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Risk tolerance decreases from Monday to Thursday and increases on Friday. Antecedents of this weekly risk cycle are difficult to investigate experimentally as manipulating the seven-day cycle is impractical. Here we used temporal disorientation during the UK COVID-19 lockdown to conduct a natural experiment. In two studies, we measured responses to risk in participants with either a strong or weak sense of weekday, after either a short or long period of disruption to their weekly routine by lockdown. In Study 1 (N = 864), the weekly risk cycle was consistent in risk attitude measures specifically to participants who reported a strong sense of weekday. In Study 2 (N = 829), the weekly risk cycle was abolished, even for participants who retained a strong sense of weekday. We propose that two factors sustain the weekly risk cycle. If the sense of weekday is lacking, then weekday will have little effect because the current day is not salient. If weekday associations decay, then weekday will have little effect because the current day is not meaningful. The weekly risk cycle is strong and consistent when (i) sense of weekday is robust and (ii) weekday associations are maintained. [ABSTRACT FROM AUTHOR]

In two pre-registered online studies during the COVID-19 pandemic and the early 2020 lockdown (one of which with a UK representative sample) we elicit risk-tolerance for 1,254 UK residents using four of the most widely applied risk-taking tasks in behavioral economics and psychology. Specifically, participants completed the incentive-compatible Balloon Analog Risk Task (BART) and the Binswanger-Eckel-Grossman (BEG) multiple lotteries task, as well as the Domain-Specific Risk-Taking Task (DOSPERT) and the self-reported questions for risk-taking used in the German Socio-economic Panel (SOEP) study. In addition, participants in the UK representative sample answered a range of questions about COVID-19-related risky behaviors selected from the UCL COVID-19 Social Survey and the ICL-YouGov survey on COVID-19 behaviors. Consistently with pre-COVID-19 times, we find that risk tolerance during the UK lockdown (i) was higher in men than in women and (ii) decreased with age. Undocumented in pre-COVID-19 times, we find some evidence for healthier participants displaying significantly higher risk-tolerance for self-reported risk measures. We find no systematic nor robust patterns of association between the COVID-19 risky behaviors and the four risk-taking tasks in our study. Moreover, we find no evidence in support of the so-called "risk compensation" hypothesis. If anything, it appears that participants who took greater risk in real-life COVID-19-relevant risky behaviors (e.g., isolating or taking precautions) also exhibited higher risk-tolerance in our experimental and self-reported risk-taking measures. [ABSTRACT FROM AUTHOR]

• Using an online randomised controlled trial, we compared the effect of a purely reflective tool, the "think", versus a hybrid nudge-think tool, the "nudge+", on (N = 611) people's willingness to choose environmentally sustainable food. • In the think condition, participants were encouraged to first reflect on a green pledge and then choose an appropriate nudge to comply with their pledge. • In the nudge+, condition, we altered the think by proposing a green default to participants who took the pledge. • We do not find any evidence of heterogeneous treatment effects by unconditional motivation levels of participants. • Nonetheless, we find nudging people, who are already motivated to eat sustainably in the short-term, after they have taken the pledge, leads to a backfire. This fades out when we control for people's overall long-term motivations. Nudging people towards sustainable diets can help mitigate agricultural emissions. Recent debate suggests "nudges" can have heterogeneous treatment effects in the population, including some backfire effects. In this paper, we present experimental evidence on backfiring effects to a nudge, after people pledge for sustainable food choices. The backfiring effect is driven by people's short-term intention to eat sustainably. Specifically, we compare a purely reflective tool, the "think", versus a hybrid "nudge-think" tool, "nudge+", in a group of 611 participants in the United Kingdom. While the think prompted people to first reflect on a green pledge and then choose an appropriate nudge to comply with their pledge, the nudge+ altered this think by proposing a green default to people who took the pledge. In both experimental conditions, participants self-reported their short- and long-term intentions to eat sustainably. We do not find any evidence of heterogeneous treatment effects by unconditional intentions of participants. Yet nudging people, who already intend to eat sustainably in the short-term, after they have taken the pledge, leads to a backfire. This fades out when we control for people's overall longer-term intentions. Our results suggest that policymakers should not be deterred by initial reactance to behavioural policies if such effects are driven by people's short-term intentions. [ABSTRACT FROM AUTHOR]

Background: Frailty is an age-related syndrome characterized by loss of strength and exhaustion and associated with multi-morbidity. Early detection and prediction of the appearance of frailty could help older people age better and prevent them from needing invasive and expensive treatments. Machine learning techniques show promising results in creating a medical support tool for such a task., Methods: This study aims to create a dataset for machine learning-based frailty studies, using Fried's Frailty Phenotype definition. Starting from a longitudinal study on aging in the UK population, we defined a frailty label for each subject. We evaluated the definition by training seven different models for detecting frailty with data that were contemporary to the ones used for the definition. We then integrated more data from two years before to obtain prediction models with a 24-month horizon. Features selection was performed using the MultiSURF algorithm, which ranks all features in order of relevance to the detection or prediction task., Results: We present a new frailty dataset of 5303 subjects and more than 6500 available features. It is publicly available, provided one has access to the original English Longitudinal Study of Ageing dataset. The dataset is balanced after grouping frailty with pre-frailty, and it is suitable for multiclass or binary classification and prediction problems. The seven tested architectures performed similarly, forming a solid baseline that can be improved with future work. Linear regression achieved the best F-score and AUROC in detection and prediction tasks., Conclusions: Creating new frailty-annotated datasets of this size is necessary to develop and improve the frailty prediction techniques. We have shown that our dataset can be used to study and test machine learning models to detect and predict frailty. Future work should improve models' architecture and performance, consider explainability, and possibly enrich the dataset with older waves., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Young adults with perinatally acquired HIV (PAH) face numerous challenges, including antiretroviral therapy (ART) adherence, managing onward HIV transmission risks and maintaining wellbeing. Sharing one's HIV status with others (onward HIV disclosure) may assist with these challenges but this is difficult. We developed and tested the feasibility of an intervention to help HIV status sharing decision-making for young adults with PAH. The study used a randomised parallel group feasibility design with 18-25-year-olds in Uganda and 18-29 year-olds in the UK. Participants were randomly assigned to intervention or standard of care (SOC) condition. The intervention consisted of four sessions (3 group, 1 individual) with follow-up support, delivered in person in Uganda and remotely in the UK. Assessments were carried out at: Pre-intervention /baseline; Post-intervention (intervention group only); Six-month follow-up. 142 participants were recruited (94 Uganda, 48 UK; 89 female, 53 male). At six-month follow-up, 92/94 (98%) participants were retained in Uganda, 25/48 (52%) in the UK. Multivariate analysis of combined data from both countries, showed a non-significant effect of intervention condition on HIV disclosure cognitions and affect (p = 0.08) and HIV disclosure intention (p = 0.09). There was a significant intervention effect on well-being (p = 0.005). This study addressed important gaps in understanding acceptable and feasible ways of delivering HIV status sharing support for young people living with PAH across two very different settings. The intervention was acceptable in both countries and feasible in Uganda. In the UK, retention may have been affected by its remote delivery.Trial registration: ISRCTN Registry, ISRCTN31852047, Registered on 21 January 2019., (© 2024. The Author(s).)

Objective: Cognitive remediation (CR) improves cognition and aids recovery in people with psychosis. An active therapist provides increased benefit, but CR training for therapists is not routinely available, so CR has limited scalability. This study describes the development and evaluation of the first online CR therapist training programme., Methods: An online CR training, based on expert and novice therapist consultations, was developed, and then pilot tested with novice trainees and changes made to produce the evaluation version. Feasibility, acceptability, and training benefits were assessed in a group of naïve UK NHS mental health professionals. Training engagement with a group of clinicians who accessed the programme for professional development was compared to those who paid fees., Results: Most mental health professionals finished training and passed the knowledge test, indicating that training enhanced clinicians' knowledge. Fee-paying trainees had significantly faster completion times and a higher proportion finished in the recommended time. Those who were successful at passing the knowledge questionnaire had significantly fewer years in practice. The majority were satisfied with the programme, felt they had made considerable progress and that training would allow them to begin practicing CR, and would recommend the training to colleagues., Conclusions: This online CR training programme was feasible, acceptable to participants and showed benefits for clinicians. It improved knowledge even in the most junior of staff who have had less time to develop clinical know-how., (© 2023 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Background: Population mental health in the United Kingdom (UK) has deteriorated, alongside worsening socioeconomic conditions, over the last decade. Policies such as Universal Basic Income (UBI) have been suggested as an alternative economic approach to improve population mental health and reduce health inequalities. UBI may improve mental health (MH), but to our knowledge, no studies have trialled or modelled UBI in whole populations. We aimed to estimate the short-term effects of introducing UBI on mental health in the UK working-age population., Methods and Findings: Adults aged 25 to 64 years were simulated across a 4-year period from 2022 to 2026 with the SimPaths microsimulation model, which models the effects of UK tax/benefit policies on mental health via income, poverty, and employment transitions. Data from the nationally representative UK Household Longitudinal Study were used to generate the simulated population (n = 25,000) and causal effect estimates. Three counterfactual UBI scenarios were modelled from 2023: "Partial" (value equivalent to existing benefits), "Full" (equivalent to the UK Minimum Income Standard), and "Full+" (retaining means-tested benefits for disability, housing, and childcare). Likely common mental disorder (CMD) was measured using the General Health Questionnaire (GHQ-12, score ≥4). Relative and slope indices of inequality were calculated, and outcomes stratified by gender, age, education, and household structure. Simulations were run 1,000 times to generate 95% uncertainty intervals (UIs). Sensitivity analyses relaxed SimPaths assumptions about reduced employment resulting from Full/Full+ UBI. Partial UBI had little impact on poverty, employment, or mental health. Full UBI scenarios practically eradicated poverty but decreased employment (for Full+ from 78.9% [95% UI 77.9, 79.9] to 74.1% [95% UI 72.6, 75.4]). Full+ UBI increased absolute CMD prevalence by 0.38% (percentage points; 95% UI 0.13, 0.69) in 2023, equivalent to 157,951 additional CMD cases (95% UI 54,036, 286,805); effects were largest for men (0.63% [95% UI 0.31, 1.01]) and those with children (0.64% [95% UI 0.18, 1.14]). In our sensitivity analysis assuming minimal UBI-related employment impacts, CMD prevalence instead fell by 0.27% (95% UI -0.49, -0.05), a reduction of 112,228 cases (95% UI 20,783, 203,673); effects were largest for women (-0.32% [95% UI -0.65, 0.00]), those without children (-0.40% [95% UI -0.68, -0.15]), and those with least education (-0.42% [95% UI -0.97, 0.15]). There was no effect on educational mental health inequalities in any scenario, and effects waned by 2026. The main limitations of our methods are the model's short time horizon and focus on pathways from UBI to mental health solely via income, poverty, and employment, as well as the inability to integrate macroeconomic consequences of UBI; future iterations of the model will address these limitations., Conclusions: UBI has potential to improve short-term population mental health by reducing poverty, particularly for women, but impacts are highly dependent on whether individuals choose to remain in employment following its introduction. Future research modelling additional causal pathways between UBI and mental health would be beneficial., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thomson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Genetic testing is becoming rapidly more accessible to the general populous either through or outside healthcare systems. Few large-scale studies have been carried out to gauge public opinion in this growing area. Here, we undertook the largest cross-sectional study on genetic testing in the UK. The primary purpose of this study is to identify the differences in attitudes toward genetic testing across ethnic groups. A cohort of 6500 individuals from a diverse population completed a 72-item survey in a cross-sectional study. Responses between ethnic minority and white individuals in the UK were compared using a wilcoxon rank-sum and chi-square tests. The white cohort was approximately twice as likely to have taken a genetic test and 13% more had heard about genetic testing before the survey. The ethnic minority cohort appeared more apprehensive about the impact of genetic testing on employability. This study highlights that in the UK, significant differences in opinions regarding genetic testing exist between white individuals and ethnic minority individuals. There is an urgent need to develop more inclusive strategies to equally inform individuals from all backgrounds to avoid disparities in the utilisation of genetic testing., (© 2023. The Author(s).)

In Europe, the mental health law legal framework has had several changes throughout the years to achieve and develop new reforms, better mental health care, and protect the human rights of patients. The UK national data shows rising detention rates and the disproportionate use of the legal framework among people from black and minority ethnic groups. At the national level, compulsory admissions are lower in Italy; it also shows that it has increased in the last few years in both countries. The lack of ethnic national data, especially in Italy, limited the ability to understand compulsory admission, discrimination, and stigma in mental health. The present study aims to compare the legal framework of mental health law and compulsory hospital admission in Italy and the UK. A review of each country's latest amendments to mental health law and the number of compulsory hospital admissions was conducted to understand the impact of changes in mental health care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Aguirre, Padovano, Scopetti, La Russa, Manetti, D’Errico, Frati and Fineschi.)

Objective: Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55-64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective., Methods: A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to explore the uncertainty around the parameters., Results: The novel tissue valve was potentially associated with higher quality-adjusted life years (QALYs) of 0.01 per person. Potential cost savings were greatest for those aged 55-64 (£408) versus those aged 65+(£53). DSA indicated the results to be most dependent on relative differences in general mortality, procedure costs, and reoperation rates. PSA estimated around 75% of the iterations to be cost-effective at £20,000 per QALY for those aged 55-64, and 57% for those aged 65+., Conclusions: The exploratory analysis suggests that the novel tissue valve could be a cost-effective intervention for people over the age of 55 with AS who are suitable for SAVR in the UK.

Aim: In a randomized control trial mid-regional proadrenomedullin (MR-proADM)-guided decision-making has been proven to safely reduce hospital admissions based on an accurate assessment of disease severity in the Emergency Department (ED). This study aimed to assess the impact of a MR-proADM-Guided Triage (MR-GT) versus standard Hospital Triage (HT) on clinical and economic outcomes in ED patients with suspected infection in Spain, Italy, Germany, and the UK, using Patient-Level Data (PLD) from two observational studies., Methods: PLD was collected from patients enrolled at a Spanish hospital during two observational studies. Logistic regression was used to identify predictors of hospitalization. A patient-level simulation model was subsequently developed to evaluate the clinical and economic impact of MR-GT versus HT using results from the statistical analysis and country-specific cost data from the published literature. Probabilistic and deterministic sensitivity analyses were carried out., Results: Four hundred seventy-three patients were enrolled in this study. MR-proADM had the strongest association with hospital admission, followed by age and National Early Warning Score (NEWS). In the simulation model, MR-GT was associated with an overall reduction in hospitalization relative to HT, equal to 22.6 percentage points (40.9 vs. 63.5%). In addition, the use of MR-GT would reduce the total hospital cost per patient presenting to the ED with suspected infection by roughly 30%, with a mean cost saving per patient of €626, €1,484, €1,154, and £1,113 in Spain, Italy, Germany, and the UK, respectively. The robustness of these findings was confirmed by sensitivity analyses., Limitations: The statistical analyses were not performed on the same population simulated in the model. Clinical input parameters were assumed to be the same for all countries., Conclusions: MR-proADM showed to be the main predictor of hospitalization. An MR-proADM decision algorithm provides cost savings in Spain, Italy, Germany, and the UK.

Competing Interests: Competing interests: none declared

Competing Interests: Competing interests: none declared.

Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection., Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients' death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974., Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4-57·8) from cancer diagnosis and 44 days (28-329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p<0·0001), complicated COVID-19 (p<0·0001), and COVID-19 therapy (p=0·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113-148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio [HR] 1·80 [95% CI 1·18-2·75]) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15·0%) permanently discontinued therapy, and 178 (38·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3·53 [95% CI 1·45-8·59]), but dose or regimen adjustments were not (0·84 [0·35-2·02])., Interpretation: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients., Funding: National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust., Competing Interests: Declaration of interests DJP reports lecture fees from ViiV Healthcare, Bayer Healthcare, Bristol Myers Squibb, Roche, Eisai, and Falk Foundation; travel expenses from Bristol Myers Squibb and Bayer Healthcare; consulting fees from Mina Therapeutics, Eisai, Roche, DaVolterra, and Astra Zeneca; and research funding (to institution) from Merck Sharp and Dohme and Bristol Myers Squibb, outside of the submitted work. MLa acted as consultant for Roche, Novartis, Lilly, and AstraZeneca, outside of the submitted work, and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, and Sandoz, outside of the submitted work. EF reports research funding to institution from Pfizer, outside of the submitted work, and travel expenses from Lilly, Novartis, Pfizer, and Esai, outside of the submitted work. TN-D reports consulting fees from Amgen, Bayer, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Otsuka, Pfizer, Roche, and Takeda, outside of the submitted work; speakers fees from AstraZeneca, Merck Sharp and Dohme, Roche, and Takeda, outside of the submitted work; and travel, accommodation, and expenses from AstraZenca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck Sharp and Dohme, Otsuka, Roche, and Takeda, outside of the submitted work. JB reports consulting fees for Merck Sharp and Dohme and Astra Zeneca, outside of the submitted work. APr reports personal honoraria from Pfizer, Roche, Merck Sharp and Dohme Oncology, Eli Lilly, and Daiichi Sankyo, outside of the submitted work; travel, accommodations, and expenses by Daiichi Sankyo, outside of the submitted work; research funding (to institution) from Roche and Novartis, outside of the submitted work; and consulting fees from NanoString Technologies, Amgen, Roche, Novartis, Pfizer, and Bristol-Myers Squibb, outside of the submitted work. APar reports consulting fees from Takeda and Novartis, outside of the submitted work. MT reports travel grants from Roche, Bristol-Myers Squibb, AstraZeneca, and Takeda, outside of the submitted work; and honoraria as a medical writer from Novartis and Amgen, outside the submitted work. AG reports consulting fees from Roche, Merck Sharp and Dohme, Eli Lilly, Pierre Fabre, Eisai, and Daichii Sankyo, outside the submitted work; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, AstraZeneca, Celgene, and Daichii Sankyo, outside the submitted work; research funds (to institution) from Eisai, Eli Lilly, and Roche, outside the submitted work; support for attending meetings or travel from Bristol-Myers Squibb, Merck Sharp and Dohme, Novartis, and Roche, outside the submitted work; and personal research funding from Associazione Italiana per la Ricerca sul Cancro Foundation UPO aging project, outside the submitted work. GG reports personal research funding outside of the submitted work from Associazione Italiana per la Ricerca sul Cancro Foundation, outside the submitted work; consulting fees from Janssen, Abbvie, AstraZeneca, and BeiGene, outside the submitted work; and speaker fees from Janssen and Abbvie, outside the submitted work. LR reports consulting fees from Servier, Amgen, ArQule, AstraZeneca, Basilea, Bayer, Bristol Myers Squibb, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, Merck Sharp and Dohme, Nerviano Medical Sciences, Roche, Sanofi, and Zymeworks, outside the submitted work; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, and Sanofi, outside the submitted work; travel expenses from Ipsen, outside the submitted work; and institutional research funding (to institution) from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, Merck Sharp and Dohme, Nerviano Medical Sciences, Roche, and Zymeworks, outside the submitted work. JT reports having a scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, Merck Sharp and Dohme, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, and TheraMyc, outside of the submitted work; educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource, outside of the submitted work; and institutional financial interest in form of financial support for clinical trials or contracted research for Amgen, Array Biopharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Healt, Merck Sharp and Dohme, Merus, Mirati, Novartis Farmacéutica, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho, Spanish Association Against Cancer Scientific Foundation, and Cancer Research UK, outside the submitted work. ACo reports consulting fees from Merck Sharp and Dohme, Bristol Myers Squibb, AstraZeneca, and Roche, outside the submitted work; and speaker fees from AstraZeneca, Merck Sharp and Dohme, Novartis, and Astellas, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: All authors declare no competing interests. We acknowledge support from the NIHR/UKRI grant, COV0170 Humoral Immune Correlates of COVID-19 (HICC; based at the Laboratory of Viral Zoonotics, University of Cambridge), the Royal Papworth Hospital NHS Trust (RPH; supporting HB), and the EU FETopen Grant Virofight (supporting RW and SE). AN is supported by Project OVEL (BBSRC, UKRI). We thank the RPH Trust and clinical studies team, health-care workers, and outpatients who participated in this study. We also thank members of the HICC consortium. AN and DC contributed equally to this work. HB and JLH contributed equally to this work.

Introduction: Refractory angina (RA) is considered the end-stage of coronary artery disease, and often has no interventional treatment options. Coronary sinus Reducer (CSR) is a recent addition to the therapeutic arsenal, but its efficacy has only been evaluated on small populations. The RESOURCE registry provides further insights into this therapy., Methods: The RESOURCE is an observational, retrospective registry that includes 658 patients with RA from 20 centers in Europe, United Kingdom and Israel. Prespecified endpoints were the amelioration of anginal symptoms evaluated with the Canadian Cardiovascular Society (CCS) score, the rates of procedural success and complications, and MACEs as composite of all-cause mortality, acute coronary syndromes, and stroke., Results: At a median follow-up of 502 days (IQR 225-1091) after CSR implantation, 39.7% of patients improved by ≥2 CCS classes (primary endpoint), and 76% by ≥1 class. Procedural success was achieved in 96.7% of attempts, with 3% of procedures aborted mostly for unsuitable coronary sinus anatomy. Any complication occurred in 5.7% of procedures, but never required bailout surgery nor resulted in intra- or periprocedural death or myocardial infarction. One patient developed periprocedural stroke after inadvertent carotid artery puncture. At the last available follow-up, overall mortality and MACE were 10.4% and 14.6% respectively. At one, three and five years, mortality rate at Kaplan-Meier analysis was 4%, 13.7%, and 23.4% respectively., Conclusions: CSR implantation is safe and reduces angina in patients with refractory angina., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The question of whether depression is associated with worse survival in people with cancer remains unanswered because of methodological criticism of the published research on the topic. We aimed to study the association in a large methodologically robust study., Methods: We analyzed data on 20,582 patients with breast, colorectal, gynecological, lung, and prostate cancers who had attended cancer outpatient clinics in Scotland, United Kingdom. Patients had completed two-stage screening for major depression as part of their cancer care. These data on depression status were linked to demographic, cancer, and subsequent mortality data from national databases. We estimated the association of major depression with survival for each cancer using Cox regression. We adjusted for potential confounders and interactions between potentially time-varying confounders and the interval between cancer diagnosis and depression screening, and used multiple imputation for missing depression and confounder data. We pooled the cancer-specific results using fixed-effects meta-analysis., Results: Major depression was associated with worse survival for all cancers, with similar adjusted hazard ratios (HRs): breast cancer (HR = 1.42, 95% confidence interval [CI] = 1.15-1.75), colorectal cancer (HR = 1.47, 95% CI = 1.11-1.94), gynecological cancer (HR = 1.36, 95% CI = 1.08-1.71), lung cancer (HR = 1.39, 95% CI = 1.24-1.56), and prostate cancer (HR = 1.76, 95% CI = 1.08-2.85). The pooled HR was 1.41 (95% CI = 1.29-1.54, p < .001, I2 = 0%). These findings were not materially different when we only considered the deaths (90%) that were attributed to cancer., Conclusions: Major depression is associated with worse survival in patients with common cancers. The mechanisms of this association and the clinical implications require further study., (Copyright © 2021 by the American Psychosomatic Society.)

It is currently unknown how post-COVID-19 syndrome (PCS) may affect those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This longitudinal study includes healthcare staff who tested positive for SARS-CoV-2 between March and April 2020, with follow-up of their antibody titers and symptoms. More than half (21 of 38) had PCS after 7-8 months. There was no statistically significant difference between initial reverse-transcription polymerase chain reaction titers or serial antibody levels between those who did and those who did not develop PCS. This study highlights the relative commonality of PCS in healthcare workers and this should be considered in vaccination scheduling and workforce planning to allow adequate frontline staffing numbers., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Aggressive behavior in school is an ongoing concern. The current focus is on specific manifestations such as bullying, but the behavior is broad and heterogenous. Children spend a substantial amount of time in school, but their behaviors in the school setting tend to be less well characterized than at home. Because aggression may index multiple behavioral problems, we used three validated instruments to assess means, correlations and gender differences of teacher-rated aggressive behavior with co-occurring externalizing/internalizing problems and social behavior in 39,936 schoolchildren aged 7-14 from 4 population-based cohorts from Finland, the Netherlands, and the UK. Correlations of aggressive behavior were high with all other externalizing problems (r: 0.47-0.80) and lower with internalizing problems (r: 0.02-0.39). A negative association was observed with prosocial behavior (r: -0.33 to -0.54). Mean levels of aggressive behavior differed significantly by gender. Despite the higher mean levels of aggressive behavior in boys, the correlations were notably similar for boys and girls (e.g., aggressive-hyperactivity correlations: 0.51-0.75 boys, 0.47-0.70 girls) and did not vary greatly with respect to age, instrument or cohort. Thus, teacher-rated aggressive behavior rarely occurs in isolation; boys and girls with problems of aggressive behavior likely require help with other behavioral and emotional problems. Important to note, higher aggressive behavior is not only associated with higher amounts of other externalizing and internalizing problems but also with lower levels of prosocial behavior., Competing Interests: All authors declare no conflicts of interest.

Background: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions., Methods: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London)., Findings: 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model., Interpretation: The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19., Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London., (Copyright © 2021 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.)

Previous analyses suggest that children with tuberculosis (TB) are no more or no less likely to have multidrug (MDR)- or rifampicin-resistant (RR)-TB than adults. However, the availability of new data, particularly for high MDR/RR-TB burden countries, suggest updates of country-specific estimates are warranted.We used data from population-representative surveys and surveillance collected between 2000 and 2018 to compare the odds ratio of MDR/RR-TB among children (aged <15 years) with TB, compared to the odds of MDR/RR-TB among adults (aged ≥15 years) with TB.In most settings (45 out of 55 countries), and globally as a whole, there is no evidence that age is associated with odds of MDR/RR-TB. However, in some settings, such as former Soviet Union countries in general, and Georgia, Kazakhstan, Lithuania, Tajikistan and Uzbekistan in particular, as well as Peru, MDR/RR-TB is positively associated with age ≥15 years. Meanwhile, in Western Europe in general, and the United Kingdom, Poland, Finland and Luxembourg in particular, MDR/RR-TB is positively associated with age <15 years. 16 countries had sufficient data to compare over time between 2000-2011 and 2012-2018, with evidence for decreases in the odds ratio in children compared to adults in Germany, Kazakhstan and the United States of America.Our results support findings that in most settings a child with TB is as likely as an adult with TB to have MDR/RR-TB. However, setting-specific heterogeneity requires further investigation. Furthermore, the odds ratio for MDR/RR-TB in children compared to adults is generally either stable or decreasing. There are important gaps in detection, recording and reporting of drug resistance among paediatric TB cases, limiting our understanding of transmission risks and measures needed to combat the global TB epidemic., Competing Interests: Conflict of interest: C.F. McQuaid has nothing to disclose. Conflict of interest: T. Cohen has nothing to disclose. Conflict of interest: A.S. Dean has nothing to disclose. Conflict of interest: R.M.G.J. Houben has nothing to disclose. Conflict of interest: G.M. Knight has nothing to disclose. Conflict of interest: M. Zignol has nothing to disclose. Conflict of interest: R.G. White has nothing to disclose., (Copyright ©ERS 2021.)

Dealing with confounds is an essential step in large cohort studies to address problems such as unexplained variance and spurious correlations. UK Biobank is a powerful resource for studying associations between imaging and non-imaging measures such as lifestyle factors and health outcomes, in part because of the large subject numbers. However, the resulting high statistical power also raises the sensitivity to confound effects, which therefore have to be carefully considered. In this work we describe a set of possible confounds (including non-linear effects and interactions that researchers may wish to consider for their studies using such data). We include descriptions of how we can estimate the confounds, and study the extent to which each of these confounds affects the data, and the spurious correlations that may arise if they are not controlled. Finally, we discuss several issues that future studies should consider when dealing with confounds., (Copyright © 2020. Published by Elsevier Inc.)

Background: Cognitive difficulties are a core deficit for people with schizophrenia and are generally assessed with neuropsychological tests. Self-report assessments are also useful in understanding difficulties from the service user's perspective. This study aims to introduce and test the shorter version of the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) to improve its acceptability and comprehensibility. Methods: In consultation with service users and clinicians, we identified items from the original 21-item SSTICS that were found difficult and these were excluded. The reduced scale was explored with Confirmatory Factor Analysis (CFA) in two independent samples in the UK and Canada. Convergent validity with symptoms and IQ was assessed and compared between the original and the reduced scale. Results: Six-hundred and seven people with schizophrenia and first-episode psychosis took part in this study. Seven items were removed to produce the SSTICS-Brief. This had good reliability and the CFA confirmed a unidimensional structure. Convergent validity with symptoms and IQ were optimal between the long and short versions. Conclusions: The SSTICS-B has better acceptability than its longer form and could be administered in less time. The resulting measure is likely to be a valuable short self-assessment of cognitive complaints for people with schizophrenia.

Thermal disease presents a major burden to individual patient morbidity, healthcare cost as well as to over all economy. Burns also also represent a significant per-patient utlilisation of finite healthcare resources. Secondary complications in these patients, such as multiple drug resistant organisms, may have a devastating effect. Laser surgery has recently come of age as an optimal tool in the secondary reconstruction of burn injury, that is able to simultaneously address significant sheet scar tightness, hypertrophic, atrophic, and keloid complications, pruritus, microstomia, ectropion, skin graft honeycombing, and improve range of movement whilst reducing the risk of infection to <1%. Yet, cutaneous laser surgery is often underutilised due to the perceived concerns about the sustainability of a new service with relatively high startup cost. We present a dual methodology to explore this concern: an evidence-based background review of the last 5 years of current best evidence, and a 22-year cost-analysis comparison at an established, high volume UK Centre of reconstructive surgery. We report that fiscal viability for laser surgery services for secondary burn reconstruction is supported by: level 2 (one systematic review) level 4 evidence (2 studies) and level 5 evidence (expert reports). Evidence over 22 years from an established super-regional NHS laser centre shows that introduction of this service led to sustained and substantial cost saving, producing excellent surgical results at a fraction of the cost of traditional surgery. Analysis of the potential dollar-effect of these advantages to the general population supports state investment in expertise and capital equipment as a medium to long-term cost saving strategy, which may also aid re-integrating patients into the workforce making a meaningful contribution to the economy., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess the validity of the WHO concept of intrinsic capacity in a longitudinal study of ageing; to identify whether this overall measure disaggregated into biologically plausible and clinically useful subdomains; and to assess whether total capacity predicted subsequent care dependence., Design: Structural equation modelling of biomarkers and self-reported measures in the English Longitudinal Study of Ageing including exploratory factor analysis, exploratory bi-factor analysis and confirmatory factor analysis. Longitudinal mediation and moderation analysis of incident care dependence., Settings: Community, United Kingdom., Participants: 2560 eligible participants aged over 60 years., Main Outcome Measures: Activities of daily living (ADL) and instrumental activities of daily living (IADL)., Results: One general factor (intrinsic capacity) and five subfactors emerged: locomotor, cognitive; psychological; sensory; and 'vitality'. This structure is consistent with biological theory and the model had a good fit for the data (χ 2 =71.2 (df=39)). The summary score of intrinsic capacity and specific subfactors showed good construct validity. In a causal path model examining incident loss of ADL and IADL, intrinsic capacity had a direct relationship with the outcome-root mean square error of approximation ( RMSEA ) =0.02 ( 90% CI 0.001 to 0.05 ) and RMSEA=0.008 ( 90% CI0.001 to 0.03 ) respectively- and was a strong mediator for the effect of age, sex, wealth and education. Multimorbidity had an independent direct relationship with incident loss of ADLs but not IADLs, and also operated through intrinsic capacity. More of the indirect effect of personal characteristics on incident loss of ADLs and IADLs was mediated by intrinsic capacity than multimorbidity., Conclusions: The WHO construct of intrinsic capacity appears to provide valuable predictive information on an individual's subsequent functioning, even after accounting for the number of multimorbidities. The proposed general factor and subdomain structure may contribute to a transformative paradigm for future research and clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: The recent interest in targeting the dorsal root ganglion (DRG) has led to the development of new techniques of electrode placement. In this article, we describe a new "Transgrade" approach to the DRG, accessing the contralateral interlaminar space and steering the lead out the opposite foramen., Objectives: The purpose of this study was to evaluate the Transgrade technique to the DRG in the management of focal neuropathic pain, predominately complex regional pain syndrome in terms of efficacy and safety., Study Design: A retrospective, observational review of all patients selected for DRG stimulation using the Transgrade technique to the DRG., Setting: Pain Management and Neuromodulation Centre, Guys and St. Thomas NHS Foundation Trust, London, United Kingdom., Methods: Data were taken from a hospital password-protected database. All patients were contacted by telephone for Numeric Rating Scale (NRS-11) score, Patient Global Impression of Change (PGIC) score, and complications. A patient responder was defined as having a PGIC score of 6 or 7, and a 2-point reduction from baseline NRS-11., Results: A total of 39 patients (46% women) with a mean age of 46 years (± 2) underwent a trial of DRG stimulation that resulted in an implantation rate of 82% (32 of 39). The responder rates, according to NRS-11 and PGIC results, were 87% (28 of 32) at 6 weeks and 66% (21 of 32) at a mean of 18 months (± 1.8) follow-up. Pocket pain was the most common complication, occurring in 7 of 32 (22%) patients, and the lead migration rate was 3 out of 57 leads placed (5.2%). A burst protocol was the favored method of stimulation in the majority of patients, 25 of 32 (78%)., Limitations: Retrospective nature of design, small sample size., Conclusions: The Transgrade technique of placing DRG leads offers an alternative method that is safe and effective. New methods of stimulation to the DRG offer more choice and potentially better efficacy for patients with chronic neuropathic pain., Key Words: Neuromodulation, dorsal root ganglion, neuropathic pain, complex regional pain syndrome, spinal cord stimulation, chronic pain, implantable neurostimulators, spinal nerve root stimulation.

Safety citizenship behaviors (SCBs) are important participative organizational behaviors that emerge in work-groups. SCBs create a work environment that supports individual and team safety, encourages a proactive management of workplace safety, and ultimately, prevents accidents. In spite of the importance of SCBs, little consensus exists on research issues like the dimensionality of safety citizenship, and if any superordinate factor level of safety citizenship should be conceptualized, and thus measured. The present study addressed this issue by examining the dimensionality of SCBs, as they relate to behaviors of helping, stewardship, civic virtue, whistleblowing, voice, and initiating change in current practices. Data on SCBs were collected from four industrial plants (N = 1065) in four European countries (Italy, Russia, Switzerland, United Kingdom). The results show that SCBs structure around two superordinate second-order factors that reflect affiliation and challenge. Multi-group analyses supported the structure and metric invariance of the two-factor model across the four national subsamples., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Changes in UK psychiatric wards have been difficult to implement. Specific areas of nursing staff resistance remain unclear. Previous healthcare research suggests that burnout is common and that managers' regard changes more positively than direct care staff. We will therefore examine whether burnout and workforce characteristics influence psychiatric nurses' perceptions of barriers to change. Psychiatric nurses (N = 125) completed perceptions measures of 'barriers to change' (VOCALISE: subscales included 'powerlessness, confidence and demotivation'); and 'burnout' (Maslach Burnout Inventory: subscales included 'emotional exhaustion, personal accomplishment and depersonalization '). Staff characteristics, such as length of employment, occupational status, education, ethnicity, gender and age, were also collected. Correlations between these measures informed random-effects regression models, which were conducted to predict the barriers to change score and to explore differential effects in the subscales of VOCALISE. Perceptions of barriers to change (VOCALISE) were correlated with burnout (r = 0.39), occupational status (r = -0.18) and age (r = 0.22). Burnout (Coef. β: 10.52; P > 0.001) and occupational status (Coef. β: -4.58; P = 0.05) predicted VOCALISE. Emotional exhaustion (Coef. β: 0.18; P < 0.001) and low personal accomplishment (Coef. β: 0.21; P = 0.001) predicted powerlessness. Emotional exhaustion predicted low motivation regarding changes (Coef. β: 0.11; P = 0.005). Low confidence predicted high levels of depersonalization (Coef β: 0.23; P = 0.01). Direct care staff expressed significantly more powerlessness (Coef. β: -2.60; P = 0.02) and significantly less confidence (Coef. β: -3.07; P = 0.002) than managers. For changes to be successful in psychiatric wards, burnout will need to be addressed. Future change strategies may consider involving direct care staff to improve perceptions of barriers to change., (© 2018 The Authors International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd on behalf of Australian College of Mental Health Nurses Inc.)

Purpose: Several studies have demonstrated the accuracy, precision, and reproducibility of proton density fat fraction (PDFF) quantification using vendor-specific image acquisition protocols and PDFF estimation methods. The purpose of this work is to validate a confounder-corrected, cross-vendor, cross field-strength, in-house variant LMS IDEAL of the IDEAL method licensed from the University of Wisconsin, which has been developed for routine clinical use., Methods: LMS IDEAL is implemented using a combination of patented and/or published acquisition and some novel model fitting methods required to correct confounds which result from the imaging and estimation processes, including: water-fat ambiguity; T2* relaxation; multi-peak fat modelling; main field inhomogeneity; T1 and noise bias; bipolar readout gradients; and eddy currents. LMS IDEAL has been designed to use image acquisition protocols that can be installed on most MRI scanners and cloud-based image processing to provide fast, standardized clinical results. Publicly available phantom data were used to validate LMS IDEAL PDFF calculations against results from originally published IDEAL methodology. LMS PDFF and T2* measurements were also compared with an independent technique in human volunteer data (n = 179) acquired as part of the UK Biobank study., Results: We demonstrate excellent agreement of LMS IDEAL across vendors, field strengths, and over a wide range of PDFF and T2* values in the phantom study. The performance of LMS IDEAL was then assessed in vivo against widely accepted PDFF and T2* estimation methods (LMS Dixon and LMS T2*, respectively), demonstrating the robustness of LMS IDEAL to potential sources of error., Conclusion: The development and clinical validation of the LMS IDEAL algorithm as a chemical shift-encoded MRI method for PDFF and T2* estimation contributes towards robust, unbiased applications for quantification of hepatic steatosis and iron overload, which are key features of chronic liver disease., Competing Interests: The authors of this manuscript have the following competing interests: Perspectum Diagnostics employees: Chloe Hutton, Michael L. Gyngell, Matteo Milanesi, Alexandre Bagur, Michael Brady; Perspectum Diagnostics stockholders: Chloe Hutton, Michael L. Gyngell, Matteo Milanesi, Alexandre Bagur, Michael Brady. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: There is an urgent need to identify the earliest biological changes within the neuropathological cascade of Alzheimer's disease (AD) processes. Recent findings in a murine model of AD showed significant preclinical loss of dopaminergic neurons in the ventral tegmental area (VTA), accompanied by reduced hippocampal innervation and declining memory. It is unknown if these observations can be translated in humans., Objective: We tested the hypothesis that VTA volume is associated with the typical clinical markers of AD in a cohort of patients and healthy controls., Methods: Structural and resting state functional MRI scans, and neuropsychological scores were acquired for 51 healthy adults, 30 patients with a diagnosis of mild cognitive impairment, and 29 patients with a diagnosis of AD dementia. VTA volume was quantified together with other control nuclei. The association between nuclei volume, hippocampal size, memory performance, and linguistic-executive skills was tested. The effect of VTA functional connectivity was also tested., Results: VTA size, but not of control nuclei, yielded a strong association with both hippocampal size and memory competence (but not linguistic-executive performance), and this was particularly strong in healthy adults. In addition, functional connectivity between the VTA and hippocampus was significantly associated with both markers of AD., Conclusion: Diminished dopaminergic VTA activity may be crucial for the earliest pathological features of AD and might suggest new strategies for early treatment. Memory encoding processes may represent cognitive operations susceptible to VTA neurodegeneration.