Citric acid is more effective than sodium thiosulfate in chelating calcium in a dissolution model of calcinosis.

Calcinosis cutis affects 20-40% of patients with systemic sclerosis. This study tests the hypothesis that calcium-chelating polycarboxylic acids can induce calcium dissolution without skin toxicity or irritancy. We compared citric acid (CA) and ethylenediaminetetraacetic acid (EDTA) to sodium thiosulfate (STS) for their ability to chelate calcium in vitro using a pharmaceutical dissolution model of calcinosis (hydroxyapatite (HAp) tablet), prior to evaluation of toxicity and irritancy in 2D in vitro skin models.

International consensus to define outcomes for trials of chemoradiotherapy for anal cancer (CORMAC-2): defining the outcomes from the CORMAC core outcome set.

Variation in outcomes definitions and reporting limit the utility of clinical trial results. The Core Outcome Research Measures in Anal Cancer (CORMAC) project developed a core outcome set (COS) for chemoradiotherapy trials for anal squamous cell carcinoma (ASCC) through an international healthcare professional and patient consensus process. The CORMAC-COS comprises 19 outcomes across 4 domains (disease activity, survival, toxicity, life impact).

Cross-sectional relationships of circadian misalignment and rest-activity rhythms with occupational attainment in UK Biobank participants.

Circadian misalignment and disrupted rest-activity rhythms have been linked to adverse health and educational outcomes, yet few studies have considered their relationships with economic outcomes. We investigate associations between multiple accelerometer-measured circadian misalignment traits (Composite Phase Deviation and the Sleep Regularity Index) and rest-activity rhythm traits (Inter-daily Stability, Intra-daily variability and relative amplitude), with occupational attainment, measured using the average wage paid to an individual's occupation. We use data from 20 356 UK Biobank participants who wore an accelerometer (2013-16), provided employment data for the year they wore the accelerometer, and supplied covariate data at recruitment (2006-10).

Non-pharmacological approaches to chronic cough.

While cough is a protective reflex it can occur in the absence of any physical need to clear the airway. In chronic cough, cough can be triggered by innocuous stimuli and persist despite medical treatment. Non-pharmacological interventions such as cough control therapy, provided by speech pathologists, have gained popularity in recent years.

Characterising a Novel Therapeutic Target for Psoriasis, TYK2, Using Functional Genomics.

Psoriasis (Ps) is a debilitating immune-mediated chronic skin condition. It affects about 1-3% of the world population, with an 8-11% prevalence in Northern European populations. Tyrosine kinase 2 (TYK2) is a newly identified target for Ps.

The Effect of Inhaled Beta-2 Agonists on Heart Rate in Patients With Asthma: Sensor-Based Observational Study.

Background: Beta-2 agonists play an important role in the management of asthma. Inhaled long-acting beta-2 agonists (LABAs) and short-acting beta-2 agonists (SABAs) cause bronchodilation by stimulating adrenoceptors. These receptors are also present in cardiac cells and, as a side effect, could also be stimulated by inhaled beta-2 agonists.

Excess weight by degree and duration and cancer risk (ABACus2 consortium): a cohort study and individual participant data meta-analysis.

Background: Elevated body mass index (BMI) ≥25 kg/m is a major preventable cause of cancer. A single BMI measure does not capture the degree and duration of exposure to excess BMI. We investigate associations between adulthood overweight-years, incorporating exposure time to BMI ≥25 kg/m and cancer incidence, and compare this with single BMI.

Safety and Efficacy of Deucravacitinib in Moderate to Severe Plaque Psoriasis For Up to 3 Years: An Open-Label Extension of Randomized Clinical Trials.

Importance: Safe and effective long-term treatments for moderate to severe plaque psoriasis are needed.

Objective: To evaluate the long-term safety and efficacy of deucravacitinib through 3 years (week 148) in the randomized POETYK PSO-1, PSO-2, and nonrandomized long-term extension (LTE) trials.

Design, Setting, And Participants: PSO-1/PSO-2 were global, 52-week, randomized, double-blinded phase 3 trials in patients with moderate to severe plaque psoriasis.

Bimekizumab Efficacy in High-Impact Areas: Pooled 2-Year Analysis in Scalp, Nail, and Palmoplantar Psoriasis from Phase 3/3b Randomized Controlled Trials.

Introduction: Psoriasis in high-impact areas, including the scalp, nails, palms, and soles, can disproportionately impair patient quality of life. Here, we evaluate the 2-year efficacy of bimekizumab treatment in patients with moderate to severe plaque psoriasis in post hoc analyses of five phase 3/3b trials.

Methods: High-impact area efficacy data were pooled through 2 years across five phase 3/3b trials: BE VIVID, BE READY, BE SURE, their ongoing open-label extension (OLE) BE BRIGHT, and BE RADIANT (including its double-blinded treatment period and the first year of its OLE).

Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses.

Objective: Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages.

Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping.

Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate.

Association between Accelerometer-Measured Irregular Sleep Duration and Longitudinal Changes in Body Mass Index in Older Adults.

Irregular sleep duration may disrupt circadian rhythms and contribute to metabolic, behavioral, and mood changes, potentially increasing the risk for obesity. However, quantitative data on the relationship between sleep duration irregularity and weight change are lacking. In this prospective study, we analyzed data from 10,572 participants (mean age: 63 years) in the UK Biobank who wore accelerometers for a week between 2013-2015 and had two body mass index (BMI; kg/m) measurements on average 2.

Use of over-the-counter supplements, sleep aids and analgesic medicines in rheumatology: results of a cross-sectional survey.

Objectives: Pain, fatigue and sleep disturbances are common symptoms in patients with rheumatic and musculoskeletal diseases (RMDs) that may prompt the use of over-the-counter (OTC) supplements, sleep aids and analgesics as self-management strategies. This study evaluated the prevalence of OTC supplements, sleep aids and pain relievers and the financial burden associated with their use in rheumatology.

Methods: A web-based survey developed with patients was administered in rheumatology clinics in an English hospital.

Strategies to optimise the health equity impact of digital pain self-reporting tools: a series of multi-stakeholder focus groups.

Background: There are avoidable differences (i.e., inequities) in the prevalence and distribution of chronic pain across diverse populations, as well as in access to and outcomes of pain management services.

Comparative risk of mortality in new users of prescription opioids for noncancer pain: results from the International Pharmacosurveillance Study.

Although opioids continue to be used internationally for noncancer pain, evidence to date on the comparative safety of different opioids is sparse and conflicting. The aim of this study was to examine the comparative risk of all-cause mortality in patients newly initiated on opioids for noncancer pain, across 3 jurisdictions in the United Kingdom (UK), United States, and Canada. A multicentre retrospective, population-based cohort study was conducted.

Proactive therapeutic drug monitoring of biologic drugs in adult patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis: a clinical practice guideline.

Clinical Question: In adult patients with inflammatory bowel disease, inflammatory arthritis (rheumatoid arthritis, spondyloarthritis, psoriatic arthritis), or psoriasis taking biologic drugs, does proactive therapeutic drug monitoring (TDM) improve outcomes as compared with standard care?

Context And Current Practice: Standard care for immune mediated inflammatory diseases includes prescribing biologic drugs at pre-determined doses. Dosing may be adjusted reactively, for example with increased disease activity. In proactive TDM, serum drug levels and anti-drug antibodies are measured irrespective of disease activity, and the drug dosing is adjusted to achieve target serum drug levels, usually within pre-specified therapeutic ranges.

Efficacy and safety of filgotinib in patients with rheumatoid arthritis: week 156 interim results from a long-term extension study.

Background: Janus kinase inhibitors are an effective option for achieving sustained remission or low disease activity in patients with rheumatoid arthritis (RA) following inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. Filgotinib is a Janus kinase 1-preferential inhibitor available in two doses for moderate-to-severe RA. We report the long-term efficacy and safety of filgotinib.

Influence of Ethnicity and Deprivation on Occurrence of Paget'S Disease in Greater Manchester, UK.

There is important variation in the occurrence of Paget's disease in different regions and populations. There are though few data concerning the occurrence of clinically diagnosed disease in black and ethnic minority groups in the United Kingdom (UK). We undertook an anonymised search using an integrated primary and secondary care-based database in Greater Manchester, covering a population of over 3 million people.