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Several letters to the editor are presented which express the authors' opinion regarding the decision of the Department for Environment, Food, and Rural Affairs (Defra) to reduce the price for Merial's bluetongue virus serotype 8 (BTV-8) vaccine.

Introduction: Health inequality is a global public health challenge, limited by insufficient high-quality data and analysis. Musculoskeletal (MSK) pain disorders are more prevalent among ethnic minority groups disproportionately affected by socioeconomic disparities and poor health outcomes. Ethnicity data collection enables NHS organisations and policymakers to understand specific healthcare needs and ensure equitable access and care provision., Objective: To understand the baseline clinical characteristics across ethnic population groups accessing MSK care at Sandwell and West Birmingham (SWB) NHS Trust., Methods: Retrospective analysis of routine data collected using patient self-report surveys (August 2020-February 2023). Core metrics included demographics, pain characteristics, and Patient Reported Outcome Measures (PROMs) including the Musculoskeletal Health Questionnaire (MSK-HQ) and Numeric Pain Rating Scale (NPRS). Descriptive statistics and statistical tests were undertaken, with means, percentage values and variation by ethnic groups across baseline MSK-HQ and pain scores reported., Results: Survey data were provided by 13,248 patients, with 7295 (55.06%) stating their ethnicity. Statistical differences were found between baseline MSK-HQ and NPRS scores between ethnic groups. The mean MSK-HQ score was 24.1 overall, lowest in the Asian group (22.3) and highest in the Mixed group (24.8). Mean baseline pain intensity was (7.8), highest in the Asian group (8.3). One or more comorbidities were present in 46% of patients, with the highest percentage in the White and Black groups sequentially., Conclusion: Baseline health inequalities exist among ethnic groups accessing the SWB MSK service. Disparities may be associated with patient or system barriers and require further exploration., (© 2024 The Author(s). Musculoskeletal Care published by John Wiley & Sons Ltd.)

Introduction: Spinal cord stimulation (SCS) is a well-established treatment for chronic pain and is supported by numerous studies. However, some recent articles have questioned its efficacy. This article examines a cohort of >1800 patients with SCS from the UK and Ireland National Neuromodulation Registry. It is intended to provide a "real-world" assessment of efficacy and compare its effects with other procedures performed for painful indications., Materials and Methods: Quality of life (QoL) data (EuroQoL five-level [EQ5D]) and demographic data were extracted from the National Neuromodulation Registry for all patients (N = 1811) who underwent SCS for chronic pain in 27 centers in the UK between February 2018 and July 2022. These were compared with data from the published literature for other commonly performed elective surgical procedures., Results: The EQ5D utility index increased by a mean of 0.202 in the 1236 patients with paired pre- and postoperative utility scores. The median utility was 0.263 (interquartile range [IQR] = 0.384; n = 1811) preoperatively, whereas at six months after the operation, it was 0.550 (IQR = 0.396; n = 1025), p < 0.0001, Wilcoxon rank sum test. The median utility score at 12 months postoperation was 0.548 (IQR = 0.417; n = 970). There was no difference in utility scores at six months and 12 months after implantation (p = 0.15, Wilcoxon rank sum test). There was a significant improvement in QoL in all five domains of the five-level EQ5D tool at six months after baseline (p < 0.01, for all subcategories), and this was sustained at one year after implantation. The baseline utility was lower than in patients who underwent elective surgery for other painful conditions, and the absolute (and proportionate) increase in utility produced by SCS was greater than that achieved with most other interventions., Conclusions: SCS increases the QoL in patients requiring surgery for pain. Similar results were seen regardless of SCS indication. When comparing analogous data bases, SCS produces a greater percentage improvement in EQ5D utility than do many other elective surgical procedures for painful conditions, including spinal surgery and some joint replacements., Competing Interests: Conflict of Interest Ganesan Baranidharan has received consulting fees from Abbott, Boston Scientific, Medtronic, and Saluda Medical; has received honoraria from Abbott, Boston Scientific, Mainstay Medical, Saluda Medical, Stryker, and Nevro Corp; and sits on the international data safety board for Saluda Medical. Stana Bojanić sits on the board of the International Neuromodulation Society. Sam Eldabe has received departmental grants from Boston Scientific and Saluda Medical; and consulting fees from Medtronic, Saluda Medical, Mainstay Medical, and Esteve Pharmaceutical. James J. FitzGerald has received institutional research grants from Merck and UCB; consulting fees from Abbott and Lilly; educational honoraria from Abbott; and advisory board fees from Medtronic and Abbott. Sarah Love-Jones has received travel honoraria from Boston Scientific, Nevro Corp, Abbott, Medtronic, and Saluda Medical; research grants from Boston Scientific, Mainstay Medical, Nevro Corp, Saluda Medical, Nalu Medical, and Abbott; and sits on the medical advisory board for Boston Scientific, Nevro Corp, Saluda Medical, Medtronic, and Pfizer. Vivek Mehta has received consulting fees from Mainstay Medical, Lundbeck, Pfizer, Boston Scientific, and Medtronic; holds an advisory position with Medtronic, Pfizer, and Man & Science; and sits on the board of the Neuromodulation Society of UK and Ireland, and the Education Committee of the North American Neuromodulation Society. Simon Thomson has received grants, honoraria, and consulting fees from Boston Scientific, Mainstay Medical, and Saluda Medical and holds an advisory position with Galvani Bioelectronics. The remaining authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Engaging in clinical research includes confronting challenges about the uncertainty around outcomes and ramifications the results may have on practice. This is pertinent for osteopathy where little is known about the experiences of osteopaths involved in clinical trials. The aim of this study was to explore the lived experience of osteopaths who participated in a randomised controlled trial for infantile colic. The study was informed by a principles-based approach to clinical ethics and their application to practice., Design: Qualitative study using semi-structured interviews and reflexive thematic analysis., Setting: An international two-arm pragmatic randomised controlled trial (the CUTIES trial) to evaluate the effectiveness of osteopathic care for infantile colic., Methods: A principles-based approach to clinical ethics and their application to practice for osteopaths asked to make decisions about participating in a clinical trial was used. Osteopaths from the UK and Australia who completed the CUTIES trial training were invited to be interviewed about their experiences, regardless of whether they went on to recruit infants in the trial. Interviewees were asked about their reasons for wanting to participate in the CUTIES trial, why they decided to continue or not to continue in the trial and, for those who completed the trial, their personal experiences as participants in the trial. Data were analysed using reflexive thematic analysis., Results: Nine osteopaths were interviewed. Three themes were identified from the data: Paradigm dilemma - observed clinical outcomes vs scientific evidence for mechanism of effects; trial-related ethical dilemmas; and trial outcome dilemmas., Conclusion: Participating in the CUTIES trial required osteopaths to overcome clinical ethical dilemmas for the benefit of patients, the research, and the profession., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the genetic basis of COVID-19 vaccine seroconversion is crucial to study the role of genetics on vaccine effectiveness. In our study, we used UK Biobank data to find the genetic determinants of COVID-19 vaccine-induced seropositivity and breakthrough infections. We conducted four genome-wide association studies among vaccinated participants for COVID-19 vaccine seroconversion and breakthrough susceptibility and severity. Our findings confirmed a link between the HLA region and seroconversion after the first and second doses. Additionally, we identified 10 genomic regions associated with breakthrough infection (SLC6A20, ST6GAL1, MUC16, FUT6, MXI1, MUC4, HMGN2P18-KRTCAP2, NFKBIZ and APOC1), and one with breakthrough severity (APOE). No significant evidence of genetic colocalisation was found between those traits. Our study highlights the roles of individual genetic make-up in the varied antibody responses to COVID-19 vaccines and provides insights into the potential mechanisms behind breakthrough infections occurred even after the vaccination., (© 2024. The Author(s).)

The transition of Freud's Die Traumdeutung into its first English language incarnation as The Interpretation of Dreams , translated by A.A. Brill, took several years to effect, the process being beset with conceptual, practical, legal, and political obstacles. Anxieties over possible obscenity charges in Britain led to novel forms of censorship being applied to the first edition by its London publisher in 1913, while issues relating to the politics of translation and local British efforts to standardise psychoanalytic nomenclature would bedevil the text over its first two decades. In the context of the launch of the Revised Standard Edition ( RSE ), the present paper reveals these earlier issues for the first time. Having then considered the book's reception in both Britain and the United States, its sales and varying editions, the paper concludes with a discussion of the covert and contentious reediting of the work's third English edition, published in 1933. The shadow of this history inevitably falls on the RSE .

Objective: The chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample., Design: Cross-sectional study., Setting: Community-dwelling cohort., Participants: Twins from the TwinsUK cohort PRIMARY AND SECONDARY OUTCOME MEASURES: We compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing., Results: In N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance., Conclusion: Our findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Pulmonary fibrosis results from alveolar injury, leading to extracellular matrix remodelling and impaired lung function. This study aimed to classify patients with pulmonary fibrosis according to blood biomarkers to differentiate distinct disease patterns, known as endotypes., Methods: In this cluster analysis, we first classified patients from the PROFILE study, a multicentre, prospective, observational cohort of individuals with incident idiopathic pulmonary fibrosis or non-specific interstitial pneumonia in the UK (Nottingham University Hospitals, Nottingham; and Royal Brompton Hospital, London). 13 blood biomarkers representing extracellular matrix remodelling, epithelial stress, and thrombosis were measured by ELISA in the PROFILE study. We classified patients by unsupervised consensus clustering. To evaluate generalisability, a machine learning classifier trained on biomarker signatures derived from consensus clustering was applied to a replication dataset from the Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR). Biomarker associations with mortality and change in percentage of predicted forced vital capacity (FVC%) were assessed, adjusting for age, gender, baseline FVC%, and antifibrotic treatment and steroid treatment before and after baseline. Mortality risk associated with the clusters in the PROFILE cohort was evaluated with Cox proportional hazards models, and mixed-effects models were used to analyse how clustering was associated with longitudinal FVC% in the PROFILE and AIPFR cohorts., Findings: 455 of 580 participants from the PROFILE study (348 [76%] men and 107 [24%] women; mean age 72·4 years [SD 8·3]) were included in the analysis. Within this group, three clusters were identified based on blood biomarkers. A basement membrane collagen (BM) cluster (n=248 [55%]) showed high concentrations of PRO-C4, PRO-C28, C3M, and C6M, whereas an epithelial injury (EI) cluster (n=109 [24%]) showed high concentrations of MMP-7, SP-D, CYFRA211, CA19-9, and CA-125. The third cluster (crosslinked fibrin [XF] cluster; n=98 [22%]) had high concentrations of X-FIB. In the replication dataset (117 of 833 patients from AIPFR; 87 [74%] men and 30 [26%] women; mean age 72·9 years [SD 7·9]), we identified the same three clusters (BM cluster, n=93 [79%]; EI cluster, n=8 [7%]; XF cluster, n=16 [14%]). These clusters showed similarities with clusters in the PROFILE dataset regarding blood biomarkers and phenotypic signatures. In the PROFILE dataset, the EI and XF clusters were associated with increased mortality risk compared with the BM cluster (EI vs BM: adjusted hazard ratio [HR] 1·88 [95% CI 1·42-2·49], p<0·0001; XF vs BM: adjusted HR 1·53 [1·13-2·06], p=0·0058). The EI cluster showed the greatest annual FVC% decline, followed by the BM and XF clusters. A similar FVC% decline pattern was observed in these clusters in the AIPFR replication dataset., Interpretation: Blood biomarker clustering in pulmonary fibrosis identified three distinct blood biomarker signatures associated with lung function and prognosis, suggesting unique pulmonary fibrosis biomarker patterns. These findings support the presence of pulmonary fibrosis endotypes with the potential to guide targeted therapy development., Funding: None., Competing Interests: Declaration of interests YM reports personal fees for advisory board work from Boehringer Ingelheim and Roche, outside the submitted work. TJC reports fees for work on scientific advisory boards for Boehringer Ingelheim, Roche, Bristol Myers Squibb, Vicore, Pliant, Endeavour Bioscience, and DevPro, and grants from Boehringer Ingelheim, Roche, Bristol Myers Squibb, Galapagos, and Biogen, outside the submitted work. DJL and JMBS are employees and shareholders of Nordic Bioscience. MAK is an employee and shareholder of Nordic Bioscience and holds patents relating to neoepitopes. AUW reports receiving consulting, lecture, or educational fees from Boehringer Ingelheim and Veracyte, and holds the honorary position of President of the World Association of Sarcoidosis and Other Granulomatous Diseases. LVW reports funding from, consultancy for, or collaboration with GSK, Genentech, Orion Pharma, and Galapagos. PLM has received, via his institution, industry-academic funding from AstraZeneca and has received speaker and consultancy fees from Boehringer Ingelheim and Roche, outside the submitted work. TMM has received industry-academic funding from GSK R&D and UCB, and consultancy or speaker's fees from Apellis, AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Galapagos, GSK R&D, Indalo, Pliant, ProMetic, Roche, Samumed, UCB, and Celgene. RGJ has grants or contracts from AstraZeneca, Biogen, Galecto, GSK, Nordic Bioscience, Redx, and Pliant, with all payments going to his institutions. RGJ has also served as a consultant to Bristol Myers Squibb, Chiesi, Daewoong, Veracyte, Resolution Therapeutics, and Pliant, has received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Chiesi, Roche, PatientMPower, and AstraZeneca, has participated on a data safety monitoring board or advisory board for Boehringer Ingelheim, Galapagos, and Vicore, and has an unpaid role in an advisory board at NuMedii. RGJ is also a trustee of Action for Pulmonary Fibrosis. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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

Effective prevention strategies for post-COVID complications are crucial for patients, clinicians, and policy makers to mitigate their cumulative burden. This study evaluated the association of modifiable lifestyle factors (smoking, alcohol intake, BMI, physical activity, sedentary time, sleep duration, and dietary habits) with COVID-19 multisystem sequelae, death, and hospitalization in the UK Biobank cohort (n = 68,896). A favorable lifestyle (6-10 healthy factors; 46.4%) was associated with a 36% lower risk of multisystem sequelae (HR, 0.64; 95% CI, 0.58-0.69; ARR at 210 days, 7.08%; 95% CI, 5.98-8.09) compared to an unfavorable lifestyle (0-4 factors; 12.3%). Risk reductions spanned all 10 organ systems, including cardiovascular, coagulation, metabolic, gastrointestinal, kidney, mental health, musculoskeletal, respiratory disorders, and fatigue. This beneficial effect was largely attributable to direct lifestyle impacts independent of corresponding pre-infection comorbidities (71% for any sequelae). A favorable lifestyle was also related to the risk of post-COVID death (HR 0.59, 0.52-0.66) and hospitalization (HR 0.78, 0.73-0.84). These associations persisted across acute and post-acute infection phases, irrespective of hospitalization status, vaccination, or SARS-CoV-2 variant. These findings underscore the clinical and public health importance of adhering to a healthy lifestyle in mitigating long-term COVID-19 adverse impacts and enhancing future pandemic preparedness., (© 2024. The Author(s).)

Background: The prevalence of depression in Multiple Sclerosis (MS) is often assessed by administering patient reported outcome measures (PROMs) examining depressive symptomatology to population cohorts; a recent review summarised 12 such studies, eight of which used the Hospital Anxiety and Depression Scale-Depression (HADS-D). In clinical practice, depression is diagnosed by an individual structured clinical interview; diagnosis often leads to treatment options including antidepressant medication. It follows that an MS population will include those whose current depressive symptoms meet threshold for depression diagnosis, plus those who previously met diagnostic criteria for depression and have been treated such that depressive symptoms have improved below that threshold. We examined a large MS population to establish a multi-attribute estimate of depression, taking into account probable depression on HADS-D, as well as anti-depressant medication use and co-morbidity data reporting current treatment for depression. We then studied associations with demographic and health status measures and the trajectories of depressive symptoms over time., Methods: Participants were recruited into the UK-wide Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study, with demographic and disease data from clinical records, PROMs collected at intervals of at least 9 months, as well as co-morbidities and medication. Interval level conversions of PROM data followed Rasch analysis. Logistic regression examined associations of demographic characteristics and symptoms with depression. Finally, a group-based trajectory model was applied to those with depression., Results: Baseline data in 5633 participants showed the prevalence of depression to be 25.3 % (CI: 24.2-26.5). There were significant differences in prevalence by MS subtype: relapsing 23.2 % (CI: 21.8- 24.5), primary progressive 25.8 % (CI: 22.5-29.3), secondary progressive 31.5 % (CI: 29.0-34.0); disability: EDSS 0-4 19.2 % (CI: 17.8-20.6), EDSS ≥4.5 31.9 % (CI: 30.2-33.6); and age: 42-57 years 27.7 % (CI: 26.0-29.3), above or below this range 23.1 % (CI: 21.6-24.7). Fatigue, disability, self-efficacy and self esteem correlated with depression with a large effect size (>0.8) whereas sleep, spasticity pain, vision and bladder had an effect size >0.5. The logistic regression model (N = 4938) correctly classified 80 % with 93 % specificity: risk of depression was increased with disability, fatigue, anxiety, more comorbidities or current smoking. Higher self-efficacy or self esteem and marriage reduced depression. Trajectory analysis of depressive symptoms over 40 months in those with depression (N = 1096) showed three groups: 19.1 % with low symptoms, 49.2 % with greater symptoms between the threshold of possible and probable depression, and 31.7 % with high depressive symptoms. 29.9 % (CI: 27.6-32.3) of depressed subjects were untreated, conversely of those treated, 26.1 % still had a symptom level consistent with a probable case (CI: 23.5-28.9)., Conclusion: A multi-attribute estimate of depression in MS is essential because using only screening questionnaires, diagnoses or antidepressant medication all under-estimate the true prevalence. Depression affects 25.3 % of those with MS, almost half of those with depression were either untreated or still had symptoms indicating probable depression despite treatment. Services for depression in MS must be pro-active and flexible, recognising the heterogeneity of outcomes and reaching out to those with ongoing symptoms., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1 UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1 global strains, invasive M1 UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1 UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1 UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1 UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1 UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks., (© 2024. The Author(s).)

Introduction: Sickle cell disease (SCD) is one of the most common genetic disorders in the UK, with over 15 000 people affected. Proliferative sickle cell retinopathy (SCR) is a well-described complication of SCD and can result in significant sight loss, although the prevalence in the UK is not currently known. There are currently no national screening guidelines for SCR, with wide variations in the management of the condition across the UK., Methods and Analysis: The Sickle Eye Project is an epidemiological, cross-sectional, non-interventional study to determine the prevalence of visual impairment due to SCR and/or maculopathy in the UK. Haematologists in at least 16 geographically dispersed hospitals in the UK linked to participating eye clinics will offer study participation to consecutive patients meeting the inclusion criteria attending the sickle cell clinic. The following study procedures will be performed: (a) best corrected visual acuity with habitual correction and pinhole, (b) dilated slit lamp biomicroscopy and funduscopy, (c) optical coherence tomography (OCT), (d) OCT angiography where available, (e) ultrawide fundus photography, (f) National Eye Institute Visual Function Questionnaire-25 and (g) acceptability of retinal screening questionnaire. The primary outcome is the proportion of people with SCD with visual impairment defined as logarithm of the minimum angle of resolution ≥0.3 in at least one eye. Secondary outcomes include the prevalence of each stage of SCR and presence of maculopathy by age and genotype; correlation of stage of SCR and maculopathy to severity of SCD; the impact of SCR and presence of maculopathy on vision-related quality of life; and the acceptability to patients of routine retinal imaging for SCR and maculopathy., Ethics and Dissemination: Ethical approval was obtained from the South Central-Oxford A Research Ethics Committee (REC 23/SC/0363). Findings will be reported through academic journals in ophthalmology and haematology., Competing Interests: Competing interests: CD reports receiving institutional research grant, consulting fees and speaker fees from Roche. KB and JT have received consulting and speaker fees from Roche., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The aim of this study was to explore motivations women describe for using pornography. A qualitative online interview study was conducted with 30 women ( Mean age 30.23, range 20-47; residing in the UK and in Greece; of varied sexual orientations and relationship status) about their pornography use, motivations for use, and preferences. Reflexive thematic analysis was used. Results were organized into four themes: Sexual Precursors, Non-sexual Precursors, Intended Outcomes, and Unintended Outcomes. The findings highlight that pornography use for women can have both positive and negative ramifications for women's sexual lives. Implications for clinical practice and education are discussed.

Preconception bariatric surgery improves obesity-related maternal pregnancy complications but may reduce the absorption of nutrients required for healthy fetal growth and development. Women who receive preconception nutritional support after bariatric surgery are less likely to have adverse pregnancy outcomes. This study aimed to investigate the provision of preconception and pregnancy-specific nutritional support for women having bariatric surgery in the UK. A mixed-methods survey was distributed to healthcare professionals working in obesity or maternity services between December 2018 and October 2019. We collected both quantitative and qualitative data which were analysed using a mixed-methods approach. We received 135 responses from online ( n = 99) and postal ( n = 36) questionnaires. Only 45% of participants reported being 'very familiar' with the preconception/pregnancy nutritional needs of this population. Barriers to providing nutritional support included: a lack of resources and time; poor communication both across services and with women; not having contact with women preconception; and a lack of information and guidance. Respondents felt that dietitians have the expertise in nutrition necessary to provide support; however, GPs and midwives have the most frequent patient access post-surgery, both before and during pregnancy. Optimal preconception and pregnancy-related nutritional support requires multidisciplinary care pre- and post-surgery, and healthcare professionals require training and guidance to inform practice.

Contraflow cycling on one-way streets is a low cost intervention that research shows can improve the cycling experience and increase participation. Evidence from several studies suggest that cyclists on contraflows have a lower crash risk. However, implementing contraflow cycling is often controversial, including in the United Kingdom (UK). In this paper we examine whether contraflow cycling on one-way streets alters crash or casualty rates for pedal cyclists. Focusing on inner London boroughs between 1998 and 2019, we identified 508 road segments where contraflow cycling was introduced on one-way streets. We identified road traffic crashes occurring within 10 m of these segments and labelled them as pre-contraflow, contraflow or contraflow removed crashes. We calculated rates using the number of crashes or casualties divided by the time exposed and generated 95 % confidence intervals using bootstrap resampling. We adjusted the rates for changes in cordon cycling volume and injury severity reporting. There were 1498 crashes involving pedal cyclists: 788 pre-contraflow, 703 contraflow and 7 following contraflow removal. There was no change in adjusted overall pedal cyclist crash or casualty rates when contraflow cycling was introduced. Proximity to a junction doubled the crash rate. The crash rate when pedal cyclists were travelling contraflow was the same as those travelling with flow. We have found no evidence that introducing contraflow cycling increases the crash or casualty rate for pedal cyclists. It is possible that such rates may indeed fall when contraflow cycling is introduced if more accurate spatio-temporal cycling volume data was available. We recommend all one-way streets are evaluated for contraflow cycling but encourage judicious junction design and recommend UK legislative change for mandatory-two-way cycling on one-way streets unless exceptional circumstances exist., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Multiple myeloma is a plasma cell malignancy that accounts for 1%-2% of newly diagnosed cancers.At diagnosis, approximately 20% of patients can be identified, using cytogenetics, to have inferior survival (high-risk). Additionally, standard-risk patients, with detectable disease (minimal residual disease (MRD)-positive) postautologus stem cell transplant (ASCT), fare worse compared with those who do not (MRD-negative). Research is required to determine whether a risk-adapted approach post-ASCT could further improve patient outcomes., Methods: RADAR is a UK, multicentre, risk-adapted, response-guided, open-label, randomised controlled trial for transplant-eligible newly diagnosed multiple myeloma patients, using combinations of lenalidomide (R), cyclophosphamide (Cy), bortezomib (Bor), dexamethasone (D) and isatuximab (Isa).Participants receive RCyBorD(x4) induction therapy, followed by high-dose melphalan and ASCT. Post-ASCT, there are three pathways as follows:A phase III discontinuation design to assess de-escalating therapy in standard-risk MRD-negative patients. Participants receive 12 cycles of Isa maintenance. Those who remain MRD-negative are randomised to either continue or stop treatment.A phase II/III multiarm multistage design to test treatment strategies for treatment escalation in standard-risk MRD-positive patients. Participants are randomised to either; R, RBorD(x4) +R, RIsa, or RBorIsaD(x4) + RIsa.A phase II design to assess the activity of intensive treatment strategies in high-risk patients. Participants are randomised to RBorD(x4) +R or RBorIsaD(x4) + RIsa.1400 participants will be registered to allow for 500, 450 and 172 participants in each pathway. Randomisations are equal and treatment is given until disease progression or intolerance., Ethics and Dissemination: Ethical approval was granted by the London-Central Research Ethics Committee (20/LO/0238) and capacity and capability confirmed by the appropriate local research and development department for each participating centre prior to opening recruitment. Participant informed consent is required before trial registration and reconfirmed post-ASCT. Results will be disseminated by conference presentations and peer-reviewed publications., Trial Registration Number: ISCRTN46841867., Competing Interests: Competing interests: ABC, KLR, DAC, AH, CO, LBai, LBar, AP and RL report grants and non-financial support from BMS/Celgene, grants and non-financial support from Merck Sharpe & Dohme, grants and non-financial support from Amgen, grants and non-financial support from Takeda, during the conduct of the trial. DAC also reports travel support from Celgene Corporation. KY, RDT, CB, GJ, GP, MC, BD, DM, GC, HA, KR,SA and AC have no conflicting interests to declare. MC declares, Bristol Myers Squibb- employee, Honoraria/travel support in the last 3 years from, Amgen, BMS/Celgene, Janssen, Takeda, Abbvie. CP declares BMS/Celgene Ad boards and speaker fees, Sanotif—Ad board, speaker fees, conference registration fees. JS reports Carrying out consultancy work (Advisory Board) for Sanofi. And an educational speaking engagement for Celgene/BMS RP declares; Honoraria—Jannsen, BMS, Abbvie, GSK. Consultancy: GSK, Janssen. Meeting support: Janssen, Takeda, BMS. RO declares- Janssen - advisory board, honoraria, Celegene— honoraria, Beigene - advisory board, honoraria, Astra Zeneca—honoraria. MK declares inter-relationships: AbbVie: consultancy; Amgen: honoraria; BMS/Celgene: consultancy, research funding (institution); GSK: consultancy; Janssen: consultancy, research funding (institution); Karyopharm: consultancy; Pfizer: consultancy; SeattleGenetics: consultancy; Takeda: consultancy; Sanofi: honoraria. MD reports owning stock in Abingdon Health. SQ is the founder and CSO of Achilles therapeutics a company developing T cell therapies for solid tumours., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Immunoglobulin D (IgD) myeloma is a subtype often considered to have adverse features and inferior survival, but there is a paucity of data from large clinical studies. We compare the clinical characteristics and outcomes of patients with IgD myeloma from UK phase 3 myeloma trials analyzed in 2 groups: old (1980-2002) and recent (2002-2016) clinical trials, based on the time of adoption of novel myeloma therapies. Patients with IgD myeloma comprised 44 of 2789 (1.6%) and 70 of 5773 (1.2%) of the old and recent trials, respectively. Overall, IgD myeloma was associated with male predominance, low-level paraproteinemia (<10g/L), and λ light chain preference. The frequency of ultra-high-risk cytogenetics was similar in IgD myeloma compared with other subtypes (4.3% vs 5.3%, P > .99). Despite the old trial series being a younger group (median age: 59 vs 63 years, P = .015), there was a higher frequency of bone lesions, advanced stage at diagnosis, worse performance status, and severe renal impairment compared with the recent trials. Furthermore, the early mortality rate was significantly higher for the old trial series (20% vs 4%, P = .01). The overall response rate following induction therapy was significantly higher in the recent trials (89% vs 43%, P < .0001), and this was consistent with improved median overall survival (48 months; 95% confidence interval [CI] 35-67 months vs 22 months; 95% CI, 16-29 months). Survival outcomes for IgD myeloma have significantly improved and are now comparable to other myeloma types because of earlier diagnosis, novel therapies, and improved supportive care. This trial was registered at clinicaltrials.gov as # NCT01554852., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life., Methods and Analysis: Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. Overall, 740 participants will be registered into the trial to allow 720 and 478 to be randomised at induction and maintenance, respectively.All participants will receive IRD induction with the dosing strategy randomised (1:1) at trial entry. Patients randomised to the standard, reactive arm will commence at the full dose followed by toxicity dependent reactive modifications. Patients randomised to the adaptive arm will commence at a dose level determined by their International Myeloma Working Group frailty score. Following 12 cycles of induction treatment, participants alive and progression free will undergo a second (double-blind) randomisation on a 1:1 basis to maintenance treatment with lenalidomide+placebo versus lenalidomide+ixazomib until disease progression or intolerance., Ethics and Dissemination: Ethical approval has been obtained from the North East-Tyne & Wear South Research Ethics Committee (19/NE/0125) and capacity and capability confirmed by local research and development departments for each participating centre prior to opening to recruitment. Participants are required to provide written informed consent prior to trial registration. Trial results will be disseminated by conference presentations and peer-reviewed publications., Trial Registration Number: ISRCTN17973108, NCT03720041., Competing Interests: Competing interests: ABC, K-LR, DAC, AH, CO, RH and PB report grants and non-financial support from BMS/Celgene, grants and non-financial support from Merck Sharpe & Dohme, grants and non-financial support from Amgen, grants and non-financial support from Takeda, during the conduct of the trial. DAC also reports travel support from Celgene Corporation. CPawlyn reports receiving honoraria and/or travel support from Amgen, BMS/Celgene, Janssen, Sanofi and Takeda. MK consultancy: AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm, Seattle Genetics, Takeda; honoraria: BMS/Celgene, Janssen, Takeda; Research funding: BMS/Celgene; Travel/educational support: BMS/Celgene, Janssen, Takeda. SB reports receiving research funding from Takeda. KB—Advisory Boards Janssen: BMS/Celgene, Takeda, Novartis. Speaker Honoraria: Janssen, BMS/Celgene, Sanofi, Takeda. Support to attend educational meetings: Janssen, BMS/Celgene, Takeda, GSK. GJ reports research funding from Takeda, Onyx, MSD & BMS/Celgene with consultancy from Janssen, Takeda, Sanofi, Oncopeptides, Karyopharm, Pfizer, Roche & BMS/Celgene. GC reports research funding from Janssen, Takeda, Amgen & BMS/Celgene with consultancy from Janssen, Takeda, Sanofi, Oncopeptides, Karyopharm, Pfizer, Roche & BMS/Celgene. MD reports Stock held in Abingdon Health. JB, RdT, NR, JJ, CParrish, HG, DM, BD, RO, MJ and BK have no declared competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Vitamin D is truly unique-not a 'vital' amine in the true sense of the word, but rather a prohormone, which is produced in the skin during exposure to sunlight (UVB radiation at 290-315 nm) and which can also be obtained from food and from supplements. A high prevalence of low vitamin D status has been reported across the world in a wide range of population groups, and this includes communities living in low latitude areas despite the abundance of sunlight. It is accepted that vitamin D status is reflected by the level of the circulating metabolite 25-hydroxyvitamin D (25[OH]D), which is produced by hepatic hydroxylation of vitamin D, derived either from the skin from UV exposure or the gut from oral intake. Vitamin D has been associated with a wide range of health outcomes, but controversies remain as to their exact nature and extent and whether associations are in the causal pathway. In order to enable wider discussions on this nutrient, a 'Hot Topic' Vitamin D Workshop achieved funding from the UK Nutrition Research Partnership Medical Research Council call. The objectives of the workshop were (1) to elucidate the role of vitamin D in human health and (2) develop strategies to improve vitamin D status in the UK population. This paper provides a detailed resume of the discussions of the workshop; of the presentations and concomitant Q&As; and of identified areas for future research., (© 2022 British Nutrition Foundation.)

Background: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa., Methods: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak., Results: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers., Conclusions: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Outbreak control measures during COVID-19 outbreaks in a large UK prison consisted of standard (e.g., self-isolation) and novel measures, including establishment of: (i) reverse cohorting units for accommodating new prison admissions; (ii) protective isolation unit for isolating symptomatic prisoners, and (iii) a shielding unit to protect medically vulnerable prisoners., Methods: Single-centre prospective longitudinal study (outbreak control study), implementing novel and traditional outbreak control measures to prevent a SARS-COV-2 outbreak. The prison held 977 prisoners and employed 910 staff at that start of the outbreak., Results: 120 probable and 25 confirmed cases among prisoners and staff were recorded between March and June 2020 during the first outbreak. Over 50% of initial cases among prisoners were on the two wings associated with the index case. During the second outbreak, 182 confirmed cases were recorded after probable reintroduction from a staff member. Widespread testing identified 145 asymptomatic prisoners, 16.9% of the total prisoner cases. The cohorting units prevented re-infection from new prison admissions and the shielding unit had no COVID-19 infections linked to either outbreak., Conclusions: Identifying and isolating infected prisoners, cohorting new admissions and shielding vulnerable individuals helped prevent uncontrollable spread of SARS-COV-2. These novel and cost-effective approaches can be implemented in correctional facilities globally., (© 2022. The Author(s).)

Objective: This national cross-sectional study aims to establish the prevalence and potential impact of performance anxiety among surgeons and investigate its association with psychological traits and wellbeing., Summary and Background Data: Despite a growing awareness that human factors, non-technical skills and wellbeing in healthcare affect patient outcomes, an area that has remained unexplored is surgical performance anxiety (SPA)., Methods: A prospectively registered, cross-sectional study using mixed methods was conducted across the United Kingdom. Data captured included demographics, surgical specialty, trait anxiety, trait perfectionism, SPA, and surgical perfectionism scores. Wellbeing was assessed using The Short Warwick-Edinburgh Mental Wellbeing Scale, whereas qualitative data were collected regarding surgeons' experiences of SPA., Results: A total of 631 responses were collected. Mean age was 41·2 years and mean surgical experience 15·3 years. A total of 62% were male and 52% of consultant/attending grade. A total of 100% felt that SPA affected surgeons, with 87% having experienced it themselves. A total of 65% reported SPA negatively impacted surgical performance and 96% felt SPA negatively impacted surgeons' wellbeing. Male surgeons reported significantly better wellbeing than female surgeons. Surgeons with SPA reported significantly worse wellbeing compared with surgeons who did not experience SPA. Surgeons in general experienced significantly lower mental wellbeing compared with population norms. Thematic analysis highlighted a reticence to share SPA openly and need for cultural change., Conclusions: Surgical performance anxiety is a very common and significant challenge among surgeons across all specialties at all levels of experience in the United Kingdom. It is perceived by surgeons to affect surgical performance adversely and is associated with worse psychological wellbeing. A more open culture of sharing and acknowledgment has been identified to be beneficial., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

On 11th March 2020, the UK government announced plans for the scaling of COVID-19 testing, and on 27th March 2020 it was announced that a new alliance of private sector and academic collaborative laboratories were being created to generate the testing capacity required. The Cambridge COVID-19 Testing Centre (CCTC) was established during April 2020 through collaboration between AstraZeneca, GlaxoSmithKline, and the University of Cambridge, with Charles River Laboratories joining the collaboration at the end of July 2020. The CCTC lab operation focussed on the optimised use of automation, introduction of novel technologies and process modelling to enable a testing capacity of 22,000 tests per day. Here we describe the optimisation of the laboratory process through the continued exploitation of internal performance metrics, while introducing new technologies including the Heat Inactivation of clinical samples upon receipt into the laboratory and a Direct to PCR protocol that removed the requirement for the RNA extraction step. We anticipate that these methods will have value in driving continued efficiency and effectiveness within all large scale viral diagnostic testing laboratories., (© 2022. The Author(s).)

Objectives: A substantial reduction in self-harm recorded in primary care occurred during the first wave of COVID-19 but effects on primary care management of self-harm are unknown. Our objectives were to examine the impact of COVID-19 on clinical management within 3 months of an episode of self-harm., Design: Retrospective cohort study., Setting: UK primary care., Participants: 4238 patients with an index episode of self-harm recorded in UK primary care during the COVID-19 first-wave period (10 March 2020-10 June 2020) compared with 48 739 patients in a prepandemic comparison period (10 March-10 June, 2010-2019)., Outcome Measures: Using data from the UK Clinical Practice Research Datalink, we compared cohorts of patients with an index self-harm episode recorded during the prepandemic period versus the COVID-19 first-wave period. Patients were followed up for 3 months to capture subsequent general practitioner (GP)/practice nurse consultation, referral to mental health services and psychotropic medication prescribing. We examined differences by gender, age group and Index of Multiple Deprivation quintile., Results: Likelihood of having at least one GP/practice nurse consultation was broadly similar (83.2% vs 80.3% in the COVID-19 cohort). The proportion of patients referred to mental health services in the COVID-19 cohort (4.2%) was around two-thirds of that in the prepandemic cohort (6.1%). Similar proportions were prescribed psychotropic medication within 3 months in the prepandemic (54.0%) and COVID-19 first-wave (54.9%) cohorts., Conclusions: Despite the challenges experienced by primary healthcare teams during the initial COVID-19 wave, prescribing and consultation patterns following self-harm were broadly similar to prepandemic levels. We found no evidence of widening of digital exclusion in terms of access to remote consultations. However, the reduced likelihood of referral to mental health services warrants attention. Accessible outpatient and community services for people who have self-harmed are required as the COVID-19 crisis recedes and the population faces new challenges to mental health., Competing Interests: Competing interests: NK reports grants and personal fees from the UK Department of Health and Social Care, the National Institute of Health Research (NIHR), the National Institute for Health and Care Excellence (NICE) and the Healthcare Quality and Improvement Partnership, outside the submitted work; works with NHS England on national quality improvement initiatives for suicide and self-harm; is a member of the advisory group for the National Suicide Prevention Strategy of the Department of Health and Social Care; has chaired NICE guideline committees for Self-harm and Depression; and is currently the Topic Advisor for the new NICE Guidelines for self-harm. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Antibiotics have led to considerable increases in life expectancy. However, over time, antimicrobial resistance has accelerated and is now a significant global public health concern. Understanding societal preferences for the use of antibiotics as well as eliciting the willingness to pay for future research is crucial., Objective: To investigate preferences for different strategies to optimize antibiotic use and to understand the willingness to pay for future research in antimicrobial resistance and antimicrobial drug development., Methods: A discrete-choice experiment was administered to a sample of the UK general population. Respondents were asked to make nine choices, each offering three options-two hypothetical "doctor and antibiotics" and one "no doctor-no antibiotics"-defined by five attributes: treatment, days needed to recover, risk of bacterial infection that needs antibiotics, risk of common side effects, and risk of antimicrobial resistance by 2050. Data were analyzed using random parameters logit models. A double-bounded contingent valuation was also included in the survey to explore the willingness to pay for policies to contain antimicrobial resistance., Results: Among the 2579 respondents who completed the survey, 1151 always selected "no doctor-no antibiotics" and 57 never varied their choices; therefore, 1371 responses were used in the analysis. Risk of antimicrobial resistance by 2050 was the most important attribute and the "treatment" was the least important attribute, although this was sensitive to a higher risk of bacterial infection. The aggregate annual willingness to pay for containing antimicrobial resistance was approximately £8.35 billion (~£5-£10 billion)., Conclusions: The antimicrobial resistance risk is relevant and important to the general public. The high willingness to pay suggests that large investments in policies or interventions to combat antimicrobial resistance are justified., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Within the UK, child mortality from all causes has declined for all ages over the last three decades. However, distinct inequality remains, as child mortality rates are generally found to be higher in males. A significant proportion of childhood deaths in the UK occur in Paediatric Intensive Care Units (PICU). We studied the association of sex with infant mortality in PICUs. We included all infants (0 to 12 months old) admitted to UK PICUs from 01/01/2005 to 31/12/2015 using the Paediatric Intensive Care Audit Network (PICANet) dataset. We considered first admissions to PICU and fitted a cause-specific-hazard-ratio (CSHR) model, and a logistic model to estimate the adjusted association between sex and mortality in PICU. Pre-defined subgroups were children less than 56-days old, and those with a primary diagnosis of infection. Of 71,243 cases, 1,411/29,520 (4.8%) of females, and 1,809/41,723 (4.3%) of males died. The adjusted male/female CSHR was 0.87 (95%-CI 0.81 to 0.92) representing a 13% higher risk of death for females. The adjusted OR for male to female mortality is 0.86 (95%-CI 0.80 to 0.93). Analyses in subgroups yielded similar findings. In our analysis, female infants have a higher rate of PICU mortality compared to male infants., (© 2021. The Author(s).)

Background: The effects of COVID-19 on the shift to remote consultations remain to be properly investigated., Objective: To quantify the extent, nature and clinical impact of the use of telepsychiatry during the COVID-19 pandemic and compare it with the data in the same period of the 2 years before the outbreak., Methods: We used deidentified electronic health records routinely collected from two UK mental health Foundation Trusts (Oxford Health (OHFT) and Southern Health (SHFT)) between January and September in 2018, 2019 and 2020. We considered three outcomes: (1) service activity, (2) in-person versus remote modalities of consultation and (3) clinical outcomes using Health of the Nation Outcome Scales (HoNOS) data. HoNOS data were collected from two cohorts of patients (cohort 1: patients with ≥1 HoNOS assessment each year in 2018, 2019 and 2020; cohort 2: patients with ≥1 HoNOS assessment each year in 2019 and 2020), and analysed in clusters using superclasses (namely, psychotic, non-psychotic and organic), which are used to assess overall healthcare complexity in the National Health Service. All statistical analyses were done in Python., Findings: Mental health service activity in 2020 increased in all scheduled community appointments (by 15.4% and 5.6% in OHFT and SHFT, respectively). Remote consultations registered a 3.5-fold to 6-fold increase from February to June 2020 (from 4685 to a peak of 26 245 appointments in OHFT and from 7117 to 24 987 appointments in SHFT), with post-lockdown monthly averages of 23 030 and 22 977 remote appointments/month in OHFT and SHFT, respectively. Video consultations comprised up to one-third of total telepsychiatric services per month from April to September 2020. For patients with dementia, non-attendance rates at in-person appointments were higher than remote appointments (17.2% vs 3.9%). The overall HoNOS cluster value increased only in the organic superclass (clusters 18-21, n=174; p<0.001) from 2019 to 2020, suggesting a specific impact of the COVID-19 pandemic on this population of patients., Conclusions and Clinical Implications: The rapid shift to remote service delivery has not reached some groups of patients who may require more tailored management with telepsychiatry., Competing Interests: Competing interests: AC has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation and Angelini Pharma, outside the submitted work. AT has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials) and Angelini Pharma, outside the submitted work. PP reports grants from NovoNordisk, other from Queen Mary University of London, other from John Wiley & Sons, outside the submitted work. SR reports educational support from Janssen, Otsuka and Lundbeck, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Phenotypic diversity in urinary metabolomes of different geographical populations has been recognized recently. In this study, urinary metabolic signatures from Western (United Kingdom) and South-East Asian (Thai) cholangiocarcinoma patients were characterized to understand spectral variability due to host carcinogenic processes and/or exogenous differences (nutritional, environmental and pharmaceutical). Urinary liquid chromatography mass spectroscopy (LC-MS) spectral profiles from Thai (healthy = 20 and cholangiocarcinoma = 14) and UK cohorts (healthy = 22 and cholangiocarcinoma = 10) were obtained and modelled using chemometric data analysis. Healthy metabolome disparities between the two distinct populations were primarily related to differences in dietary practices and body composition. Metabolites excreted due to drug treatment were dominant in urine specimens from cholangiocarcinoma patients, particularly in Western individuals. Urine from participants with sporadic (UK) cholangiocarcinoma contained greater levels of a nucleotide metabolite (uridine/pseudouridine). Higher relative concentrations of 7-methylguanine were observed in urine specimens from Thai cholangiocarcinoma patients. The urinary excretion of hippurate and methyladenine (gut microbial-host co-metabolites) showed a similar pattern of lower levels in patients with malignant biliary tumours from both countries. Intrinsic (body weight and body composition) and extrinsic (xenobiotic metabolism) factors were the main causes of disparities between the two populations. Regardless of the underlying aetiology, biological perturbations associated with cholangiocarcinoma urine metabolome signatures appeared to be influenced by gut microbial community metabolism. Dysregulation in nucleotide metabolism was associated with sporadic cholangiocarcinoma, possibly indicating differences in mitochondrial energy production pathways between cholangiocarcinoma tumour subtypes. Mapping population-specific metabolic disparities may aid in interpretation of disease processes and identification of candidate biomarkers., (© 2021. The Author(s).)

The domestic cat is one of the most popular pets in the world. It is estimated that 89-92% of domestic cats in the UK are non-pedigree Domestic shorthair (DSH), Domestic longhair (DLH), or Domestic semi-longhair cats (DSLH). Despite their popularity, little is known of the UK non-pedigree cats' population structure and breeding dynamics. Using a custom designed single nucleotide variant (SNV) array, this study investigated the population genetics of 1344 UK cats. Principal components analysis (PCA) and fastSTRUCTURE analysis verified that the UK's DSH, DLH, and DSLH cats are random-bred, rather than admixed, mix breed, or crossbred. In contrast to pedigree cats, the linkage disequilibrium of these random-bred cats was least extensive and decayed rapidly. Homozygosity by descent (HBD) analysis showed the majority of non-pedigree cats had proportionally less of their genome in HBD segments compared to pedigree cats, and that these segments were older. Together, these findings suggest that the DSH, DLH, and DSLH cats should be considered as a population of random-bred cats rather than a crossbred or pedigree-admixed cat. Unexpectedly, 19% of random-bred cat genomes displayed a higher proportion of HBD segments associated with more recent inbreeding events. Therefore, while non-pedigree cats as a whole are genetically diverse, they are not impervious to inbreeding and its health risks.

Background: The coronavirus disease 2019 (COVID-19) pandemic may have a greater impact on people with disabilities than non-disabled people. Our aim was to compare the short-term impact of the 2020 COVID-19 pandemic and first lockdown on the employment and financial security of working age adults with and without disabilities in the UK., Methods: Secondary analysis of data collected in Wave 9 and the special April, May and June COVID-19 monthly surveys of 'Understanding Society', the UK's main annual household panel study., Results: During the first 3 months of the introduction of the COVID-19 lockdown in the UK, respondents with disability were more likely than their peers to be working reduced hours and experience higher levels of financial stress. These differences were attenuated, but not eliminated, when estimates were adjusted to take account of pre-lockdown financial status., Conclusions: Working age adults with disability were particularly disadvantaged by the financial impact of the COVID-19 lockdown in the UK. The UN Secretary-General António Guterres has stated the need for a disability-inclusive COVID-19 government response. The results of our analysis suggest that these pleas have either not been heeded, or if measures have been implemented, they have so far been ineffectual in the UK., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The number of people over the age of 65 attending Emergency Departments (ED) in the United Kingdom (UK) is increasing. Those who attend with a mental health related problem may be referred to liaison psychiatry for assessment. Improving responsiveness and integration of liaison psychiatry in general hospital settings is a national priority. To do this psychiatry teams must be adequately resourced and organised. However, it is unknown how trends in the number and type referrals of older people to liaison psychiatry teams by EDs are changing, making this difficult., Methods: We performed a national multi-centre retrospective service evaluation, analysing existing psychiatry referral data from EDs of people over 65. We described trends in the number, rate, age, mental health presentation, and time taken to assessment over a 7 years period., Results: Referral data from 28 EDs across England and Scotland were analysed (n = 18,828 referrals). There was a general trend towards increasing numbers of people referred to liaison psychiatry year on year. Variability in referral numbers between different departments, ranged from 0.1 to 24.3 per 1000 ED attendances. The most common reasons for referral were mood disorders, self-harm and suicidal ideas. The majority of referrals were assessed within 60 min, however there is variability between departments, some recording waits over 11 h., Discussion: The data suggests great inter-departmental variability in referral numbers. Is not possible to establish the cause of variability. However, the data highlights the importance of asking further questions about why the differences exist, and the impact that has on patient care., (© 2021 John Wiley & Sons Ltd.)

Objectives: In response to demographic and health system pressures, the development of non-medical advanced clinical practice (ACP) roles is a key component of National Health Service workforce transformation policy in the UK. This review was undertaken to establish a baseline of evidence on ACP roles and their outcomes, impacts and implementation challenges across the UK., Design: A scoping review was undertaken following JBI methodological guidance., Methods: 13 online databases (Medline, CINAHL, ASSIA, Embase, HMIC, AMED, Amber, OT seeker, PsycINFO, PEDro, SportDiscus, Osteopathic Research and PenNutrition) and grey literature sources were searched from 2005 to 2020. Data extraction, charting and summary was guided by the PEPPA-Plus framework. The review was undertaken by a multi-professional team that included an expert lay representative., Results: 191 papers met the inclusion criteria (any type of UK evidence, any sector/setting and any profession meeting the Health Education England definition of ACP). Most papers were small-scale descriptive studies, service evaluations or audits. The papers reported mainly on clinical aspects of the ACP role. Most papers related to nursing, pharmacy, physiotherapy and radiography roles and these were referred to by a plethora of different titles. ACP roles were reported to be achieving beneficial impacts across a range of clinical and health system outcomes. They were highly acceptable to patients and staff. No significant adverse events were reported. There was a lack of cost-effectiveness evidence. Implementation challenges included a lack of role clarity and an ambivalent role identity, lack of mentorship, lack of continuing professional development and an unclear career pathway., Conclusion: This review suggests a need for educational and role standardisation and a supported career pathway for advanced clinical practitioners (ACPs) in the UK. Future research should: (i) adopt more robust study designs, (ii) investigate the full scope of the ACP role and (iii) include a wider range of professions and sectors., Competing Interests: Competing interests: RC is Clinical Lead for Musculoskeletal Practitioners in Primary Care and Lead of the Centre for Advancing Practice, Health Education England. JC is a Research Advisor to Health Education England., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Research has suggested that exposure to loneliness can have a powerful detrimental impact on health, including mental health. Addressing socially determined health inequity requires understanding of the situation of marginalized or vulnerable groups. People with disability are increasingly being recognized as one such group. Little population-based research has addressed the association between loneliness and health among working age adults with and without disability., Methods: Secondary analysis of data collected in waves 8 and 9 of Understanding Society, the UK's main annual household panel study., Results: Rates of exposure to substantial loneliness were 25.4% (95%CI 23.5-27.3%) among adults with persistent disability (disability at W8 and W9), 15.4% (13.3-17.5%) among adults with disability onset (disability at W9 only), 12.3% (10.1-14.5%) among adults with disability offset (disability at W8 only), and 6.9% (6.5-7.3%) among adults with no disability. Exposure to loneliness was positively associated with the incidence (GHQ-12) and prevalence (SF-12 Mental) of mental health problems, but not the prevalence of physical health problems (SF-12 Physical). Disability status appeared to moderate the association between loneliness and health, with the difference between the persistent disability and no disability group increasing with exposure to greater levels of loneliness., Conclusion: Loneliness may be an important determinant of the poorer mental health of working age adults with disability in the UK. Exposure rates are significantly higher than among the non-disabled population. The strength of association between exposure to loneliness and poorer mental health is greater for people with persistent disability than people with no disability., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Allogeneic islet transplantation is a standard of care treatment for patients with labile type 1 diabetes in many countries around the world, including Japan, the United Kingdom, Australia, much of continental Europe, and parts of Canada. The United States is now endorsing islet cell treatment for type 1 diabetes, but the FDA has chosen to consider islets as a biologic that requires licensure, making the universal implementation of the procedure in the clinic very challenging and opening the manufacture of islet grafts to private companies. The commercialization of human tissues raises significant legal and ethical issues and ironically leads to a situation where treatments developed as a result of the scientific and economic efforts of academia over several decades become exploited exclusively by for-profit entities., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

There are significant concerns regarding prescription and misuse of prescription opioids in the perioperative period. The Faculty of Pain Medicine at the Royal College of Anaesthetists have produced this evidence-based expert consensus guideline on surgery and opioids along with the Royal College of Surgery, Royal College of Psychiatry, Royal College of Nursing, and the British Pain Society. This expert consensus practice advisory reproduces the Faculty of Pain Medicine guidance. Perioperative stewardship of opioids starts with judicious opioid prescribing in primary and secondary care. Before surgery, it is important to assess risk factors for continued opioid use after surgery and identify those with chronic pain before surgery, some of whom may be taking opioids. A multidisciplinary perioperative care plan that includes a prehabilitation strategy and intraoperative and postoperative care needs to be formulated. This may need the input of a pain specialist. Emphasis is placed on optimum management of pain pre-, intra-, and postoperatively. The use of immediate-release opioids is preferred in the immediate postoperative period. Attention to ensuring a smooth care transition and communication from secondary to primary care for those taking opioids is highlighted. For opioid-naive patients (patients not taking opioids before surgery), no more than 7 days of opioid prescription is recommended. Persistent use of opioid needs a medical evaluation and exclusion of chronic post-surgical pain. The lack of grading of the evidence of each individual recommendation remains a major weakness of this guidance; however, evidence supporting each recommendation has been rigorously reviewed by experts in perioperative pain management., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

This Review, in addressing the unacceptably high mortality of patients with liver disease admitted to acute hospitals, reinforces the need for integrated clinical services. The masterplan described is based on regional, geographically sited liver centres, each linked to four to six surrounding district general hospitals-a pattern of care similar to that successfully introduced for stroke services. The plan includes the establishment of a lead and deputy lead clinician in each acute hospital, preferably a hepatologist or gastroenterologist with a special interest in liver disease, who will have prime responsibility for organising the care of admitted patients with liver disease on a 24/7 basis. Essential for the plan is greater access to intensive care units and high-dependency units, in line with the reconfiguration of emergency care due to the COVID-19 pandemic. This Review strongly recommends full implementation of alcohol care teams in hospitals and improved working links with acute medical services. We also endorse recommendations from paediatric liver services to improve overall survival figures by diagnosing biliary atresia earlier based on stool colour charts and better caring for patients with impaired cognitive ability and developmental mental health problems. Pilot studies of earlier diagnosis have shown encouraging progress, with 5-6% of previously undiagnosed cases of severe fibrosis or cirrhosis identified through use of a portable FibroScan in primary care. Similar approaches to the detection of early asymptomatic disease are described in accounts from the devolved nations, and the potential of digital technology in improving the value of clinical consultation and screening programmes in primary care is highlighted. The striking contribution of comorbidities, particularly obesity and diabetes (with excess alcohol consumption known to be a major factor in obesity), to mortality in COVID-19 reinforces the need for fiscal and other long delayed regulatory measures to reduce the prevalence of obesity. These measures include the food sugar levy and the introduction of the minimum unit price policy to reduce alcohol consumption. Improving public health, this Review emphasises, will not only mitigate the severity of further waves of COVID-19, but is crucial to reducing the unacceptable burden from liver disease in the UK., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Recruitment to clinical research in the National Health Service remains challenging. One barrier is accessing patients to discuss research participation. Two general approaches are used in the United Kingdom to facilitate this: an 'opt-in' approach (when clinicians communicate research opportunities to patients) and an 'opt-out' approach (all patients have the right to be informed of relevant research opportunities). No evidence-based data are available, however, to inform the decision about which approach is preferable. This study aimed to collect information from 'opt-in' and 'opt-out' Trusts and identify which of the two approaches is optimal for ensuring National Health Service patients are given opportunities to discuss research participation., Method: This sequential mixed methods study comprised three phases: (1) an Appreciative Inquiry across UK Trusts, (2) online surveys and (3) focus groups with National Health Service staff and patients at a representative mental health Trust., Results: The study was conducted between June and October 2019. Out of seven National Health Service Mental Health Trusts contacted (three 'opt-out' and four 'opt-in'), only four took part in phase 1 of the study and three of them were 'opt-out' Trusts. Benefits of an 'opt-out' approach included greater inclusivity of patients and the removal of research gatekeepers, while the involvement of research-active clinicians and established patient-clinician relationships were cited as important to 'opt-in' success. Phases 2 and 3 were conducted at a different Trust (Oxford Health NHS Foundation Trust) which was using an 'opt-in' approach. Of 333 staff and member survey responders, 267 (80.2%) favoured moving to an 'opt-out' approach (phase 2). Nineteen staff and 16 patients and carers participated in focus groups (phase 3). Concern was raised by staff regarding the lack of time for clinical research, with clinical work taking precedence over research; patients were concerned about a lack of research activity; all considered research to be beneficial and were supportive of a move to 'opt-out'., Conclusion: Findings suggest that 'opt-out' is more beneficial than 'opt-in', with the potential to vastly increase patient access to research opportunities and to enable greater equality of information provision for currently marginalised groups. This should ensure that healthcare research is more representative of the entire population, including those with a mental health diagnosis.

Background: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme., Methods: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive., Findings: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4-7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80-1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86-1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001)., Interpretation: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer., Funding: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Rugby football (Union and League) provides physical activity (PA) with related physical and mental health benefits. However, as a collision sport, rugby research and media coverage predominantly focus on injuries in elite players while the overall impact on health and well-being remains unclear. This study aims to provide a greater understanding of the risks and benefits of rugby participation in a diverse sample of men and women, current and former rugby Union and League players from recreational to the elite level of play. We will explore: (1) joint-specific injuries and concussion; (2) joint pain and osteoarthritis (OA); (3) medical and mental health conditions; (4) PA and sedentary behaviour and (5) well-being (quality of life, flourishing and resilience)., Methods and Analysis: The Rugby Health and Well-being Study is designed in two phases: (1) a UK-wide cross-sectional survey and (2) cross-validation using health register data from Scotland. Participants will be at least 16 years old, current or former rugby players who have played rugby for at least one season. We will report standardised, level of play-, sex- and age-stratified prevalence of joint injury, concussion, medical conditions and PA. We will describe injury/concussion prevention expectations and protective equipment use. Rugby-related factors associated with injury, pain, OA, PA, health and well-being will be explored in regression models. We will compare joint pain intensity and duration, elements of pain perception and well-being between recreational and elite players and further investigate these associations in regression models while controlling for confounding variables. In the second phase, we will validate self-reported with health register data, and provide further information on healthcare use., Ethics and Dissemination: The Yorkshire and the Humber-Leeds East Research Ethics Committee (REC reference: 19/HY/0377) has approved this study (IRAS project ID 269424). The results will be disseminated through scientific publications, conferences and social media., Competing Interests: Competing interests: NKPP, MRR, SRF, LG, RH and NKA declare no competing interests. SAG works as a Sports Medicine Training Fellow for the Rugby Football Union and receives remuneration for clinical work in the sport. AM receives remuneration from Scottish Rugby Union for clinical work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Nausea and vomiting are experienced by most women during pregnancy. The onset is usually related to Last Menstrual Period (LMP) the date of which is often unreliable. This study describes the time to onset of nausea and vomiting symptoms from date of ovulation and compares this to date of last menstrual period METHODS: Prospective cohort of women seeking to become pregnant, recruited from 12 May 2014 to 25 November 2016, in the United Kingdom. Daily diaries of nausea and vomiting were kept by 256 women who were trying to conceive. The main outcome measure is the number of days from last menstrual period (LMP) or luteinising hormone surge until onset of nausea or vomiting., Results: Almost all women (88%) had Human Chorionic Gonadotrophin rise within 8 to 10 days of ovulation; the equivalent interval from LMP was 20 to 30 days. Many (67%) women experience symptoms within 11 to 20 days of ovulation., Conclusions: Onset of nausea and vomiting occurs earlier than previously reported and there is a narrow window for onset of symptoms. This indicates that its etiology is associated with a specific developmental stage at the foetal-maternal interface., Trial Registration: NCT01577147 . Date of registration 13 April 2012.

Background: In an effort to address the increasing demand for heart transplantation within the United Kingdom (UK), we established a clinical program of heart transplantation from donation after circulatory-determined death (DCD) donors in 2015. After 5 years, we report the clinical early outcomes and impact of the program., Methods: This is a single-center, retrospective, matched, observational cohort study comparing outcomes of hearts transplanted from DCD donors from March 1, 2015 to February 29, 2020 with those from matched donation after brain death (DBD) donors at Royal Papworth Hospital (RPH) (Cambridge, UK). DCD hearts were either retrieved using thoracoabdominal normothermic regional perfusion or the direct procurement and perfusion technique. All DBD hearts were procured using standard cold static storage. The primary outcomes were recipient 30-day and 1-year survival., Results: During the 5-year study, DCD heart donation increased overall heart transplant activity by 48% (79 for DCD and 164 for DBD). There was no difference in survival at 30 days (97% for DCD vs 99% for DBD, p = 1.00) or 1 year (91% for DCD vs 89% for DBD, p = 0.72). There was no difference in the length of stay in the intensive care unit (7 for DCD vs 6 for DBD days, p = 0.24) or in the hospital (24 for DCD vs 25 for DBD days, p = 0.84)., Conclusions: DCD heart donation increased overall heart transplant activity at RPH by 48%, with no difference in 30-day or 1-year survival in comparison with conventional DBD heart transplantations. DCD heart donation is set to make a dramatic difference in the number of patients who can benefit from heart transplantation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

On 12 March 2020 the UK entered the 'delay phase' of the COVID-19 pandemic response. The Public Health England Emergency Department Syndromic Surveillance System (EDSSS) carries out daily (near real-time) public health surveillance of emergency department (ED) attendances across England. This retrospective observational analysis of EDSSS data aimed to describe changes in ED attendances during March-April 2020, and identify the attendance types with the largest impact. Type 1 ED attendances were selected from 109 EDs that reported data to EDSSS for the period 1 January 2019 to 26 April 2020. The daily numbers of attendances were plotted by age group and acuity of presentation. The 2020 'COVID-19' period (12 March 2020 to 26 April 2020) attendances were compared with the equivalent 2019 'pre-COVID-19' period (14 March 2019 to 28 April 2019): in total; by hour and day of the week; age group(<1, 1-4, 15-14, 15-44, 45-64 and 65+ years); gender; acuity; and for selected syndromic indicators(acute respiratory infection, gastroenteritis, myocardial ischaemia). Daily ED attendances up to 11 March 2020 showed regular trends, highest on a Monday and reduced in children during school holidays. From 12 March 2020 ED attendances decreased across all age groups, all acuity levels, on all days and times. Across age groups the greatest percentage reductions were seen in school age children (5-14 years). By acuity, the greatest reduction occurred in the less severe presentations. Syndromic indicators showed that the greatest reductions were in non-respiratory indicators, which fell by 44-67% during 2020 COVID-19, while acute respiratory infection was reduced by -4.4% (95% CI -9.5% to 0.6%). ED attendances in England have been particularly affected during the COVID-19 pandemic due to changes in healthcare seeking behaviour. EDSSS has enabled real-time daily monitoring of these changes, which are made publicly available to facilitate action. The EDSSS provides valuable surveillance of ED attendances in England. The flexibility of EDSSS allowed rapid development of new indicators (including COVID-19-like) and reporting methods., Competing Interests: Competing interests: TCH is a director of L2S2 Ltd., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Common causes of death in COVID-19 due to SARS-CoV-2 include thromboembolic disease, cytokine storm and adult respiratory distress syndrome (ARDS). Our aim was to develop a system for early detection of disease pattern in the emergency department (ED) that would enhance opportunities for personalised accelerated care to prevent disease progression. A single Trust's COVID-19 response control command was established, and a reporting team with bioinformaticians was deployed to develop a real-time traffic light system to support clinical and operational teams. An attempt was made to identify predictive elements for thromboembolism, cytokine storm and ARDS based on physiological measurements and blood tests, and to communicate to clinicians managing the patient, initially via single consultants. The input variables were age, sex, and first recorded blood pressure, respiratory rate, temperature, heart rate, indices of oxygenation and C-reactive protein. Early admissions were used to refine the predictors used in the traffic lights. Of 923 consecutive patients who tested COVID-19 positive, 592 (64%) flagged at risk for thromboembolism, 241/923 (26%) for cytokine storm and 361/923 (39%) for ARDS. Thromboembolism and cytokine storm flags were met in the ED for 342 (37.1%) patients. Of the 318 (34.5%) patients receiving thromboembolism flags, 49 (5.3% of all patients) were for suspected thromboembolism, 103 (11.1%) were high-risk and 166 (18.0%) were medium-risk. Of the 89 (9.6%) who received a cytokine storm flag from the ED, 18 (2.0% of all patients) were for suspected cytokine storm, 13 (1.4%) were high-risk and 58 (6.3%) were medium-risk. Males were more likely to receive a specific traffic light flag. In conclusion, ED predictors were used to identify high proportions of COVID-19 admissions at risk of clinical deterioration due to severity of disease, enabling accelerated care targeted to those more likely to benefit. Larger prospective studies are encouraged., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The potential impact of the COVID-19 pandemic on population mental health is of increasing global concern. We examine changes in adult mental health in the UK population before and during the lockdown., Methods: In this secondary analysis of a national, longitudinal cohort study, households that took part in Waves 8 or 9 of the UK Household Longitudinal Study (UKHLS) panel, including all members aged 16 or older in April, 2020, were invited to complete the COVID-19 web survey on April 23-30, 2020. Participants who were unable to make an informed decision as a result of incapacity, or who had unknown postal addresses or addresses abroad were excluded. Mental health was assessed using the 12-item General Health Questionnaire (GHQ-12). Repeated cross-sectional analyses were done to examine temporal trends. Fixed-effects regression models were fitted to identify within-person change compared with preceding trends., Findings: Waves 6-9 of the UKHLS had 53 351 participants. Eligible participants for the COVID-19 web survey were from households that took part in Waves 8 or 9, and 17 452 (41·2%) of 42 330 eligible people participated in the web survey. Population prevalence of clinically significant levels of mental distress rose from 18·9% (95% CI 17·8-20·0) in 2018-19 to 27·3% (26·3-28·2) in April, 2020, one month into UK lockdown. Mean GHQ-12 score also increased over this time, from 11·5 (95% CI 11·3-11·6) in 2018-19, to 12·6 (12·5-12·8) in April, 2020. This was 0·48 (95% CI 0·07-0·90) points higher than expected when accounting for previous upward trends between 2014 and 2018. Comparing GHQ-12 scores within individuals, adjusting for time trends and significant predictors of change, increases were greatest in 18-24-year-olds (2·69 points, 95% CI 1·89-3·48), 25-34-year-olds (1·57, 0·96-2·18), women (0·92, 0·50-1·35), and people living with young children (1·45, 0·79-2·12). People employed before the pandemic also averaged a notable increase in GHQ-12 score (0·63, 95% CI 0·20-1·06)., Interpretation: By late April, 2020, mental health in the UK had deteriorated compared with pre-COVID-19 trends. Policies emphasising the needs of women, young people, and those with preschool aged children are likely to play an important part in preventing future mental illness., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)