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Objective: Performance visualisation tools are increasingly being applied in healthcare to enhance decision-making and improve quality of care. However, there is a lack of comprehensive synthesis of their overall effectiveness and the contextual factors that influence their success in different clinical settings. This study aims to provide a broad synthesis of visualisation interventions not limited to a specific department., Design: Systematic review., Data Sources: MEDLINE and Embase were searched until December 2022., Eligibility Criteria: Randomised controlled trials (RCTs) and observational studies in English involving a visualisation intervention, either alone or as a core intervention, that reported quantitative outcomes including process and outcome indicators., Data Extraction and Synthesis: Data on study characteristics, intervention characteristics, outcome measures and results were extracted. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach, and risk of bias was evaluated with Risk of Bias 2 for RCTs and Risk of Bias in Non-randomised Studies - of Interventions for non-randomised studies. RESULTS : Of the 12 studies included, 2 were RCTs and 10 were observational studies, including 1 before-after study and 1 interrupted time series study. Five studies (42%) were conducted in teaching hospital settings. Compared with the control group or baseline, 10 studies reported a statistically significant change in at least one of their outcome measures. A majority of the studies reported a positive impact, including prescription adherence (6/10), screening tests (3/10) and monitoring (3/10). Visualisation tool factors like type, clinical setting, workflow integration and clinician engagement, may have some influence on the effectiveness of the intervention, but no reliable evidence was identified., Conclusion: Performance visualisation tools have the potential to improve clinical performance indicators. More studies with standardised outcome measures and integrating qualitative methods are needed to understand the contextual factors that influence the effectiveness of these interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To evaluate temporal and regional variation in biologic and targeted synthetic DMARD (b/tsDMARD) initiation for rheumatoid arthritis (RA) in England and Wales., Methods: An observational cohort study was conducted for people with RA enrolled in the National Early Inflammatory Arthritis Audit (NEIAA) between May 2018 and April 2022 who had 12-month follow-up data. Temporal trends in escalation to b/tsDMARDs within 12 months of initial rheumatology assessment were explored, including comparisons before and after publication (July 2021) of national guidelines that lowered the threshold for b/tsDMARD initiation to include moderate-severity RA. Case-mix-adjusted, mixed-effects regression was used to evaluate regional and hospital-level variation in b/tsDMARD initiation., Results: Of 6,098 RA patients with available follow-up, 508 (8.3%) initiated b/tsDMARDs within 12 months of initial assessment. b/tsDMARD escalation increased marginally towards the end of the study period (9.2% in May 2021/22); however, no significant differences were evident after guidelines were published permitting b/tsDMARDs for moderate-severity RA. The proportion of individuals escalated to b/tsDMARDs varied considerably between regions, ranging from 5.1% in Wales to 10.7% in North-West England. Following case-mix adjustment, the intraclass correlation (ICC) for hospitals within regions was 0.17, compared with a between-region ICC of 0.0, suggesting that the observable regional variation reflected hospital-level differences rather than systematic differences between regions themselves., Conclusion: There is marked variation in escalation to b/tsDMARDs for people newly-diagnosed with RA throughout England and Wales, despite a universal healthcare system. These disparities must be addressed if we are to deliver equitable access to b/tsDMARDs, regardless of geography., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Postural orthostatic tachycardia syndrome (POTS) is a poorly understood chronic disorder characterized by an unexplained excessive increase in heartbeat upon standing. The aim of this study was to investigate psychosocial and physiological correlates and predictors of symptom severity over time in patients presenting with POTS-like symptoms., Methods: Longitudinal cohort study of patients under investigation for POTS ( n = 149). Patients completed questionnaires at 1 month preclinic appointment and 6 months later. Diagnosis, blood pressure (BP), and heart rate (HR) measures were collected from medical records. Data were analyzed using hierarchical linear multiple regression., Results: Orthostatic and small fiber neuropathy (SFN) symptoms remained stable over time and were significantly correlated with distress, cardiac anxiety, threatening views of the illness, and cognitive-behavioral responses to symptoms, but not with emotional reactivity or social support. Baseline psychosocial factors collectively explained 48% ( F = 5.37, p < .001) of the variance in orthostatic symptoms, and 35% ( F = 3.49, p < .001) of the variance of SFN symptoms at baseline, but a nonsignificant amount of variance in symptoms at 6 months when controlling for baseline symptoms. Hemodynamic measures explained a significant 4% ( F = 3.37, p = .026) of variance of orthostatic symptoms at 6 months., Conclusion: Symptom burden in patients with suspected POTS remained high over 6 months. Psychosocial factors explained a large amount of the variance in symptoms at baseline. As symptoms did not change/improve over time, baseline symptoms accounted for most of the variance in symptoms at 6 months. An integrated approach addressing psychosocial factors alongside medical treatments may promote adjustment to the condition and lessen symptom burden for this group., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Abstract: Chronic pain in inflammatory arthritis (IA) reflects a complex interplay between active disease in a peripheral joint and central pronociceptive mechanisms. Because intra-articular lidocaine may be used to abolish joint-specific peripheral input to the central nervous system, we aimed to validate its use as a clinical tool to identify those patients with IA whose pain likely incorporates centrally mediated mechanisms. We began by investigating whether there was a placebo response of intra-articular injection in patients with IA 1:1 randomised to receive intra-articular lidocaine or control (0.9% saline). After, in a larger patient cohort not randomized to placebo vs lidocaine groups, we tested whether patients with IA could be stratified into 2 cohorts based on their response to intra-articular lidocaine according to markers of centrally mediated pain. To this end, we evaluated postlidocaine pain numerical rating scale (NRS) scores alongside baseline painDETECT, fibromyalgia criteria fulfillment, and quantitative sensory testing outcomes. Numerical rating scale scores were collected at baseline and 3-, 5-, and 10-minutes postinjection. Firstly, the placebo effect of intra-articular injection was low: compared to baseline, the mean pain NRS score 5-minutes postinjection was reduced by 3.5 points in the lidocaine group vs 1.2 points in the control group. Secondly, postlidocaine NRS scores were significantly higher in those with a high (>18) baseline painDETECT score, fibromyalgia, and low-pressure pain threshold at the trapezius ( P = 0.002, P = 0.001, P = 0.005, respectively). Persistent high pain after intra-articular lidocaine injection could be used as an indicator of pronociceptive mechanisms that are centrally mediated, informing centrally targeted analgesic strategies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Objectives: The impact of autoantibody profiles on the prognosis for idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with myositis-specific antibodies (MSAs) remains unclear. This retrospective cohort study examined whether serological profiles were associated with mortality or longitudinal lung function change., Methods: The baseline clinical/demographic characteristics and follow-up lung function data of consecutive adult patients with IIM-ILD or interstitial pneumonia with autoimmune features (IPAF) positive for MSAs (IPAF-MSA) were extracted from three hospitals. Univariate and multivariate Cox proportional hazards analyses were used to compare mortality between groups of patients with different autoantibodies. Regression models were used to analyse their lung function trends., Results: Of the 430 included patients, 81% met the IIM criteria, and the remaining 19% were diagnosed with IPAF-MSA. On univariate analysis, the risk factors associated with mortality included higher age, Charlson Comorbidity Index, and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared with anti-MDA5 negativity, anti-MDA5 positivity (MDA5+) was associated with higher mortality in the first 3 months [hazard ratio (HR) 65.2, 95% CI 14.1, 302.0], while no significant difference was seen thereafter (HR 0.55, 95% CI 0.14, 2.28). On multivariate analysis, combined anti-synthetase antibodies were associated with a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in patients with anti-Jo1+ (HR 0.61, 95% CI 0.4-0.87) and increased in patients with anti-PL7+ (HR 2.07, 95% CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards., Conclusion: Among the autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ conferred higher mortality risks in patients with IIM-ILD. Survivors of an early peak of mortality in anti-MDA5+ disease appeared to have a favourable prognosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: In view of the conflicting results from previous studies, the benefit of paclitaxel-coated balloons for arteriovenous fistulas is uncertain and equipoise remains. Although an industry-led trial testing the efficacy of sirolimus-coated balloons in AVFs is in progress, the benefit of sirolimus-coated balloons for arteriovenous fistulas is currently unknown. The purpose of this trial is to compare the efficacy of additional paclitaxel-coated or sirolimus-coated balloons on outcomes after a plain balloon fistuloplasty to preserve the patency of arteriovenous fistulae used for haemodialysis., Methods: The study design is a multicentre randomised controlled trial. Following a successful plain balloon fistuloplasty, participants will be randomised to further treatment with a paclitaxel-coated balloon, a sirolimus-coated balloon, or an uncoated control balloon. We will recruit 642 patients, each with one or two treatment segments, over a 3-year period. Patients will remain in the trial and be followed up for 1 year. The primary endpoint is time to loss of treatment segment primary patency. Cox-proportional hazards models will be used to estimate hazard ratios for the time to loss of treatment segment primary patency for each treatment group relative to the control group. Analysis of the primary endpoint will be based on treatment segments rather than participants and a shared frailty will be estimated to account for the clustering of treatment segments within patients. Secondary endpoints are time to loss of primary patency at any treatment segment; time to end of access circuit primary patency; time to AVF abandonment; number of radiological or surgical interventions; adverse events; intima-media thickness and degree of stenosis at 3 months on ultrasound; and patient quality of life assessed by EQ-5D-5L and VASQoL., Discussion: The three-armed design in this proposal will provide an answer on the efficacy of both paclitaxel- and sirolimus-coated balloons in the same trial. This trial is likely to provide a clear answer regarding the efficacy of drug-coated balloons for arteriovenous fistulas., Trial Registration: ISRCTN ISRCTN40182296. Registered on 4 August 2023., (© 2024. The Author(s).)

Complex decongestive therapy is the current gold standard for non-surgical clinical lymphedema management and consists of manual therapy, compression exercise, skincare, and education. Complex decongestive therapy involves an intensive volume reduction phase (Phase I) followed by a maintenance phase (Phase II). The aim of the maintenance phase is to promote life-long control of lymphedema through use of self-management strategies and the provision of ongoing reduction therapies as needed. Compression therapies are the mainstay of lymphedema self-management. Poor adherence to self-management practices has been associated with increased volume and progression of lymphedema to more advanced stages, supporting the importance of education and regular monitoring to promote adherence to the Phase II maintenance recommendations. In this editorial, we provide consensus recommendations on the essential components of the maintenance phase, including education, skin care practices, managing infection/cellulitis, compression therapies, health and weight management, exercise, and ongoing follow-up care., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Quantifying health-care inequality is essential to addressing the imbalance in outcomes attributable to age, sex, race or ethnicity, and multimorbidity. In this study, we analysed differences in the initiation of biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis within the universal health-care system of England and Wales, UK., Methods: An observational cohort study was conducted using the National Early Inflammatory Arthritis Audit (NEIAA) dataset. We included all patients with rheumatoid arthritis who were enrolled in NEIAA between May 8, 2018, and April 30, 2022, and who had 12-month follow-up data available. Modified Poisson regression was used to explore factors associated with the initiation of biological and targeted synthetic DMARDs within 12 months of initial rheumatology assessment. The factors evaluated included age, sex, ethnicity, socioeconomic status (index of multiple deprivation), smoking status, and relevant comorbidities (lung disease, cardiovascular disease, cancer, and depression). NEIAA is supported by people with lived experience of rheumatoid arthritis, who contributed to study design and the interpretation of findings., Findings: 6098 patients in NEIAA had new diagnoses of rheumatoid arthritis and available follow-up data. The mean age was 59·2 years (SD 14·9); 3912 (64·2%) patients were women and 2186 (35·8%) were men. 6047 (99·2%) patients had available ethnicity data, of whom 5215 (86·2%) were White, 152 (2·5%) were Black, 478 (7·9%) were Asian, and 202 (3·3%) were of mixed or other ethnicities. 508 (8·3%) of 6098 patients initiated biological and targeted synthetic DMARDs within 12 months. Patients younger than 40 years were more likely to be initiated on biological and targeted synthetic DMARDs than individuals older than 65 years (multivariable-adjusted risk ratio 2·41 [95% CI 1·83-3·19]; p<0·0001). Asian individuals were less likely to be initiated on biological and targeted synthetic DMARDs than White individuals (0·52 [0·36-0·76]; p=0·0007), which persisted after adjustment for socioeconomic status, comorbidities, baseline disease severity, and the initial response to conventional synthetic DMARDs. These differences were evident for Asian women but not Asian men. Black individuals were more likely to be initiated on biological and targeted synthetic DMARDs than White individuals (1·54 [1·10-2·16]; p=0·012), which became non-significant after adjusting for baseline disease severity and autoantibody status., Interpretation: The initiation of biological and targeted synthetic DMARDs for patients with newly diagnosed rheumatoid arthritis varies markedly by ethnicity and age in the universal health-care system of England and Wales. This study demonstrates the importance of providing tailored information and ensuring equitable access to high-quality care for underserved patient groups. The one-size-fits-all approach must be reconsidered if health disparities are to be mitigated effectively., Funding: Sandoz UK., Competing Interests: Declaration of interests JBG has received honoraria from AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, and UCB; and grant funding from Sandoz UK. MDR has received honoraria from AbbVie, Lilly, Galapagos, Menarini, UCB, and Viforpharma; grant funding from Sandoz UK; advisory board fees from Biogen; and support for attending educational meetings from Lilly, Pfizer, Janssen, and UCB. APC has received grant funding from BMS; consulting fees from Galvani/GSK, BMS, UCB, and Janssen; honoraria from Galapagos, AbbVie, and BMS; support for attending meetings from AbbVie; and has participated in a data or advisory board for Galvani/GSK. KB has received grant funding from the National Institute for Health and Care Research; honoraria from Galapagos, UCB, and Viforpharma; and educational support from UCB. EA has received support for attending meetings from UCB. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Poor adherence to photoprotection in Xeroderma Pigmentosum (XP) increases morbidity and shortens lifespan due to skin cancers., Objective: To test a highly personalised intervention (XPAND) to reduce the dose of ultraviolet radiation (UVR) reaching the face in adults with XP, designed using known psychosocial determinants of poor photoprotection., Methods: A two-arm parallel group randomised controlled trial, including patients with sub-optimal photoprotection to receive XPAND or a delayed intervention control arm that received XPAND the following year. XPAND comprises seven one-to-one sessions targeting photoprotection barriers (e.g., misconceptions about UVR) supported by personalised text messages, activity sheets, and educational materials incorporating behaviour change techniques. The primary outcome, mean daily UVR dose-to-face across 21 days in June-July 2018, was calculated by combining UVR exposure at the wrist with a face photoprotection activity diary. Secondary outcomes were UVR dose-to-face across 21 days in August 2018, time spent outside, photoprotective measures used outside, mood, automaticity, confidence-to-photoprotect. Financial costs and quality-adjusted life years (QALYs) were calculated., Results: 16 patients were randomised, 13 provided sufficient data for primary outcome analysis. The XPAND group (n=8) had lower mean daily UVR dose-to-face [0.03 SED (SD 0.02] compared to control (n=7) [0.36 SED (SD 0.16)] (adjusted difference=-0.25, p<0.001, Hedge's g=2.2). No significant between-group differences were observed in time spent outside, photoprotection outside, mood, or confidence. The delayed intervention control showed improvements in UVR dose-to-face (adjusted difference=-0.05, Hedge's g=-0.1) , time outside (adjusted difference=-69.9, Hedge's g=-0.28), and photoprotection (adjusted difference=-0.23, Hedge's g=0.45), after receiving XPAND. XPAND was associated with lower treatment costs (£-2642; 95% CI: -£8715 to £3873) and fewer QALYs (-0.0141; 95% CI: -0.0369 to 0.0028)., Conclusions: XPAND was associated with a lower UVR dose-to-face in XP patients and was cost-effective., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Introduction: Co-morbid anxiety and depression (distress) in inflammatory bowel disease (IBD) results in poorer outcomes and increased healthcare burden. IBD services require scalable treatment pathways for distress to meet this need. This real-world longitudinal study evaluates the implementation of a new integrated care pathway for distress including: 1) routine mental health screening and 2) therapist-guided, digital CBT tailored to the challenges of living with IBD (compass with adaptations for IBD: COMPASS-IBD) in a UK National Health Service (NHS) large gastroenterology service (∼ 5000 patients)., Methods: We describe a mixed-methods, observational, real-world longitudinal study. Routine mental health screening in the IBD service will identify patients with distress (using pre-defined clinical cut-offs), who will be triaged to determine appropriate treatment pathways (including participation in the COMPASS-IBD study). Participants will receive COMPASS-IBD online for ∼12 weeks (including 6 × 30-min therapist sessions). Key implementation outcomes will assess reach and adoption of the new pathway using aggregate data on uptake of mental health screening, eligibility, and consent rates for COMPASS-IBD, and number of COMPASS-IBD sessions completed. Interviews with patients and healthcare providers will primarily assess acceptability of the new pathway. Potential effectiveness will be assessed using participant questionnaires at pre-intervention, 12-weeks (post-intervention), and 6-month follow-up. The primary effectiveness outcome will be pre-post changes in distress (PHQ-ADS scores). Quantitative data will be summarised using descriptive statistics and qualitative data analysed using reflexive thematic analysis., Conclusion: Study findings will inform treatment pathways for co-morbid distress in IBD, and highlight adaptations required to increase future scalability and effectiveness., Trial Registration Number: NCT05330299 (clinicaltrials.gov)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RMM reports personal fees from training in CBT for irritable bowel syndrome outside the submitted work. She received payment for consultancy to Mahana Therapeutics, has share options in Mahana therapeutics, and is a beneficiary of a licence agreement between Mahana therapeutics and King's College London. She has received reimbursement for travel and speaker fees from EABM, APS and BABCP conferences. All other authors report no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: We developed a telephonic outreach and care coordination program for children in immigrant and refugee families (CIRF) at a federally qualified health center (FQHC) in North Carolina to address unmet health-related social needs (HRSN)., Methods: Participants were recruited between December 2020 and October 2021. Eligible children were ages 0-5, non-English speaking, and were seen at the FQHC in the 2 years prior. A bicultural/bilingual case manager completed telephonic outreach to caregivers of participants with HRSN screening. Bilingual patient navigators made follow-up calls to assess connection to resources and to develop strategies for addressing unmet needs., Results: Three hundred forty-two families received outreach; 212 (62.0%) completed the baseline questionnaire. The majority (N = 160, 75.5%) completed at least one follow-up. The majority (N = 186, 88.1%) were Spanish-speaking, and over two-thirds (N = 149, 70.3%) were uninsured. Most participants had between 3-5 HRSNs identified (N = 121, 57.1%); "employment" (n = 158, 74.5%) and "food" (n = 138, 65.1%) were the most common. Despite repeated assistance, the majority of participants struggled to link to a community resource for their highest priority need (N = 123, 78.3%)., Conclusion: Proactive phone-based HRSN screening may be a feasible and effective intervention to facilitate the identification of social needs for CIRF. The delivery of the intervention in languages other than English may have further contributed to program acceptability. Despite program feasibility and acceptability, community-level barriers to the resolution of HRSNs persist. While similar care coordination models can be considered to identify the high burden of unmet HRSN among CIRF, addressing the limited capacity of community-based resources for this population will be a critical component to ensuring the sustainability of such programs., (© 2024. W. Montague Cobb-NMA Health Institute.)

Background: Depression is common in people with chronic kidney disease, yet little is known about how depression is identified and managed as part of routine kidney care., Objectives: The primary objective was to survey all UK adult kidney centres to understand how depression is identified and managed. A secondary objective was to broadly describe the variability in psychosocial care., Design: Online survey., Methods: The survey comprised of three sections: (1) general kidney care, (2) psychological provision and (3) social work provision., Results: 48/68 (71%) of centres responded to the general survey with 20 and 13 responses from psychological and social work module respectively. Only 31.4% reported having both in centre psychological and social work practitioners. Three centres reported no access to psychosocial provision. Of the 25 centres who reported on pathways, 36.0% reported having internal pathways for the identification and management of depression. Within services with psychological provision, screening for depression varied across modality/group (e.g., 7.1% in mild/moderate chronic kidney disease vs. 62.5% in kidney donors). Cognitive Behavioural Therapy and Acceptance and Commitment Therapy were the most common interventions offered. Most psychosocial services were aware of the National Institute for Health and Care Excellence guidelines for managing depression in long-term conditions (n = 18, 94.7%) yet few fully utilised (n = 6, 33.3%). Limited workforce capacity was evident., Conclusions: There is considerable variability in approaches taken to identify and treat depression across UK kidney services, with few services having specific pathways designed to detect and manage depression. Workforce capacity remains a significant issue., (© 2024 The Authors. Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Objective: This proof-of-principle pharmacovigilance study used Electronic Health Record (EHR) data to examine the safety of sotrovimab, paxlovid and molnupiravir in prehospital treatment of Covid-19., Method: With NHS England approval, we conducted an observational cohort study using OpenSAFELY-TPP, a secure software-platform which executes analyses across EHRs for 24 million people in England. High-risk individuals with Covid-19 eligible for prehospital treatment were included. Adverse events (AEs) were categorised into events in the drug's Summary of Product Characteristics (SmPC), drug-reactions and immune-mediated. Cox models compared risk across treatments. A pre-pandemic record analysis was performed for comparative purposes., Results: Between 2021-2023, 37,449 patients received sotrovimab, paxlovid or molnupiravir whilst 109,647 patients made up an eligible-but-untreated population. The 28-day rates of AEs were low: SmPC 0.34 per 1000 patient-years (95% CI 0.32-0.36); drug-reactions 0.01 (95% CI 0.01-0.02) and immune-mediated 0.03 (95% CI 0.03-0.04), and similar or lower than the pre-pandemic period. Compared with the eligible but untreated population, sotrovimab and paxlovid associated with a risk of SmPC AE [adjHR 1.36 (95% CI 1.15-1.62) and 1.28 (95% CI 1.05-1.55), respectively], whilst sotrovimab associated with a risk of drug-reactions [adjHR 2.95 (95% CI 1.56-5.55)] and immune-mediated events [adjHR 3.22 (95% CI 1.86-5.57)]., Conclusion: Sotrovimab, paxlovid and molnupiravir demonstrate acceptable safety profiles. Although the risk of AEs was greatest with sotrovimab, event rates were lower than comparative pre-pandemic period., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AG, BMK, BZ, RMS, SB, SN and ZY have no known competing financial interests. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AM is a senior clinical researcher at the University of Oxford in the Bennett Institute, which is funded by contracts and grants obtained from the Bennett Foundation, Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, Mohn-Westlake Foundation, and NHS England. AMe received 3 days of consultancy for https://inductionhealthcare.com/ (last date feb 2022) - paid direct to me. Member of RCGP health informatics group and the NHS Digital GP data Professional Advisory Group that advises on access to GP Data for Pandemic Planning and Research (GDPPR); payment direct to me for the GDPPR role. Last invoiced Dec 2022. BG has received research funding from the Laura and John Arnold Foundation, NIHR, NIHR School of Primary Care Research, NHS England, NIHR Oxford Biomedical Research Centre, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, the World Health Organisation, UKRI MRC, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; he is a Non-Executive Director at NHS Digital; he also receives personal income from speaking and writing for lay audiences on the misuse of science. JBG has received honoraria from Abbvie, Amgen, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sobi, and UCB, and has research funding from Amgen, Aztra-Zeneca, Gilead, Janssen, Medicago, Novovax and Pfizer. KB has received honoraria from Galapagos, UCB and Viforpharma. MDR has received honoraria from AbbVie, Biogen, Lilly, Galapagos, Menarini, UCB, and Viforpharma., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: This study examines the outcomes of high-grade renal trauma in pediatric patients and evaluates the intervention rate. In our hospital, we routinely consult urology on all high-grade injuries. We anticipated minimal intervention, casting doubt on the need for routine urology consultation and follow-up., Methods: We conducted a retrospective review at a single pediatric trauma center from January 2018 to June 2023, focusing on patients with severe (grade III-V) renal injuries. Data collected included demographics, trauma-related variables, hospital course, interventions, and follow-up. When the grade was not readily available in the electronic medical record, we had a board-certified pediatric radiologist review the imaging and provide the grade. Follow-up was included only if it was with a pediatric urologist., Results: There were 92 patients that met our inclusion criteria. Of these, 47 were grade III, 32 were grade IV, and 13 were grade V. Six (6.5%) patients required inpatient renal stent procedures. Follow-up occurred in 55/92 (60%) patients with a pediatric urologist. Follow-up by grade is as follows: 22/47 (47%) grade III, 22/32 (69%) grade IV, and 11/13 (85%) grade V. Overall 5.8% of patients required antihypertensive medications and this was more likely as injury grade increased. All stents were removed outpatient and there were 3 (3.3%) additional outpatient interventions, all in patients that were symptomatic., Conclusion: Given the low prevalence of interventions after discharge, routine consultation and follow-up with urology is likely unnecessary in the absence of an inpatient urologic procedure during the index hospitalization. Patients with high-grade injuries should instead follow up with a trauma clinic or general provider with urology follow-up based on symptoms., Type of Study: Retrospective Review., Level of Evidence: Level III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Patients with rheumatoid arthritis have higher rates of mental health conditions compared to the general population. It is believed that affective distress and rheumatoid arthritis have a bi-directional relationship. This review will examine the associations between affective distress and rheumatoid arthritis outcomes over time. Several disease outcomes are included covering disease activity, function, and disability to provide a broad picture of the various ways patients are impacted. A quality assessment was also conducted. There were 71 studies included in the review. Three measures (disease activity, disability, and mortality) had enough data to complete meta-analyses of odds ratios or hazard ratios. The outcomes included were disease activity, tender joint count, swollen joints, pain, physician global assessment, patient global assessment, physical disability, acute phase reactants, stiffness, fatigue, work disability, and mortality. Numerous measures were included for most of the outcomes due to the variability across studies of measures used. Patients with affective distress had lower rates of remission according to the DAS-28, greater disability, and higher mortality. All of the outcomes covered had studies with mixed results, but swollen joint count, tender joint count, patient global assessment, and physician global assessment had the strongest evidence that they were associated with mental health longitudinally. The relationships between affective distress and disease outcomes are complex and vary depending on the measures. Overall, the effects fade over time. It is important for clinicians to be aware of the differing manifestations of the relationship between affective distress and rheumatoid arthritis outcomes., (© 2024. The Author(s).)

Objectives: To evaluate a strategy designed to optimize care and increase uptake of urate-lowering therapy (ULT) during hospitalizations for gout flares., Methods: We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment and re-hospitalization rates, were compared between patients hospitalized for flares in the 12 months post-implementation and a retrospective cohort of hospitalized patients from 12 months pre-implementation., Results: One hundred and nineteen and 108 patients, respectively, were hospitalized for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio [aOR] 11.5; 95% CI 4.36, 30.5; P < 0.001). After implementation, more patients achieved a serum urate ≤360 μmol/l within 6 months of discharge (10.6% pre-implementation vs 26.8% post-implementation; aOR 3.04; 95% CI 1.36, 6.78; P = 0.007). The proportion of patients re-hospitalized for flares was 14.9% pre-implementation vs 9.3% post-implementation (aOR 0.53; 95% CI 0.22, 1.32; P = 0.18)., Conclusion: Over 90% of patients were initiated on ULT after implementing a strategy to optimize hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalizations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalized gout patients to achieve urate targets, closer primary-secondary care integration is still needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Biologic therapies have led to increasing numbers of patients with psoriasis who have clear or nearly clear skin. It is current practice to continue biologic therapy indefinitely in these patients, which contributes to a substantial long-term drug and healthcare burden. 'As needed' biologic therapy in psoriasis may address this; however, our understanding of patient and clinician perceptions of this strategy is limited., Objectives: The aim of this mixed-methods study was to gain insight into the perspectives of both patients and clinicians regarding the acceptability of an 'as needed' approach to biologic therapy in psoriasis, including potential barriers and enablers to implementation in routine care., Methods: We first conducted UK-wide online scoping surveys of patients with psoriasis and dermatology clinicians to explore their views on 'as needed' biologic therapy. Using topic guides informed by these survey findings, we then carried out qualitative focus groups with patients and clinicians. Themes were identified using reflexive thematic analysis., Results: Of 67 patients and 27 clinicians completing the scoping surveys, 67% (43 of 64 patients) and 78% (21 of 27 clinicians) supported the use of 'as needed' biologic therapy, respectively. Respondents highlighted advantages such as a reduction in healthcare burden and greater ownership of care. Challenges included logistics of 'as needed' drug provision and potential risks of disease flare and drug immunogenicity. Focus groups comprised 15 patients with psoriasis [9 female patients (60%), average disease duration 32 years (range 9-64)] and 9 dermatology clinicians [8 female clinicians (89%), average dermatology experience 20 years (range 8-33)]. Both patients and clinicians felt that an 'as needed' treatment approach will deliver a reduction in treatment burden and present an opportunity for patient-led ownership of care. Both groups highlighted the importance of ensuring ongoing access to medication and discussing the potential impact of psoriasis recurrence. Patient preferences were influenced by their lived experiences, particularly previous difficulties with medication delivery logistics and establishing disease control. Clinician perspectives were informed by personal experience of their patients adapting their own dosing schedules. Clinicians highlighted the importance of targeted patient selection for an 'as needed' approach, ongoing disease monitoring, and prompt reaccess to medications upon psoriasis recurrence., Conclusions: These data indicate that 'as needed' biologic therapy in psoriasis is acceptable for both patients and clinicians. Formal assessment of clinical effectiveness and cost-effectiveness is warranted to enable the real-world potential of this approach to be realized., Competing Interests: Conflicts of interest D.G. has received educational support from Lilly. L.M. has attended conferences, spoken at meetings and attended advisory boards for the following companies: AbbVie, Almirall, BMS, Janssen-Cilag, LEO, Lilly, Novartis, ONO Pharma, Pfizer and UCB. H.M. and G.S. are employed by the Psoriasis Association, which has received unrestricted educational grants over the past two years from Almirall, AbbVie, Janssen, Amgen, Eli Lilly, Dermal, UCB, LEO Pharma, Bristol Myers Squibb and Novartis. J.N.W.N.B. has attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Samsung, Sienna, Sun Pharma and UCB. C.H.S. reports grants from a Medical Research Council-funded stratified medicine consortium with multiple industry partners (PSORT.org), grants from an IMI (Horizon 2020)-funded European consortium with multiple industry partners (BIOMAP-IMI.eu, HIPPOCRATES-IMI.eu, and others) and grants from AbbVie, Novartis, Pfizer, Sanofi, Boehringer Ingelheim and Swedish Orphan Biovitrum, outside the submitted work; and is Chair of UK guidelines on biologic therapy in psoriasis. S.K.M. reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Sanofi and UCB, outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Persistently active rheumatoid arthritis (pactiveRA) may be due to the interplay between biological and non-biological factors. The role of socioeconomic factors remains unclear., Objectives: To explore which biological and non-biological factors associate with pactiveRA., Methods: Adults with early RA in the National Early Inflammatory Arthritis Audit, recruited from May 2018 to October 2022, were included if having pactiveRA or persistently low RA (plowRA). The pactiveRA was defined as three consecutive Disease Activity Score-28 joints (DAS28) of >3.2 at baseline, 3 and 12 months. The plowRA was defined as DAS28 ≤3.2 at 3 and 12 months. Stepwise forward logistic regression was used to explore associations with pactiveRA (outcome). Age and gender were included a priori, with socioeconomic factors and comorbidities as exposure variables., Results: 682 patients with pactiveRA and 1026 plowRA were included. Compared with plowRA, patients with pactiveRA were younger (58, IQR: 49-67) versus (62, IQR: 52-72), and included more women (69% vs 59%). The pactiveRA was associated with worse scores in patient-reported outcomes at baseline, and anxiety and depression screens. Overall, there was clear social patterning in pactiveRA, with age-by-gender interaction. Logistic regression indicated age, gender, social deprivation and previous or current smoking, were independently associated with pactiveRA, after controlling for disease severity markers (seropositivity). Depression, lung disease, gastric ulcers and baseline corticosteroid use, were also associated with pactiveRA (p<0.05 for all)., Conclusion: Socioeconomic factors and deprivation were associated with pactiveRA, independent of clinical and disease characteristics. Identifying 'adverse' socioeconomic drivers of pactiveRA can help tailor interventions according to individual need., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Inflammatory arthritis causes significant work disability. Studies regarding this frequently fail to report important contextual information such as employment type. Our objective was to explore work participation, by gender and occupation type, in early inflammatory arthritis., Methods: Data are from the National Early Inflammatory Arthritis Audit for 2018-2020. At diagnosis, clinicians collected information on demographics, inflammatory arthritis disease activity, and working status. Participants completed patient-reported outcomes at baseline, 3 months and 12 months, including occupation and Work Productivity and Activity Impairment (WPAI). Descriptive analyses of work participation and WPAI scores by occupational class at all time points were performed. Regression models were used to examine associations between WPAI score and occupation., Results: In all, 12 473 people received a diagnosis of inflammatory arthritis and reported employment status, among whom 5999 (47%) were in paid work for at least 20 hours/week. At diagnosis, the working cohort had statistically significant lower measures of disease activity (P < 0.001). Occupational data were available for 3694 individuals. At diagnosis, 2793 completed a WPAI; 200 (7.2%) had stopped work and 344 (12.3%) changed jobs because of inflammatory arthritis symptoms. There was a high burden of absenteeism (30%) and presenteeism (40%). Compared with managerial or professional workers, the burden of work disability was greater among those in routine (manual) occupations. During follow-up, 9.4% of WPAI completers stopped work and 14.6% changed roles. Work drop-out occurred almost entirely among people doing routine jobs., Conclusion: It is easier to retain work in certain employment sectors. Participation in routine jobs is more affected, which may widen health inequalities., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Serious illness conversations may help patients avoid unwanted treatments. We previously piloted the telehealth Serious Illness Care Program (SICP) for older adults with acute myeloid leukemia and myelodysplastic syndrome., Objective: In this study, we aimed to understand the experience of the telehealth SICP from the clinician's perspective., Methods: We studied 10 clinicians who delivered the telehealth SICP to 20 older adults with acute myeloid leukemia or myelodysplastic syndrome. Quantitative outcomes included confidence and acceptability. Confidence was measured using a 22-item survey (range 1-7; a higher score is better). Acceptability was measured using an 11-item survey (5-point Likert scale). Hypothesis testing was performed at α=.10 (2-tailed) due to the pilot nature and small sample size. Clinicians participated in audio-recorded qualitative interviews at the end of the study to discuss their experience., Results: A total of 8 clinicians completed the confidence measure and 7 clinicians completed the acceptability measure. We found a statistically significant increase in overall confidence (mean increase of 0.5, SD 0.6; P=.03). The largest increase in confidence was in helping families with reconciliation and goodbye (mean 1.4, SD 1.5; P=.04). The majority of clinicians agreed that the format was simple (6/7, 86%) and easy to use (6/7, 86%). Clinicians felt that the telehealth SICP was effective in understanding their patients' values about end-of-life care (7/7, 100%). A total of three qualitative themes emerged: (1) the telehealth SICP deepened relationships and renewed trust; (2) each telehealth SICP visit felt unique and personal in a positive way; and (3) uninterrupted, unrushed time optimized the visit experience., Conclusions: The telehealth SICP increased confidence in having serious illness conversations while deepening patient-clinician relationships., Trial Registration: ClinicalTrials.gov NCT04745676; https://www.clinicaltrials.gov/study/NCT04745676., (©Marissa LoCastro, Ying Wang, Tristan Yu, Soroush Mortaz-Hedjri, Jason Mendler, Sally Norton, Rachelle Bernacki, Thomas Carroll, Heidi Klepin, Lucy Wedow, Sean Goonan, Hannah Erdos, Brenda Bagnato, Jane Liesveld, Eric Huselton, Benzi Kluger, Kah Poh Loh. Originally published in JMIR Formative Research (https://formative.jmir.org), 27.06.2024.)

Background: Patients with membranous nephropathy (MN) and poor kidney function or active disease despite previous immunosuppression are underrepresented in clinical trials. It is unknown how effective rituximab is in this population., Methods: This prospective, multi-centre, single-arm, real-world study of patients with active MN [urine protein-creatinine ratio (uPCR) >350 mg/mmol and serum albumin <30 g/L, or a fall in estimated glomerular filtration rate (eGFR) of at least 20% or more over at least 3 months] evaluated rituximab in those with contraindications to calcineurin inhibitors and cytotoxic therapy. The primary outcome was change in rate of eGFR decline before and after rituximab. Complete or partial remission were defined as uPCR <30 mg/mmol or uPCR <350 mg/mmol with a ≥50% fall from baseline, respectively., Results: A total of 180 patients [median age 59 years, interquartile range (IQR) 48-68] received rituximab and were followed up for a median duration of 17 months. Seventy-seven percent had prior immunosuppression. Median eGFR and uPCR at baseline were 49.2 mL/min/1.73 m 2 (IQR 34.4-80.6) and 766 mg/mmol (IQR 487-1057), respectively. The annual rate of decline of eGFR fell from 13.9 to 1.7 mL/min/1.73 m 2 /year following rituximab (Z score = 2.48, P  < .0066). At 18 months 12% and 42% of patients were in complete or partial remission, respectively. Rituximab was well tolerated; patient survival was 95.6% at 2 years and in patients in whom eGFR was available, kidney survival was 93% at 2 years., Conclusion: Rituximab significantly reduced the rate of eGFR decline in active MN including those who had received prior immunosuppression or with poor baseline kidney function., Competing Interests: All authors declare that they have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objectives: This study aims to explore patients' and clinicians' experiences in managing and living with refractory disease (RD) and persistent physical and emotional symptoms (PPES) in patients with RA or polyarticular JIA from their perspectives through interviews and/or focus groups., Methods: A qualitative exploration with 25 patients and 32 multidisciplinary rheumatology healthcare professionals (HCPs) was conducted to obtain participants respective understanding and experiences of managing RD/PPES and its impact on the patient-professional relationship. A pragmatic epistemology approach with framework analysis was employed., Results: Four key themes were identified from both patients and professionals in the management of RD/PPES: risk/perpetuating factors/triggers; need for a patient-centred holistic approach to care, diagnosis and treatment; discordance and impact on the patient-practitioner relationship and current problems in managing RD/PPES. These themes covered 22 subthemes, with none being patient specific and seven being HCP specific. Suggestions for potential management strategies were highlighted throughout, such as involving other specialties or a multidisciplinary team, assessing/treating patient-reported outcome measures and psychosocial factors, patient (re)education, need for adjustments/aids or adaptations, checking the diagnosis and further investigations/imaging and optimizing medications., Conclusion: Management strategies need to be developed that enable appropriate treatment plans for those with RD/PPES that account for wider biopsychosocial factors beyond inflammation and reduce discordance in the patient-practitioner relationship., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Enteric fever carries appreciable morbidity in non-endemic settings, particularly in returned travelers. This study aimed to characterize the healthcare burden of enteric fever in a low-incidence setting and to identify risk factors and opportunities for preventative interventions., Methods: Analysis of a retrospective case series from a tertiary pediatric center (2015-2019), augmented by public health notification and microbiological laboratory data (2018-2019), from Western Sydney, Australia, a region with frequent travel links to South Asia., Results: Eighty-nine (89) patients were diagnosed with enteric fever, including 43 children with complete demographic and travel data. Enteric fever cases increased over time (by 4.9 % per year) and incidence was three times higher in the pediatric population (<15 years old) compared to adults. Travel to India and visiting friends and relatives (VFR) travel were risk factors. Few children received enteric fever vaccination prior to travel, as pre-travel advice most commonly was not sought., Conclusions: Children visiting relatives in high-incidence countries are increasingly at risk for enteric fever, particularly when travelling to South Asia. Targeted health advice to travelers visiting friends and relatives is warranted to mitigate the healthcare burden of enteric fever in low-incidence settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Masson SAS. All rights reserved.)

Background: To evaluate the clinical efficacy of COMPASS, a therapist-supported digital therapeutic for reducing psychological distress (anxiety/depression) in people living with long-term physical health conditions (LTCs)., Methods: A two-armed randomized-controlled trial recruiting from LTC charities. Participants with anxiety and/or depression symptoms related to their LTC(s) were randomized (concealed allocation via independent administrator) to COMPASS (access to 11 tailored modules plus five thirty-minute therapist support sessions) or standard charity support (SCS). Assessments were completed online pre-randomization, at 6- and 12-weeks post-randomization. Primary outcome was Patient Health Questionnaire Anxiety and Depression Scale; PHQ-ADS measured at 12-weeks. Analysis used intention-to-treat principles with adjusted mean differences estimated using linear mixed-effects models. Data-analyst was blinded to group allocation., Results: 194 participants were randomized to COMPASS ( N = 94) or SCS ( N = 100). At 12-weeks, mean level of psychological distress was 6.82 (95% confidence interval; CI 4.55-9.10) points lower ( p < 0.001) in the COMPASS arm compared with SCS (standardized mean difference of 0.71 (95% CI 0.48-0.95)). The COMPASS arm also showed moderate significant treatment effects on secondary outcomes including depression, anxiety and illness-related distress and small significant effects on functioning and quality-of-life. Rates of adverse events were comparable across the arms. Deterioration in distress at 12-weeks was observed in 2.2% of the SCS arm, and no participants in the COMPASS arm., Conclusion: Compared with SCS, COMPASS digital therapeutic with minimal therapist input reduces psychological distress at post-treatment (12-weeks). COMPASS offers a potentially scalable implementation model for health services but its translation to these contexts needs further evaluating., Trial Registration: NCT04535778.

Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.

Objectives: To evaluate trust-level performance in time to initiation of DMARD therapy in patients with early inflammatory arthritis (EIA), with identification of the change in performance trajectories over time and investigation of trust characteristics associated with this change., Methods: We included 130 trusts from the UK contributing to the National Early Inflammatory Arthritis Audit (NEIAA) from 2018 to 2020. The primary outcome was days from referral to initiation of DMARD therapy in patients with EIA. Latent class growth mixture models were applied to identify distinct groups of trusts with similar trajectories of performance change over time. We used mixed effects linear and multinomial logistic regression models to evaluate the association between delay in treatment and trust-level characteristics., Results: The mean time to DMARD initiation was 53 days (s.d. 18), with an average 0.3-day decrease with each month over time. Four latent trajectories were identified in our cohort, with >77% of individual trusts showing ongoing improvements in decreasing treatment waiting times. Prior to separating by latent class, time to DMARD initiation was shorter in trusts with higher rheumatology staffing, a local EIA treatment pathway and those with access to musculoskeletal ultrasound. Trusts with more nurses in the rheumatology department were less likely to be in the worst performance group [odds ratio 0.69 (95% CI 0.49, 0.93)]., Conclusion: In this cohort study, we observed a reduction in treatment waiting time over time. Trusts with better staffed and improved EIA clinical structure are likely to initiate definitive treatment earlier in patients with EIA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during 12-months following IA diagnosis, mapping these against clinical outcomes to identify associations., Methods: This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient reported outcomes (PROs) at baseline, 3-months and 12-months were collected, including psychological distress (assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)). Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time., Results: Of 6,873 eligible patients, 3,451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3-months and 12-months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female, and non-white patients. Clinical factors, including higher counts of comorbidities, prior depression, and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatment response by EULAR criteria., Conclusion: Half of patients with IA show significant mental health comorbidity at presentation, which associated with worse disease outcomes and quality of life. Screening for anxiety and depression should be a universal standard, and access to effective mood therapies alongside arthritis treatments is essential. Strategies should be culturally valid and consider multi-morbidities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA., Methods: We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool., Results: Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo., Conclusion: Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction: Soft-tissue thumb defects are common reconstructive challenges, the main goals being restoration of tactile sensibility, range of movement, pulp padding, length, and cosmesis. The reverse-flow dorsoulnar and dorsoradial collateral artery flaps are homodigital flaps used to cover both distal dorsal and volar thumb defects. These flaps can be used as compound flaps including skin, fat, and/or nerves. As there is no critical analysis of these studies, this study aims to create a synthesized comprehensive systematic review., Methods: Systematic review was performed using the databases PubMed, Embase, and Medline. Eligible studies followed the inclusion criteria: English language and all studies published to date. The primary outcome was flap survival. Other data collected included anatomical area of the defect, flap constituents and dimensions, donor-site closure and complications, transfer method, reoperation, revision, and functional outcomes., Results: A total of 19 articles incorporating 189 flaps met the inclusion criteria. These flaps were categorized and analyzed as dorsoradial (50%), dorsoulnar (39%), and turnover flaps (11%). Dorsoradial flaps were used in fasciocutaneous fashion alone. Partial flap failures occurred in five cases. Dorsoulnar flaps were used as fasciocutaneous or as osteocutaneous flaps. Complete flap failure was reported in one patient alone, whereas partial necrosis was reported in four patients. Adipofascial turnover flaps had two partial flap failures reported but no complete failures. The overall complete and partial flap failure rates were 0.5 and 6.5%, respectively., Conclusion: Reverse-flow homodigital random or axial-based flaps provide a reliable means of reconstruction for soft-tissue defects with reasonable success rate and good functional outcomes. They have a consistent anatomy with a good potential for personalization and therefore increased versatility., (© 2024 Published by Elsevier B.V. on behalf of Society for Indian Hand Surgery and Micro Surgeons.)

Background: According to epidemiological studies, psychosocial factors are known to be associated with disease activity, physical activity, pain, functioning, treatment help-seeking, treatment waiting times and mortality in people with rheumatoid arthritis (RA). Limited qualitative inquiry into the psychosocial factors that add to RA disease burden and potential synergistic interactions with biological parameters makes it difficult to understand patients' perspectives from the existing literature., Aim: This study aimed to gather in-depth patient perspectives on psychosocial determinants that drive persistently active disease in RA, to help guide optimal patient care., Methods: Patient research partners collaborated on the research design and materials. Semistructured interviews and focus groups were conducted online (in 2021) with patients purposively sampled from diverse ethnicities, primary languages, employment status and occupations. Data were analysed using inductive thematic analysis., Results: 45 patients participated across 28 semistructured interviews and three focus groups. Six main themes on psychosocial determinants that may impact RA management were identified: (1) healthcare systems experiences, (2) patient education and health literacy, (3) employment and working conditions, (4) social and familial support, (5) socioeconomic (dis)advantages, and (6) life experiences and well-being practices., Conclusion: This study emphasises the importance of clinicians working closely with patients and taking a holistic approach to care that incorporates psychosocial factors into assessments, treatment plans and resources. There is an unmet need to understand the relationships between interconnected biopsychosocial factors, and how these may impact on RA management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Despite better therapies and strategies, many people with rheumatoid arthritis (RA) have persistent pain, often from abnormal pain processing, now termed nociplastic pain. However, RA patients with fibromyalgia (FM), a central nociplastic pain syndrome, also have power doppler ultrasound (PDUS+) joint inflammation. To understand the complex causes of pain, we performed clinical examination and patient-reported outcome measures (PROMs) plus comprehensive PDUS evaluation not previously combined., Methods: In a cross-sectional study of sequential RA patients with at least moderate DAS28 erythrocyte sedimentation rate disease activity, we assessed 66/68 joints for swelling and tenderness, respectively, FM American College of Rheumatology 2010 diagnostic criteria, completed PROMs for function, quality of life and mood, alongside PDUS examination of 44 joints. Statistical analysis included logistic regression modelling and regularised (lasso) logistic regression methods., Results: From 158 patients, 72 (46%) patients met FM criteria, with significantly worse tender joint counts and PROMs, but no differences in PDUS compared with the non-FM group. Categorising patients by PDUS+ joint presence and/or FM criteria, we identified four distinct groups: 43 (27.2%) patients with -FM-PD, 43 (27.2%) with -FM+PD, 42 (26.6%) with +FM-PD and 30 (19%) with +FM+PD. Both FM+ groups had worse PROMs for fatigue, mood and pain, compared with the FM- groups. We were unable to develop algorithms to identify different groups., Conclusion: The unexpected group -FM-PD group may have peripheral nociplastic pain, not commonly recognised in rheumatology. Only 46% of patients demonstrated PDUS+ inflammation. However clinical examination and PROMs did not reliably differentiate groups, emphasising PDUS remains an important tool., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Depression is prevalent across the spectrum of Chronic Kidney Disease and associated with poorer outcomes. There is limited evidence regarding the most effective interventions and care pathways for depression in Chronic Kidney Disease., Objectives: To investigate how depression is identified and managed in adults with Chronic Kidney Disease., Design: Scoping review., Methods: Systematic search of eight databases with pre-defined inclusion criteria. Data relevant to the identification and/or management of depression in adults with Chronic Kidney Disease were extracted., Results: Of 2147 articles identified, 860 were included. Depression was most identified using self-report screening tools (n = 716 studies, 85.3%), with versions of the Beck Depression Inventory (n = 283, 33.7%) being the most common. A total of 123 studies included data on the management of depression, with nonpharmacological interventions being more frequently studied (n = 55, 45%). Cognitive Behavioural Therapy (n = 15) was the most common nonpharmacological intervention, which was found to have a significant effect on depressive symptoms compared to controls (n = 10). However, how such approaches could be implemented as part of routine care was not clear. There was limited evidence for antidepressants use in people with Chronic Kidney Disease albeit in a limited number of studies., Conclusions: Depression is commonly identified using validated screening tools albeit differences exist in reporting practices. Evidence regarding the management of depression is mixed and requires better-quality trials of both pharmacological and nonpharmacological approaches. Understanding which clinical care pathways are used and their evidence, may help facilitate the development of kidney care specific guidelines for the identification and management of depression., (© 2023 The Authors. Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Background: Chronic wounds include lower extremity ulcers, diabetic foot ulcers, and pressure injuries, and can take months or years to heal. Wounds place a high burden on outpatient and inpatient care settings. This burden is expected to increase markedly in the United States as the population ages and with increased rates of diabetes, obesity, and COVID-19., Purpose: To articulate the effect of chronic, hard-to-heal wounds on acute care facilities, and how a few days of inpatient care can have a significant effect on the healing trajectory., Methods: An expert panel of 7 members, all with extensive knowledge and experience in the assessment and treatment of chronic wounds in an acute care setting, was convened in March 2022. The panel discussed the role of hospitals as part of the longer-term healing pathway of chronic wounds., Results: Chronic wounds have a significant effect on hospitals that includes unseen costs, bed occupancy, demands on bedside nurses, and wound complications that lead to extended stays or readmissions. A successful inpatient wound program offers appropriate identification of previously undiagnosed wounds, elevation of bedside care through simplified protocols, quickly and easily understood education and easy dressing selection, and comprehensive discharge planning with a multidisciplinary team for continuity of care and reduced risk of readmission., Conclusion: Hospitals can play a key role in the management of chronic wounds, thus reducing the effect on each facility and the wider care network.

Background: Individuals from marginalised groups experience higher levels of mental health difficulties and lower levels of wellbeing which may be due to the exposure to stress and adversity. This study explores trajectories of mental health over time for young women and girls and young people with other marginalised identities., Methods: We conducted a secondary analysis on N = 14,215 children and young people (7,501 or 52.8% female, 6,571 or 46.2% male, and 81 or 0.6% non-binary or questioning) who completed a survey at age 11 to 12 years and at least one other annual survey aged 12 to 13 years and/or aged 13 to 14 years. We used group-based trajectory models to examine mental health difficulties., Results: Except for behavioural difficulties, young women's and girls' trajectories showed that they consistently had higher levels of mental health difficulties compared to young men and boys. A similar pattern was shown for non-binary and questioning children and young people. Children and young people with economic disadvantage and/or special education needs, and/or for whom there were welfare concerns, were generally more likely to experience higher levels of mental health difficulties., Conclusions: This information could inform public policy, guidance and interventions., (© 2024. The Author(s).)

Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirming their activity through orthogonal functional assays is crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) in stem cells and forebrain organoids to evaluate the activity of ~ 7000 gene-linked enhancers previously identified in human fetal tissues and brain organoids. We used a Gaussian mixture model to evaluate the contribution of background noise in the measured activity signal to confirm the activity of ~ 35% of the tested enhancers, with most showing temporal-specific activity, suggesting their evolving role in neurodevelopment. The temporal specificity was further supported by the correlation of activity with gene expression. Our findings provide a valuable gene regulatory resource to the scientific community., (© 2024. The Author(s).)

Background: Psychoneuroimmunological mechanisms and the gut-brain axis appear relevant to disease activity and progression in Inflammatory Bowel Disease (IBD). A recent review showed no effect of psychological therapies on self-reported disease activity in IBD. This meta-analysis aims to establish whether interventions targeting mood outcomes (e.g., depression, anxiety and stress) impact inflammation levels in IBD and possible moderators of these effects., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We searched five electronic databases and included randomised controlled trials where interventions targeted mood and assessed inflammatory outcomes pre- and post-intervention in adults with IBD. Independent reviewers screened studies, extracted data, and assessed methodological quality. Data were pooled to estimate standardised mean differences (SMDs) with 95% Confidence Intervals (CIs). A random-effects robust variance estimation accounted for studies measuring multiple biomarkers. Intervention type, mood as a primary or secondary outcome, effect on mood outcomes and IBD subtype were investigated as treatment effect moderators. Where there were sufficient biomarkers, individual meta-analyses were run (Pre-registration PROSPERO: CRD42023389401)., Findings: 28 RCTs involving 1789 participants met inclusion criteria. Interventions demonstrated small, statistically significant effects on biomarkers (-0.35, 95% CI: -0.48, -0.22, p < 0.001) and medium effects on mood outcomes (-0.50, 95% CI: -0.73, -0.27, p < 0.001), without evidence of substantive heterogeneity or publication bias. Individual analyses showed small effects for improved faecal calprotectin (-0.19, 95% CI: -0.34, -0.03, p = 0.018) and C-Reactive Protein (-0.29, 95% CI: -0.47, -0.10, p = 0.002). Effect sizes were larger for psychological therapy interventions (compared with exercise or antidepressants) and when there was an effect (SMD ≥0.2) on mood., Interpretation: Treatments which address mood outcomes have beneficial effects on generic inflammation as well as disease-specific biomarkers (faecal calprotectin and C-Reactive Protein). Psychological interventions and interventions with larger treatment effects on mood accentuated the effect on biomarkers. More research is required to understand the biological or behavioural mechanisms underlying this effect., Funding: The Medical Research Council and the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre., Competing Interests: Declaration of interests None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Vaccination against pneumococcus reduces the risk of infective events, hospitalisation, and death in individual with inflammatory arthritis, particularly in those on immunomodulating therapy who are at risk of worse outcomes from pneumococcal disease. The objective of this study was to investigate the serological protection following vaccination against pneumococcal serovars over time. Methods: This was a single centre, retrospective cohort study of individuals with rheumatoid arthritis, psoriatic arthritis, or axial spondylarthritis who had previously received the PPSV23 polysaccharide pneumococcal vaccine (Pneumovax). Data were retrieved between January 2021 to August 2023. Dates of previous pneumococcal vaccination were identified using linked primary care records. Serum serotype levels were collected. The primary outcome was serological response defined as a titre ≥0.35 mcg/mL in at least five from a total of 12 evaluated pneumococcal serovars, examined using a Luminex platform. Multivariate logistic regression models adjusting for age, gender, ethnicity, co-morbidities, and the use of prednisolone, conventional synthetic and biological DMARDs were used to determine the odds of a sustained serological response according to time categorised into ≤5 years, 5-10 years, and ≥10 years since vaccination. Results: Serological response was measured in 296 individuals with inflammatory arthritis, with rheumatoid arthritis the most common diagnosis (74% of patients). The median time between pneumococcal vaccine administration and serological assessment was 6 years (interquartile range 2.4 to 9.9). A positive serological response to at least 5 serovars was present in 195/296 (66%) of patients. Time since vaccination did not significantly associate with serological protection compared with those vaccinated <5 years, the adjusted ORs of vaccine response was 1.15 (95% CI 0.64 to 2.07) in those 5-10 years and 1.26 (95% CI: 0.64 to 2.48) in those vaccinated over 10 years ago. No individual variable from the multivariate model reached statistical significance as an independent predictor of vaccine response, although steroid use at the time of vaccine had a consistent detrimental impact on serological immunity. Conclusions: We demonstrated that antibody titres following vaccination against pneumococcal serovars do not appear to wane over time. It appears more critical to focus on maximising the initial vaccine response, which is known to be diminished in this patient population.

Many patients with inflammatory arthritis (IA) were instructed to shield during the COVID-19 pandemic. Despite the ending of lockdowns and vaccination, large proportions of IA patients were continuing to shield when it is no longer needed. Given the detrimental effects of shielding on mental and physical health, understanding the rates and reasons for shielding is needed to help clinicians advise patients accordingly. This study was a 12-month prospective study following participants with IA during the COVID-19 pandemic. The proportions of IA patients shielding at each time point were calculated. Additionally, regressions and odds ratios for shielding were determined to assess medication type, mental health, and risk perception. While the extent of shielding fluctuated over the year of lockdowns, nearly all IA patients (93.5%) were still engaging in some shielding in 2021, with nearly half (43%) still shielding most or all of the time. Medications that were previously considered higher risk were not significantly associated with higher rates of shielding (OR = 1.60, p = 0.29), but greater symptoms of depression in June 2020 (OR = 1.07, p = 0.03) was both associated with increased the odds of shielding in June 2021. The high rates of IA patients continuing to shield in 2021 put more strain on patients and professionals as social isolation is linked with worsening mental and physical health, as well as greater difficulty with self-management. It is important for clinicians to be aware of this trend to ease the stress on patients., (© 2023. The Author(s).)

Background: Individuals with a strong family history of pancreatic cancer or a known hereditary cancer syndrome that is associated with pancreatic cancer are considered at high risk for developing pancreatic cancer. Living with a high risk for often fatal cancer is accompanied by high levels of uncertainty. Uncertainty is also independently associated with negative health outcomes. By understanding issues, sources, and responses to uncertainty, targeted supportive care strategies can be provided., Objectives: This study aimed to examine how uncertainty manifests in the experience of being at high risk to develop pancreatic cancer and to describe issues, sources of, and responses to uncertainty., Methods: In this secondary qualitative descriptive study, we analyzed 19 interviews with persons living with inherited pancreatic cancer risk. Analysis was guided by a conceptual framework of uncertainty and responses to uncertainty., Results: Participants described multiple personal, practical, and scientific issues of uncertainty, centering on what to expect for their future health. Participants also expressed positive and negative cognitive, emotional, and behavioral responses to uncertainty, including engaging in surveillance. Uncertainty sources were both individual experiences as well as perceptions of healthcare provider uncertainty with managing pancreatic cancer risk., Conclusion: Pancreatic cancer risk includes issues of uncertainty related to personal mortality, defining and managing risk, and experiencing surveillance. Positive and negative responses to this uncertainty could be targeted through interventions., Implication for Practice: The oncology nurse should assess for sources of and responses to uncertainty in persons at risk for pancreatic cancer and offer psychosocial and educational support., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) feel shocked and bewildered when diagnosed. Serious illness conversations (SICs) may increase disease understanding and preparations for the future. However, SICs often happen late, in part because of clinician-perceived patient discomfort. Telehealth may promote patient comfort by allowing SICs to take place at home. This study assesses the feasibility and usability of a telehealth-delivered Serious Illness Care Program (SICP) for older adults with AML and MDS. We conducted a single-arm pilot study including 20 older adults with AML and MDS. Feasibility was measured using retention rate, with >80% considered feasible. Usability was measured using telehealth usability questionnaire (TUQ; range, 1-7): >5 considered usable. We collected other outcomes including acceptability and disease understanding and conducted post-visit qualitative interviews to elicit feedback. Hypothesis testing was performed at α = 0.10 owing to the pilot nature and small sample size. Retention rate was 95% (19/20); mean TUQ scores were 5.9 (standard deviation [SD], 0.9) and 5.9 (SD, 1.1) for patients and caregivers, respectively. We found the SICP to be acceptable. The majority of patients found the SICP to be very or extremely worthwhile (88.2%; 15/17), and reported it increased closeness with their clinician (75.0%; 12/16). After their visit, patient estimates of curability, and overall life expectancy aligned more closely with those of their clinicians. In qualitative interviews, most patients said that they would recommend this program to others (89.5%, 17/19). This study demonstrated that delivery of the telehealth SICP to older patients with AML and MDS is feasible, usable, and acceptable. This trial is registered at www.clinicaltrials.gov as #NCT04745676., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background and Aims: International endoscopy societies vary in their approach for credentialing individuals in endoscopic ultrasound (EUS) to enable independent practice; however, there is no consensus in this or its implementation. In 2019, the Joint Advisory Group on GI Endoscopy (JAG) commissioned a working group to examine the evidence relating to this process for EUS. The aim of this was to develop evidence-based recommendations for EUS training and certification in the UK., Methods: Under the oversight of the JAG quality assurance team, a modified Delphi process was conducted which included major stakeholders from the UK and Ireland. A formal literature review was made, initial questions for study were proposed and recommendations for training and certification in EUS were formulated after a rigorous assessment using the Grading of Recommendation Assessment, Development and Evaluation tool and subjected to electronic voting to identify accepted statements. These were peer reviewed by JAG and relevant stakeholder societies before consensus on the final EUS certification pathway was achieved., Results: 39 initial questions were proposed of which 33 were deemed worthy of assessment and finally formed the key recommendations. The statements covered four key domains, such as: definition of competence (13 statements), acquisition of competence (10), assessment of competence (5) and postcertification mentorship (5). Key recommendations include: (1) minimum of 250 hands-on cases before an assessment for competency can be made, (2) attendance at the JAG basic EUS course, (3) completing a minimum of one formative direct observation of procedural skills (DOPS) every 10 cases to allow the learning curve in EUS training to be adequately studied, (4) competent performance in summative DOPS assessments and (5) a period of mentorship over a 12-month period is recommended as minimum to support and mentor new service providers., Conclusions: An evidence-based certification pathway has been commissioned by JAG to support and quality assure EUS training. This will form the basis to improve quality of training and safety standards in EUS in the UK and Ireland., Competing Interests: Competing interests: IP is British Society of Gastroenterology Vice President and chair of the Endoscopy Committee from 2019-2021.Dr Huggett has received paid honoraria from Boston Scientific, Cook Endoscopy and Olympus Keymed., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice., Methods: The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes., Results: Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff., Conclusion: Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions., (© 2023. The Author(s).)

Introduction: In adults, muscle disease (MD) is typically a chronic long-term condition that can lead to a reduced quality of life (QoL). Previous research suggests that a psychological intervention, in particular Acceptance and Commitment Therapy (ACT), may help improve QoL for individuals living with chronic conditions such as MD., Methods: This nested qualitative study was incorporated within a randomized controlled trial which evaluated a guided self-help ACT intervention for people living with MD to explore their experiences of the intervention. Semi-structured interviews ( n = 20) were conducted with those who had received ACT. Data were analyzed via thematic analysis., Results: There were four overarching themes. (1) Views on whether therapy sessions would help with a medical condition: participants' expectations regarding ACT varied. Some participants were skeptical about mindfulness. (2) I was able to look at things in a different way: participants described increased meaningful activity, greater awareness of thoughts and emotions and acceptance or adaptation to mobility problems. Some described improvement in the quality of relationships and a sense of feeling free. (3) Treating the body and the mind together: following the intervention participants noted that a holistic approach to healthcare is beneficial. (4) Intervention delivery: The remote delivery was generally seen as helpful for practical reasons and allowed participants to speak openly. Participants voiced a need for follow-up sessions., Discussion: Overall, the intervention was experienced as acceptable. Suggested improvements included de-emphasizing the role of mindfulness and adding follow-up sessions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Edwards, Vari, Rose, Graham, O'Connell, Taylor, McCracken, Radunovic, Rakowicz, Norton and Chalder.)

Background: From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19., Methods: TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464)., Findings: Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62-1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88-2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group., Interpretation: Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation., Funding: UK Medical Research Council, UK National Institute for Health Research Cambridge Biomedical Research Centre, Eli Lilly and Company, Alexion Pharmaceuticals, and Addenbrooke's Charitable Trust., Competing Interests: Declaration of interests FCH has received contributions towards trial running costs from Alexion Pharmaceuticals and Eli Lilly and Company; towards randomisation and investigational medicinal product distribution from UK Research and Innovation (UKRI); and towards research infrastructure from the UK National Institute for Health and Care Research (NIHR). FCH reports payment for weekend shifts for Clinical Investigators from Addenbrooke's Charitable Trust. JC has received funding (via his institution) from Alexion and Lilly, as well as UKRI, for partial funding of the TACTIC-R trial, and funding from AstraZeneca and GSK for other clinical trial work. APC has received support for the current manuscript in the form of funding for drugs from Lilly and Alexion. JG has received payment for the delivery of an educational talk on rheumatoid arthritis from Eli Lilly and Company (manufacturer of baricitinib). IW has received payments (via his institution) from UKRI and NIHR. EB-H is employed by the UK National Health Service; however, 50% of his time is seconded to GSK. MK received a monthly consulting fee for the design and conduct of early-phase trials (not associated with this trial or COVID-19) and is an investigator for GSK (not including any therapeutic or vaccine trials for COVID-19). MK is also co-founder and 50% shareholder of Cambridge Early Phase Clinical Trials (which has not undertaken any work for the trial). WGP has received speaker honoraria from Novartis. JU holds a UK Medical Research Council grant investigating blood–brain barrier dysfunction following bloodstream infection and COVID-19, and has received honoraria from Gilead Sciences (manufacturer of remdesivir) for educational material and from Celltrion Healthcare for participation on an advisory board regarding regdanvimab, an antibody treatment for COVID-19 (unavailable in the UK). DRJ has received consulting fees from AstraZeneca, GSK, Roche, Takeda, UCB, and Vifor; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational services from UCB and Vifor; and holds stock or stock options in Aurinia. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Patients with inflammatory arthritis were especially vulnerable to the psychosocial and health impacts of coronavirus disease 2019 (COVID-19) and the lockdowns. This study investigated the impact of these changes on mental health, physical health and quality of life for inflammatory arthritis patients over 1 year following the initial lockdown in the UK., Methods: Three hundred and thirty-eight participants with inflammatory arthritis completed an ambidirectional study consisting of online questionnaires at four time points for 1 year. The questionnaires assessed demographic information, inflammatory arthritis condition, mental health, physical symptoms, self-management behaviours, COVID-19 status and impacts. Means, linear regressions and structural equation modelling for mediations were conducted over 12 months., Results: Physical health concerns peaked during June 2020, then declined, but did not return to baseline. Depression was associated with worse quality of life at baseline, as shown by the beta coefficient, (β= 0.94, P  < 0.01), September (β = 0.92, P  < 0.01), November (β= 0.77, P  < 0.01) and 1 year (β = 0.77, P  < 0.01). Likewise, anxiety was associated with worse quality of life at baseline (β = 1.92, P  < 0.01), September (β = 2.06, P  < 0.01), November (β = 1.66, P  = 0.03) and 1 year (β = 1.51, P  = 0.02). The association between depression and quality of life was mediated by physical activity (β= 0.13, P  < 0.01) at baseline. The association between anxiety and quality of life was also mediated by physical activity (β = 0.25, P  = 0.04) at baseline., Conclusion: Physical health continued to be worse 1 year later compared with before the COVID-19 lockdowns in patients with inflammatory arthritis. Mental health showed long-term effects on quality of life, with an impact for ≥12 months. Lastly, physical activity mediated between mental health and quality of life in the short term., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute for Health and Care Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our objective was to compare the chance of a seroconversion following vaccination against pneumococcus in patients with inflammatory arthritis to that in the general population, as well as to compare the chance of seroconversion across different targeted therapies., Methods: We searched MEDLINE, Embase and the Cochrane Library databases from inception until 20 June 2023. We included randomized controlled trials and observational studies. Aggregate data were used to undertake a pairwise meta-analysis. Our primary outcome of interest was vaccine seroconversion. We accepted the definition of serological response reported by the authors of each study., Results: Twenty studies were identified in the systematic review (2807 patients) with ten reporting sufficient data to be included in the meta-analysis (1443 patients). The chance of seroconversion in patients receiving targeted therapies, relative to the general population, was 0.61 (95% CI 0.35 to 1.08). The reduced odds of response were skewed strongly by the effects of abatacept and rituximab with no difference between patients on TNF inhibitors (TNFis) or IL-6 inhibition and healthy controls. Within different inflammatory arthritis populations the findings remained consistent, with rituximab having the strongest negative impact on vaccine response. TNF inhibition monotherapy was associated with a greater chance of vaccine response compared with methotrexate (2.25 (95% CI 1.28 to 3.96)). JAK inhibitor (JAKi) studies were few in number and did not present comparable vaccine response endpoints to include in the meta-analysis. The information available does not suggest any significant detrimental effects of JAKi on vaccine response., Conclusion: This updated meta-analysis confirms that, for most patients with inflammatory arthritis, pneumococcal vaccine can be administered with confidence and that it will achieve comparable seroconversion rates to the healthy population. Patients on rituximab were the group least likely to achieve a response and further research is needed to explore the value of multiple-course pneumococcal vaccination schedules in this population.

Objective: The inflammatory arthritides (IAs) make up a significant proportion of conditions followed up in rheumatology clinics. These patients require regular monitoring, but this is increasingly difficult with rising patient numbers and demand on clinics. Our objective is to evaluate the clinical impact of electronic patient-reported outcome measures (ePROMs) as a digital remote-monitoring intervention on disease activity, treatment decisions, and health care resource use in patients with IA., Methods: Five databases (MEDLINE, Embase, PubMed, Cochrane Library, and Web of Science) were searched, with randomized controlled trials and (nonrandomized) controlled clinical trials included, and meta-analysis and forest plots conducted for each outcome. Risk of bias was assessed using the Risk of Bias-2 tool and Risk of Bias in Nonrandomized Studies of Interventions., Results: Eight studies were included with a total of 4,473 patients, with seven studies assessing patients with rheumatoid arthritis. Compared with control, the disease activity in the ePROM group was lower (standardized mean difference [SMD] -0.15; 95% confidence interval [CI] -0.27 to -0.03) and rates of remission/low disease activity were higher (odds ratio1.65; 95% CI 1.02-2.68), but five of eight studies provided additional combined interventions (e.g., disease education). Fewer face to face visits were needed in the remote ePROM group (SMD -0.93; 95% CI -2.14-0.28)., Conclusion: Most studies were at high risk of bias with significant heterogeneity in design, but our results suggest there is an advantage in using ePROM monitoring in patients with IAs, with the potential for reduction in health care resource use without detrimental impact in disease outcomes., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)