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The Winchcombe meteorite fell on February 28, 2021 and was the first recovered meteorite fall in the UK for 30 years, and the first UK carbonaceous chondrite. The meteorite was widely observed by meteor camera networks, doorbell cameras, and eyewitnesses, and 213.5 g (around 35% of the final recovered mass) was collected quickly—within 12 h—of its fall. It, therefore, represents an opportunity to study very pristine extra‐terrestrial material and requires appropriate careful curation. The meteorite fell in a narrow (600 m across) strewn field ~8.5 km long and oriented approximately east–west, with the largest single fragment at the farthest (east) end in the town of Winchcombe, Gloucestershire. Of the total known mass of 602 g, around 525 g is curated at the Natural History Museum, London. A sample analysis plan was devised within a month of the fall to enable scientists in the UK and beyond to quickly access and analyze fresh material. The sample is stored long term in a nitrogen atmosphere glove box. Preliminary macroscopic and electron microscopic examinations show it to be a CM2 chondrite, and despite an early search, no fragile minerals, such as halite, sulfur, etc., were observed. [ABSTRACT FROM AUTHOR]

Background: Performing an episiotomy where clinically indicated is a key intervention in the Obstetric Anal Sphincter Injury Care Bundle (OASI‐CB) implemented across England and Wales to reduce the risk and increase the detection of severe perineal trauma after birth. Standards of consent provided to people in maternity care generally and for episiotomy specifically have been reported as suboptimal. Compromising birthing people's personal autonomy or sense of control has been linked to a dissatisfying birth experience, negative psychological sequelae, and litigation. Methods: This study explored experienced midwives' practice of informed consent for episiotomy during a midwife‐led birth. We sampled 43 midwives across eight NHS Trusts in England and Wales using online focus groups and telephone interviews about their experience of consent in episiotomy. Using qualitative content analysis and art‐based co‐analysis methods with eight midwives from across the research sites, we co‐analyzed and co‐constructed three themes and four practice recommendations from the data. Results: Three themes were constructed from the data: Assent rather than consent, Change in culture to support best practice, and Standardized information. These themes informed the shaping of four recommendations for best practice in episiotomy informed consent. Conclusion: This study has shown how variations in midwifery practice and culture may impact birthing people's experience of informed consent in episiotomy. Midwives may not have the knowledge or skills to conduct a detailed consent conversation, leading to variation in practice and messages for birthing people. The use of antenatal discussion aids can offer women the opportunity to become informed and fully participate in the decision‐making process. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate current education and training of student and registered midwives across the UK and Spain; analysing both pelvic floor teaching and practical experience.Study Design: A cross-sectional survey was carried out by 711 student and 384 registered midwives across different universities and regions in the UK and Spain.Results: The vast majority (91.5 % n = 382) of UK students complete training without ever cutting or repairing an episiotomy. This compares to 39.4 % (n = 85) of registered midwives who did not cut an episiotomy during training. Only 20 % (n = 9) of Spanish and 10 % (n = 45) of UK registered midwives felt confident undertaking these techniques. In Spain just 15 % (n = 6) of students, compared to 54.8 % (n = 80) of registered midwives had received teaching on longer-term pelvic floor complications.Conclusion: There is a considerable deficit in the current training practices for midwives regarding episiotomies. This lack of practice and confidence may be impacting on the increased rates of perineal tears and pelvic dysfunction in post-partum women. Across registered midwives there are gaps in education regarding longer-term pelvic floor complications. Our study was limited by a smaller sample size from Spain compared to the UK. Our results show practical assessment of skills during training is desirable and could improve both the confidence and competence of midwives upon registration. [ABSTRACT FROM AUTHOR]

Background: Clozapine is an antipsychotic medication used in treatment resistant schizophrenia. However, clozapine is associated with a significant adverse effect profile and extensive monitoring is required to optimise consumer safety. Traditionally, clozapine can only be prescribed by a psychiatrist and dispensed at a hospital or hospital affiliated pharmacy in Australia. These restrictions could result in significant treatment burden for consumers taking clozapine. Objective: To identify (1) the different models of supply that exist for people living in the community taking clozapine in Australia and compare to those in New Zealand and the United Kingdom, and (2) explore how these supply models may impact on consumer burden from the perspective of professionals involved in the supply of clozapine. Method: Key informants were interviewed (n=8) from Australia, New Zealand and the United Kingdom regarding how consumers, who lived in the community, accessed clozapine. Data were analysed and led to the development of four clozapine supply models. These four models were further validated by an online survey of a wider sample (n=30). Data were analysed thematically and via simple descriptive statistics. Results: Clozapine supply varied depending on location. A secondary care model was utilised in the United Kingdom compared to a community based (primary care) model in New Zealand; Australia utilised a mixture of both secondary and primary care. A key theme from all study participants was that community pharmacy should be utilised to dispense clozapine to consumers living in the community, provided adequate training and safeguards are in place. It was noted that the utilisation of community pharmacies could improve access and flexibility, thereby reducing treatment burden for these consumers. Conclusion: There are predominately two models for supply of clozapine to consumers living in the community in Australia, New Zealand and the United Kingdom. One model utilises secondary care facilities and the other community services. Community pharmacy is ideally placed to increase access to clozapine for consumers living in the community, provided appropriate training and support is given to pharmacists providing this professional service. [ABSTRACT FROM AUTHOR]

We examine gender differences in the relative poverty of men and women in eight industrialized countries. The analyses are based on data from the Luxembourg Income Study, which includes data from the United States, Canada, Australia, the United Kingdom, West Germany, Sweden, Italy, and the Netherlands. We examine the importance of the gender-specific demographic compositions of marriage, parenthood, and employment in accounting for differences in men's and women's poverty rates, both within and across countries. The cross-national comparisons suggest that the relative importance of demographic characteristics differs by country and that factors such as religion, culture, and government policies also help determine the gap between women's and men's poverty rates. [ABSTRACT FROM AUTHOR]

Objective: Multiple treatment options are recommended for Systemic Lupus Erythematosus (SLE) by clinical guidelines. This study aimed to explore SLE treatment patterns as there is limited real-world data of SLE medication utilisation, especially in childhood-onset SLE (cSLE)., Methods: We conducted a longitudinal cohort study using five routinely collected healthcare databases from four European countries (United Kingdom, France, Germany, and Spain). We described the characteristics of adult and paediatric patients at time of SLE diagnosis. We calculated the percentage of patients commencing SLE treatments in the first month and year after diagnosis, reported number of prescriptions, starting dose, cumulative dose, and duration of each treatment, and characterised the line of therapy., Results: We characterised 11,255 patients with a first diagnosis of SLE and included 5718 in our medication utilisation analyses. The majority of adult SLE patients were female (range 80-88 %), with median age of 49 to 54 years at diagnosis. In the paediatric cohort (n = 378), 66-83 % of SLE patients were female, with median age of 12 to 16 years at diagnosis. Hydroxychloroquine and glucocorticoids were common first-line treatments in both adults and children, with second-line treatments including mycophenolate mofetil and methotrexate. Few cases of monoclonal antibody use were seen in either cohort. Initial glucocorticoid dosing in paediatric patients was often higher than in adults., Conclusion: Treatment choices for adult SLE patients across four European countries were in line with recent therapeutic consensus guidelines. High glucocorticoid prescriptions in paediatric patients suggests the need for steroid-sparing treatment alternatives and paediatric specific guidelines., Competing Interests: Declarations of competing interest DPA's department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department. James Brash and Hanne van Ballegooijen are employees of IQVIA. All other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Barriers to accessing and using primary care services among minoritised ethnic communities have been extensively evidenced in the UK. However, the impact of the rapid digitalisation of these services on these communities remains under-researched., Aim: To explore the impact of digitalisation on access to and use of primary care services among minoritised ethnic communities., Design and Setting: Underpinned by a critical realist intersectional approach, and employing qualitative research methods, this study explores minoritised ethnic individuals' experiences of digital primary care in the UK., Method: In total, 100 minoritised ethnic adults who identify as Black African, Black Caribbean, Bangladeshi, Indian, Pakistani, Chinese, and of mixed or multiple ethnic heritage in four sites in the UK were purposively recruited and interviewed. Interviews were thematically analysed to increase understanding of how individuals' ethnicity intersects with other characteristics (for example, language, age, gender, socioeconomic status) to identify constraints and enablements to accessing health care., Results: Minoritised ethnic individuals' access to digital primary care is impeded by factors such as digital precarity (for example, inadequate devices, internet connectivity, and digital literacy skills), a lack of language support, and staff shortcomings in responding to ethnically diverse populations. Intergenerational support and bespoke offerings by general practices in some areas enable some individuals to overcome some of the constraints., Conclusion: The rapid digitalisation of primary care services is replicating and potentially exacerbating barriers to using these services among minoritised ethnic communities, a finding that merits urgent attention by practitioners and policymakers., (© The Authors.)

Objective: To identify patient-safety-related unintended consequences of healthcare technologies experienced by their primary users: patients, carers and healthcare providers (HCPs)., Design: Qualitative study based on data collected in online focus groups. Transcripts were analysed inductively after each focus group using reflexive thematic analysis, focusing on identifying unintended consequences of healthcare technologies with implications for patient safety. Patient safety was broadly conceptualised to include a more subjective concept of 'feeling safe' as well as risks of actual harm., Setting: Patient/public and HCP participants from the UK with experience in healthcare technologies were recruited using a mixture of purposive, convenience and snowball sampling., Participants: 40 participants (29 patients/public, 11 HCPs) took part in 5 focus groups between November 2021 and February 2022., Results: We identified five main themes of unintended consequences with implications for patient safety: inequity of access, increased end-user burden, loss of the human element of healthcare, over-reliance on technology and unclear responsibilities. Both groups of participants identified unintended consequences directly affecting patients; HCPs also described those affecting themselves. Some unintended consequences are described in previous literature, including alert fatigue, the 'illusion of communication', reduced opportunities for face-to-face interactions and increased end-user burden. Others are potentially novel, including patients' psychological dependence on technologies, 'gaming' of data entry and incorrect interpretation of health data., Conclusions: Drawing on the perspectives of patients/public as well as HCPs, we identified five areas of patient-safety-related unintended consequences associated with healthcare technologies. These should be considered when developing tools to identify and mitigate the patient-safety-related unintended consequences of healthcare technologies., Competing Interests: Competing interests: ALN and BDF are theme leads of the NIHR North West London Patient Safety Research Collaboration (PSRC). BDF is also director of this PSRC. SA is a research assistant in this PSRC. JL and JN, the PPI partners in this study, received honoraria as per the NIHR INVOLVE guidelines. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA., Objectives: To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD., Methods: We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits., Results: We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively)., Conclusions: This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up., Competing Interests: Conflicts of interest The full conflicts of interest statement is provided in Appendix 3., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Research, mainly conducted in Europe and North America, has shown an inequitable burden of internalising mental health problems among adolescents from poorer households. We investigated whether these mental health inequalities differ across a diverse range of countries and multiple measures of economic circumstances., Methods: In this longitudinal observational cohort study, we analysed data from studies conducted in eight countries (Australia, Ethiopia, India, Mexico, Peru, South Africa, the UK, and Viet Nam) across five global regions. All studies had self-reported measures of internalising symptoms using a validated scale at two timepoints in adolescence; a measure of household income, household consumption expenditure, or subjective wealth; and data collected between 2000 and 2019. Household income (measured in four countries), consumption expenditure (six countries), and adolescents' subjective assessment of household wealth (five countries) were measured in mid-adolescence (14-17 years). The primary outcome (internalising symptoms, characterised by negative mood, affect, and anxiety) was measured later in adolescence between age 17 and 19 years. Analyses were linear regression models with adjustment. Effect estimates were added to random-effects meta-analyses to aid understanding of cross-country differences., Findings: The overall pooled sample of eight studies featured 18 910 adolescents (9568 [50·6%] female and 9342 [49·4%] male). Household income had a small or null association with adolescents' internalising symptoms. Heterogeneity (I 2 statistic) was 71·04%, falling to 39·71% after adjusting for baseline symptoms. Household consumption expenditure had a stronger association with internalising symptoms (decreases of 0·075 SD in Peru [95% CI -0·136 to -0·013], 0·034 SD in South Africa [-0·061 to -0·006], and 0·141 SD in Viet Nam [-0·202 to -0·081] as household consumption expenditure doubled). The I 2 statistic was 74·24%, remaining similar at 74·83% after adjusting for baseline symptoms. Adolescents' subjective wealth was associated with internalising symptoms in four of the five countries where it was measured. The I 2 statistic was 57·09% and remained similar after adjusting for baseline symptoms (53·25%). We found evidence for cross-country differences in economic inequalities in adolescents' internalising symptoms, most prominently for inequalities according to household consumption expenditure. Subjective wealth explained greater variance in symptoms compared with the objective measures., Interpretation: Our study suggests that economic inequalities in adolescents' mental health are prevalent in many but not all countries and vary by the economic measure considered. Variation in the magnitude of inequalities suggests that the wider context within countries plays an important role in the development of these inequalities., Funding: Wellcome Trust., Competing Interests: Declaration of interests SE-L reports grants from the UK Medical Research Council, the National Institute for Health and Care Research, and the Economic and Social Research Council. KR-C reports support through a UK Research and Innovation Future Leaders Fellowship; grants from UK Research and Innovation and WHO; and previous membership on the Global Alliance for Chronic Disease expert advisory panel. 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: Hospitalized COVID-19 patients with troponin elevation have a higher prevalence of cardiac abnormalities than control individuals. However, the progression and impact of myocardial injury on COVID-19 survivors remain unclear., Objectives: This study sought to evaluate myocardial injury in COVID-19 survivors with troponin elevation with baseline and follow-up imaging and to assess medium-term outcomes., Methods: This was a prospective, longitudinal cohort study in 25 United Kingdom centers (June 2020 to March 2021). Hospitalized COVID-19 patients with myocardial injury underwent cardiac magnetic resonance (CMR) scans within 28 days and 6 months postdischarge. Outcomes were tracked for 12 months, with quality of life surveys (EuroQol-5 Dimension and 36-Item Short Form surveys) taken at discharge and 6 months., Results: Of 342 participants (median age: 61.3 years; 71.1% male) with baseline CMR, 338 had a 12-month follow-up, 235 had a 6-month CMR, and 215 has baseline and follow-up quality of life surveys. Of 338 participants, within 12 months, 1.2% died; 1.8% had new myocardial infarction, acute coronary syndrome, or coronary revascularization; 0.8% had new myopericarditis; and 3.3% had other cardiovascular events requiring hospitalization. At 6 months, there was a minor improvement in left ventricular ejection fraction (1.8% ± 1.0%; P < 0.001), stable right ventricular ejection fraction (0.4% ± 0.8%; P = 0.50), no change in myocardial scar pattern or volume (P = 0.26), and no imaging evidence of continued myocardial inflammation. All pericardial effusions (26 of 26) resolved, and most pneumonitis resolved (95 of 101). EuroQol-5 Dimension scores indicated an overall improvement in quality of life (P < 0.001)., Conclusions: Myocardial injury in severe hospitalized COVID-19 survivors is nonprogressive. Medium-term outcomes show a low incidence of major adverse cardiovascular events and improved quality of life. (COVID-19 Effects on the Heart; ISRCTN58667920)., Competing Interests: Funding Support and Author Disclosures This work was supported by NIHR (National Institute for Health and Care Research) and UK Research and Innovation (COV0254). West Yorkshire and Humber Clinical Research Network (CV070) funded the patient information leaflet translation. Dr Berry has received British Heart Foundation support (RE/18/6134217). Dr Artico received funding from the European Association of Cardiovascular Imaging (EACVI Research Grant App000073878). Dr McCann is funded by a NIHR Research Professorship (RP-2017-08-ST2-007). Dr Manisty is funded by a NIHR Clinician Scientist Award (CS-2015-15-003). Drs Ferreira, Piechnik, and Neubauer acknowledge the NIHR Oxford BRC for support of this study. Dr Bucciarelli-Ducci is in part supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS (National Health Service) Foundation Trust and the University of Bristol. Additional support was provided by the NIHR Leicester Biomedical Research Centre and the NIHR Leeds Clinical Research Facility. Dr Dweck is supported by the British Heart Foundation (FS/SCRF/21/32010). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. Dr Moon has served on Advisory Boards for Sanofi and Genzyme. Dr Miller has served on Advisory Boards for Novartis, Boehringer Ingelheim and Lilly Alliance, and AstraZeneca; serves as an advisor for HAYA Therapeutics and PureTech Health; and has received research support from Amicus Therapeutics, Guerbet Laboratories Limited, Roche, and Univar Solutions B.V. Dr Bucciarelli-Ducci is the chief executive officer (part-time) of the Society for Magnetic Resonance. Dr Berry is employed by the University of Glasgow, which holds research and/or consultancy agreements with AstraZeneca, Abbott Vascular, Boehringer Ingelheim, GlaxoSmithKline, HeartFlow, Opsens, and Novartis. 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: Internationally, intermittent auscultation (IA) is recommended for monitoring the fetal heart rate during labour and birth for women with uncomplicated pregnancies. IA can identify changes in the fetal heart rate that may indicate the need for additional care or intervention. IA is a central facet of midwifery practice, but there is little evidence about women's experience of IA., Aim: Our study aimed to explore women's experiences of IA in the UK., Methods: Between February and May 2023, 23 women were recruited through social media, service user organisations and charities, for a single episode, online interview or focus group with informed consent. Audio recordings were transcribed and thematically analysed., Findings: The analysis constructed two over-arching themes: 'Choice takes work' and 'Impact of IA monitoring on the labouring woman'., Discussion: Women reported a lack of informed decision-making in relation to intrapartum fetal monitoring. The experience of our participants showed that not all women for whom IA would be recommended according to current clinical guidelines were offered it, while others experienced IA without understanding its function or the availability of other options., Conclusion: Limited antenatal communication from maternity care professionals about fetal monitoring in labour has an impact on women's opportunities to make informed decisions. A committed approach to informed decision making in the antenatal period could reduce practice variation and better support midwives to support women in their birth choices., Competing Interests: Conflict of Interest statement The authors have no conflicts of interest to declare, (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Aims: To estimate healthcare resource utilization (HCRU) and healthcare costs by body mass index (BMI) in a UK cohort and to explore how this varied by defined BMI strata., Materials and Methods: This retrospective open cohort study used Discover, a linked primary and secondary electronic health records database covering 2.7 million individuals. Adults were stratified by BMI as: overweight (25-<30 kg/m 2 ); obesity class I (30-<35 kg/m 2 ); obesity class II (35-<40 kg/m 2 ); or obesity class III (≥40 kg/m 2 ). Cost data, comprising primary care, secondary care (inpatient admissions, outpatient appointments and emergency room visits) and prescriptions, were reported for 2015-2019., Results: Overall, 1 008 101 individuals were overweight, 278 782 had obesity class I; 80 621 had obesity class II, and 42 642 had obesity class III. Healthcare costs and HCRU events per person per year increased over time (2015: £851-£1321 and 10.6-13.4 events; 2019: £1143-£1871 and 11.4-14.9 events), and were higher for each successive BMI group. Groups with chronic kidney disease or cardiovascular disease incurred particularly high costs. In 270 493 individuals with obesity in 2019, more than 72% of total healthcare costs were incurred by the highest cost quintile, which had a higher mean age and more obesity-related complications (ORCs) than lower cost quintiles., Conclusions: The economic impact of obesity could be alleviated by weight management support based on unmet need, to limit the effects of BMI progression and ORC development., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: To use a standardised reporting tool to identify potential eligible candidates for cochlear implant (CI) referral and quantify the proportion of adults who had a CI referral discussion after presenting with an audiogram within United Kingdom (UK) audiometric criteria., Design: Retrospective multicentre 6-month audit of Audiology clinic databases., Study Sample: A total of 810 adults from five geographically diverse UK Audiology sites., Results: Data were collected in late 2019 after UK CI audiometric candidacy criteria changed; one site collected only 3 months of data. The proportion of potential eligible adults (based only on audiometry) considered for CI referral was 64% (521 out of 810) and varied by site (from 50% to 83%). About 24% of patients (123 out of 521) declined CI referral; this also varied across sites (12-45%). The median age of patients where CI referral was not considered was 80 years - significantly higher than the group where CI referral was considered (73 years)., Conclusions: CI referral is dependent on where adults live, and how old they are. Older adults are significantly less likely to be considered for CI referral by Audiologists. Audiology clinics need more support to empower staff to talk to patients about CI referral.

Aim: To assess the prevalence of individual obesity-related complications (ORCs) and multimorbidity (≥ 1, ≥ 2 and ≥ 3 ORCs), and multimorbidity-associated healthcare costs, over 10 years., Methods: This retrospective open cohort study used Discover, a UK database of linked primary and secondary electronic health records. Adults were stratified by body mass index (BMI; overweight: 25-< 30 kg/m 2 ; obesity class I: 30-< 35 kg/m 2 ; obesity class II: 35-< 40 kg/m 2 ; obesity class III: ≥ 40 kg/m 2 ). Outcomes by year since baseline were assessed for serial cross sections across the study period (1 January 2004 to 31 December 2019; the index date was the date of first eligible BMI measurement)., Results: Across 1 410 146 individuals (overweight: 1 008 101; obesity class I: 278 782; obesity class II: 80 621; obesity class III: 42 642), ORC prevalence was higher in successive BMI groups, and increases over time were generally greater for obesity relative to overweight. In those with ORC multimorbidity, both higher BMI and the presence of more ORCs were associated with higher annual per-person healthcare costs. Costs increased over time in those individuals with obesity and one or more ORC, as well as in those with obesity and two or more ORCs., Conclusions: Higher BMI was associated with higher baseline ORC prevalence and a greater increase in ORC prevalence over time, and with higher healthcare costs in those with multimorbidity. To reduce the burden of overweight and obesity on patients and healthcare systems, the presence, number and type of ORCs should be considered in developing effective, targeted prevention and management care pathways., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: Traumatic brain injury (TBI) brings about inevitable and significant changes for family members. Mental health effects for family members are well documented but there are significant gaps in support options across services. Here, we describe our protocol for a study that seeks to investigate the potential for a narrative, creative approach, the 'Life Threads' approach, as a low intensity, accessible means of support that can be applied across service contexts., Methods: We will recruit 20 family members of someone who sustained a TBI from services in an area of the UK with a diverse demographic. Family members will be provided with the 'Life Threads' approach materials and guided in their use. The study is planned to run from March 2023 to July 2024., Analysis: Collection of data on potential usefulness, feasibility and acceptability will be through focus groups and individual interviews. Transcripts will be analysed using reflexive thematic analysis, conducted within a relativist, constructivist orientation., Ethics and Dissemination: Ethical approvals have been sought and gained (Nottingham 1 Research Ethics Committee, 23/EM/0185, 4 September 2023), and the study has been registered with ISRCTN. As a research team, we are guided by our own personal, professional and research experiences of TBI which we will consider reflexively throughout the research process. Results will be disseminated in collaboration with our patient and public involvement group through open peer-reviewed journal publication and scientific conference, with lay summaries shared via recruitment sites., Trial Registration Number: ISRCTN17392794., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Receiving donor human milk for a baby can have a protective effect upon parental wellbeing. A growing body of research also finds that being able to donate milk to a milk bank, particularly after infant loss, can also boost maternal wellbeing through feelings of altruism and purpose. However, most studies are qualitative, with small sample sizes outside the United Kingdom, and often do not include the experiences of those who have been unable to donate. Our aim was therefore to examine the impact of being able to donate milk, as well as the impact of not being able to do so, using a survey containing open and closed questions in a large UK sample. Overall, 1149 women completed the survey, 417 (36.3%) who donated their milk and 732 (63.7%) who did not. Most women who donated found it had a positive impact upon their wellbeing, feeling proud, useful and that they had achieved something important. Conversely, those unable to donate often felt rejected, frustrated, and excluded, especially if they received no response or felt that restrictions were unfair. Thematic analysis found that being able to donate could help women heal from experiences such as birth trauma, difficult breastfeeding experiences, neonatal unit stays, and infant loss; however, being unable to donate could exacerbate negative emotions arising from similar experiences. A minority of women who donated experienced raised anxiety over following guidelines. These findings further extend the impacts of milk banking services beyond infant health and development and support expanded service delivery., (© 2024 The Author(s). Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Purpose: Step count is an intuitive measure of physical activity frequently quantified in health-related studies; however, accurate step counting is difficult in the free-living environment, with error routinely above 20% in wrist-worn devices against camera-annotated ground truth. This study aimed to describe the development and validation of step count derived from a wrist-worn accelerometer and assess its association with cardiovascular and all-cause mortality in a large prospective cohort., Methods: We developed and externally validated a self-supervised machine learning step detection model, trained on an open-source and step-annotated free-living dataset. Thirty-nine individuals will free-living ground-truth annotated step counts were used for model development. An open-source dataset with 30 individuals was used for external validation. Epidemiological analysis was performed using 75,263 UK Biobank participants without prevalent cardiovascular disease (CVD) or cancer. Cox regression was used to test the association of daily step count with fatal CVD and all-cause mortality after adjustment for potential confounders., Results: The algorithm substantially outperformed reference models (free-living mean absolute percent error of 12.5% vs 65%-231%). Our data indicate an inverse dose-response association, where taking 6430-8277 daily steps was associated with 37% (25%-48%) and 28% (20%-35%) lower risk of fatal CVD and all-cause mortality up to 7 yr later, compared with those taking fewer steps each day., Conclusions: We have developed an open and transparent method that markedly improves the measurement of steps in large-scale wrist-worn accelerometer datasets. The application of this method demonstrated expected associations with CVD and all-cause mortality, indicating excellent face validity. This reinforces public health messaging for increasing physical activity and can help lay the groundwork for the inclusion of target step counts in future public health guidelines., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Objectives: To evaluate the delivery of rehabilitation using implicit motor learning principles in an acute stroke setting., Design: Pilot, assessor-blind, cluster randomised controlled trial with nested qualitative evaluation., Setting: Eight inpatient stroke units, UK., Participants: People within 14 days of stroke onset, presenting with lower limb hemiplegia., Interventions: Participants at control clusters received usual care. Participants at intervention clusters received rehabilitation using an Implicit Learning Approach (ILA); primarily consisting of reduced frequency instructions/feedback, and promotion of an external focus of attention. Video recording was used to understand the ability of intervention site therapists to adhere to the implicit learning principles, and to compare differences between groups., Measures: Ability to recruit and retain clusters/participants; suitability and acceptability of data collection processes; appropriateness of fidelity monitoring methods; and appropriateness of chosen outcome measures., Results: Eight stroke units participated, with four assigned to each group (intervention/control). Fifty-one participants were enrolled (intervention group 21; control group 30). Mean time since stroke was 6 days (SD 3.42; 0-14); mean age was 73 years (SD 14, 25-94). Of those approached to take part, 72% agreed. We found clear differences between groups with respect to the frequency and type of instructional statement. The ILA was acceptable to both patients and therapists., Conclusion: It is feasible to evaluate the application and effectiveness of motor learning principles within acute stroke rehabilitation, using a cluster randomised design. A larger study is required to evaluate the benefits of each approach; we provide a range of sample size estimates required for this., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract: Growing evidence from pharmacovigilance data and postmortem toxicology reports highlights the misuse potential of gabapentinoids. This study aimed to investigate the risk of serious adverse outcomes (drug misuse, overdose, major trauma), and their risk factors, in primary care patients who are prescribed gabapentinoids. Using the UK Clinical Practice Research Datalink, a matched cohort study calculated adverse event rates separately for gabapentinoid-exposed and unexposed cohorts. In the exposed cohort, event rates for exposure to a range of potential risk factors were calculated. Event rates were compared using Cox proportional hazards models, adjusted for age, sex, deprivation, previous mental health diagnosis, and coprescribing with potentially interacting medicines. Substance misuse (gabapentin adjusted hazard ratio [95% CI]: 2.40 [2.25-2.55]), overdose (2.99 [2.56-3.49]), and major trauma (0-2.5 years: 1.35 [1.28-1.42]; 2.5 to 10 years: 1.73 [1.56-1.95]) were more common among patients prescribed gabapentinoids than matched individuals who were not. The association with overdose was stronger for pregabalin than gabapentin. All adverse outcomes were significantly associated with smoking, history of substance misuse, overdose, or a mental health condition and prescription of opioids, benzodiazepines, antidepressants, and Z-drug hypnotics (eg, gabapentin hazard ratios for association of concurrent opioid use: misuse 1.49 [1.47-1.51]; overdose 1.87 [1.78-1.96]; major trauma 1.28 [1.26-1.30]). Our findings highlight the importance of careful patient selection when prescribing gabapentinoids and the need to educate prescribers about the risks of these drugs, particularly in combination with other central nervous system depressants., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

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: When premature infants cannot receive their own mother's milk, donor human milk (DHM) is the first-line recommended option, with growing demand for DHM use outside of neonatal units. To meet the potential need, we need to consider whether DHM supply can increase. This study aimed to explore the reasons that prevent women who wish to donate their milk in the United Kingdom from doing so to understand which barriers may be modifiable., Methods: Women who wanted to donate their milk but did not do so completed an online survey. Open and closed questions examined the response they received, their reasons for not donating and what they did with any milk that they had already stored., Results: Out of 732 mothers, 391 (53.4%) did not enquire as they did not think it was possible for them, 218 (29.8%) enquired but were told that they could not donate, 59 (8.1%) enquired but decided not to proceed and 64 (8.7%) received no response. Reasons for being told they could not donate included the use of certain medications, infant age, inadequate staffing, geographic barriers and incorrect storage. Process aspects (e.g., blood tests, practicalities) and lifestyle limitations led mothers to decide not to donate., Conclusions: Although some women will be prevented from donating due to medication or health issues, investment in milk banking staffing and infrastructure and awareness campaigns could increase DHM supply, enabling guidelines to extend eligibility criteria for receiving DHM such as for late preterm infants, gestational diabetes or to support low maternal milk supply., (© 2024 The Author(s). Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Background: Low leukocyte mitochondrial DNA (mtDNA) abundance has been associated with a higher risk of atherosclerotic cardiovascular disease, but through unclear mechanisms. We aimed to investigate whether low mtDNA abundance is associated with worse metabolomic profiling, as being potential intermediate phenotypes, using cross-sectional and genetic studies., Methods: Among 61,186 unrelated European participants from UK Biobank, we performed multivariable-adjusted linear regression analyses to examine the associations between mtDNA abundance and 168 NMR-based circulating metabolomic measures and nine metabolomic principal components (PCs) that collectively covered 91.5% of the total variation of individual metabolomic measures. Subsequently, we conducted Mendelian randomization (MR) to approximate the causal effects of mtDNA abundance on the individual metabolomic measures and their metabolomic PCs., Results: After correction for multiple testing, low mtDNA abundance was associated with 130 metabolomic measures, predominantly lower concentrations of some amino acids and higher concentrations of lipids, lipoproteins and fatty acids; moreover, mtDNA abundance was associated with seven out of the nine metabolomic PCs. Using MR, genetically-predicted low mtDNA abundance was associated with lower lactate (standardized beta and 95% confidence interval: -0.17; -0.26, -0.08), and higher acetate (0.15; 0.07,0.23), and unsaturation degree (0.14; 0.08,0.20). Similarly, genetically-predicted low mtDNA abundance was associated with lower metabolomic PC2 (related to lower concentrations of lipids and fatty acids), and higher metabolomic PC9 (related to lower concentrations of glycolysis-related metabolites)., Conclusion: Low mtDNA abundance is associated with metabolomic perturbations, particularly reflecting a pro-atherogenic metabolomic profile, which potentially could link low mtDNA abundance to higher atherosclerosis risk., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Anaesthetic training has always had patient safety as part of the curriculum. However, there is limited emphasis on what happens when things do not go to plan. Our aims were to understand the impact of involvement in patient safety incidents on anaesthetic trainees in our region, to describe the range of support currently offered and put forward suggestions for improvement., Methods: An initial electronic survey was sent to all anaesthetic trainees in a single UK healthcare region to capture qualitative and quantitative information on patient safety incidents. After completing the questionnaire, participants were asked to consent to involvement in a semi-structured interview to provide a more detailed understanding of the impact of safety incidents. Data were analysed from the questionnaires and interview transcripts using descriptive statistics and thematic analysis., Results: Thirty-four completed questionnaires were analysed revealing 27 trainees had been involved in a patient safety incident. Ten semi-structured interviews were conducted and six themes were identified: team dynamics (including adequacy of staffing and supportive departmental culture); context of the event; reflex immediate support post-event; working environment pending completion of the investigation; personal impact (including physical and mental health); and suggestions for future support., Conclusion: This study has shown the significant impact of safety incidents on anaesthetic trainees in one training region in the UK and highlights the importance of implementing early, tailored debriefs led by trained facilitators, the value of a supportive work environment and the need to raise awareness of system-based approaches to learning from incident investigations. Further research should guide the format and delivery of support for trainees to provide more helpful and timely interventions after patient safety incidents and reduce the risk of future harm to both patients and trainees., (© 2024 The Author(s). Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

In this paper, we conceptualize the days of mourning that followed the passing of Queen Elizabeth II. as constituting a liminal occasion, a moment of in-betweenness through which we can explore sense-making in times of transition. How do people navigate through liminal occasions, and are they always transformative? Through a rapid response ethnography (N interviews  = 64, N participants  = 122), we were able to capture the raw moments within which a collective comes together, as part of a national ritual, to transition from 'here' to 'there'. In our data, liminality prompted participants to strategically define British national identity and its future by positioning the Queen as representative of Britishness, her loss as a national identity loss. No longer taken for granted, participants reasserted the value of the monarchy as an apolitical and unifying feature in an otherwise divided society, characterizing the continuity of the institution as an essential part of British identity and society. The analysis illustrates how liminality offers a useful conceptual tool for addressing how temporality and change are negotiated in relation to a shared identity, and how navigating transitional moments brings with it political implications for the future., (© 2024 The Author(s). British Journal of Social Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Background: Young adults represent a third of the United Kingdom prison population and are at risk of poor health outcomes, including drug and alcohol misuse, self-harm and suicide. Court diversion interventions aim to reduce the negative consequences of criminal sanctions and address the root causes of offending. However, evidence of their effectiveness has not yet been established. The Gateway programme, issued as a conditional caution, aimed to improve the life chances of young adults committing low-level offences. Participants agreed not to reoffend during the 16-week caution and, following a needs assessment, received individual support from a Gateway navigator and attended two workshops encouraging analysis of own behaviour and its consequences., Objective: To evaluate the effectiveness and cost-effectiveness of Gateway in relation to health and well-being of participants compared to usual process (court summons or a different conditional caution)., Design, Setting and Participants: Pragmatic, multisite, parallel-group, superiority randomised controlled trial with two 6-month internal pilots and a target sample size of 334. Randomisation between Gateway and usual process was on a 1 : 1 basis. Four Hampshire Constabulary sites recruited 18- to 24-year-old residents of Hampshire and Isle of Wight who were questioned for an eligible low-level offence. Semistructured interviews were also held with a sample of Gateway programme participants, staff and police study recruiters., Main Outcome Measures: Primary outcome was the Warwick-Edinburgh Mental Wellbeing Scale score at 12 months. Secondary outcomes included health status, alcohol and drug use, recidivism and resource use., Results: Recruitment commenced in October 2019 and the trial stopped in April 2021. A total of 191 participants were recruited, with 109 randomised to Gateway and 82 to usual process. Due to an initial overestimation of potentially eligible young people and low retention rates, recruitment targets were adjusted, and a range of mitigating measures introduced. Although recruitment broadly met study progression criteria [35/50 (70%) Pilot 1: 64/74 (86%) Pilot 2], retention was low throughout (overall: data collected at week 4 was 50%: at week 16 it was 50%: 1-year 37%). Low retention was multifactorial, with one of the main barriers being difficulties contacting participants. It was therefore not possible to complete the randomised controlled trial or the health economics analyses. Qualitative interviews held with 58 individuals yielded rare insights into the benefits and limitations of this type of intervention, as well as barriers and facilitators in relation to recruitment in this setting., Limitations: Despite close collaboration with the police to address recruitment and consent issues, expansion of the inclusion criteria and recruitment area and introducing other measures, the researchers were unable to collect sufficient data within an acceptable timeframe., Conclusions: The Gateway study was a unique endeavour to gather evidence for a potentially life-changing intervention for an underserved population. The experience gained indicates that randomised controlled trials of interventions, with a health-related outcome, are possible in this setting but point towards the need for conservative recruitment and retention estimates in this target population. Other study designs should be considered. The qualitative evaluation provided a range of valuable lessons for those seeking to design similar interventions or conduct research in similar settings., Study Registration: This study is registered as ISRCTN11888938., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research ; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information.

Weather and climate patterns play an intrinsic role in societal health, yet a comprehensive synthesis of specific hazard-mortality causes does not currently exist. Country-level health burdens are thus highly uncertain, but harnessing collective expert knowledge can reduce this uncertainty, and help assess diverse mortality causes beyond what is explicitly quantified. Here, surveying 30 experts, we provide the first structured expert judgement of how weather and climate directly impact mortality, using the UK as an example. Current weather-related mortality is dominated by short-term exposure to hot and cold temperatures leading to cardiovascular and respiratory failure. We find additional underappreciated health outcomes, especially related to long-exposure hazards, including heat-related renal disease, cold-related musculoskeletal health, and infectious diseases from compound hazards. We show potential future worsening of cause-specific mortality, including mental health from flooding or heat, and changes in infectious diseases. Ultimately, this work could serve to develop an expert-based understanding of the climate-related health burden in other countries., Competing Interests: Declaration of interests YTEL was funded by a University of Bristol fellowship in Climate and Health. EB was funded by Policy Bristol. CR is funded by a UKRI Future Leaders Fellowship (MR/V021672). NSF received support of H2020 MSCA IF (grant ID 846824). AG was supported by the Medical Research Council-UK (MR/V034162/1). 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.)

English anatomical terminology has evolved over the long history of anatomical practice, with major influences from ancient Greek, classical Latin, Arabic, and post-classical Latin. Beginning in the nineteenth century, there have been various attempts to standardise and rationalise anatomical language, beginning in 1887, and culminating in the publication in 2019 of the second edition of the Terminologia Anatomica. This paper presents a brief historical overview of the development of anatomical terminology and usage in English, followed by a summary of the results of an anonymised survey of current practices that was sent out by email to anatomy educators at 45 medical schools in the United Kingdom. This is followed by personal reflections by six senior academics and/or clinicians, reviewing their extensive experience of teaching, researching, and communicating the language of anatomy within United Kingdom medical and clinical institutions., (© 2024. The Author(s), under exclusive licence to Japanese Association of Anatomists.)

It is unclear whether poverty and mental illness are causally related. Using UK Biobank and Psychiatric Genomic Consortium data, we examined evidence of causal links between poverty and nine mental illnesses (attention deficit and hyperactivity disorder (ADHD), anorexia nervosa, anxiety disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder and schizophrenia). We applied genomic structural equation modelling to derive a poverty common factor from household income, occupational income and social deprivation. Then, using Mendelian randomization, we found evidence that schizophrenia and ADHD causally contribute to poverty, while poverty contributes to major depressive disorder and schizophrenia but decreases the risk of anorexia nervosa. Poverty may also contribute to ADHD, albeit with uncertainty due to unbalanced pleiotropy. The effects of poverty were reduced by approximately 30% when we adjusted for cognitive ability. Further investigations of the bidirectional relationships between poverty and mental illness are warranted, as they may inform efforts to improve mental health for all., (© 2024. The Author(s).)

BackgroundLynch syndrome (LS) is an inherited cancer predisposition syndrome caused by genetic variants affecting DNA mismatch repair (MMR) genes MLH1 , MSH2 , MSH6 and PMS2 Cancer risk in LS is estimated from cohorts of individuals ascertained by individual or family history of cancer, which may upwardly bias estimates., Methods: 830 carriers of pathogenic or likely pathogenic ( path&#95;MMR ) MMR gene variants classified by InSiGHT were identified in 454 756 UK Biobank (UKB) participants using whole-exome sequence. Nelson-Aalen survival analysis was used to estimate cumulative incidence of colorectal, endometrial and breast cancer (BC)., Results: Cumulative incidence of colorectal and endometrial cancer (EC) by age 70 years was elevated in path&#95;MMR carriers compared with non-carriers (colorectal: 11.8% (95% confidence interval (CI): 9.5% to 14.6%) vs 1.7% (95% CI: 1.6% to 1.7%), endometrial: 13.4% (95% CI: 10.2% to 17.6%) vs 1.0% (95% CI: 0.9% to 1.0%)), but the magnitude of this increase differed between genes. Cumulative BC incidence by age 70 years was not elevated in path&#95;MMR carriers compared with non-carriers (8.9% (95% CI: 6.3% to 12.4%) vs 7.5% (95% CI: 7.4% to 7.6%)). Cumulative cancer incidence estimates in UKB were similar to estimates from the Prospective Lynch Syndrome Database for all genes and cancers, except there was no evidence for elevated EC risk in carriers of pathogenic PMS2 variants in UKB., Conclusion: These results support offering incidentally identified carriers of any path&#95;MMR surveillance to manage colorectal cancer risk. Incidentally identified carriers of pathogenic variants in MLH1 , MSH2 and MSH6 would also benefit from interventions to reduce EC risk. The results suggest that BC is not an LS-related cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

This manuscript reports on a landmark symposium on the ethical, legal and technical challenges of xenotransplantation in the UK. King's College London, with endorsement from the British Transplantation Society (BTS), and the European Society of Organ Transplantation (ESOT), brought together a group of experts in xenotransplantation science, ethics and law to discuss the ethical, regulatory and technical challenges surrounding translating xenotransplantation into the clinical setting. The symposium was the first of its kind in the UK for 20 years. This paper summarises the content of the expert lectures showcasing the progress which has been made in xenotransplantation including-the history of xenotransplantation, advances in gene edited animals and progress towards clinical xenotransplantation. We then set out the ethical and legal issues still to be resolved. Finally, we report the themes of the roundtable discussion highlighting areas of consensus and controversy. While the detail of the legal discussion was directed towards the UK, the principles and summary reported here are intended to be applicable to any jurisdiction seeking to implement clinical xenotransplantation., Competing Interests: Competing interests: David Ayares is the chief scientific officer of Revivicor, Inc. David Cooper Consultant to eGenesis Bio, Cambridge, MA, USA. Jayme Locke receives grant salary support from Lung Biotechnology PBC, a subsidiary of United Therapeutics., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

School is a key site for prevention and early intervention in public mental health, with sexual and gender minority students being a priority group for action. Context is important in understanding how school inclusion of sexual and gender minorities shapes mental health and well-being, with rapidly changing social and political forces necessitating ongoing research. This coproduced UK secondary school-based study aimed to understand (a) key components of mentally, socially and emotionally healthy school environments for LGBTQ+ students considerate of intersecting minoritised identities; (b) staff information, skills and capacity needs and (c) factors influencing uptake and implementation. Online interviews and focus groups were conducted with 63 participants (22 staff, 32 students (aged 13-19 years), and 9 training providers), diverse in relation to gender and sexual identity, ethnicity, religious and social context. Data were analysed thematically. One overarching theme captured the need for an intersectionality-informed, contextually adaptable, whole school approach which 'shifts the narrative' away from deficit thinking, challenging prevailing cis/heteronormative and White norms. This underpinned four themes: (1) 'Feeling safe, seen and celebrated: embedding intersectional signs, signals and symbols', (2) 'Everyone's business: the need for collaboration', (3) 'Embedding a culture of change', and (4) 'Re-locating the problem: challenging deficit thinking'. Contextually diverse research is needed which critically addresses ways in which social power enacted interpersonally and structurally serves to hinder schools from enacting LGBTQ+ inclusivity. Evidence to inform and develop implementation strategies for institutional changes and to advocate for wider socio-political support is also key to mitigate the potential for widening inequities linked to inequitable school environments., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Morgan 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: Dyslipoproteinemia often involves simultaneous derangements of multiple lipid traits. We aimed to evaluate the phenotypic and genetic characteristics of combined lipid disturbances in a general population-based cohort., Methods: Among UK Biobank participants without prevalent coronary artery disease, we used blood lipid and apolipoprotein B concentrations to ascribe individuals into 1 of 6 reproducible and mutually exclusive dyslipoproteinemia subtypes. Incident coronary artery disease risk was estimated for each subtype using Cox proportional hazards models. Phenome-wide analyses and genome-wide association studies were performed for each subtype, followed by in silico causal gene prioritization and heritability analyses. Additionally, the prevalence of disruptive variants in causal genes for Mendelian lipid disorders was assessed using whole-exome sequence data., Results: Among 450 636 UK Biobank participants: 63 (0.01%) had chylomicronemia; 40 005 (8.9%) had hypercholesterolemia; 94 785 (21.0%) had combined hyperlipidemia; 13 998 (3.1%) had remnant hypercholesterolemia; 110 389 (24.5%) had hypertriglyceridemia; and 49 (0.01%) had mixed hypertriglyceridemia and hypercholesterolemia. Over a median (interquartile range) follow-up of 11.1 (10.4-11.8) years, incident coronary artery disease risk varied across subtypes, with combined hyperlipidemia exhibiting the largest hazard (hazard ratio, 1.92 [95% CI, 1.84-2.01]; P =2×10 -16 ), even when accounting for non-HDL-C (hazard ratio, 1.45 [95% CI, 1.30-1.60]; P =2.6×10 -12 ). Genome-wide association studies revealed 250 loci significantly associated with dyslipoproteinemia subtypes, of which 72 (28.8%) were not detected in prior single lipid trait genome-wide association studies. Mendelian lipid variant carriers were rare (2.0%) among individuals with dyslipoproteinemia, but polygenic heritability was high, ranging from 23% for remnant hypercholesterolemia to 54% for combined hyperlipidemia., Conclusions: Simultaneous assessment of multiple lipid derangements revealed nuanced differences in coronary artery disease risk and genetic architectures across dyslipoproteinemia subtypes. These findings highlight the importance of looking beyond single lipid traits to better understand combined lipid and lipoprotein phenotypes and implications for disease risk., Competing Interests: P. Natarajan reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/ Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/ Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio, scientific co-founder of TenSixteen Bio, equity in MyOme, Preciseli, and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals, all unrelated to the resent work. The other authors report no conflicts.

Introduction: The issue of how emergency services (police, fire, ambulance, local authorities) respond to pandemics has received greater research focus recently in relation to the COVID-19 outbreak, which saw agencies going beyond usual roles to support communities for prolonged periods. A critical appraisal is needed of this published evidence to take stock of what is known about the effectiveness of emergency service response to Covid-19., Method: A scoping review of scientific and grey literature identified 17 qualitative (N = 9), quantitative (N = 6), or mixed methods (N = 2) studies from across the UK and internationally that focus on the effectiveness of emergency service response to the Covid-19 outbreak. A narrative review was conducted using an interpretive approach. Papers were read, summarised, and then sorted into inductive themes that addressed some aspect of the review question. Eight critical themes emerged from the narrative review., Results: Across countries, emergency services were required to quickly adapt working practices to reduce spread of infection, support partner agencies facing unprecedented demands, and make effective use of limited resources. Use of technology, access to timely, accurate and relevant information, strong leadership, prior experience, and emergency training were critical to this. However, most research is descriptive rather than evaluative., Conclusions: Overall, findings highlight the need for further research that examines what mechanisms facilitate and hinder emergency response to pandemics. This scoping review provides a knowledge framework for informing future research that can support emergency services in preparing for events of national and international significance., (© 2024 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.)

Background: Breastfeeding impacts positively on multiple health outcomes, but < 50% of UK women breastfeed at 8 weeks. Women with long-term conditions face additional challenges in breastfeeding., Objectives: To synthesise global and UK evidence to co-create an implementation and evaluation toolkit for cost-effective breastfeeding support in the NHS., Design: Evidence syntheses with stakeholder engagement., Review Methods: Systematic reviews examined effectiveness of breastfeeding support for (1) healthy women and (2) women with long-term conditions using Cochrane Pregnancy and Childbirth Group methods. Mixed-methods systematic reviews synthesised process evaluations of effective breastfeeding support interventions for healthy women and experiences of receiving/providing support for breastfeeding women with long-term conditions. Cross-study synthesis integrated qualitative and quantitative findings. Systematic reviews synthesised evidence on the incremental costs and cost-effectiveness of breastfeeding support following National Institute for Health and Care Excellence guidance. All searches were conducted from May 2021 to October 2022. Stakeholder engagement and toolkit development comprised online discussions, a modified Delphi study, focus groups and four workshops. Participants were 23 stakeholders, 16 parents in the parents' panels, 15 women in the focus groups and 87 stakeholders who attended the workshops., Results: We found considerably more interventions designed for healthy women (review 1) than aimed at women with long-term conditions (reviews 1 and 4); approximately half of the studies were targeted at groups at higher risk of poor breastfeeding outcomes, and the impact of support may be different in these populations. Despite this, studies from review 2 found that women perceived the provision of support as positive, important and needed. Studies from review 5 echoed a range of suggestions from participants regarding potential strategies to improve breastfeeding support, with the most widely reported being the need to acknowledge the role and influence of other sources of support (e.g. partners, family, friends, peers, external professionals, web-based resources) and involving these sources in the provision of breastfeeding support for women with long-term conditions. In reviews 3 and 6, there was uncertainty about the cost-effectiveness of breastfeeding support interventions due to the limited number of studies and lack of good-quality evidence., Limitations: There was a lack of evidence for the effectiveness and cost-effectiveness of breastfeeding interventions in the UK. There was often insufficient information reported about intervention characteristics., Conclusions: 'Breastfeeding only' support probably reduces the number of women stopping any or exclusive breastfeeding. The evidence for 'breastfeeding plus' interventions is less consistent, but these may reduce the number of women stopping exclusive breastfeeding at 4-6 weeks and at 6 months. We found no evidence of differential intervention effects regarding mode of provision or provider. Cost-effectiveness is uncertain due to the lack of good-quality evidence. Key enablers of successful implementation were responsiveness and tailoring of interventions to both women's and supporters' needs. Breastfeeding support as delivered in the included studies probably has little to no effect on breastfeeding outcomes for women with long-term conditions. The mixed-methods synthesis and stakeholder work identified that existing interventions may not address the complex needs of these women. The main study output is a co-produced toolkit to guide implementation and evaluation of breastfeeding support services in the UK., Future Work: Evaluation of breastfeeding support for all women, particularly those at risk of poor breastfeeding outcomes (e.g. long-term conditions, deprivation). This could involve tailoring the toolkit to local contexts via implementation and effectiveness studies or using quality improvement studies., Study Registration: This study is registered as PROSPERO CRD42022337239, CRD42021229769 and CRD42022374509. The reviews of economic evidence were not registered; however, the review protocol can be accessed via the repository held by Queen's University Belfast Research Portal (https://pure.qub.ac.uk/)., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR130995) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 20. See the NIHR Funding and Awards website for further award information.

Background: Following Kabul's fall in August 2021, there was influx of Afghan refugees in the UK. Southampton's Bridging Hotel provided temporary shelter to 22 families, totaling 116 individuals. The Living Well Partnership (LWP); assumed primary care provision for these vulnerable residents facing health inequalities., Aim: Enhancing refugee healthcare access and integration into the NHS system. Improving healthcare education, boosting confidence in appropriate healthcare use, and utilisation of electronic consultations effectively., Method: Working with the local authorities, primary care services were brought to the hotel. Regular 3-hour drop-in sessions with a health and wellbeing coach were established and attended by residents. Non-identifiable data was recorded in individual patient care records and summarised quantitatively.  Qualitative data was collected via a pre-established questionnaire during the sessions.   RESULTS: Identified issues included language barriers, mental health problems, infectious diseases, contraception, and healthcare access. Language barriers were addressed with interpreters. Fifty-nine patients accessed support services, with 13 benefiting from e-consultations, and nine requiring on-site medical consultations in a 3-month period. Mental health support and infectious disease referrals were facilitated. Access challenges were mitigated by transitioning to e-consultations or face-to-face appointments. Outcomes included improved patient independence, awareness of healthcare processes, familiarity with LWP services, and confidence in navigating the NHS., Conclusion: A multifaceted approach is vital for addressing language and access barriers for refugees. Providing educational resources through facilitated groups empowered refugees and improved healthcare access. This initiative highlights the importance of organised support for vulnerable populations during crises and can be applied more widely., (© British Journal of General Practice 2024.)

Background: Smokers are at increased risk of type 2 diabetes (T2D), but the underlying mechanisms are unclear. We investigated if the smoking-T2D association is mediated by alterations in the metabolome and assessed potential interaction with genetic susceptibility to diabetes or insulin resistance., Methods: In UK Biobank (n = 93,722), cross-sectional analyses identified 208 metabolites associated with smoking, of which 131 were confirmed in Mendelian Randomization analyses, including glycoprotein acetyls, fatty acids, and lipids. Elastic net regression was applied to create a smoking-related metabolic signature. We estimated hazard ratios (HR) of incident T2D in relation to baseline smoking/metabolic signature and calculated the proportion of the smoking-T2D association mediated by the signature. Additive interaction between the signature and genetic risk scores for T2D (GRS-T2D) and insulin resistance (GRS-IR) on incidence of T2D was assessed as relative excess risk due to interaction (RERI)., Findings: The HR of T2D was 1·73 (95% confidence interval (CI) 1·54 - 1·94) for current versus never smoking, and 38·3% of the excess risk was mediated by the metabolic signature. The metabolic signature and its mediation role were replicated in TwinGene. The metabolic signature was associated with T2D (HR: 1·61, CI 1·46 - 1·77 for values above vs. below median), with evidence of interaction with GRS-T2D (RERI: 0·81, CI: 0·23 - 1·38) and GRS-IR (RERI 0·47, CI: 0·02 - 0·92)., Interpretation: The increased risk of T2D in smokers may be mediated through effects on the metabolome, and the influence of such metabolic alterations on diabetes risk may be amplified in individuals with genetic susceptibility to T2D or insulin resistance., (© 2024. The Author(s).)

Objective: To examine the impact of a Patient and Public Involvement exercise on the development of British Congenital Cardiac Association Fetal Cardiology Standards 2021., Design: Open-ended, semi-structured interviews were undertaken to inform the design of a study to improve the quality of parents' experiences during antenatal and perinatal care of their child with CHD. This Patient and Public Involvement exercise was used to inform the final version of the drafted 'Standards'., Setting: One-on-one interviews with parents who responded to a request on the closed Facebook page of the user group "Little Hearts Matter": "Would you be interested in helping us to design a study about parents' experience on learning that their child had CHD"?, Patients: Parents of children with single ventricle CHD., Results: Twenty-one parents (18 mothers, 3 fathers) participated. Parents responses were reported to have variably reinforced, augmented, and added specificity in the later stages of drafting to six of the seven subsections of Section C Information and Support for Parents including: "At the time of the Scan"; "Counselling following the identification of an abnormality"; "Written information/resources"; "Parent support"; "Communication with other teams and ongoing care"; and "Bereavement support"., Conclusions: This Patient and Public Involvement exercise successfully informed the development of Standards after the initial drafting. It contributed to the establishment of face validity of the 'Standards', especially when consistent with what is reported in the literature. Further research is needed to explore approaches to involving and standardising Patient and Public Involvement in the development of clinical standards.

Purpose: This study examines the association between mental health problems in adolescence and general practice (GP) costs during adulthood up to age 50 in the UK., Methods: We conducted secondary analyses of three British birth cohorts (individuals born in single weeks in 1946, 1958 and 1970). Data for the three cohorts were analysed separately. All respondents who participated in the cohort studies were included. Adolescent mental health status was assessed in each cohort using the Rutter scale (or, for one cohort, a forerunner of that scale) completed in interviews with parents and teachers when cohort members were aged around 16. Presence and severity of conduct and emotional problems were modelled as independent variables in two-part regression models in which the dependent variable was costs of GP services from data collection sweeps up to mid-adulthood. All analyses were adjusted for covariates (cognitive ability, mother's education, housing tenure, father's social class and childhood physical disability)., Results: Adolescent conduct and emotional problems, particularly when coexisting, were associated with relatively high GP costs in adulthood up to age 50. Associations were generally stronger in females than males., Conclusion: Associations between adolescent mental health problems and annual GP cost were evident decades later, to age 50, suggesting that there could be significant future savings to healthcare budgets if rates of adolescent conduct and emotional problems could be reduced., Trial Registration: Not applicable., (© 2023. The Author(s).)

Rationale & Objective: Individuals with a low estimated glomerular filtration rate (eGFR) are at a high risk of death. However, the causes underpinning this association are largely uncertain. This study aimed to assess the causal relationship of low eGFR with all-cause and cause-specific mortality., Study Design: Retrospective cohort study incorporating Mendelian randomization (MR)., Setting & Participants: Individual-level data from 436,214 White participants (54.3% female; aged 56.8±8.0 years) included in the UK Biobank., Exposures: eGFR estimated using cystatin C (eGFR cyst )., Outcomes: The outcomes of interest included all-cause mortality, cardiovascular mortality, cancer mortality, infection mortality, and other-cause mortality., Analytical Approach: Cox proportional hazards analysis for the conventional observational analyses; linear and nonlinear MR analyses implemented using genetic allele scores as instrumental variables representing kidney function to estimate the effect of kidney function on the survival outcomes., Results: During a median follow-up of 12.1 years, there were 30,489 deaths, 6,098 of which were attributed to cardiovascular events, 15,538 to cancer, 1,516 to infection, and 7,227 to other events. In the conventional observational analysis, eGFR cyst exhibited a nonlinear association with all the outcomes. MR analysis suggested that a genetically predicted lower eGFR cyst was linearly associated with a higher rate of cardiovascular mortality (HR, 1.43; 95% CI, 1.18-1.75) across the entire measurement range (every 10-mL/min/1.73m 2 decrement). Nonetheless, no causal associations between eGFR cyst and all-cause mortality (HR, 1.07; 95% CI, 0.98-1.17) or any types of noncardiovascular mortality were detected., Limitations: Potential misclassification of the actual cause of death, a nonrepresentative sample, and potential error in the interpretation of the magnitude of associations generated in MR analyses., Conclusions: These findings suggest a potential causal association between low eGFR and cardiovascular mortality in the general population, but no causal relationship with all-cause mortality or noncardiovascular mortality was observed. Further studies in other populations are warranted to confirm these findings., Plain-Language Summary: This study investigated the existence of a causal relationship between lower kidney function and death of different causes. Using data from 436,214 people in the United Kingdom, we applied conventional statistical analyses and those incorporating genetic data to implement Mendelian randomization, an approach that estimates causal associations. The observational analysis showed a nonlinear association between kidney function and various types of mortality outcomes. However, Mendelian randomization analysis suggested a linear increase in the risk of cardiovascular mortality with lower kidney function, but no causal link between the level of kidney function and all-cause or noncardiovascular mortality was identified. Managing kidney health may help reduce cardiovascular mortality, but caution is needed in interpreting the magnitudes of these results. Further validation in other populations and in those with advanced kidney failure is needed., (Copyright © 2023 The Authors. Published by Elsevier Inc. 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.)

Objective: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS., Methods: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome-wide association study and was tested using regression., Results: A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta-analyses identified that in MS, each 1-SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09-1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease., Interpretation: Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Informal carers play an important role in the everyday care of patients and the delivery of health care services. They aid patients in transportation to and from appointments, and they provide assistance during the appointments (eg, answering questions on the patient's behalf). Video consultations are often seen as a way of providing patients with easier access to care. However, few studies have considered how this affects the role of informal carers and how they are needed to make video consultations safe and feasible., Objective: This study aims to identify how informal carers, usually friends or family who provide unpaid assistance, support patients and clinicians during video consultations., Methods: We conducted an in-depth analysis of the communication in a sample of video consultations drawn from 7 clinical settings across 4 National Health Service Trusts in the United Kingdom. The data set consisted of 52 video consultation recordings (of patients with diabetes, gestational diabetes, cancer, heart failure, orthopedic problems, long-term pain, and neuromuscular rehabilitation) and interviews with all participants involved in these consultations. Using Linguistic Ethnography, which embeds detailed analysis of verbal and nonverbal communication in the context of the interaction, we examined the interactional, technological, and clinical work carers did to facilitate video consultations and help patients and clinicians overcome challenges of the remote and video-mediated context., Results: Most patients (40/52, 77%) participated in the video consultation without support from an informal carer. Only 23% (12/52) of the consultations involved an informal carer. In addition to facilitating the clinical interaction (eg, answering questions on behalf of the patient), we identified 3 types of work that informal carers did: facilitating the use of technology; addressing problems when the patient could not hear or understand the clinician; and assisting with physical examinations, acting as the eyes, ears, and hands of the clinician. Carers often stayed in the background, monitoring the consultation to identify situations where they might be needed. In doing so, copresent carers reassured patients and helped them conduct the activities that make up a consultation. However, carers did not necessarily help patients solve all the challenges of a video consultation (eg, aiming the camera while laying hands on the patient during an examination). We compared cases where an informal carer was copresent with cases where the patient was alone, which showed that carers provided an important safety net, particularly for patients who were frail and experienced mobility difficulties., Conclusions: Informal carers play a critical role in making video consultations safe and feasible, particularly for patients with limited technological experience or complex needs. Guidance and research on video consulting need to consider the availability and work done by informal carers and how they can be supported in providing patients access to digital health care services., (©Lucas Martinus Seuren, Sara Shaw. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.05.2024.)

Background: The extent to which the relationships between clinical risk factors and coronary artery disease (CAD) are altered by CAD polygenic risk score (PRS) is not well understood. Here, we determine whether the interactions between clinical risk factors and CAD PRS further explain risk for incident CAD., Methods: Participants were of European ancestry from the UK Biobank without prevalent CAD. An externally trained genome-wide CAD PRS was generated and then applied. Clinical risk factors were ascertained at baseline. Cox proportional hazards models were fitted to examine the incident CAD effects of CAD PRS, risk factors, and their interactions. Next, the PRS and risk factors were stratified to investigate the attributable risk of clinical risk factors., Findings: A total of 357,144 individuals of European ancestry without prevalent CAD were included. During a median of 11.1 years of follow-up (interquartile range 10.4-14.1 years), CAD PRS was associated with 1.35-fold (95% confidence interval [CI] 1.332-1.368) risk per SD for incident CAD. The prognostic relevance of the following risk factors was relatively diminished for those with high CAD PRS on a continuous scale: type 2 diabetes (hazard ratio [HR] interaction 0.91, 95% CI interaction 0.88-0.94), increased body mass index (HR interaction 0.97, 95% CI interaction 0.96-0.98), and increased C-reactive protein (HR interaction 0.98, 95% CI interaction 0.96-0.99). However, a high CAD PRS yielded joint risk increases with low-density lipoprotein cholesterol (HR interaction 1.05, 95% CI interaction 1.04-1.06) and total cholesterol (HR interaction 1.05, 95% CI interaction 1.03-1.06)., Conclusion: The CAD PRS is associated with incident CAD, and its application improves the prognostic relevance of several clinical risk factors., Funding: P.N. (R01HL127564, R01HL151152, and U01HG011719) is supported by the National Institutes of Health., Competing Interests: Declaration of interests P.N. reports grants from Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis; personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech/Roche, Novartis, and TenSixteen Bio; equity in geneXwell, TenSixteen Bio, and Vertex; and spousal employment at Vertex. P.N. is a cofounder of TenSixteen Bio, a company focusing on somatic mutations in blood cells to reduce risks for blood cancer and atherosclerotic cardiovascular disease; his interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict-of-interest policies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This process evaluation was conducted in parallel to the randomised controlled feasibility trial of NIDUS-Professional, a manualised remote dementia training intervention for homecare workers (HCWs), delivered alongside an individualised intervention for clients living with dementia and their family carers (NIDUS-Family). The process evaluation reports on: (i) intervention reach, dose and fidelity; (ii) contexts influencing agency engagement and (iii) alignment of findings with theoretical assumptions about how the intervention might produce change., Methods: We report proportions of eligible HCWs receiving any intervention (reach), number of sessions attended (dose; attending ≥4/6 main sessions was predefined as adhering), intervention fidelity and adherence of clients and carers to NIDUS-Family (attending all 6-8 planned sessions). We interviewed HCWs, managers, family carers and facilitators. We integrated and thematically analysed, at the homecare agency level, qualitative interview and intervention recording data., Results: 32/141 (23%) of eligible HCWs and 7/42 (17%) of family carers received any intervention; most who did adhered to the intervention (89% and 71%). Intervention fidelity was high. We analysed interviews with 20/44 HCWs, 3/4 managers and 3/7 family carers, as well as intervention recordings involving 32/44 HCWs. All agencies reported structural challenges in supporting intervention delivery. Agencies with greater management buy-in had higher dose and reach. HCWs valued NIDUS-Professional for enabling group reflection and peer support, providing practical, actionable care strategies and increasing their confidence as practitioners., Conclusion: NIDUS-Professional was valued by HCWs. Agency management, culture and priorities were key barriers to implementation; we discuss how to address these in a future trial., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

The UK is experiencing a nursing shortage, making it challenging to maintain the staffing levels required to deliver effective patient care. One way of enhancing the care delivered by the existing workforce could be to optimise nurse productivity; however, previous efforts to do this have been largely ineffective, due in part to a focus on the processes of care delivery rather than the nursing activities within these processes. In this article, the author explores the concept of nurse productivity and suggests that enhancing productivity requires the identification of nursing activities and consideration of how these may be undertaken in a more time-efficient manner - or removed altogether. The author discusses two such activities: intentional (hourly) rounding, and fixed-time manual vital signs for patients on general wards. The author also considers the potential of using automatic continuous remote monitoring on general hospital wards to free up nurses' time for other care activities., Competing Interests: None declared, (© 2024 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)