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The increased prevalence of psychological stressors in individuals diagnosed with melanoma, compared to the general population, is well-documented. Understanding the psychological experiences of patients with advanced unresectable stage 3 or 4 melanoma is essential for providing holistic treatment and supporting the unique physical, emotional, and mental health needs of this population. Literature searches were conducted in MEDLINE, PubMed, and Google Scholar to identify studies that focused on the psychological experiences of patients with unresectable stage 3 or 4 melanoma, resulting in a narrative review. Records (n=482) were screened to include peer-reviewed studies published in the last 25 years, primary research involving melanoma patients, or systematic reviews and meta-analyses involving melanoma and mental health. The studies reviewed (n=13) consistently observed psychological changes in melanoma patients, with many reporting higher rates of anxiety and depression compared to the general population. Despite these findings, research on advanced melanoma and its psychological impact remains diverse but lacks specificity regarding the experiences of patients with unresectable stage 3 or 4 melanoma. While valuable insights have been gained into the assessment tools, prevalence, and potential treatments for psychological stressors, no study has explored these psychological experiences in-depth from the patient's perspective. Further investigation into the psychological experiences of this patient group is critical to improving psychological support and fostering more comprehensive care for oncology patients.

IntroductionOptimising emergency department (ED) patient experience is vital to ensure care quality. However, there are few validated instruments to measure the experiences of specific patient groups, including older adults. We previously developed a draft 82-item Patient Reported Experience Measure (PREM-ED 65) for adults ≥65 attending the ED. This study aimed to derive a final item list and provide initial validation of the PREM-ED 65 survey.MethodsA cross-sectional study involving patients in 18 EDs in England. Adults aged 65 years or over, deemed eligible for ED discharge, were recruited between May and August 2021 and asked to complete the 82-item PREM at the end of the ED visit and 7–10 days post discharge. Test–retest reliability was assessed 7—10 days following initial attendance. Analysis included descriptive statistics, including per-item proportions of responses, hierarchical item reduction, exploratory factor analysis (EFA), reliability testing and assessment of criterion validity.ResultsFive hundred and ten initial surveys and 52 retest surveys were completed. The median respondent age was 76. A similar gender mix (men 47.5% vs women 50.7%) and reason for attendance (40.3% injury vs 49.0% illness) was observed. Most participants self-reported their ethnicity as white (88.6%).Hierarchical item reduction identified 53/82 (64.6%) items for exclusion, due to inadequate engagement (n=33), ceiling effects (n=5), excessive inter-item correlation (n=12) or significant differential validity (n=3). Twenty-nine items were retained.EFA revealed 25 out of the 29 items demonstrating high factor loadings (>0.4) across four scales with an Eigenvalue >1. These scales were interpreted as measuring ‘relational care’, ‘the ED environment’, ‘staying informed’ and ‘pain assessment’. Cronbach alpha for the scales ranged from 0.786 to 0.944, indicating good internal consistency. Test–retest reliability was adequate (intraclass correlation coefficient 0.67). Criterion validity was fair (r=0.397) when measured against the Friends and Families Test question.ConclusionsPsychometric testing demonstrates that the 25-item PREM-ED 65 is suitable for administration to adults ≥65 years old up to 10 days following ED discharge.

INTRODUCTION:Chronic obstructive pulmonary disease (COPD) is a progressive, longterm group of respiratory diseases that encompasses chronic bronchitis and emphysema, and is typically caused by chronic cigarette smoke (CS) exposure. Although it is currently listed as the third leading cause of mortality worldwide by the WHO, current understanding of COPD pathophysiology is limited and as such the disease is frequently underdiagnosed or misdiagnosed. One of the hallmark characteristics of COPD is chronic and persistent inflammation, and much of our current understanding of the immunopathogenic mechanisms of COPD comes from the use of whole-body or nose-or-head only CS-exposure mouse models. Despite the existence of such models, these are not permitted for use under UK laws protecting the use of animals in science, as the model systems are considered to place mice under significant unnecessary stress and harm, and phenotypic outcomes do not accurately mimic human disease. Therefore, this project aims to develop a novel CS-exposure murine model of COPD that encompasses the three Rs of animal research (replacement, refinement and reduction) to improve model design in regards to both animal welfare and applicability to human disease.METHODS:Prior to model development, a 24-colour spectral flow cytometry was developed and optimised for the characterisation of major innate and adaptive immune cells. In addition to this, a reverse phase protein microarray (RPPA) panel to assess proteomics of the lungs was tested for cross-reactivity to mouse samples, though after no cross-reactivity was detected an RT-qPCR panel was developed to assess changes in gene expression in tissues. Mice were exposed intranasally to an aqueous cigarette smoke extract (CSE) to minimise stress of restraint and handling, and provide an exposure methodology more reflective of human exposure methods. Once per week, microsampling of tail vein blood was obtained to assess impact of CSE exposure on peripheral immune cells via flow cytometry. Following 12 weeks of CSE exposure, mice were culled and tissues were isolated for RT-qPCR and histological analysis.RESULTS:Due to low cell numbers in peripheral blood as a result of microsampling restrictions, no differences were detected in peripheral immune cell profiles between control groups and two disease groups (light-smoker and heavysmoker). Despite this, both conventional gating strategies and unbiased clustering analysis displayed comparable cell profiles, demonstrating the effectiveness of the comprehensive flow panel. Although no differences in systemic immunopathophysiology were observed, significant differences in gene expression, neutrophilia and airway remodelling were observed in the lungs, dependent on either CSE dose or sex. In particular, whilst most inflammatory and immune signalling pathway genes were upregulated in males, these were downregulated in females. Additionally, pulmonary neutrophilia and alveolar diameter were significantly increased in both male and female heavysmoker mice in comparison to control groups, and these findings were more pronounced in females in comparison to males.CONCLUSIONS:Overall, we have developed the foundations of a novel murine model of COPD that better encompasses the 3Rs and mimics the pulmonary manifestations of COPD. Whilst no differences in systemic immune cell profiles were observed, marked alterations to lung structure were observed akin to results reported in both humans and mice with COPD, and these appeared to be exacerbated in females.