9 at Week 1; 3590.0 at Week 6; 290.6 at Week 12); post-TAcs, only two of eight patients had quantifiable SF TA at Week 6 (7.7 pg/mL). Following FX006, plasma TA gradually increased to peak (836.4 pg/mL) over 24 h and slowly declined to <110 pg/mL over Weeks 12-20; following TAcs, plasma TA peaked at 4 h (9628.8 pg/mL), decreased to 4991.1 pg/mL at 24 h, and was 149.4 pg/mL at Week 6, the last post-treatment time point assessed. AEs were similar between groups.Conclusion: In knee OA patients, microsphere-based TA delivery via a single IA injection prolonged SF joint residency, diminished peak plasma levels, and thus reduced systemic TA exposure relative to TAcs. [ABSTRACT FROM AUTHOR]

Objectives: Meniscal pathology is integral to knee osteoarthritis (OA) and its progression; it provides a progression biomarker and a potential treatment target. Magnetic resonance imaging (MRI) demonstrates large heterogeneity in meniscal damage; this structural complexity means measurement is difficult. The aim of this study was to apply novel 3D image analysis to determine which meniscal pathologies demonstrated most change during OA progression.Methods: Knee images were selected from the progression cohort of the Osteoarthritis Initiative choosing participants with risk factors for medial OA progression. Medial and lateral menisci were manually segmented then analysed using a statistical shape model of the tibia as a reference surface. Responsiveness was assessed at 1 year using standardised response means (SRMs) for four constructs: meniscal volume, extrusion volume, thickness and tibial coverage; anatomical sub-regions of these constructs were also explored.Results: Paired images from 86 participants (median age 61.5, 49% female, 56% obese) were included. Reliability of the novel meniscal measurements was very good intraclass correlation coefficients (ICCs all > 0.98). Meniscal volume and extrusion demonstrated no significant change. Moderate responsiveness was observed for medial meniscus thickness (SRM -0.35) and medial tibial coverage (SRM -0.36). No substantial change was seen for the lateral meniscus measures. Sub-region analysis did not improve responsiveness; while greater change was seen in the posterior medial compartment, it was associated with increased variance of the change.Conclusions: The location of meniscal damage was consistently in the posterior medial region, and two measurements (thickness and tibial coverage) were most responsive. Meniscal measures should add to discriminatory power in OA progression assessment. [ABSTRACT FROM AUTHOR]

Efficient building design, and management of this through to the building's operation is critical as sub-optimal performance becomes difficult to detect and assess once in the operational stage. Building energy modelling can facilitate this through identifying operational drift away from the optimal building performance. However existing energy modelling tools fail to meet many of the needs to manage this process, due to the excessive complexity of modelling frameworks. Furthermore, models are not typically integrated with operational information from buildings to facilitate and maintain building performance in the operational stage. The aim of this project is to demonstrate an innovative energy modelling framework for clusters of buildings to improve their design, operation, compliance, data management and analytics. This case study considers new and existing buildings within the BCA Academy Campus in Singapore over three phases to compare and determine the potential for optimal building performance across the campus. Phase 1 creates a 3D masterplanning model used to store, visualise and compare key building parameters to enable advanced design and compliance planning. In Phase 2, more detailed building energy models are created for two proposed new campus buildings, which are used to simulate and analyse the impact of various design options, and guide optimal building design in line with BCA requirements. Phase 3 focuses on creating a highly calibrated detailed model of an existing building, where measured data is used to improve the level of accuracy between the model and the actual performance to with-in +/-5%. This allows for accurate simulation to assess and further improve the buildings performance virtually, ahead of making actual changes in the building. [ABSTRACT FROM AUTHOR]

Objective: To investigate short-term efficacy and safety of a novel lipid ibuprofen formulation 1200 mg/day compared with standard ibuprofen 1200 mg/day and 2400 mg/day in episodic knee arthralgia/flaring pain.Design: Multicentre, randomised, double-blind, 3-arm, non-inferiority trial conducted at 27 primary care centres. Adults with ≥1 knee flare episode within 12 months were recruited within 24 h of new flare with pain severity ≥5 on a 0-10 numerical rating scale (NRS). Primary outcome was change from baseline in WOMAC pain subscale over 5 days. Main secondary outcome was Gastrointestinal Symptom Rating Scale (GSRS) change from baseline. Other endpoints included assessment of WOMAC total subscale scores and self-reported NRS for pain, subject nominated activity, stiffness and swelling.Results: 462 patients were enrolled (58.9% males; mean age 52.2 years). Treatment allocation comprised 148 lipid 1200 mg, 155 soft-gel 1200 mg, 159 soft-gel 2400 mg. WOMAC pain subscale scores decreased in all groups, with lipid 1200 mg being non-inferior to soft-gel 1200 mg (adjusted mean difference -0.26 [95% confidence interval [CI] -0.69, 0.17]) and to soft-gel 2400 mg (difference 0.19 [95% CI -0.24, 0.62]). No differences were seen in mean GSRS total scores. NRS secondary endpoints suggested greater improvements in the lipid 1200 mg group compared to soft-gel 1200 mg, with similar results to soft-gel 2400 mg. The most frequent drug-related adverse events (AEs) were gastrointestinal (GI) disorders, with statistically fewer events for lipid 1200 mg vs soft-gel 2400 mg (P = 0.01, post-hoc analysis).Conclusions: Ibuprofen 1200 mg/day lipid formulation was non-inferior to standard ibuprofen soft-gel capsules 1200 mg and 2400 mg/day in relieving flaring knee pain. NRS endpoints showed lipid 1200 mg was numerically similar to soft-gel 2400 mg.Trial Registration Number: EudraCT number: 2014-004254-33. [ABSTRACT FROM AUTHOR]

Foot and ankle involvement is common in rheumatic and musculoskeletal diseases, yet high-quality evidence assessing the effectiveness of treatments for these disorders is lacking. The Outcome Measures in Rheumatology (OMERACT) Foot and Ankle Working Group is developing a core outcome set for use in clinical trials and longitudinal observational studies in this area. A scoping review was performed to identify outcome domains in the existing literature. Clinical trials and observational studies comparing pharmacological, conservative or surgical interventions involving adult participants with any foot or ankle disorder in the following rheumatic and musculoskeletal diseases (RMDs) were eligible for inclusion: rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthropathies, crystal arthropathies and connective tissue diseases. Outcome domains were categorised according to the OMERACT Filter 2.1. Outcome domains were extracted from 150 eligible studies. Most studies included participants with foot/ankle OA (63% of studies) or foot/ankle involvement in RA (29% of studies). Foot/ankle pain was the outcome domain most commonly measured (78% of studies), being the most frequently specified outcome domain across all RMDs. There was considerable heterogeneity in the other outcome domains measured, across core areas of manifestations (signs, symptoms, biomarkers), life impact, and societal/resource use. The group's progress to date, including findings from the scoping review, was presented and discussed during a virtual OMERACT Special Interest Group (SIG) in October 2022. During this meeting, feedback was sought amongst delegates regarding the scope of the core outcome set, and feedback was received on the next steps of the project, including focus group and Delphi methods. Findings from the scoping review and feedback from the SIG will contribute to the development of a core outcome set for foot and ankle disorders in RMDs. The next steps are to determine which outcome domains are important to patients, followed by a Delphi exercise with key stakeholders to prioritise outcome domains. [Display omitted] [ABSTRACT FROM AUTHOR]

Field-based agronomic and genetic research relies heavily on data generated from field trials. Therefore, it is imperative to optimize the precision of yield estimates in cultivar evaluation trials. Experimental error in yield trials is sensitive to several factors, some of which are classified as experimental design factors (i.e., plot size, block size, and number of replicates). The objective of this study was to conduct a retrospective case-study analysis of long-term perennial ryegrass (Lolium perenne L.), Italian ryegrass [Lolium perenne L. ssp. multiflorum (Lam.) Husnot], and hybrid ryegrass (Lolium boucheanum) forage yield trials to quantify the eff ects of block size, block shape, plot size, and number of replicates on trial precision. A total of 142 forage yield trials sown 2001 to 2011 across five locations by the Department of Agriculture, Food and the Marine (DAFM), Ireland, were considered. The contribution of row and column sum of squares (SS) to total SS decreased with increasing block size from 6 (71% of total SS) to 33 cultivars per block (51% of total SS). Empirical estimates of LSD decreased with increasing number of replicates only for square blocks, but not for rectangular blocks. Across different block sizes from 6 to 42 plots per block, row-column designs were 36% more efficient than complete blocks. Increasing plot size was consistently ineffective. Use of incomplete block designs would significantly improve precision for the DAFM trials. This case study provides a template by which any research with long-term data can be used to design more efficient field trials. [ABSTRACT FROM AUTHOR]

Osteoarthritis has become a major chronic pain condition. It affects more than 10% of adults and accounts for almost 10% of health service resources. The impact of osteoarthritis is amplified by underuse of effective muscle strengthening exercises and a focus on often less effective and poorly tolerated analgesic therapies. Although traditionally considered to be primarily a disease of cartilage, there is now ample evidence that typical clinical osteoarthritis involves multiple tissue pathologies. Increased BMI is associated with a higher incidence of knee osteoarthritis. Anatomical abnormalities such as valgus alignment or previous joint trauma including meniscectomy, anterior cruciate ligament rupture and fracture through the joint are also associated with increased incidence of osteoarthritis. Pain is the main presenting symptom. However, we still have a poor understanding of the causes of pain in osteoarthritis. In patients aged 45 or over the diagnosis should be made clinically without investigations if the patient has activity-related joint pain in addition to early morning joint stiffness lasting less than 30 minutes. Muscle strengthening and aerobic exercise have been shown to improve joint pain and function. Weight loss not only improves joint pain and function but has a myriad of other health benefits, reducing the incidence of lifestyle associated diseases such as cardiovascular disease and type 2 diabetes, and mechanical stress on the joints. [ABSTRACT FROM AUTHOR]