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Background: Nearly half of adult patients undergoing surgery experience moderate or severe postoperative pain. Inadequate pain management hampers postoperative recovery and function and may be associated with adverse outcomes. This multidisciplinary consensus statement provides principles that might aid postoperative recovery, and which should be applied throughout the entire peri-operative pathway by healthcare professionals, institutions and patients., Methods: We conducted a directed literature review followed by a four-round modified Delphi process to formulate recommendations for organisations and individuals., Results: We make recommendations for the entire peri-operative period, covering pre-admission; admission; intra-operative; post-anaesthetic care unit; ward; intensive care unit; preparation for discharge; and post-discharge phases of care. We also provide generic principles of peri-operative pain management that clinicians should consider throughout the peri-operative pathway, including: assessing pain to facilitate function; use of multimodal analgesia, including regional anaesthesia; non-pharmacological strategies; safe use of opioids; and use of protocols and training for staff in caring for patients with postoperative pain., Conclusions: We hope that with attention to these principles and their implementation, outcomes for adult patients having surgery might be improved., (© 2024 Association of Anaesthetists.)

Background: Migrants to the UK face disproportionate risk of infections, non-communicable diseases, and under-immunisation compounded by healthcare access barriers. Current UK migrant screening strategies are unstandardised with poor implementation and low uptake. Health Catch-UP! is a collaboratively produced digital clinical decision support system that applies current guidelines (UKHSA and NICE) to provide primary care professionals with individualised multi-disease screening (7 infectious diseases/blood-borne viruses, 3 chronic parasitic infections, 3 non-communicable disease or risk factors) and catch-up vaccination prompts for migrant patients., Methods: We carried out a mixed-methods process evaluation of Health Catch-UP! in two urban primary healthcare practices to integrate Health Catch-UP! into the electronic health record system of primary care, using the Medical Research Council framework for complex intervention evaluation. We collected quantitative data (demographics, patients screened, disease detection and catch-up vaccination rates) and qualitative participant interviews to explore acceptability and feasibility., Results: Ninety-nine migrants were assessed by Health Catch-UP! across two sites (S1, S2). 96.0% (n = 97) had complete demographics coding with Asia 31.3% (n = 31) and Africa 25.2% (n = 25), the most common continents of birth (S1 n = 92 [48.9% female (n = 44); mean age 60.6 years (SD 14.26)]; and S2 n = 7 [85.7% male (n = 6); mean age 39.4 years (SD16.97)]. 61.6% (n = 61) of participants were eligible for screening for at least one condition and uptake of screening was high 86.9% (n = 53). Twelve new conditions were identified (12.1% of study population) including hepatitis C (n = 1), hypercholesteraemia (n = 6), pre-diabetes (n = 4), and diabetes (n = 1). Health Catch-UP! identified that 100% (n = 99) of patients had no immunisations recorded; however, subsequent catch-up vaccination uptake was poor (2.0%, n = 1). Qualitative data supported acceptability and feasibility of Health Catch-UP! from staff and patient perspectives, and recommended Health Catch-UP! integration into routine care (e.g. NHS health checks) with an implementation package including staff and patient support materials, standardised care pathways (screening and catch-up vaccination, laboratory, and management), and financial incentivisation., Conclusions: Clinical Decision Support Systems like Health Catch-UP! can improve disease detection and implementation of screening guidance for migrant patients but require robust testing, resourcing, and an effective implementation package to support both patients and staff., (© 2024. The Author(s).)

Importance: The prognosis of idiopathic sudden onset sensorineural hearing loss (iSSNHL) is uncertain, which creates challenges in clinical decision-making for ear, nose, and throat (ENT) physicians and adds to the burden of the condition experienced by patients., Objective: To develop and internally validate a prognostic model for hearing recovery among patients with iSSNHL to support ENT surgeons in making informed and individualized treatment decisions., Design, Settings, and Participants: This prognostic study and model used cohort data from the Sudden Onset Sensorineural Hearing Loss study, which included 812 patients (age ≥16 years) diagnosed with iSSNHL at 76 National Health Service ENT departments in the UK from December 2019 to May 2022. Nine variables previously reported as independent prognostic factors for complete recovery of patients with iSSNHL were selected for inclusion. The final model was internally validated using bootstrapping with 500 repetitions, then coefficients were adjusted for the degree of optimism in the model. The model intercept was reassessed after adjustment of model coefficients. Impact of individual predictors was evaluated by estimating odds ratios with corresponding 95% CIs. Model performance was re-evaluated after internal validation and expressed by discrimination, calibration, and clinical utility. Data analyses were performed from March 2022 to April 2024., Intervention: Routine treatment (per National Health Service standards), including oral steroids and intratympanic steroid injections., Main Outcome and Measures: Complete hearing recovery defined as a return to within 10 dB of the patient's before iSSNHL hearing levels at all frequencies in the affected ear at 6 to 16 weeks after iSSNHL symptom onset., Results: The study sample included 498 patients (mean [SD] age, 58.7 [16.0] years; 215 [46.9%] females and 243 [53.1%] males) who met the criteria for inclusion in the model. Of those, 210 (46%) were classified as having experienced complete hearing recovery. Five variables were found to be independent predictors for complete hearing recovery: steroid treatment within 7 days from symptom onset (OR, 5.23 vs no treatment ), lower severity of hearing loss at presentation (OR, 0.19 if loss is mild), absence of vertigo (OR, 0.56 vs no vertigo), younger patient age (OR, 0.64 per year), and a history of cardiovascular disease (OR, 1.84 vs no cardiovascular disease). The model showed good performance after internal validation with a c-index of 0.77 (95% CI, 0.7-0.81). Predictions for complete recovery aligned well with observed complete recovery rates, and greater clinical utility than treat all or treat none strategies was shown., Conclusion and Relevance: This prognostic model evaluated in this study may be able to assist ENT surgeons in making informed treatment decisions for individual patients with iSSNHL. It is available online at no cost.

Introduction: Approximately 1% of the UK population take oral corticosteroids for ≥ 28 days each year, for broadly two reasons: deficiency in corticosteroid requiring replacement; or therapeutic corticosteroid for inflammatory conditions. Acute deficiency can occur at times of physiological stress (e.g. surgery), potentially leading to major complications. The Association of Anaesthetists' 2020 consensus guideline provides detailed advice for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency. This national audit aimed to assess compliance with this guideline., Methods: Data were collected from 59 Trusts over 14 consecutive days for all eligible patients undergoing procedures under the care of an anaesthetist. Patients who were prescribed ≥ 5 mg oral prednisolone equivalents pre-operatively, in whom supplementary corticosteroid would be indicated, were compared with those prescribed < 5 mg oral prednisolone equivalents., Results: Operations for 21,731 patients were audited: 277 (1.3%) patients were taking therapeutic corticosteroids. Detailed peri-operative data were collected for all patients receiving therapeutic corticosteroids: 201/277 (73%) were ASA physical status ≥ 3; 184/277 (66%) underwent elective procedures; and 252/277 (91%) were prescribed prednisolone pre-operatively, of whom 219/277 (79%) were prescribed ≥ 5 mg oral prednisolone equivalents. In the patients who were prescribed ≥ 5 mg oral prednisolone equivalents, 186/219 (85%) received pre-operative glucocorticoid supplementation and 97/219 (42%) received it postoperatively; however, only 67/219 (31%) and 43/219 (20%) respectively received glucocorticoid supplementation according to the guidelines. Overall, peri-operative prescribing was compliant in 19/219 (9%) patients. A similar proportion, 30/219 (14%), received no supplementation. In the patients taking < 5 mg oral prednisolone equivalents pre-operatively, 28/58 (48%) received inappropriate supplementation., Conclusions: Despite 125/277 (45%) of anaesthetists reporting Association of Anaesthetists' guidelines use, compliance remained low, with adherence in only 27/125 (22%) patients. Further research is required to identify the correct peri-operative strategy for patients taking therapeutic corticosteroids., (© 2024 Association of Anaesthetists.)

Diagnosis of essential thrombocythaemia (ET) is challenging in patients lacking JAK2/CALR/MPL mutations. In a retrospective evaluation of 320 patients with 'triple-negative thrombocytosis', we assessed utility of bone marrow histology (90.9% of patients) and myeloid gene panel (MGP, 55.6%). Supportive histology ('myeloproliferative neoplasm-definite/probable', 36.8%) was associated with higher platelet counts and varied between centres. 14.6% MGP revealed significant variants: 3.4% JAK2/CALR/MPL and 11.2% other myeloid genes. Final clinical diagnosis was strongly predicted by histology, not MGP. 23.7% received cytoreduction (17.6% under 60 years). Real-world 'triple-negative' ET diagnosis currently depends heavily on histology; we advocate caution in MGP-negative cases and that specific guidelines are needed., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background/objectives: Maternal obesity is associated with a decreased intention and initiation of breastfeeding as well as a shortened duration of breastfeeding. This analysis was undertaken to identify breastfeeding behaviours, and relationships with maternal anthropometry and the serum metabolome at 6-months postpartum in an ethnically diverse cohort of women with obesity., Subjects/methods: A cohort analysis of 715 women from the UK Pregnancies Better Eating and Activity Trial (UPBEAT); a multi-centre randomised controlled trial of an antenatal lifestyle intervention in women with obesity. Maternal data were collected in early pregnancy and included body mass index (BMI), socio-demographic characteristics and anthropometry. At 6-months postpartum, breastfeeding behaviours, anthropometry and 158 maternal metabolic measures from blood samples were recorded. Kaplan-Meier curves of breastfeeding duration were constructed and were stratified by obesity class (I: BMI 30.0-34.9 kg/m 2 , II: 35.0-39.9 kg/m 2 , III: ≥40.0 kg/m 2 ). Relationships between breastfeeding behaviours, socio-demographic characteristics, the metabolome, and anthropometry were determined using regression analyses., Results: Eighty-two percent (591/715) of the cohort-initiated breastfeeding and at the 6-month follow-up 40% (283/715) were breastfeeding exclusively or partially. Duration of exclusive breastfeeding decreased with increasing BMI: Compared to BMI class I (mean 90.4 ± 64 days) the difference in mean for classes II and III were -15.8 days (95% confidence interval: -28.5, -3.1, p < 0.05) and -16.7 (95% CI: -32.0 to -1.35, p < 0.05), respectively. Compared to no breastfeeding, any breastfeeding at 6-months postpartum was associated with improvements in metabolites towards a healthier profile, reduced weight retention by -1.81 kg (95% CI -0.75, -2.88, p < 0.05 ) and reduced anthropometric measures, including mid-upper arm and hip circumferences. The breastfeeding related changes in anthropometry were not evident in women of Black ethnicity., Conclusions: Greater emphasis on enabling breastfeeding for women with obesity could improve duration, women's weight management and metabolic health. The lack of breastfeeding related anthropometric effects in Black women requires further investigation., Clinical Trial Registry: ISRCTN reference 89971375., (© 2024. The Author(s).)

Objectives: To report the UK experience of rolling out Transfusion Camp., Background: Transfusion Camp is a structured education programme developed in Toronto, with the aim of reducing knowledge gaps in transfusion medicine in postgraduate trainees. It consists of didactic lectures viewed online by the participants, then interactive, locally delivered seminars. Since 2015, it has been rolled out in the United Kingdom, and is now available in four centres. Here, we report the UK experience of Transfusion Camp and outcomes., Methods: Trainees are recruited via the training programme directors in each region. Pre- and post-course assessments are administered using the validated BEST (Biomedical Excellence for Safer Transfusion) test, with possible scores 0-20, and confidence measured on an A-E Likert scale., Results: Since 2015, 130 trainees have participated in Transfusion Camp in the United Kingdom. Trainees from all specialties significantly improved their BEST-test scores after attending the course (mean score 11.6/20 before the course, compared with 14.3/20 after the course), and confidence in managing transfusion-related issues was also significantly improved., Conclusion: We recommend that all centres consider offering Transfusion Camp to trainees in haematology and other specialties that frequently use blood transfusions, such as anaesthesia/ICU, Internal Medicine and others., (© 2024 The Author(s). Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)

Introduction: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics., Methods: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia., Results: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV., Conclusion: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Human health is inextricably linked to planetary health. The desire to nurture and protect both concurrently requires the mitigation of healthcare-associated environmental harms and global initiatives that support sustainable lifestyles. Health leadership is important to bring adequate attention and action to address planetary health challenges. Health professionals are central to this endeavour, but the will and energy of a few will not be adequate to address this urgent challenge., Study: We present an appraisal of the current UK health professional standards, frameworks and curricula to identify content related to planetary health and environmental sustainability., Results: No current UK health professional standard provides statements and competencies to guide practising and trainee health professionals to focus on and advance the sustainability agenda within their clinical practice and across wider healthcare systems., Conclusion: Update of health professional standards is needed to ensure that health professionals in every specialty are supported and encouraged to lead the implementation of environmentally sustainable practices within the health sector and advocate for planetary health., Competing Interests: Competing interests: SW and EPB are associates of the Centre for Sustainable Healthcare. BW is an employee of the Centre for Sustainable Healthcare. SW is a Trustee of the Healthcare Infection Society., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Increasing numbers of patients experience a prolonged stay in intensive care. Yet existing quality improvement (QI) tools used to improve safety and standardize care are not designed for their specific needs. This may result in missed opportunities for care and contribute to worse outcomes. Following an experience-based codesign process, our objective was to build consensus on the most important actionable processes of care for inclusion in a QI tool for adults with prolonged critical illness., Design: Items were identified from a previous systematic review and interviews with former patients, their care partners, and clinicians. Two rounds of an online modified Delphi survey were undertaken, and participants were asked to rate each item from 1 to 9 in terms of importance for effective care; where 1-3 was not important, 4-6 was important but not critical, and 7-9 was critically important for inclusion in the QI tool. A final consensus meeting was then moderated by an independent facilitator to further discuss and prioritize items., Setting: Carried out in the United Kingdom., Patients/subjects: Former patients who experienced a stay of over 7 days in intensive care, their family members and ICU staff., Interventions: None., Measurements and Main Results: We recruited 116 participants: 63 healthcare professionals (54%), 45 patients (39%), and eight relatives (7%), to Delphi round 1, and retained 91 (78%) in round 2. Of the 39 items initially identified, 32 were voted "critically important" for inclusion in the QI tool by more than 70% of Delphi participants. These were prioritized further in a consensus meeting with 15 ICU clinicians, four former patients and one family member, and the final QI tool contains 25 items, including promoting patient and family involvement in decisions, providing continuity of care, and structured ventilator weaning and rehabilitation., Conclusions: Using experience-based codesign and rigorous consensus-building methods we identified important content for a QI tool for adults with prolonged critical illness. Work is underway to understand tool acceptability and optimum implementation strategies., Competing Interests: Ms. Allum is a Clinical Doctoral Research Fellow and is funded by Health Education England/National Institute of Health Research for this research project. Dr. Rose received funding from the European Society of Intensive Care Medicine for this research project. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Pulmonary fibrosis results from alveolar injury, leading to extracellular matrix remodelling and impaired lung function. This study aimed to classify patients with pulmonary fibrosis according to blood biomarkers to differentiate distinct disease patterns, known as endotypes., Methods: In this cluster analysis, we first classified patients from the PROFILE study, a multicentre, prospective, observational cohort of individuals with incident idiopathic pulmonary fibrosis or non-specific interstitial pneumonia in the UK (Nottingham University Hospitals, Nottingham; and Royal Brompton Hospital, London). 13 blood biomarkers representing extracellular matrix remodelling, epithelial stress, and thrombosis were measured by ELISA in the PROFILE study. We classified patients by unsupervised consensus clustering. To evaluate generalisability, a machine learning classifier trained on biomarker signatures derived from consensus clustering was applied to a replication dataset from the Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR). Biomarker associations with mortality and change in percentage of predicted forced vital capacity (FVC%) were assessed, adjusting for age, gender, baseline FVC%, and antifibrotic treatment and steroid treatment before and after baseline. Mortality risk associated with the clusters in the PROFILE cohort was evaluated with Cox proportional hazards models, and mixed-effects models were used to analyse how clustering was associated with longitudinal FVC% in the PROFILE and AIPFR cohorts., Findings: 455 of 580 participants from the PROFILE study (348 [76%] men and 107 [24%] women; mean age 72·4 years [SD 8·3]) were included in the analysis. Within this group, three clusters were identified based on blood biomarkers. A basement membrane collagen (BM) cluster (n=248 [55%]) showed high concentrations of PRO-C4, PRO-C28, C3M, and C6M, whereas an epithelial injury (EI) cluster (n=109 [24%]) showed high concentrations of MMP-7, SP-D, CYFRA211, CA19-9, and CA-125. The third cluster (crosslinked fibrin [XF] cluster; n=98 [22%]) had high concentrations of X-FIB. In the replication dataset (117 of 833 patients from AIPFR; 87 [74%] men and 30 [26%] women; mean age 72·9 years [SD 7·9]), we identified the same three clusters (BM cluster, n=93 [79%]; EI cluster, n=8 [7%]; XF cluster, n=16 [14%]). These clusters showed similarities with clusters in the PROFILE dataset regarding blood biomarkers and phenotypic signatures. In the PROFILE dataset, the EI and XF clusters were associated with increased mortality risk compared with the BM cluster (EI vs BM: adjusted hazard ratio [HR] 1·88 [95% CI 1·42-2·49], p<0·0001; XF vs BM: adjusted HR 1·53 [1·13-2·06], p=0·0058). The EI cluster showed the greatest annual FVC% decline, followed by the BM and XF clusters. A similar FVC% decline pattern was observed in these clusters in the AIPFR replication dataset., Interpretation: Blood biomarker clustering in pulmonary fibrosis identified three distinct blood biomarker signatures associated with lung function and prognosis, suggesting unique pulmonary fibrosis biomarker patterns. These findings support the presence of pulmonary fibrosis endotypes with the potential to guide targeted therapy development., Funding: None., Competing Interests: Declaration of interests YM reports personal fees for advisory board work from Boehringer Ingelheim and Roche, outside the submitted work. TJC reports fees for work on scientific advisory boards for Boehringer Ingelheim, Roche, Bristol Myers Squibb, Vicore, Pliant, Endeavour Bioscience, and DevPro, and grants from Boehringer Ingelheim, Roche, Bristol Myers Squibb, Galapagos, and Biogen, outside the submitted work. DJL and JMBS are employees and shareholders of Nordic Bioscience. MAK is an employee and shareholder of Nordic Bioscience and holds patents relating to neoepitopes. AUW reports receiving consulting, lecture, or educational fees from Boehringer Ingelheim and Veracyte, and holds the honorary position of President of the World Association of Sarcoidosis and Other Granulomatous Diseases. LVW reports funding from, consultancy for, or collaboration with GSK, Genentech, Orion Pharma, and Galapagos. PLM has received, via his institution, industry-academic funding from AstraZeneca and has received speaker and consultancy fees from Boehringer Ingelheim and Roche, outside the submitted work. TMM has received industry-academic funding from GSK R&D and UCB, and consultancy or speaker's fees from Apellis, AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Galapagos, GSK R&D, Indalo, Pliant, ProMetic, Roche, Samumed, UCB, and Celgene. RGJ has grants or contracts from AstraZeneca, Biogen, Galecto, GSK, Nordic Bioscience, Redx, and Pliant, with all payments going to his institutions. RGJ has also served as a consultant to Bristol Myers Squibb, Chiesi, Daewoong, Veracyte, Resolution Therapeutics, and Pliant, has received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Chiesi, Roche, PatientMPower, and AstraZeneca, has participated on a data safety monitoring board or advisory board for Boehringer Ingelheim, Galapagos, and Vicore, and has an unpaid role in an advisory board at NuMedii. RGJ is also a trustee of Action for Pulmonary Fibrosis. 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.)

Aim: To identify research priorities regarding the effectiveness of interventions for children and young people (CYP) with childhood neurological conditions (CNCs). These include common conditions such as epilepsies and cerebral palsy, as well as many rare conditions., Method: The National Institute for Health and Care Research (NIHR) and the James Lind Alliance (JLA) champion and facilitate priority setting partnerships (PSPs) between patients, caregivers, and clinicians (stakeholders) to identify the most important unanswered questions for research (uncertainties). A NIHR-JLA and British Paediatric Neurology Association collaboration used the JLA PSP methodology. This consisted of two surveys to stakeholders: survey 1 (to identify uncertainties) and survey 2 (a prioritization survey). The final top 10 priorities were agreed by consensus in a stakeholder workshop., Results: One hundred and thirty-two charities and partner organizations were invited to participate. In survey 1, 701 participants (70% non-clinicians, including CYP and parent and caregivers) submitted 1800 uncertainties from which 44 uncertainties were identified for prioritization in survey 2; from these, 1451 participants (83% non-clinicians) selected their top 10 priorities. An unweighted amalgamated score across participant roles was used to select 26. In the final workshop, 14 health care professionals, 11 parent and caregivers, and two CYP ranked the 26 questions to finalize the top 10 priorities. Ten top priority questions were identified regarding interventions to treat CYP with CNCs and their associated comorbidities, for example, sleep, emotional well-being, and distressing symptoms., Interpretation: The results of this study will inform research into the effectiveness of interventions for children with neurological conditions., (© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Background: Pulmonary embolism (PE) is a well-recognised complication of coronavirus disease 2019 (COVID-19) infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established., Methods: We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5 months post-hospital discharge according to existing risk scores using symptoms, ECG and N-terminal pro-brain natriuretic peptide., Results: By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month; p=0.252). Of 334 confirmed CTEPD/CTEPH cases, four (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further three (0.9%) CTEPD without PH. Of 1094 patients (mean age 58 years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT., Conclusion: A priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation., Competing Interests: Conflict of interest: J.D. Chalmers has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Trudell; received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell and Zambon; and is Chief Editor of the European Respiratory Journal. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Rationale: Despite evidence demonstrating a prognostic role for computed tomography (CT) scans in idiopathic pulmonary fibrosis (IPF), image-based biomarkers are not routinely used in clinical practice or trials. Objectives: To develop automated imaging biomarkers using deep learning-based segmentation of CT scans. Methods: We developed segmentation processes for four anatomical biomarkers, which were applied to a unique cohort of treatment-naive patients with IPF enrolled in the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study and tested against a further United Kingdom cohort. The relationships among CT biomarkers, lung function, disease progression, and mortality were assessed. Measurements and Main Results: Data from 446 PROFILE patients were analyzed. Median follow-up duration was 39.1 months (interquartile range, 18.1-66.4 mo), with a cumulative incidence of death of 277 (62.1%) over 5 years. Segmentation was successful on 97.8% of all scans, across multiple imaging vendors, at slice thicknesses of 0.5-5 mm. Of four segmentations, lung volume showed the strongest correlation with FVC ( r  = 0.82; P  < 0.001). Lung, vascular, and fibrosis volumes were consistently associated across cohorts with differential 5-year survival, which persisted after adjustment for baseline gender, age, and physiology score. Lower lung volume (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.96-0.99]; P  = 0.001), increased vascular volume (HR, 1.30 [95% CI, 1.12-1.51]; P  = 0.001), and increased fibrosis volume (HR, 1.17 [95% CI, 1.12-1.22]; P  < 0.001) were associated with reduced 2-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR, 3.41 [95% CI, 1.36-8.54]; P  = 0.009) and increasing fibrosis volume (HR, 2.23 [95% CI, 1.22-4.08]; P  = 0.009) were associated with differential survival. Conclusions: Automated models can rapidly segment IPF CT scans, providing prognostic near and long-term information, which could be used in routine clinical practice or as key trial endpoints.

Advances in medicine allow children with previously fatal conditions to survive longer and present as transplant candidates; some requiring multiple solid-organ transplants (MSOT). There is limited data on clinical outcomes and no data on quality of life (QoL). In this mixed methods cohort study clinical outcomes from the NHSBT registry were analysed for all patients who received a kidney and one other solid-organ transplant as a child between 2000 and 2021 in the UK. QoL was measured using the PedsQL 3.0 Transplant Module questionnaire. 92 children met the inclusion criteria: heart/heart-lung and kidney (n = 15), liver and kidney (n = 72), pancreas and kidney (n = 4) and multivisceral (n = 1). Results showed excellent patient and graft survival, comparable to single-organ transplants. Allograft survival and rejection were significantly better in patients with combined liver and kidney transplants compared to patients with sequential liver and kidney transplants. QoL was excellent with a mean score of 74%. Key findings included a significant improvement in QoL post-transplant. This is the first study to look at clinical and QoL outcomes in MSOT recipients. The results indicate excellent long-term outcomes. All children born with conditions leading to end-stage disease in multiple solid-organs should be assessed as transplant candidates., 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 © 2024 Paessler, Maple, Cortes, Simmonds, Tse, Raja, Muorah, Kessaris and Stojanovic.)

Background: Second trimester miscarriage and preterm birth is a significant global problem. Surgical cervical cerclage is performed to prevent pregnancy loss and preterm birth. It utilises either a monofilament or braided suture. It is hypothesised that a braided material becomes colonised with pathogenic bacteria that causes vaginal dysbiosis, infection and cerclage failure., Objectives: The primary objective of the study was to examine the effectiveness of using a monofilament suture material as opposed to a braided suture material on pregnancy loss in women requiring a vaginal cervical cerclage., Design: Superiority open randomised controlled trial., Setting: Seventy-five maternity sites across the UK., Participants: Women experiencing a singleton pregnancy requiring a cervical cerclage., Interventions: Monofilament suture or braided suture., Main Outcome Measures: The primary outcome was pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life). Secondary outcomes included the core outcome set for preterm birth., Methods: Women were randomised on a 1 : 1 basis to monofilament or braided cerclage utilising a bespoke randomisation service with minimisation dependent on the site, indication for cerclage, intention to use progesterone and planned surgical technique. The inclusion criteria were three or more previous mid-trimester losses or preterm births, insertion of a cerclage in a previous pregnancy, a history of a mid-trimester loss or preterm birth with a shortened cervical length in the current pregnancy or in women who clinicians deemed at risk of preterm birth. The exclusion criteria were an emergency or rescue cerclage, age of < 18 years, being unable to give informed consent or the cerclage having to be placed abdominally. The original sample size was calculated based on a relative risk reduction of 41% from a pregnancy loss rate of 19% in the braided group to 11% in the monofilament group with 90% power and alpha at p = 0.05. The independent data monitoring committee noted a lower-than-anticipated pooled event rate within the trial and recommended an increase in sample size to 2050. The outcome data were collected using clinical record forms from the maternal and neonatal medical records and reported to Birmingham Clinical Trials Unit., Results: A total of 2049 women were randomised, after withdrawals and loss to follow-up, data on 1005 women in the monofilament group and 993 women in the braided group were included. The baseline demographics between the groups were similar. There was no evidence of a difference in pregnancy loss rates between the monofilament and braided groups (80/1003 vs. 75/993; adjusted risk ratio: 1.05, 95% confidence interval: 0.79 to 1.40; adjusted risk difference: 0.002, 95% confidence interval: -0.02 to 0.03)., Limitations: The trial did not collect long-term paediatric outcomes. There were no safety concerns., Conclusions: There was no evidence of a difference in pregnancy loss between a monofilament suture and a braided suture., Future Work: Long-term follow-up of neonates born within the C-STICH (cerclage suture type for an insufficient cervix and its effects on health outcomes) trial., Trial Registration: This trial is registered as ISRCTN15373349., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/04/107) and is published in full in Health Technology Assessment ; Vol. 28, No. 40. See the NIHR Funding and Awards website for further award information.

Optic neuritis (ON) is an inflammation of or around the optic nerve, frequently caused by infectious or immune-mediated inflammatory disorders. In the UK, its strongest association is with Multiple Sclerosis (MS), though the combined prevalence of other associated infectious and immune-mediated inflammatory diseases (I-IMID) is similar to that of MS-ON. Prompt identification and understanding of ON's underlying cause informs tailored management and prognosis. Several IMIDs linked to ON, such as aquaporin-4 antibody-associated optic neuritis (AQP4-ON), myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON), and neuro-sarcoidosis, show remarkable response to corticosteroid treatment. Therefore, urgent investigation and treatment are crucial in cases 'atypical' for MS-ON. Following the 1992 Optic Neuritis Treatment Trial, clinical practice has evolved, with short-course high-dose corticosteroids considered safe and effective for most people. Timely recognition of patients who could benefit is critical to avoid irreversible vision loss. This review provides a practical guide and a summary of evidence on the investigation and management of acute optic neuritis. It reflects the knowledge and limitations of current evidence, framed through the neuro-ophthalmic perspective of clinical practice at multiple UK academic centres., (© 2024. The Author(s).)

Objective: To evaluate the provision of imaging at diagnosis of myeloma from the service user perspective with a specific focus on how the experiences of patients align with the National Institute for Health and Care Excellence (NICE) guidelines (NG35, 2016) on first-line imaging practice for myeloma in the United Kingdom., Methods: A national survey was performed to evaluate access to imaging from the patient's perspective. Patients with myeloma who received their diagnosis between 2017 and March 2022 were invited to participate. Data were collected using an online survey from 895 patients and carers between 4 and 14 March 2022., Results: Most patients had more than one imaging test. First-line MRI was used in 69.2% of respondents. First-line skeletal survey (SS, whole body X-rays) remained common (48.7% of respondents). 18F-fluorodexyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was used least often (23.1% of respondents). SS was used more often in East England (57.9%) and Scotland (61.2%) than in South East England (36.3%)., Conclusions: Despite NICE recommendations, first-line MRI was not used in a third of patients surveyed, with geographical variation in imaging practice. Patients are still undergoing multiple imaging tests at diagnosis. Healthcare professionals should continue to emphasize the superiority of MRI compared to SS to drive for improvements in care., Advances in Knowledge: Current recommendations on first-line imaging for myeloma are not provided consistently across the United Kingdom. There is a need to drive change and support healthcare professionals to deliver guidance-based recommendations to improve experience and outcomes for patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Global longitudinal strain (GLS) is reported to be more reproducible and prognostic than ejection fraction. Automated, transparent methods may increase trust and uptake., Objectives: The authors developed open machine-learning-based GLS methodology and validate it using multiexpert consensus from the Unity UK Echocardiography AI Collaborative., Methods: We trained a multi-image neural network (Unity-GLS) to identify annulus, apex, and endocardial curve on 6,819 apical 4-, 2-, and 3-chamber images. The external validation dataset comprised those 3 views from 100 echocardiograms. End-systolic and -diastolic frames were each labelled by 11 experts to form consensus tracings and points. They also ordered the echocardiograms by visual grading of longitudinal function. One expert calculated global strain using 2 proprietary packages., Results: The median GLS, averaged across the 11 individual experts, was -16.1 (IQR: -19.3 to -12.5). Using each case's expert consensus measurement as the reference standard, individual expert measurements had a median absolute error of 2.00 GLS units. In comparison, the errors of the machine methods were: Unity-GLS 1.3, proprietary A 2.5, proprietary B 2.2. The correlations with the expert consensus values were for individual experts 0.85, Unity-GLS 0.91, proprietary A 0.73, proprietary B 0.79. Using the multiexpert visual ranking as the reference, individual expert strain measurements found a median rank correlation of 0.72, Unity-GLS 0.77, proprietary A 0.70, and proprietary B 0.74., Conclusions: Our open-source approach to calculating GLS agrees with experts' consensus as strongly as the individual expert measurements and proprietary machine solutions. The training data, code, and trained networks are freely available online., Competing Interests: Funding Support and Author Disclosures Dr Rajani has received speaker fees from Siemens Healthcare and GE Medical; and has provided consultancy to Medtronic and Edwards Lifesciences. Dr Rana has provided consultancy to Philips and Occlutech. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is good evidence describing pharmacy workforce and service provision in general critical care units. However, no data exist from adult extracorporeal membrane oxygenation (ECMO) centres., Aim: To describe workforce characteristics, pharmacy service provision, and pharmaceutical care activities in critical care units (CCUs) providing an adult ECMO service in the United Kingdom (UK) and compare to national staffing standards for CCUs., Method: We conducted a multicentre, cross-sectional electronic survey inviting one pharmacy professional response per UK ECMO centre. We collated information on workforce, service provision, and pharmaceutical care activities provided by pharmacy teams in adult CCUs with an ECMO service., Results: The survey response rate was 90.9%: representatives of 10/11 tertiary hospitals providing ECMO services responded. Median critical care pharmacist to critical care bed was 1:12.1 (IQR: 1:9.4-1:14.9). Most centres (90.0%) did not meet national standards for pharmacy professionals to critical care bed staffing ratios for weekday services. Total critical care beds covered by the critical care pharmacy team varied across the UK: median (IQR) - 45 (37-80) beds. Two centres funded pharmacist time for ECMO activity, and one centre funded a pharmacy technician post. Median peak ECMO activity was 4 ECMO patients in a single day (IQR: 3-5). Most respondents reported reduced pharmacy service at weekends compared to weekday, with limited on-site support., Conclusion: Most responding ECMO centres in the UK reported pharmacy staffing ratios below nationally agreed critical care standards. There was high variability in clinical pharmacy services to ECMO patients over 7 days., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background and Aims: Despite intravenous (IV) vedolizumab being established for treatment of inflammatory bowel disease (IBD), the novel subcutaneous (SC) route of administration may provide numerous incentives to switch. However, large-scale real-world data regarding the long-term safety and effectiveness of this strategy are lacking., Methods: IBD patients on IV vedolizumab across 11 UK sites agreed to transition to SC injections or otherwise continued IV treatment. Data regarding clinical disease activity (Simple Clinical Colitis Activity Index, partial Mayo score, and modified Harvey-Bradshaw Index), biochemical markers (C-reactive protein and calprotectin), quality of life (IBD control), adverse events, treatment persistence, and disease-related outcomes (namely corticosteroid use, IBD-related hospitalization, and IBD-related surgery) were retrospectively collected from prospectively maintained clinical records at baseline and weeks 8, 24, and 52., Results: Data from 563 patients (187 [33.2%] Crohn's disease, 376 [66.8%] ulcerative colitis; 410 [72.8%] SC, 153 [27.2%] IV) demonstrated no differences in disease activity, remission rates, and quality of life between the SC and IV groups at all time points. Drug persistence at week 52 was similar (81.1% vs 81.2%; P = .98), as were rates of treatment alteration due to either active disease (12.2% vs 8.9%; P = .38) or adverse events (3.3% vs 6.3%; P = .41). At week 52, there were equivalent rates of adverse events (9.8% vs 7.8%; P = .572) and disease-related outcomes. IBD control scores were equivalent in both IV-IV and IV-SC groups., Conclusions: Switching to SC vedolizumab appears as effective, safe, and well tolerated as continued IV treatment and maintains comparable disease control and quality of life as IV treatment at 52 weeks., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To provide guidance in the form of consensus statement in the management of ketamine uropathy., Methods: A literature review of ketamine uropathy was performed. The consensus method was of a modified nominal group technique and has been use in the previous British Association of Urological Surgeons (BAUS) consensus documents and was led by the Female, Neurological and Urodynamic Urology Section of the BAUS., Results: A number of consensus statements detailing the assessment and management of urological complications relate to the recreational use of ketamine (ketamine uropathy) in both elective and emergency urology settings., Conclusion: Comprehensive management pathway for ketamine-related urinary tract dysfunction and uropathy has been detailed., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: A surgical team works in a high-performance environment and is exposed to stress. Mindfulness practice is evidenced to reduce symptoms of stress, as well as burnout, which is high amongst health workers. The operating theatre is unique, with many job-roles, needs and time-critical tasks. It is plausible that group mindfulness may benefit the surgical team. This evaluates the take-5 theatre brief, consisting of a 'check-in' and short breathwork, when used by two surgical teams as part of the regular theatre team brief., Approach: The take-5 theatre brief was evaluated using domains of acceptability and implementation. Data were collected at two district general hospitals in the United Kingdom using 5-point Likert scales hosted on electronic surveys Thematic analysis was performed of participant voice notes, strategic meeting notes and transcripts of interviews between key informants., Evaluation: There were 17 participants. Ten were from site A (59%), with the remainder being from site B (41%) and covered a range of roles within the theatre team. Participants found the take-5 theatre brief helpful (median Likert 5) and felt that it would benefit themselves (median Likert 5) as well as the team (median Likert 5) and that it fitted into the day easily (median Likert 4). There was a high demand, no financial investment was required and overall it was easy to implement; however, it became challenged in theatre lists that were late to start., Implication: The take-5 theatre brief is an acceptable initiative for these two operating theatre teams., (© 2024 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Older adults constitute a large proportion of patients undergoing surgery and present with complexity, predisposing them to adverse postoperative outcomes. Inequalities exist in the provision of surgical care across the United Kingdom evidenced by increased waiting times in areas of social deprivation, a disparity in the provision of surgical care across geographic locations as well as a variation in the medical management of comorbidities in surgical patients. Addressing inequalities in the delivery of perioperative care for older adults necessitates a multi-faceted approach. It requires implementation of an evidence-based approach to optimisation of older surgical adults using Comprehensive Geriatric Assessment and optimisation methodology at scale, development of an age-attuned, flexible, transdisciplinary workforce, a restructuring of funding to commission services addressing the needs of the older surgical population and a change in culture and professional and public understanding of the needs of the older surgical patient.

Ménière's disease is a disabling condition causing vertigo and hearing loss yet remains incompletely understood. Registry studies have the potential to answer important questions about phenotypes and natural history of clinical conditions. The aim of this study was to explore the feasibility of a patient-centered national Ménière's disease registry. This was an observational study carried out at 4 state-funded hospitals and 4 independent clinics, within 3 distinct urban and rural regions within the UK. Adults with Ménière's disease were eligible to participate. A range of patient reported data, questionnaire data and clinical data (audiometric, radiological, and specialist balance testing data) was inputted into a bespoke database. The study recruited 411 participants. The majority of participants chose online recruitment (73%) and 27% chose via paper-based methods for participation. A small majority (57%) of participants were female. 96% of participants were of white ethnicity. Data completeness from online or postal data collection was similar. Around 20% of participants had audiological evidence of bilateral Ménière's disease. This feasibility study has successfully piloted methods for recruitment of hundreds of participants diagnosed with Ménière's disease. Participants actively contributed their data to a robust and extensive data collection platform. The positive outcomes from this initial feasibility study are anticipated to serve as a foundation for the future expansion of the registry. This expansion holds the potential to address a broad spectrum of request, encompassing all aspects of the nature of Ménière's disease.

Background: Testing positive for COVID-19 was associated with higher rates of detrimental psycho-social and physical health outcomes. The COVID-19 pandemic caused unprecedented disruption to everyday life. This included major reconfiguration of maternal, child, and perinatal mental health and care services and provision. This study aimed to investigate the experiences of those who tested positive for COVID-19 during pregnancy, labour and birth, or the early postnatal period., Methods: National on-line recruitment from across the United Kingdom resulted in sixteen mothers being invited to qualitative semi-structured interviews to understand the experiences of mothers who had been infected by COVID-19 during pregnancy, labour and birth, or the early postnatal period. Interviews were conducted, recorded, and transcribed using video-conferencing software. A Grounded Theory approach was used to analyse the data gathered pertaining to women's experiences of their positive COVID-19 diagnosis during pregnancy, labour and birth, or the early postnatal period., Results: The theory of 'Oscillating Autonomy - Losing and Seeking to Regain Control by Striving for Agency' was developed, comprising three main themes: 'Anxious Anticipation: The fear of infection was worse than COVID-19 itself'; 'Fluctuating Agency: What changed when COVID-19 took control'; and 'Reclaiming Control: Seeking reassurance during COVID-19 positivity'. Testing positive for COVID-19 whilst pregnant, during labour or birth, or in the early postnatal period was associated with a perceived loss of control. Those who were able to regain that control felt more secure in their situation., Conclusions: Support was paramount to manage increased vulnerability, as was reassurance achieved by information seeking and positive action including increased health monitoring and COVID-19 vaccination., (© 2024. The Author(s).)

Background: UK guidelines for managing adults with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), published by the British Association of Dermatologists (BAD) in 2016, outline a set of audit standards., Objectives: To audit current management of SJS/TEN in adults against standards in the BAD guidelines., Methods: BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022., Results: Thirty-nine dermatology centres in the UK (29%) participated, and data for 147 adults with SJS/TEN were collected. Within 24 h of the diagnosis being made or suspected, the following were documented, per 147 submitted cases: Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) for 76 (52%), list of medications for 113 (77%) and timelines for commencement/alterations of medications for 104 (71%). The initial assessment was documented of the eyes by an ophthalmologist in 71 (48%), of the mouth in 130 (88%), of the genital skin in 103 (70%) and of the urinary tract in 93 (63%). During the first 10 days after a suspected or confirmed diagnosis of SJS/TEN, daily assessments of the mouth were documented in 26 of 147 cases (18%), of the eyes in 12 (8%), and of the urinary tract and genital skin in 14 (10%). At discharge, a drug was declared to be the cause of SJS/TEN for 130 of 147 cases (88%), while 9 (6%) were thought to be secondary to infection. Eleven of 147 (8%) had no response to this question. Documentation regarding advice was present on avoidance of the culprit drug in 76 of 130 declared SJS/TEN cases (58%), and on requesting a MedicAlert® bracelet/amulet in 9 of the 147 cases (6%)., Conclusions: This audit suggests that a clinical review checklist might be needed to enable colleagues to maintain standards outlined in the guidelines, including documentation of SCORTEN, daily assessments of mucosal areas, and advice to avoid culprit drug(s) and to request a MedicAlert® bracelet/amulet., (© British Association of Dermatologists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The number of urgent '2-week-wait' referrals to hospital for people with suspected head and neck cancer being sent by primary care is constantly growing and it is becoming increasingly difficult for head and neck cancer services to meet this demand. In order for trusts to meet their Faster Diagnosis Standards, there needs to be an effective and efficient way to ensure there is capacity for patients to receive the appropriate assessments and diagnostic investigations without compromising the quality of care delivered. This article presents the proposal of introducing a nurse-led 2-week-wait clinic to meet the ever-growing demands on the service. There is discussion of the consultant-led training programme used to upskill an advanced nurse practitioner in a single-centre study, as well as explanation of the processes followed to maintain patient safety throughout the pilot project. There will also be consideration of clinical governance and discussion of how patient satisfaction with the novel service will be measured.

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.)

Introduction: Synthetic cannabinoid receptor agonists (SCRAs) are associated with significant toxicity and are increasingly used in electronic vaping devices. We assessed the availability of SCRA vaping products to UK purchasers on the surface web., Methods: An internet snapshot survey was performed between October 2022 and January 2023 on 'google.com' using the search terms "buy c-liquid vape", "buy herbal incense vape liquid", "buy cannabis vape liquid", "buy hashish vape liquid", "buy K2 vape liquid"., Results: 62 websites selling 128 SCRA vaping brands were identified. Most were purportedly based in the USA (41 websites, 66%) and most sold other controlled substances. Purchase incentives offered included discreet packaging (38, 61%), discounts for bulk purchase (34, 55%) and tracked delivery (30, 48%). Many websites stated SCRA products were: not for human consumption (41, 66%), for research purposes only (15, 24%), or legal (28, 45%). Websites sold a median (IQR) of 16 (7-25) SCRA vaping brands. Almost all were bottles of vaping liquid (1220/1225, 99.6%). The most common bottle size was 5mL (60%), the median (IQR) total volume of SCRA liquid per sale was 50mL (10-200mL). Median (IQR) price was £3.39/mL (£2.01/mL- £5.29/mL). Price decreased with increasing volume purchased (£6.58/mL for ≤ 5mL, £1.60/mL for > 200mL)., Conclusion: SCRA vaping products are easily obtainable online, in both small and bulk quantities. Information provided to purchasers on safety and legality is lacking or misleading. Further studies are needed to confirm the chemistry of these products. Policymakers should consider steps to limit the potential harm caused by the purchase and use of these products., (© 2024. The Author(s).)

The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD).The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD., (© 2024. The Author(s).)

Background: Children and young people (CYP) with complex neurodisability experience multiple physical, communication, educational and social challenges, which require complex packages of multidisciplinary care. Part of the holistic care required includes supporting the families and parents/caregivers. The aim of the wider study was to introduce a new programme ('Ubuntu') to parents/caregivers and healthcare professionals (HCPs) in order to test the feasibility and acceptability of the concept and content, with the goal of potential adaptation for the UK in mind. Data collection and analysis uncovered rich data on caregiving journeys, navigation of health services, and perceived service gaps. This paper focuses solely on these topics. Further papers will report on the feasibility and adaptation data., Methods: Two rounds of semi-structured interviews were conducted with 12 caregivers of CYP with complex neurodisability and six HCPs from a variety of disciplines, recruited from a community child health service in London Borough of Newham, UK in 2020. The interviews included open-ended questions to explore caregiving journeys, experiences of navigating health services and perceived service gaps. Transcripts were analysed using a data-driven inductive thematic analysis., Results: Three themes were identified that related to the aim of understanding caregivers' experiences and unmet needs relating to current service provision. These were (1) Caregiver Mental Health, (2) The Information Gap and (3) The Need for Holistic Support. Mental health difficulties were reported, particularly around the period of diagnosis. Priority needs included the provision of clear information about the diagnosis and services offered, opportunities to forge peer support networks and for services across the community to collaborate., Conclusions: The delivery of health services for CYP with neurodisability should encompass the broad needs of the family as well as meeting the clinical needs of the CYP., (© 2024 The Author(s). Child: Care, Health and Development published by John Wiley & Sons Ltd.)

Background: Hidradenitis suppurativa (HS) in children and young adults (CYA) (<18 years) is uncommon. No previous observational studies have been carried out in a UK CYA HS population., Methods: This study was based on retrospective case note reviews of CYA HS patients attending tertiary-level care in the CYA HS service in a UK hospital. Patients <18 years old with a known diagnosis of HS were screened for inclusion. Exclusion criteria were those with less than one follow-up appointment., Results: Twenty-eight CYA HS patients were identified, with an M:F ratio of 1:8.3. Mean BMI was 25.2 (SD: 7.6). 17 (61%) of cases had a relevant family history. Long-term antibiotic monotherapy was the most common treatment initiated. Lymecycline was the most commonly prescribed antibiotic, accounting for 23 (56%) of the 41 courses prescribed. Additional treatments initiated included dual therapy with rifampicin and clindamycin, isotretinoin, and adalimumab, which were more commonly prescribed in patients with Hurley Stage II or III., Conclusions: This group had a female predominance with an apparent strong genetic predisposition which is seen in other HS CYA cross-sectional research. Treatment was varied in this cohort, however long courses of antibiotics, including combined therapy with rifampicin and clindamycin, were the mainstay of treatment, similar to management in the adult population. This study therefore adds to the limited information on the demographics and management of the HS CYA population., (© 2024 the International Society of Dermatology.)

Introduction: Spirometry is a point-of-care lung function test that helps support the diagnosis and monitoring of chronic lung disease. The quality and interpretation accuracy of spirometry is variable in primary care. This study aims to evaluate whether artificial intelligence (AI) decision support software improves the performance of primary care clinicians in the interpretation of spirometry, against reference standard (expert interpretation)., Methods and Analysis: A parallel, two-group, statistician-blinded, randomised controlled trial of primary care clinicians in the UK, who refer for, or interpret, spirometry. People with specialist training in respiratory medicine to consultant level were excluded. A minimum target of 228 primary care clinician participants will be randomised with a 1:1 allocation to assess fifty de-identified, real-world patient spirometry sessions through an online platform either with (intervention group) or without (control group) AI decision support software report. Outcomes will cover primary care clinicians' spirometry interpretation performance including measures of technical quality assessment, spirometry pattern recognition and diagnostic prediction, compared with reference standard. Clinicians' self-rated confidence in spirometry interpretation will also be evaluated. The primary outcome is the proportion of the 50 spirometry sessions where the participant's preferred diagnosis matches the reference diagnosis. Unpaired t-tests and analysis of covariance will be used to estimate the difference in primary outcome between intervention and control groups., Ethics and Dissemination: This study has been reviewed and given favourable opinion by Health Research Authority Wales (reference: 22/HRA/5023). Results will be submitted for publication in peer-reviewed journals, presented at relevant national and international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders., Trial Registration Number: NCT05933694., Competing Interests: Competing interests: WM is Honorary President of the Association for Respiratory Technology and Physiology (ARTP). MT is CEO of ArtiQ—a company that produces artificial intelligence enabled lung function support software. JM and KO are employees of ArtiQ., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To identify distinct clinical subtypes of Ménière's disease by analyzing data acquired from a UK registry of patients who have been diagnosed with Ménière's disease., Study Design: Observational study., Methods: Patients with Ménière's disease were identified at secondary/tertiary care clinics. Cluster analysis was performed by grouping participants sharing similar characteristics and risk factors into groups based on a defined measure of similarity., Results: A total of 411 participants were recruited into this study. Two main clusters were identified: participants diagnosed with ear infections (OR = 0.30, p < 0.014, 95% CI: 0.11-0.78) were more likely to be allocated in Cluster 1 (C1). Participants reporting tinnitus in both ears (OR = 11.89, p < 0.001, 95% CI: 4.08-34.64), low pitched tinnitus (OR = 21.09, p < 0.001, 95% CI: 7.47-59.54), and those reporting stress as a trigger for vertigo attacks (OR = 14.94, p < 0.001, 95% CI: 4.54-49.10) were significantly more likely to be in Cluster 2 (C2). Also, participants diagnosed with Benign Paroxysmal Positional Vertigo (OR = 13.14, <0.001, 95% CI: 4.35-39.74), autoimmune disease (OR = 5.97, p < 0.007, 95% CI: 1.62-22.03), depression (OR = 4.72, p < 0.056, 95% CI: 0.96-23.24), migraines (OR = 3.13, p < 0.008, 95% CI: 1.34-7.26), drug allergy (OR = 3.25, p < 0.029, 95% CI: 1.13-9.34), and hay fever (OR = 3.12, p < 0.009, 95% CI: 1.33-7.34) were significantly more likely to be clustered in C2., Conclusions: This study supports the hypothesis that Ménière's disease is a heterogeneous condition with subgroups that may be identifiable by clinical features. Two main clusters were identified with differing putative etiological factors., Level of Evidence: 3 Laryngoscope, 134:3286-3292, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

The Royal College of Emergency Medicine Toxicology Special Interest Group in collaboration with the UK National Poisons Information Service and the Clinical Toxicology Department at Guy's and St Thomas' NHS Foundation Trust has produced guidance to support clinicians working in the ED with the assessment and management of adults with acute opioid toxicity.Considerations regarding identification of acute opioid toxicity are discussed and recommendations regarding treatment options and secondary prevention are made. There is a focus on making recommendations on the best available evidence., Competing Interests: Competing interests: MB—unpaid member of RCEM Toxicology Advisory Group. RG has no declarations of interest. DMW is a member of the UK Advisory Council on the Misuse of Drugs and an expert advisor to the European Monitoring Centre for Drugs and Drug Addiction and the United Nations Office on Drugs and Crime. He is also a clinical coordinator at the UK National Confidential Enquiry into Patient Outcomes and Death (NCEPOD), and on the editorial board of the Journal of Medical Toxicology. His work on these guidelines was independent of his roles with these organisations. RT—his work on these guidelines was in his role as director of NPIS (Newcastle). CH is an editor for the Emergency Medicine Journal, has received payments from Elsevier for educational articles, has been reimbursed for travel expenses by RCEM and is a recipient of grants from the Centre for Precision Cell Therapy for the Liver. His work on these guidelines was in his role as a member of the RCEM Toxicology Special Interest Group. PID is an adviser to the UK Advisory Council on the Misuse of Drugs, the European Monitoring Centre for Drugs and Drug Addiction the United Nations Office on Drugs and Crime, and the WHO. He is also a commissioner to the UK Commission Human Medicines, on the senior editorial board of Clinical Toxicology, and is the president elect of the European Association of Poisons Control Centres and Clinical Toxicologists. His work on these guidelines was independent of his roles with these organisations., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with complications and have an associated cost to departmental resources. A growing body of international research suggests many of the PIVCs inserted in the ED are unnecessary., Methods: The objective of this study was to determine the rates of PIVC insertion and use. This was a prospective observational study conducted in one UK ED and one Italian ED. Adult ED patients with non-immediate triage categories were included over a period of three weeks in the UK ED in August 2016 and two weeks in the Italian ED in March and August 2017. Episodes of PIVC insertion and data on PIVC utilisation in adults were recorded. PIVC use was classified as necessary, unnecessary or unused. The proportion of unnecessary and unused PIVCs was calculated. PIVCs were defined as unnecessary if they were either used for phlebotomy only, or solely for IV fluids in patients that could have potentially been hydrated orally (determined against a priori defined criteria). PIVC classified as unused were not used for any purpose., Results: A total of 1,618 patients were included amongst which 977 PIVCs were inserted. Of the 977 PIVCs, 413 (42%) were necessary, 536 (55%) were unnecessary, and 28 (3%) were unused. Of the unnecessary PIVCs, 473 (48%) were used solely for phlebotomy and 63 (6%) were used for IV fluids in patients that could drink., Conclusions: More than half of PIVCs placed in the ED were unnecessary in this study. This suggests that clinical decision making about the benefits and risks of PIVC insertion is not being performed on an individual basis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Willis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: This study compares the effectiveness of different biologic therapies and sequences in patients with inflammatory bowel disease [IBD] using real-world data from a large cohort with long exposure., Methods: Demographic, disease, treatment, and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups., Results: In total, 13 222 evaluable patients received at least one biologic. In ulcerative colitis [UC] first-line vedolizumab [VDZ] demonstrated superior effectiveness over 5 years compared to anti-tumour necrosis factor [anti-TNF] agents [p = 0.006]. VDZ was superior to both infliximab [IFX] and adalimumab [ADA] after ADA and IFX failure respectively [p < 0.001 and p < 0.001]. Anti-TNF therapy showed similar effectiveness when used as first-line treatment, or after failure of VDZ. In Crohn's disease [CD] we found significant differences between first-line treatments over 10 years [p = 0.045], with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first-line anti-TNF failure in CD [p = 0.035]. Patients with UC or CD experiencing TNF failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF., Conclusions: We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

UK guidelines recommend liraglutide 3.0 mg in adults treated within specialist weight management services with BMI ≥35 kg/m 2 , prediabetes and high cardiovascular disease risk. We aimed to clinically evaluate liraglutide 3.0 mg in specialist weight management services. We evaluated liraglutide 3.0 mg in weight management services at Guys and St Thomas' NHS Foundation Trust. Objective body weight (BW) was measured at baseline and 4 months, allowing classification as 'responders' (≥5% BW reduction) and 'non-responders' (<5% BW reduction). One hundred and twenty-one patients were evaluated. At 4 months, 76.0% attended follow-up (82.6% responders, 17.4% non-responders); BW (-8.6 kg, 95%CI:-9.8, -7.4 kg), BMI (-3.2 kg/m 2 , 95%CI: -3.6, -2.8) and %-BW (-6.6%, IQR: -8.8%, -5.2%) significantly reduced. In responders, HbA1c reduced by -5.0 mmol/mol (IQR: -7.0. -4.0 mmol/mol). In responders BW continued to reduce up to 12 months (4 m: -10.2 kg, p < .0001; 6 m: -15.6 kg, p < .0001; 9 m: -16.5 kg, p < .0001; 12 m: -16.7 kg, p < .01). Those of Black African and Caribbean ethnicity experienced less BW loss than those of white ethnicity (4.12 kg, p = .017) and had a greater attrition rate. In adults with obesity and prediabetes who are treated within specialist weight management services, liraglutide 3.0 mg reduces BW and HbA1c. Those of Black African and Caribbean ethnicity experienced less BW reduction and greater attrition at 4 months. Further evaluation of the ethnic differences in response to obesity pharmacotherapy is required., (© 2024 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Introduction: Over a fifth of pregnant women are living with multiple long-term health conditions, which is associated with increased risks of adverse outcomes for mothers and infants. While there are many examples of research exploring individuals' experiences and care pathways for pregnancy with a single health condition, evidence relating to multiple health conditions is limited. This study aimed to explore experiences and care of women with multiple long-term health conditions around the time of pregnancy., Methods: Semistructured interviews were conducted between March 2022 and May 2023 with women with multiple long-term health conditions who were at least 28 weeks pregnant or had had a baby in the last 2 years, and healthcare professionals with experience of caring for these women. Participants were recruited from across the United Kingdom. Data were analysed using thematic analysis., Results: Fifty-seven women and 51 healthcare professionals participated. Five themes were identified. Women with long-term health conditions and professionals recognised that it takes a team to avoid inconsistent care and communication, for example, medication management. Often, women were required to take a care navigation role to link up their healthcare providers. Women described mixed experiences regarding care for their multiple identities and the whole person. Postnatally, women and professionals recognised a downgrade in care, particularly for women's long-term health conditions. Some professionals detailed the importance of engaging with women's knowledge, and recognising their own professional boundaries of expertise. Many participants described difficulties in providing informational continuity and subsequent impacts on care. Specifically, the setup of care systems made it difficult for everyone to access necessary information, especially when care involved multiple sites., Conclusion: Pregnant women with long-term health conditions can experience a substantial burden of responsibility to maintain communication with their care team, often feeling vulnerable, patronised, and let down by a lack of acknowledgement of their expertise. These results will be used to inform the content of coproduction workshops aimed at developing a list of care recommendations for affected women. It will also inform future interventional studies aimed at improving outcomes for these women and their babies., Patient or Public Contribution: Our Patient and Public Involvement group were involved in the design of the study and the analysis and interpretation of the data, and a public study investigator was part of the author group., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Background: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK., Methods: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG., Results: 132 pts were included. Median age was 56 years (28-91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5-6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts., Conclusion: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience., (© 2024. The Author(s).)

Background: We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response., Methods: Personalised Anti-TNF therapy in Crohn's disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients with active luminal Crohn's disease aged 6 years and older. At the end of the first year, sites were invited to enrol participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449, and is now complete., Findings: Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age 32·5 years [IQR 22·1-46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7-43·7), 34·4% (29·9-39·0), and 34·7% (29·8-39·5), and for adalimumab 35·9% (95% CI 31·2-40·5), 32·9% (26·8-39·2), and 28·9% (21·9-36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6·1-10·0 mg/L for infliximab and 10·1-12·0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34·4% (95% CI 30·4-38·2), 54·5% (49·4-59·0), and 60·0% (54·1-65·2), and for adalimumab 32·1% (26·7-37·1), 47·2% (40·2-53·4), and 68·4% (50·9-79·7), respectively. In multivariable analysis, loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45 [95% CI 0·30-0·67], adalimumab: 0·39 [0·22-0·70]). For patients treated with infliximab, loss of response was also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11-1·95]), obesity (vs not obese 1·62 [1·08-2·42]), baseline white cell count (1·06 [1·02-1·11) per 1 × 10 9 increase in cells per L), and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response (HR 1·95 [95% CI 1·17-3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1-49·4) among patients treated with infliximab and 20·3% (13·8-26·2) among those treated with adalimumab. The development of anti-drug antibodies associated with undetectable drug concentrations was significantly associated with treatment without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40 [95% CI 0·31-0·52], adalimumab 0·42 [95% CI 0·24-0·75]), and with carriage of HLA-DQA1*05 risk variant for infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13-1·88]) but not for adalimumab (HR 1·60 [0·92-2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated with increased time without the development of anti-drug antibodies associated with undetectable drug concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20-3·74]) or introduction of an immunomodulator after anti-TNF initiation (1·70 [1·11-2·59]). In years 2 and 3, 16 (4%) of 389 patients treated with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal. Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections in years 2 and 3., Interpretation: Only around a third of patients with active luminal Crohn's disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05 and mitigated by concomitant immunomodulator use for both drugs., Funding: Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion Healthcare., Competing Interests: Declaration of interests CR reports receiving salary from the National Institute of Health Research outside the submitted work. RN reports receiving non-financial support from Immunodiagnostik. CWL has received consulting fees from AbbVie, Galapagos, Takeda, Janssen, Novartis, Pfizer, GSK, BMS, Boehringer Ingelheim, Celltrion, Amgen, and Iterative Health and payment or honoraria from AbbVie, Galapagos, Takeda, Janssen, Novartis, Pfizer, GSK, BMS, Boehringer Ingelheim, Celltrion Healthcare, Amgen, and Fresnius Kabi. SS has received consulting fees from Takeda, AbbVie, Merck, Ferring, Pharmacosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene, and Tillots Pharma; payment or honoraria from AbbVie, Takeda, Celltrion Healthcare, Pfizer, Biogen, AbbVie, Janssen, Merck, Warner Chilcott, Falk Pharma, and Janssen; is chair of the Research Committee of the British Society of Gastroenterology; is chair of the Clinical Research Committee of the European Colitis and Crohns Organisation; and is co-director of research for the South Asian IBD Alliance. PMI reports research grants from Celltrion Healthcare, Takeda, Pfizer, and Galapagos; personal payments from AbbVie, Arena, Boehringer Ingelheim, BMS, Celltrion Healthcare, Elasmogen, Endpoint Health, Gilead, Janssen, Lilly, Pfizer, Sandoz, and Takeda; and travel support from Takeda, AbbVie, and Tillotts Pharma, outside the submitted work. RKR has received grants from Nestle, consulting fees from AbbVie, payment or honoraria from Tillotts Pharma and Janssen, and support for attending meetings or travel from Celltrion Healthcare. JRG reports grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, and Galapagos and non-financial support from Immundiagnostik outside the submitted work. TA reports grants or contracts from MSD, AbbVie, Hospira (Pfizer), Napp Pharmaceuticals, Celgene, Celltrion, F Hoffmann-La Roche, Biogen, Nova Pharmaceuticals, Galapagos, Takeda, and Pfizer; consulting fees from Amgen, Celltrion, Janssen, and Eli Lilly; payment or honoraria from F Hoffmann-La Roche, Pfizer, and Takeda; and support for attending meetings or travel from Tillotts Pharma and Celltrion Healthcare. NAK reports institutional grants or contracts from AbbVie, Biogen, Celgene, Celltrion Healthcare, Galapagos, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Roche, and Takeda; personal consulting fees from Amgen, Bristol Myers Squibb, Celltrion Healthcare, Falk Pharma, Galapagos, Janssen, Pfizer, Pharmacosmos, Takeda, and Tillotts Pharma; personal payments or honoraria from Amgen, Celltrion Healthcare, Falk Pharma, Galapagos, Janssen, Pharmacosmos, Galapagos, Takeda, and Tillotts Pharma; support for attending meetings or travel from AbbVie, Falk Pharma, Janssen, and Pharmacosmos; participation in the Data Monitoring Committee for BEACON study; and is chair of the British Society of Gastroenterology IBD Clinical Research Group. NC, SL, CB, BH, AT, RS, MB, and TJM decare 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: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone., Methods: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants., Findings: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group., Interpretation: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone., Funding: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895)., Competing Interests: Declaration of interests EL reports grants from Boehringer Ingelheim, Medela, Johnson & Johnson/Ethicon, Covidien/Medtronic, Guardant Health, Takeda, Lilly Oncology, and Bayer, paid to his institution, his company, or personally; consulting fees from BeiGene, Roche, and BMS; honoraria from Medela; two patents (P52435GB and P57988GB) issued to Imperial Innovations; and being founder of My Cancer Companion, Healthcare Companion. SP reports consulting fees from AnHeart Therapeutics, Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Ellipses, EQRx, Daiichi Sankyo, GSK, Guardant Health, IO Biotech, Janssen, Lilly, Merck Serono, Mirati, MSD, Novocure, Novartis, PharmaMar, Roche, Takeda, Pfizer, Pierre Fabre, and Turning Point Therapeutics; honoraria from AstraZeneca, Bayer, Guardant Health, Janssen, Merck Serono, Roche, and Takeda; fees for expert testimony from Roche and Merck Serono; support for meeting attendance from Janssen, Roche, and Gilead; and being a member of the British Thoracic Oncology Group, ALK Positive UK, Lung Cancer Europe, Ruth Strauss Foundation, Mesothelioma Applied Research Foundation, and ETOP-IBCSG Partners Foundation Board. NT reports honoraria from BMS. DF reports grants from Astex Therapeutics, Boehringer Ingelheim, Bayer Oncology, Bergen Bio, GSK, MSD, Owkin, Roche, and RS Oncology paid to his institution; consulting fees from MSD, Cambridge Clinical Laboratories, and RS Oncology; honoraria from BMS, BI, MSD, Ikena, and Owkin; and meeting support from RS Oncology and MSD, all paid to Thoracic Oncology Services where he is director. RCR reports research funding from Cancer Research UK, Asthma and Lung UK, June Hancock Mesothelioma Research Fund, Mick Knighton Mesothelioma Research Fund, and Mesobank; and participation on an advisory board for the UK Lung Cancer Coalition. PT reports honoraria from AstraZeneca. LC-S reports support for meeting attendance from Lilly. RC reports honoraria from AstraZeneca, MSD, Takeda, Janssen, Roche, and GSK; support for meeting attendance from Takeda and Janssen; participation on advisory boards for GSK, Takeda, Janssen, Pharmamar, and Amgen; and stock options with TCC and Supportive Care UK. YS reports honoraria from Amgen, AstraZeneca, AbbVie, BMS, MSD, Lilly, Roche, and Takeda; and support for meeting attendance from Takeda and Roche. ZT reports honoraria from AstraZeneca. RS reports honoraria and support for meeting attendance from Lilly and BMS. EF reports membership of the National Lung Cancer and Mesothelioma Clinical Experts Group and Northern Cancer Alliance Targeted Lung Health Check Clinical Lead. 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: The utility of the occupational medicine diploma in the UK is yet to be explored. The NHS 'Growing Occupational Health (OH) and Wellbeing' programme provides opportunities for diplomates to increase their OH work., Aims: To assess what proportion of diplomates carry out OH work, the type of work being undertaken, to identify obstacles impeding OH work, to capture their interest in future work opportunities and what additional support they require., Methods: A link to an online questionnaire was sent to diplomates via several professional bodies; we estimate that 2428 diplomates received this. The survey was open from 24 March to 31 May 2022., Results: Replies were received from 310/2428 (13%) diplomates. Fifty-two per cent of respondents were males and 35% were female. Respondents were diverse in terms of age and geographical region. Main employment settings: 13% primary care, 43% secondary care, 31% private sector, 24% public sector and 20% self-employed. Seventy-two per cent of diplomates had undertaken OH clinical work since completion of their diploma, and 90% of those were undertaking OH clinical work at the time of the survey. Specific obstacles to accessing OH work highlighted included existing workload constraints, lack of employment opportunities with OH providers and lack of time., Conclusions: Many (126/310; 41%) respondents had considered increasing their OH work in the previous 12 months. Increasing mentorship from senior OH clinicians to diplomates was suggested by 4% of respondents to enhance the utility of diplomates., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)