Pharmacological pain management in patients with rheumatoid arthritis: a narrative literature review

Background: Pain is a major challenge for patients with rheumatoid arthritis (RA), with many people suffering chronic pain. Current RA management guidelines focus on assessing and reducing disease activity using disease-modifying anti-rheumatic drugs (DMARDs). Consequently, pain care is often suboptimal, with growing evidence that analgesics are widely prescribed to patients with RA, despite potential toxicities and limited evidence for efficacy. Our review provides an overview of pharmacological treatments for pain in patients with RA, summarising their efficacy and use. Findings: Thirteen systematic reviews of drug efficacy for pain in patients with RA were included in this review. These showed moderate- to high-quality evidence from clinical trials in more contemporary time-periods (mainly 1990s/2000s for synthetic DMARDs and post-2000 for biological/targeted synthetic DMARDs) that, in patients with active RA, short-term glucocorticoids and synthetic, biologic, and targeted synthetic DMARDs have efficacy at reducing pain intensity relative to placebo. In contrast, they showed low-quality evidence from trials in more historical time-periods (mainly in the 1960s–1990s for opioids and paracetamol) that (aside from naproxen) analgesics/neuromodulators provide any improvements in pain relative to placebo, and no supportive evidence for gabapentinoids, or long-term opioids. Despite this evidence base, 21 studies of analgesic prescribing in patients with RA consistently showed substantial and sustained prescribing of analgesics, particularly opioids, with approximately one quarter and > 40% of patients receiving chronic opioid prescriptions in each year in England and North America, respectively. Whilst NSAID prescribing had fallen over time across countries, gabapentinoid prescribing in England had risen from < 1% of patients in 2004 to approximately 10% in 2020. Prescribing levels varied substantially between individual clinicians and groups of patients. Conclusions: In patients with active RA, DMARDs have efficacy at reducing pain, supporting the role of treat-to-target strategies. Despite limited evidence that analgesics improve pain in patients with RA, these medicines are widely prescribed. The reasons for this are unclear. We consider that closing this evidence-to-practice gap requires qualitative research exploring the drivers of this practice, high-quality trials of analgesic efficacy in contemporary RA populations, alongside an increased focus on pain management (including pharmacological and non-pharmacological options) within RA guidelines

Monitoring for 5-aminosalicylate nephrotoxicity in adults with inflammatory bowel disease: prognostic model development and validation using data from the Clinical Practice Research Datalink

Objective: To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate nephrotoxicity. Methods: This UK retrospective cohort study used data from the Clinical Practice Research Datalink Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease and established on 5-aminosalicylic acid (5-ASA) treatment between 1 January 2007 and 31 December 2019. Drug discontinuation associated with 5-ASA nephrotoxicity defined as a prescription gap of ≥90 days with decline in kidney function was the outcome. Patients prescribed 5-ASAs for ≥6 months were followed-up for up to 5 years. Penalised Cox regression was used to develop the risk equation with bootstrapping for internal validation and optimism adjustment. Model performance was assessed in terms of calibration and discrimination. Results: 13 728 and 7318 participants who contributed 40 378 and 20 679 person-years follow-up formed the development and validation cohorts with 170 (1.2%) and 98 (1.3%) outcome events respectively. Nine predictors were included in the final model, including chronic kidney disease stage 3 and hazardous alcohol use as strong predictors. Age and Body Mass Index were weak predictors. The optimism-adjusted calibration slope, C and D statistics in the development and validation data were 0.90, 0.64 and 0.98, and 1.01, 0.66 and 0.94 respectively. Conclusion: This prognostic model used information from routine clinical care and performed well in an independent validation cohort. It can be used to risk-stratify blood test monitoring during established 5-ASA treatment. A key limitation is that the decline in kidney function could have been due to factors other than 5-ASA nephrotoxicity

Investigating a structured diagnostic approach for chronic breathlessness in primary care: a mixed-methods feasibility cluster randomised controlled trial

Background: There is a need to reduce delays to diagnosis for chronic breathlessness to improve patient outcomes. Objective: To conduct a mixed-methods feasibility study of a larger cluster randomised controlled trial (cRCT) investigating a structured symptom-based diagnostic approach versus usual care for chronic breathlessness in primary care. Methods: 10 general practitioner practices were cluster randomised to a structured diagnostic approach for chronic breathlessness including early parallel investigations (intervention) or usual care. Adults over 40 years old at participating practices were eligible if presenting with chronic breathlessness without an existing explanatory diagnosis. The primary feasibility outcomes were participant recruitment and retention rate at 1 year. Secondary outcomes included number of investigations at 3 months, and investigations, diagnoses and patient-reported outcome measures (PROMs) at 1 year. Semistructured interviews were completed with patients and clinicians, and analysed using thematic analysis. Results: Recruitment rate was 32% (48/150): 65% female, mean (SD) age 66 (11) years, body mass index 31.2 kg/m2 (6.5), median (IQR) Medical Research Council dyspnoea 2 (2–3). Retention rate was 85% (41/48). At 3 months, the intervention group had a median (IQR) of 8 (7–9) investigations compared with 5 (3–6) investigations with usual care. 11/25 (44%) patients in the intervention group had coded diagnosis for breathlessness at 12 months compared with 6/23 (26%) with usual care. Potential improvements in symptom burden and quality of life were observed in the intervention group above usual care. Conclusions: A cRCT investigating a symptom-based diagnostic approach for chronic breathlessness is feasible in primary care showing potential for timely investigations and diagnoses, with PROMs potentially indicating patient-level benefit. A further refined fully powered cRCT with health economic analysis is needed

A humanised thrombus-on-a-chip model utilising tissue-engineered arterial constructs: A method to reduce and replace mice used in thrombosis and haemostasis research [version 1; peer review: awaiting peer review]

The study of in vivo thrombus formation has principally been performed using intravital microscopy in mice and other species. These have allowed us to visualise the molecular and cellular processes that regulate thrombus formation inside the body. However current in vivo arterial thrombosis models are difficult to standardise between labs and frequently produce results that do not reliably translate successfully in human clinical trials. Here we provide a step-by-step description with accompanying video tutorials to demonstrate how to produce a 3D humanised thrombus-on-a-chip model, which uses perfusion of fluorescently-labelled human blood over a mechanically-injured human tissue engineered arterial construct (TEAC) within a 3D printed microfluidic flow chamber to replicate thrombus formation within a healthy artery. We also provide a written methodology on how to use 3D printing to produce a mechanical injury press that can reproducibly damage the TEAC as a stimulus for thrombus formation as part of a mechanical injury model. Perfusion of the uninjured TEAC with whole human blood containing DiOC6-labelled platelets without initiating notable thrombus formation. The mechanical injury press was shown to induce a reproducible puncture wound in the TEAC. Fluorescence microscopy was used to demonstrate that thrombus formation could be observed reproducibly around sites of injury. This humanised thrombosis-on-a-chip model can replace the use of animals in in vivo thrombosis models for preclinical assessment of anti-thrombotic therapies. This method also offers multiple scientific advantages: allowing new drugs to be directly tested on human blood from a diverse array of donors, facilitating use of a realistic and reproducible injury modality as well as removing the potential confounding effects of general anaesthetics in animal studies. The use of human thrombus-on-a-chip models combining TEACs offers a new methodology to reduce animal use whilst improving the predictive capabilities of preclinical trials of anti-thrombotic therapies

Exercising an individualized process of agency in restoring a self and repairing a daily life disrupted by fibromyalgia: A narrative analysis

Objective: Fibromyalgia is a chronic condition that has major impact on people’s lives. This study examines individuals’ illness trajectories, with a particular focus on daily life experiences and self-managing.Methods: Narrative interviews were conducted, asking participants to story their daily life experiences from illness onset to the present, and to reflect on the future. Embedded in their storying were experiences of recently being diagnosed, navigating daily life in the face of illness, and participating in a self-management intervention. The data underwent a narrative analysis.Results: In keeping with the idiographic focus of narrative research, two individuals’ stories were chosen to portray an individualized process of self-managing illness in daily life. The storylines ‘Resuming prior self and life’ and ‘Taking life and self in new direction’ illuminate how individuals with differing illness trajectories and life situations autonomously apply resources available to them in their lives. They make sense of illness by bringing together their own lifeworld experiences of stress and factual knowledge and, through a process of individual agency, discover and try out what is right to do in their own life in the face of chronic illness.Conclusions: These two storylines illustrate that a self-managing process is an individual process nested in the person’s social context. Self-management encompasses an individualized process of agency in remaking daily life and reconstructing a sense of self

Coproducing a culturally sensitive storytelling video intervention to improve psychosocial well-being: a multimethods participatory study with Nepalese migrant workers

Objective: This study aimed to coproduce a culturally adaptive storytelling video intervention to support the psychosocial well-being of Nepalese migrant workers. Design: A multimethods participatory study was conducted involving three different but interconnected phases: (1) formative research involving a systematic review, pilot survey and stakeholder consultations; (2) exploration and analysis of Nepalese literature relevant to contemporary migration; and (3) coproduction of a storytelling video intervention, using participatory workshops. Participants and settings: Convenience sample of outgoing and returnee migrant workers from the Gulf Cooperation Council (GCC) countries, their families and other relevant stakeholders in Dhading District of Bagmati Province, Nepal. Results: The systematic review of 33 included studies identified five key health issues: mental health; occupational hazards; sexual health; healthcare access; and infectious diseases. In the survey (n=60), workers reported various health problems including fever/common cold (42%); mental health problems (25%); and verbal abuse (35%). Twenty interviewees identified issues related to physical health (eg, pneumonia, kidney disease) as well as mental health (eg, anxiety, depression). Nepalese literary resources primarily portrayed themes of: separation; hopelessness and helplessness; and poor workplace environments. Drawing on these findings and iterative workshops with stakeholders, a culturally sensitive storytelling video intervention was coproduced to support the psychosocial well-being of Nepalese migrant workers in GCC countries. The intervention used an animated video format with audio narration and subtitles, presenting a story centred around the struggles of an archetypal male migrant worker and their use of coping strategies for dealing with adversities. Conclusions: This is a feasibility study conducted in a single district of Nepal; as such, the findings should be generalised cautiously. Despite these limitations, the project is testament to the value of participatory methods in the development of culturally sensitive public health interventions for marginalised groups, and points to the utility of coproduced storytelling formats in migrant health contexts. Future research is needed to evaluate feasibility and acceptability of the intervention as well as the outcomes and experiences of migrant workers who engaged with the video

Ocean crustal veins record dynamic interplay between plate-cooling-induced cracking and ocean chemistry

As ocean crust traverses away from spreading ridges, low-temperature hydrothermal minerals fill cracks to form veins, transforming the physical and chemical properties of ocean crust whilst also modifying the composition of seawater. Vein width and frequency observations compiled from the International Ocean Discovery Program (IODP) South Atlantic Transect (∼31°S) and previous scientific ocean drilling holes show that vein width distributions progressively broaden and observed strain increases with crustal age, whereas vein densities remain approximately constant. Elemental mapping and textural observations illuminate multiple precipitation and fracturing episodes that continue as the ocean crust ages. This challenges the existing notion that ocean crustal veins are passively filled; rather, they are dynamic features of ocean crust aging. These data, combined with thermal strain modelling, indicate a positive feedback mechanism where cooling of the ocean plate induces cracking and the reactivation of pre-existing veins, ultimately resulting in further cooling. Waning of this feedback provides a mechanism for the termination of the global average heat flow anomaly. Sites with total vein dilation greater than expected for their age correspond with crustal formation during periods of high atmospheric CO2. The amount of vein material thus reflects the changing balance between ocean plate cooling, ocean chemistry, and the age of the ocean crust. Our results demonstrate that ocean crust endures as an active geochemical reservoir for tens of millions of years after formation

Exploring purchase intention in metaverse retailing: Insights from an automotive platform

As an integration of cutting-edge digital technologies, the metaverse is set to revolutionize online retailing. This study employed a well-established metaverse automotive retailing platform in China to explore the paths influencing consumers' purchase intention when shopping in the metaverse. We adopted structural equation modeling to analyze the data obtained from 348 respondents who were planning to shop for a new car in the metaverse in China. The findings showed that the perceived social presence of others positively influences consumers’ purchase intention, as mediated by their metaverse identification. Moreover, consumer stickiness and the accompaniment of friends were found to positively moderate the effect of perceived social presence on metaverse identification in metaverse retailing. Likewise, product type positively moderated the effect of metaverse identification on purchase intention. Specifically, when consumers intended to purchase environmentally-friendly (vs. unfriendly) vehicles, a stronger positive impact of metaverse identification on purchase intention was observed. The results provide valuable insight for metaverse retailers

Optimized punching shear design in steel fiber-reinforced slabs: Machine learning vs. evolutionary prediction models

This research paper focuses on utilizing Artificial Neural Networks (ANN), Multi-Objective Genetic Algorithm Evolutionary Polynomial Regression (MOGA-EPR), and Gene Expression Programming (GEP) to predict the punching shear strength of Steel Fibre-Reinforced Concrete (SFRC) slabs.In order to formulate predictions, research and analysis were carried out making use of a dataset, this dataset included several parameters that impact on punching shear strength, including SFRC slabs longitudinally and transversely, using ANN, GEP, and MOGA-EPR methods. The developed models exhibited very good performance, as the soft computing techniques (GEP and MOGA-EPR) achieved R² values of 0.91 to 0.93, while the ANN technique was higher at 0.95. Furthermore, two case studies were incorporated to carry out cost analyses of the models in real-world applications. It was shown that the efficiency of the Machine Learning (ML) models in reducing the costs of materials is relatively high, as they were capable of better predictions than the standard methods employed by the codes

Integration and Potential Applications of Cardiovascular Computed Tomography in Cardio-Oncology

Purpose of Review: Cardiovascular computed tomography (CCT) is a versatile, readily available, and non-invasive imaging tool with high-resolution capabilities in many cardiovascular diseases (CVD). Our review explains the increased risk of CVD among patients with cancer due to chemoradiotherapies, shared risk factors and cancer itself and explores the expanding role of CCT in the detection, surveillance, and management of numerous CVD among these patients. Recent Findings: Recent research has highlighted the versatility and enhanced resolution capabilities of CCT in assessing a wide range of cardiovascular diseases. Early detection of cardiac changes and monitoring of disease progression in asymptomatic patients with cancer may lessen the severity of CVD. It offers an essential means to assess for coronary artery disease when patients are either unable to safely undergo stress testing for ischemia evaluation or at risk of complications from invasive coronary angiography. Furthermore, CCT extends its utility to valvular diseases, cardiomyopathies, pericardial diseases, cardiac masses, and radiation-induced cardiovascular diseases, allowing for a comprehensive, noninvasive assessment of the entire spectrum of cancer treatment associated CVD. Looking to the future, the integration of artificial intelligence and machine learning algorithms holds potential for automated image interpretation, improved precision and earlier detection of subclinical cardiac deterioration, allowing opportunities for earlier intervention and disease prevention. Summary: CCT is a useful imaging modality for assessing the myriad cardiovascular manifestations of diseases such as coronary artery disease, cardiomyopathies, pericardial disesaes, cardiac masses and radiation-induced cardiovascular diseases. CCT has several advantages. Readily available non-cardiac chest CT scans of patients with cancer may help with improved cardiovascular care, enhanced ASCVD risk stratification and toxicity surveillance