Brain multi-omic Mendelian randomisation to identify novel drug targets for gliomagenesis.

Background: Genetic variants associated with molecular traits that are also associated with liability to glioma can provide causal evidence for the identification and prioritisation of drug targets.

Methods: We performed comprehensive two-sample Mendelian randomisation (Wald ratio and/or IVW) and colocalisation analyses of molecular traits on glioma. Instrumentable traits (QTLs P < 5 × 10-8) were identified amongst 11 985 gene expression measures, 13 285 splicing isoforms and 10 198 protein abundance measures, derived from 15 brain regions.

Contribution of inflammation markers and quantitative sensory testing (QST) indices of central sensitisation to rheumatoid arthritis pain.

Background: Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation.

Methods: This was a cross-sectional analysis of data from individuals with clinically active RA.

Risk factors for psoriatic arthritis development in psoriasis patients: myths, pitfalls, and pearls.

Psoriatic arthritis (PsA) predominantly emerges in individuals previously diagnosed with psoriasis (PsO), offering a unique opportunity to study the transition from PsO to PsA. This progression provides a window to identify characteristics of PsO patients who may develop PsA, facilitating early intervention and potentially informing prevention and treatment strategies. This review evaluates a wide array of research focusing on various risk factors for PsA development.

Use of patient-reported global assessment measures in clinical trials of chronic pain treatments: ACTTION systematic review and considerations.

Establishing clinically meaningful changes in pain experiences remains important for clinical trials of chronic pain treatments. Regulatory guidance and pain measurement initiatives have recommended including patient-reported global assessment measures (eg, Patient-Global Impression of Change [PGIC]) to aid interpretation of within-patient differences in domain-specific clinical trial outcomes (eg, pain intensity). The objectives of this systematic review were to determine the frequency of global assessment measures inclusion, types of measures, domains assessed, number and types of response options, and how measures were analyzed.

The efficacy and safety of a fixed-dose combination of apocynin and paeonol, APPA, in symptomatic knee OA: A double-blind, randomized, placebo-controlled, clinical trial.

Objective: Apocynin (AP) and paeonol (PA) are low molecular weight phenolic compounds with a broad array of anti-inflammatory and immunoregulatory effects. This study assessed of a fixed-dose combination of APPA in people with symptomatic knee osteoarthritis (OA).

Methods: A multi-center, randomized, placebo-controlled, double-blind phase 2a trial enrolled participants with radiographic knee OA (Kellgren-Lawrence, KL, grades 2-3) and pain ≥40/100 on WOMAC pain subscale, and evaluated the efficacy and safety of oral APPA over a 28-day period.

Serum CCL24 as a Biomarker of Fibrotic and Vascular Disease Severity in Systemic Sclerosis.

Background: Systemic sclerosis (SSc) is a heterogeneous disease, characterized by variable tissue and vascular fibrosis in the context of autoimmune activation. CCL24 (or Eotaxin2) has been shown to promote microangiopathic, proinflammatory, and profibrotic processes in preclinical models of SSc. Here, we study serum CCL24 levels in a real-life cohort of patients with SSc, to determine its distribution across disease features and its value in predicting disease progression and related mortality.

Polyacrylamide gel versus hyaluronic acid for the treatment of knee osteoarthritis: a randomised controlled study.

Objectives: To assess non-inferiority of intra-articular injectable polyacrylamide hydrogel (iPAAG) to hyaluronic acid (HA) on symptomatic benefit in individuals with knee osteoarthritis (OA).

Methods: This randomised, controlled, multi-centre trial recruited adults with symptomatic and radiographic knee OA from 3 clinical rheumatology sites in Denmark; two private clinics and one public hospital department. Participants were randomised 1:1 to receive a single intra-articular 6 mL injection of either HA or iPAAG on an outpatient basis.

Prognostic value of B-score for predicting joint replacement in the context of osteoarthritis phenotypes: Data from the osteoarthritis initiative.

Objective: Developing new therapies for knee osteoarthritis (KOA) requires improved prediction of disease progression. This study evaluated the prognostic value of clinical clusters and machine-learning derived quantitative 3D bone shape B-score for predicting total and partial knee replacement (KR).

Design: This retrospective study used longitudinal data from the Osteoarthritis Initiative.

Enhancing current guidance for psoriatic arthritis and its comorbidities: recommendations from an expert consensus panel.

Objectives: Existing guidelines for psoriatic arthritis (PsA) cover many aspects of management. Some gaps remain relating to routine practice application. An expert group aimed to enhance current guidance and develop recommendations for clinical practice that are complementary to existing guidelines.

A phase 2 trial investigating the efficacy and safety of the mPGES-1 inhibitor vipoglanstat in systemic sclerosis-related Raynaud's.

Objective: Our objective was to test the hypothesis, in a double-blind, placebo-controlled study that vipoglanstat, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1) which decreases prostaglandin E2 (PGE2) and increases prostacyclin biosynthesis, improves RP.

Methods: Patients with systemic sclerosis (SSc) and ≥7 RP attacks during the last screening week prior to a baseline visit were randomised to four weeks treatment with vipoglanstat 120 mg or placebo. A daily electronic diary captured RP attacks (duration and pain) and Raynaud's Condition Score, with change in RP attacks/week as primary end point.

Pain-phenotyping in osteoarthritis: Current concepts, evidence, and considerations towards a comprehensive framework for assessment and treatment.

Objectives: Pain as central symptom of osteoarthritis (OA) needs to be addressed as part of successful treatment. The assessment of pain as feature of disease or outcome in clinical practice and drug development remains a challenge due to its multidimensionality and the plethora of confounders. This article aims at providing insights into our understanding of OA pain-phenotypes and suggests a framework for systematic and comprehensive assessments.

Statin use and longitudinal changes in quantitative MRI-based biomarkers of thigh muscle quality: data from Osteoarthritis Initiative.

Objective: To assess whether changes in MRI-based measures of thigh muscle quality associated with statin use in participants with and without/at-risk of knee osteoarthritis.

Methods: This retrospective cohort study used data from the Osteoarthritis Initiative study. Statin users and non-users were matched for relevant covariates using 1:1 propensity-score matching.

Prevalence, Severity, and Measures of Anxiety in Rheumatoid Arthritis: A Systematic Review.

Objective: Many studies have reported high rates of anxiety in adults with rheumatoid arthritis (RA). The aim of this systematic review was to examine those findings and determine the overall prevalence, severity, and commonly used measures of anxiety in individuals with RA.

Methods: Six databases were searched from January 2000 without restrictions on language/location, study design, or gray literature.

Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52-week clinical and ultrasound results from the randomised, double-blind ULTIMATE trial with open label extension.

Objectives: In the ULTIMATE study with an open label extension, we assessed the long-term effect of secukinumab at tissue level on synovitis and enthesitis, and across all psoriatic arthritis (PsA) manifestations, using both clinical evaluations and power Doppler ultrasonography (PDUS).

Methods: This randomised, placebo-controlled, Phase 3 study (ULTIMATE) included biologic-naïve patients with PsA with active PDUS synovitis and clinical enthesitis, and inadequate response to conventional synthetic disease-modifying antirheumatic drugs. The study consisted of 3 treatment periods; in the first period (baseline to week 12) patients were randomised to receive subcutaneous secukinumab (150 mg or 300 mg according to severity of skin psoriasis) or placebo every week until week 4 and once every 4 weeks up to week 12.

Early referral of patients with suspected polymyalgia rheumatica - A systematic review.

Introduction: Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no standardized approach to referral of suspected PMR patients to rheumatologists, leading to inconsistent management practices. The objective of this systematic review was to clarify the existing evidence regarding the following aspects of early management strategies in patients with suspected PMR: diagnostic strategies, GCA screening, glucocorticoid initiation prior to referral, value of shared care and value of fast track clinic.

Predicting Inflammatory Arthritis in At-Risk Persons: Development of Scores for Risk Stratification.

Background: Inflammatory arthritis (IA) is an immune-related condition defined by the presence of clinical synovitis. Its most common form is rheumatoid arthritis.

Objective: To develop scores for predicting IA in at-risk persons using multidimensional biomarkers.

The comparative performance of three screening questionnaires for psoriatic arthritis in a primary care surveillance study.

Objectives: The objective of this study was to compare the performance of three PsA screening questionnaires in a primary care psoriasis surveillance study.

Methods: Participants with psoriasis, and not known to have PsA, were identified from general practice databases and invited to attend a secondary care centre for a clinical assessment. The three patient-completed screening questionnaires (PEST, CONTEST and CONTESTjt) were administered, along with other patient-reported measures, and a clinical examination of skin and joints was performed.