Search

Children's ability to benefit from spatiotemporal regularities to detect goal-relevant targets was tested in a dynamic, extended context. Young adults and children (from a low-deprivation area school in the United Kingdom; N = 80; 5-6 years; 39 female; ethics approval did not permit individual-level race/ethnicity surveying) completed a dynamic visual-search task. Targets and distractors faded in and out of a display over seconds. Half of the targets appeared at predictable times and locations. Search performance in children was poorer overall. Nevertheless, they benefitted equivalently from spatiotemporal regularities, detecting more predictable than unpredictable targets. Children's benefits from predictions correlated positively with their attention. The study brings ecological validity to the study of attentional guidance in children, revealing striking behavioral benefits of dynamic experience-based predictions.

Purpose: The purpose of this study was to determine whether caffeine gum improves the performance of recreational runners completing parkruns (weekly, 5 km, mass participant running events). Methods: Thirty-six recreational runners (M = 31, F = 5; age 33.7 ± 10.7 y; BMI 23.1 ± 2.4 kg/m2) capable of running 5 km in < 25 min were recruited to a study at the Sheffield Hallam parkrun, UK. Runners were block randomized into one of three double-blind, placebo-controlled, cross-over intervention trials with caffeine gum as the treatment (n = 6 per intervention trial) or into one of three non-intervention trials that ran concurrently with the intervention trials (n = 6 per non-intervention trial). Changes in conditions across different parkruns were adjusted for using data from the non-intervention trials. Runners in the randomized cross-over intervention trials chewed gum supplying 300 mg of caffeine or a placebo gum for 5 min, starting 30 min before each parkrun. Results: Caffeine gum improved 5 km parkrun performance by a mean of 17.28 s (95% CI 4.19, 30.37; P = 0.01). Adjustment for environmental conditions using data from the non-intervention trials attenuated the statistical significance (P = 0.04). Caffeine gum also decreased RPE by 1.21 (95% CI 0.30, 2.13; P = 0·01) units relative to placebo. Conclusions: A 300 mg dose of caffeine supplied in chewing gum improved the performance of recreational runners completing 5 km parkruns by an average of 17 s. Trial Registration: The study was registered at ClinicalTrials.gov: NCT02473575 before recruitment commenced. [ABSTRACT FROM AUTHOR]

Purpose: Sexual assault is prevalent on UK University campuses, and prevention efforts are being increased. However, at present there is limited evidence about UK students' attitudes towards sexual assault prevention and what they think should be done to effectively address the issue. The purpose of this paper is to explore these views to provide a foundation for the development of a new intervention. Design/methodology/approach: A cross-sectional anonymous online survey was completed by 515 students (73 per cent women; M age: 21.56; 79 per cent heterosexual; and 82.9 per cent white). There were quantitative questions about experiences of sexual assault, attitudes towards sexual consent and victim blaming. Qualitative data were collected regarding participants' views on what universities should do to target sexual assault. Findings: In line with previous studies, the authors found evidence of commonplace and normalised sexual assault behaviours. Women had more positive attitudes towards explicit consent than men, and were less likely to blame victims of sexual assault who had been drinking. Consent behaviour was predicted by positive views towards consent and lower levels of blaming. Themes relating to "awareness," "attitudes," "environment" and "opposition" were identified in the qualitative data. Practical implications: Findings highlight the importance of engaging with students to develop effective prevention measures. Students are likely to find university-led prevention strategies acceptable, but this topic needs to be addressed in the context of the prevailing culture, which may provide an environment where certain behaviours are tolerated. New prevention programmes need to treat the issue as one that is relevant to all students and not just target men as perpetrators and women as victims. Such strategies need to do more than treat this as an isolated issue, to which the solution is re-education about the meaning of consent. Originality/value: There is at present a lack of research evidence about UK students' views on sexual assault prevention. This exploratory survey highlights areas for consideration when developing new interventions.

Frailty is associated with negative health outcomes, disability, and mortality. Physical activity is an effective intervention to improve functional health status. However, the effect of resistance training on multidimensional health in frail older adults remains unclear. This randomized controlled trial was conducted in a U.K. residential care home to assess feasibility with limited efficacy testing on health and functional outcomes and to inform a future definitive randomized controlled trial. Eleven frail older adults (>65 years) completed a 6-week machine-based resistance training protocol three times a week. Uptake and retention were greater than 80%. The measures and intervention were found to be acceptable and practicable. The analyses indicated large improvements in functional capacity, frailty, and strength in the intervention group compared with the controls. These findings support the feasibility of a definitive randomized controlled trial and reinforce the value of resistance training in this population. This trial was registered with ClinicalTrials.gov: NCT03141879. [ABSTRACT FROM AUTHOR]

Despite a link between adverse childhood experiences (ACEs) and anxiety, the role of anxiety in the pathway to chronic pain is unclear. Potentially, inflammatory biomarkers such as C-reactive protein (CRP) are involved. Objectives were to (1) examine relationships between reported ACEs, anxiety, and chronic pain, and (2) assess associations between ACEs, anxiety, and CRP levels and between CRP and chronic pain. Data from 24,172 adults who participated in the UK Biobank were used to conduct Poisson regressions to assess relationships between ACEs, anxiety, and chronic pain. For participants with CRP data who met the inclusion criteria (n = 2007), similar models were run between ACEs, anxiety, and CRP, and CRP and chronic pain. For objective 1, three statistically significant interactions were found to predict pain: frequency of physical abuse x reported muscular symptoms during anxiety (p = 0.01); frequency in which they felt hated x having discussed anxiety with a professional (p = 0.03), and reported frequency of sexual abuse x difficulties relaxing during anxiety attacks (p = 0.03). For objective 2, frequency of sexual abuse and informing a professional about anxiety significantly interacted to predict elevated CRP. For correlations, the largest was between CRP and the number of times pain was reported over the years (p = 0.01). Finally, ACEs (physical abuse, sexual abuse, and whether taken to a doctor) significantly interacted with CRP to predict pain. This study suggests mechanisms of the impact of ACEs on chronic pain may include inflammation and anxiety, which warrants further study. [ABSTRACT FROM AUTHOR]

Background: Interest in internet‐based patient reported outcome measure (PROM) collection is increasing. The NHS myHealthE (MHE) web‐based monitoring system was developed to address the limitations of paper‐based PROM completion. MHE provides a simple and secure way for families accessing Child and Adolescent Mental Health Services to report clinical information and track their child's progress. This study aimed to assess whether MHE improves the completion of the Strengths and Difficulties Questionnaire (SDQ) compared with paper collection. Secondary objectives were to explore caregiver satisfaction and application acceptability. Methods: A 12‐week single‐blinded randomised controlled feasibility pilot trial of MHE was conducted with 196 families accessing neurodevelopmental services in south London to examine whether electronic questionnaires are completed more readily than paper‐based questionnaires over a 3‐month period. Follow up process evaluation phone calls with a subset (n = 8) of caregivers explored system satisfaction and usability. Results: MHE group assignment was significantly associated with an increased probability of completing an SDQ‐P in the study period (adjusted hazard ratio (HR) 12.1, 95% CI 4.7–31.0; p = <.001). Of those caregivers' who received the MHE invitation (n = 68) 69.1% completed an SDQ using the platform compared to 8.8% in the control group (n = 68). The system was well received by caregivers, who cited numerous benefits of using MHE, for example, real‐time feedback and ease of completion. Conclusions: MHE holds promise for improving PROM completion rates. Research is needed to refine MHE, evaluate large‐scale MHE implementation, cost effectiveness and explore factors associated with differences in electronic questionnaire uptake. [ABSTRACT FROM AUTHOR]

The present study examined the relationship between habitual physical activity, life events stress, the diurnal rhythms of cortisol and DHEA, and the cortisohdehydroepiandrosterone (DHEA) ratio in older adults. Thirty-six participants aged S 65 reported their habitual physical activity, and indicated if a particular event happened to them in the past year (stress incidence) and how stressful they perceived the event to be (stress severity). Older adults with higher stress severity demonstrated a significantly higher cortisol:DHEA ratio. Individuals with higher stress incidence scores and who did not participate in aerobic exercise had a significantly higher cortisohDHEA ratio and flatter DHEA diurnal rhythm compared with those who regularly participated in aerobic exercise. In conclusion, life events stress may have a negative impact on the cortisohDHEA ratio in older adults. Under conditions of high stress exposure, exercise may protect older adults from an increased cortisohDHEA ratio and flatter DHEA diurnal rhythm. [ABSTRACT FROM AUTHOR]

Human microbiome studies are increasingly incorporating macroecological approaches, such as community assembly, network analysis and functional redundancy to more fully characterize the microbiome. Such analyses have not been applied to ancient human microbiomes, preventing insights into human microbiome evolution. We address this issue by analysing published ancient microbiome datasets: coprolites from Rio Zape (n = 7; 700 CE Mexico) and historic dental calculus (n = 44; 1770-1855 CE, UK), as well as two novel dental calculus datasets: Maya (n = 7; 170 BCE-885 CE, Belize) and Nuragic Sardinians (n = 11; 1400-850 BCE, Italy). Periodontitisassociated bacteria (Treponema denticola, Fusobacterium nucleatum and Eubacterium saphenum) were identified as keystone taxa in the dental calculus datasets. Coprolite keystone taxa included known short-chain fatty acid producers (Eubacterium biforme, Phascolarctobacterium succinatutens) and potentially disease-associated bacteria (Escherichia, Brachyspira). Overlap in ecological profiles between ancient and modern microbiomes was indicated by similarity in functional response diversity profiles between contemporary hunter-gatherers and ancient coprolites, as well as parallels between ancient Maya, historic UK, and modern Spanish dental calculus; however, the ancient Nuragic dental calculus shows a distinct ecological structure. We detected key ecological signatures from ancient microbiome data, paving the way to expand understanding of human microbiome evolution. [ABSTRACT FROM AUTHOR]

Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt. [ABSTRACT FROM AUTHOR]

Background: Mesothelioma is an aggressive thoracic tumour with a poor prognosis. The only treatment that extends survival is chemotherapy. However, in the UK, up to 50% of patients who are suitable for chemotherapy choose not to receive it, opting for active symptom control instead. The aim of this prospective, single-centre observational study was to describe the characteristics of patients who chose active symptom control over chemotherapy and explore their reasons for doing so. Methods: Two hundred consecutive patients with mesothelioma from one UK centre were included. Eligibility for chemotherapy and choice of first-line treatment were recorded prospectively. Patient characteristics and outcomes were compared using descriptive statistics, regression analysis and survival analysis. Reasons for choosing active symptom control over chemotherapy were extracted, retrospectively. Results: People who chose active symptom control were older, more likely to be female and had worse performance statuses than patients who received front-line chemotherapy. Concern over side effects, the modest survival benefit and previous adverse experiences with chemotherapy were reported as reasons for the decision. Median survival was 13.9 months in the chemotherapy group compared with 6.7 months in the active symptom control group. Conclusions: This is the first study to describe the characteristics of patients with mesothelioma who chose active symptom control over chemotherapy, in the front-line setting. Important differences were seen between this group and patients who received chemotherapy, although confounding is likely to have affected some outcomes. Future research could use qualitative methods to explore patients' reasons for choosing active symptom control, and to further elucidate the decision-making process. [ABSTRACT FROM AUTHOR]

Objective To assess use of thromboprophylaxis in UK general practise among patients with atrial fibrillation (AF); to investigate whether elderly patients are less likely to receive anticoagulation therapy than younger patients. Design Retrospective cohort study Setting UK General Practice Research Database (GPRD) Patients Aged =60 years with a new diagnosis of AF (2000-2009). Interventions None. Main outcome measures The main outcome measure was initiation of warfarin in the first year following diagnosis. Patients were categorised by stroke risk (CHADS2 score) and bleeding risk (HAS-BLED score). Results 81 381 patients were identified (21% aged 60-69 years, 37% aged 70-79 years, 42% aged 80+ years). Patients aged 80+ years were significantly less likely to be initiated on warfarin than younger patients, adjusted for gender, practice and comorbidities; 32% of patients aged 80+ years received warfarin compared with 57% aged 60-69 years (p<0.0001), and 55% aged 70-79 years (p<0.0001). For all strata of CHADS2/ HASBLED scores, patients aged 80+ years were significantly less likely to be treated with warfarin than younger patients. Logistic regression showed that female sex, low Basal Metabolic Index (BMI), age over 80 years, increasing HAS-BLED score and dementia were independently associated with reduced use of warfarin. Stroke/Transient Ischaemic Attack (TIA), hypertension, heart failure and left ventricular systolic dysfunction were associated with increased use. Patients with HASBLED> CHADS2 were less likely to be initiated on warfarin. Higher CHADS2 scores were associated with increased anticoagulation use. Conclusions Anticoagulation is being under-used in patients with AF aged 80+ years, even after taking into account increased bleeding risk in this age group. [ABSTRACT FROM AUTHOR]

Cities must transform in order to address the challenge of climate change and to achieve societal ambitions such as the sustainable development goals. However, a key impediment to achieving transformation is underdeveloped understandings of how key actors and sectors within the built environment work together to achieve goals. This paper addresses these gaps by developing and visually presenting a process map to describe: the key processes involved in producing the built environment across its life stages; key sectors of the built environment, their key actors, and the activities coordinated between them. The process map was peer reviewed by an expert reference group of built environment professionals active in Australia and the UK. The motivation for developing this process map is to facilitate future research to identify and expedite opportunities for coordinated action to address significant societal challenges such as climate change action, and the sustainable development goals – which require transformative action in cities. • Cities must transform to address climate change • We develop a process map to describe the production of the built environment • Process map describes fundamental activities for producing the built environment • Process map spans built environment life stages; identifying activities and interactions of key sectors and actors • Can be applied to inform transformative action targeted at challenges such as climate change [ABSTRACT FROM AUTHOR]

The UK National Health Service (NHS) is undergoing cataclysmic change following the election of the first Labour Government in 18 years. This is primarily embodied in the implementation of the White Paper The New NHS Modern-Dependable, which has resulted in the creation of primary care groups (PCGs) and primary care trusts (PCTs). The task facing both PCGs and PCTs is a radically new and complex one, requiring a new set of leadership skills to the traditional command and control style management. Leadership theories have evolved over the past 70 years. However, it was not until the 1980s that a major change in the paradigm of thinking around what is the nature of leadership occurred. The interaction between the leader and his/her followers is explored in what has become known as transformational leadership theories, developed by Bass and Avolio. Recent studies have, however, questioned the applicability of leadership models derived in the USA, to other cultures. This paper explores the leadership behaviours required for the management boards of PCGs and PCTs. A qualitative research method “Grounded Theory” approach was chosen for this study of leadership. The Repertory Grid technique was used to collect data. There are a number of implications arising from the findings of this study for both leadership models in general, and more specifically, for the development of leadership skills in both PCGs and PCTs. [ABSTRACT FROM AUTHOR]

Objective: To establish what staff support mechanisms are currently in place within children's hospices in the UK looking specifically at 'individual' staff support including mentoring and 'team' staff support including the use of debriefs. Design: A self-administered postal questionnaire study. Setting: Children's hospices in the UK. Main outcome measures: Looking at: use of team meetings; use and content of team debrief; availability of a bereavement counsellor for staff; availability of individual staff mentor and/or clinical supervisor and availability of internal and external training for staff. Results: There was a 76% response rate. Of the hospices that responded 100% of these held team meetings, had access to a bereavement counsellor and 'in house training' and 88% held a debrief after a significant or traumatic event. Conclusions: Looking after staff who care for dying children and their families is a priority. Children's hospices have good support structures in place for staff - the acute sector has much to learn. [ABSTRACT FROM AUTHOR]

Focuses on the management of benzodiazepine dependence in patients in Great Britain. Presence of withdrawal symptoms in affected persons; Association of psychological impairment and neuro-radiological changes in long term administration of the drug; Importance of pharmacological interventions in patients requiring hypnotics.

• Stress and other psychosocial factors are known to influence antibody response to vaccinations. • This study found that lower social cohesion was associated with a poorer antibody response to COVID-19 vaccination. • The association between social cohesion and lower antibody response was mediated by feelings of loneliness. • Those lower in social cohesion had higher levels of loneliness and this in turn was predictive of a poorer antibody response. Recent research has suggested that psychosocial factors influence the antibody response to vaccine, including SARS-CoV-2 (COVID-19) vaccines. Here we investigated whether social cohesion and loneliness were predictive of antibody response to a single dose of a COVID-19 vaccine. We also tested if the association between social cohesion and antibody response was mediated by feelings of loneliness. Participants (N = 676) COVID-19 antibody data were extracted from March 2021 wave of the Understanding Society COVID-19 study from the UK. Relevant socio-demographics, health and lifestyle, loneliness, social cohesion indices were also used in a series of hierarchical linear regression to test our main hypotheses. After controlling for covariates (e.g., age and chronic health conditions), lower social cohesion was associated with a lower antibody response. Further, the association between social cohesion and poorer antibody responses was mediated by loneliness; those reporting lower social cohesion also reported higher loneliness, which in turn was associated with lower antibody response. This study confirms that feelings of 'being in it together' relate to the strength of the antibody response to COVID-19 vaccination, emphasising the importance of the social cohesion agenda during the pandemic. [ABSTRACT FROM AUTHOR]

This paper evaluates the processes and mechanisms available for integrating different types of knowledge for environmental management. Following a review of the challenges associated with knowledge integration, we present a series of questions for identifying, engaging, evaluating and applying different knowledges during project design and delivery. These questions are used as a basis to compare three environmental management projects that aimed to integrate knowledge from different sources in the United Kingdom, Solomon Islands and Australia. Comparative results indicate that integrating different types of knowledge is inherently complex – classification of knowledge is arbitrary and knowledge integration perspectives are qualitatively very different. We argue that there is no single optimum approach for integrating local and scientific knowledge and encourage a shift in science from the development of knowledge integration products to the development of problem-focussed, knowledge integration processes. These processes need to be systematic, reflexive and cyclic so that multiple views and multiple methods are considered in relation to an environmental management problem. The results have implications for the way in which researchers and environmental managers undertake and evaluate knowledge integration projects. [Copyright &y& Elsevier]

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

We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving a phasing switch error rate of 0.18% for European samples and imputation quality of r 2  = 0.75 for variants with minor allele frequencies as low as 2 × 10 -4 in white British samples. The GEL-imputed UK Biobank genome-wide association analysis identified 70% of associations found by direct exome sequencing (P < 2.18 × 10 -11 ), while extending testing of rare variants to the entire genome. Coding variants dominated the rare-variant genome-wide association results, implying less disruptive effects of rare non-coding variants., (© 2024. The Author(s).)

Competing Interests: Declaration of interests Rhys H Thomas has received honoraria from Angelini/Arvelle, Bial, Biocodex, Eisai, Jazz/GW Pharma, NeuraxPharm, Sanofi, Takeda, UCB Pharma, UNEEG, Zogenix, and unrestricted research funding from Angelini/Arvelle and UNEEG. The UK Epilepsy Priority Setting Partnership (PSP) was funded, led and managed by the Epilepsy Research Institute UK (formerly Epilepsy Research UK). The Epilepsy Research Institute UK is a company registered in England and Wales with company number 4873718. Registered office: Churchill House, 35 Red Lion Square, London, WC1R 4SG.

Background: Adults living with severe asthma have lower physical activity levels, particularly high-intensity physical activity, compared with their healthy peers. Physical inactivity is associated with increased morbidity and mortality., Objective: To understand patient and health care professional attitudes toward exercise and physical activity to inform future strategies for the improvement of healthy lifestyle behaviors, including exercise., Methods: Participants recruited from a specialist difficult asthma service were interviewed individually, and health care professionals (HCPs) from primary care, secondary care, and a tertiary center were invited to attend focus groups. Interviews and focus groups were transcribed verbatim. We performed thematic analysis on interviews and focus groups separately, followed by an adapted framework analysis to analyze datasets together., Results: Twenty-nine people with severe asthma participated in a semi-structured interview. A total of 51 HCPs took part in eight focus groups across the East Midlands, United Kingdom. Final analysis resulted in three major themes: barriers to exercise and exercise counseling - in which patients and HCPs identified disease and non-disease factors affecting those living with severe asthma; attitudes toward HCP support for exercise - highlighting education needs for HCPs and preference for supervised exercise programs; and areas for system improvement in supporting patients and HCPs - challenges exist across health sectors that limit patient support are described., Conclusions: Patients identified the important role of HCPs in supporting and advising on lifestyle change. Despite a preference for supervised exercise programs, both patient and HCP barriers existed. To meet patients' varied support needs, improved integration of services is required and HCP skills need extending., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: There has been a decline in the number of academic clinicians in the UK, and there are ethnic/gender disparities in the academic workforce. Higher research self-efficacy (RSE) and a positive perception of research (PoR) amongst students are associated with a higher motivation to engage in academic medicine. Hence, this study aimed to determine the factors that influence RSE and PoR amongst UK medical students., Methods: This is a multicentre cross-sectional survey of medical students in 36 UK medical schools in the 2020/21 academic year. Multiple linear regression was used to investigate the association between students' demographics and RSE/PoR. P-values less than a Bonferroni-corrected significance level of .05/28 = .0018 were considered statistically significant., Results: In total, 1573 individuals participated from 36 medical schools. There were no ethnic differences in PoR or RSE scores. Although there were no gender differences in PoR, female students had lower RSE scores than male students (adjusted β = -1.75; 95% CI: -2.62, -0.89). Research experience before medical school (adjusted β = 3.02; 95% CI: 2.11, 3.93), being in the clinical training phase (adjusted β = 1.99; 95% CI: 1.09, 2.90), and completing a degree before medical school (adjusted β = 3.66; 95% CI: 2.23, 5.09) were associated with higher RSE., Conclusion: There were no associations between the predictor variables and PoR. Female students had lower self-reported RSE scores. Future studies should investigate the role of targeted research mentorship in improving RSE amongst female medical students., (© The Author(s) 2023. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality., Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality., Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis., Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated., Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization., Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19-related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86)., Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed.

Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome., Competing Interests: Declaration of interests P.-A.K. and F.I.S. are cofounders and shareholders of Dioscure Therapeutics SE. F.I.S. is a consultant and shareholder of IFM Therapeutics. J.R.H. is founder and board member of Isoplexis and PACT Pharma. J.D.G. declares contracted research with Gilead, Lilly, and Regeneron. K.H., J.M.J., and A.J.B. work at Quanterix Corporation. All other authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Malignant pleural effusions (MPEs) often cause symptoms, and guidelines recommend early definitive intervention. However, observational data suggest that systemic anticancer treatment (SACT) may control MPE caused by certain pharmacologically sensitive tumors., Research Question: Is SACT associated with higher rates of MPE resolution in people with pharmacologically sensitive tumors?, Study Design and Methods: This was a retrospective analysis of prospectively collected data from an observational cohort study of people diagnosed with MPE from lung, breast, ovarian, and hematologic malignancy between May 11, 2008, and August 6, 2017. MPE resolution (defined as radiologic resolution with removal of drain or catheter and cessation of interventions) was compared in pharmacologically sensitive (high-grade lymphoma, small cell or target-mutation-positive lung cancer, and hormone-receptor-positive breast or ovarian cancer) and nonsensitive (remainder of cohort) tumors, with and without SACT. Secondary outcomes included time to resolution, 3-month resolution rates, and total pleural interventions., Results: Of 280 patients, 127 had sensitive and 153 had nonsensitive tumors. One hundred seventy-one received SACT, and 109 did not. More patients with sensitive tumors achieved MPE resolution than those with nonsensitive tumors (53/127 [41.7%] vs 42/153 [27.5%]; P = .01), and this occurred predominantly after receipt of SACT. However, hematologic malignancies were overrepresented in the sensitive group, with high rates of SACT use and MPE resolution. After adjustment for this and other confounders, no relationship was found among pharmacologic sensitivity, SACT, and MPE resolution (adjusted OR, 1.4; 95% CI, 0.5-4.1). The strongest predictor of MPE resolution was administration of chemical pleurodesis (adjusted OR, 6.2; 95% CI, 3.3-11.7). In sensitive tumors, MPE resolution occurred without chemical pleurodesis in 14 of 52 patients (26.9%; 95% CI, 15.6%-41.1%) after SACT and in 5 of 22 patients (22.7%; 95% CI, 8.2%-47.2%) without SACT., Interpretation: In this observational study, SACT was not associated independently on MPE resolution in pharmacologically sensitive tumors. Randomized trials are required, but with current data, patients with symptomatic MPE should receive early definitive pleural intervention regardless of underlying tumor or intended treatment., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The UK has the highest incidence of mesothelioma in the world, but services vary across the country partly due to uneven geographical distribution of cases. The Mesothelioma UK-funded national organisational audit has highlighted challenges in accessing diagnostic procedures such as thoracoscopy, as well as identifying examples of best practice, including access to clinical trials and specialist therapeutic procedures. To ensure equitable and optimal patient care, cancer alliances should have established referral pathways to specialist multidisciplinary team (MDT) services for discussion of all mesothelioma patients.

Introduction: Osteoporosis and bone fractures are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to morbidity and mortality. Current national guidance on COPD management recommends addressing bone health in patients, however, does not detail how. This consensus outlines key elements of a structured approach to managing bone health and fracture risk in patients with COPD., Methods: A systematic approach incorporating multifaceted methodologies included detailed patient and healthcare professional (HCP) surveys followed by a roundtable meeting to reach a consensus on what a pathway would look like., Results: The surveys revealed that fracture risk was not always assessed despite being recognised as an important aspect of COPD management by HCPs. The majority of the patients also stated they would be receptive to discussing treatment options if found to be at risk of osteoporotic fractures. Limited time and resource allocation were identified as barriers to addressing bone health during consultations. The consensus from the roundtable meeting was that a proactive systematic approach to assessing bone health should be adopted. This should involve using fracture risk assessment tools to identify individuals at risk, investigating secondary causes of osteoporosis if a diagnosis is made and reinforcing non-pharmacological and preventative measures such as smoking cessation, keeping active and pharmacological management of osteoporosis and medicines management of corticosteroid use. Practically, prioritising patients with important additional risk factors, such as previous fragility fractures, older age and long-term oral corticosteroid use for an assessment, was felt required., Conclusion: There is a need for integrating fracture risk assessment into the COPD pathway. Developing a systematic and holistic approach to addressing bone health is key to achieving this. In tandem, opportunities to disseminate the information and educational resources are also required., Competing Interests: SH is funded for 1 session per month to work as a clinical commissioner for respiratory in Somerset CCG and works as a general practitioner partner in Somerset (five sessions per week). He is also a member of the NHS England Cardiovascular and Respiratory Programme Strategic Board and has worked as an unpaid advisor for the British Lung Foundation and Royal College of General Practitioners at a national level. KL owns a share in Primary Integrated Community Service (PICS) that employs respiratory nurses in the community and is also the medical director of PICS. JS has no direct conflict of interest with this publication but has received support or honorarium from Astra Zeneca, Nutricia, ARNS, Chiesi, Mundipharma, ROCHE, Boehringer Ingelheim, Teva, PCRS-UK, MIMS, Mark Allen Group, ADMIT, NIP and Mylan. Prof. CEB reports grants from British Lung Foundation, during the conduct of the study. All authors declare they have no other conflicts of interest in relation to this article., (© 2020 Gupta et al.)

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the bla KPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of bla KPC ). In the United Kingdom, K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn 4401 ). In the United Kingdom, bla KPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of bla KPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 bla KPC -positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of bla KPC (predominantly bla KPC-2 ; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn 4401a , 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), bla KPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non- bla KPC and bla KPC plasmids and the common presence of multiple replicons within bla KPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control., (Copyright © 2020 American Society for Microbiology.)

Background: The management of severe asthma poses many challenges related to treatment, adherence, and psychosocial morbidity. There is little direct data from the patient perspective to understand and negotiate the complexities of managing severe asthma., Objective: To explore the patient perceptions of living with severe asthma and the experience of managing severe asthma, in order to better understand the support that might promote more effective self-management for severe asthma., Methods: Participants were recruited from a specialist Difficult Asthma Service. Semistructured interviews were conducted by researchers independent of the patient's care. Interviews were transcribed verbatim and inductive thematic analysis was performed., Results: Twenty-nine participants (13 male: mean [standard deviation] age, 49.5 [13.6] years: mean Asthma Control Questionnaire 2.2 [1.2]) participated in an interview. Analysis resulted in 4 major themes describing the experience and challenges to managing severe asthma: understanding of severe asthma, emotional impact of living with severe asthma (subtheme: fear of hospitalization), public perceptions of asthma, and concerns about medications., Conclusions: Health care professionals need to consider and discuss with patients their perceptions of severe asthma and the relevant treatments; particular attention should focus around education of disease control and actively exploring thoughts around hospitalization. Our data highlight the potential for psychological and social support to enhance self-management by directly addressing the wide-ranging individual challenges patients face. There is also a need for greater public awareness and education about severe asthma to minimize patient distress particularly in the work environment., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: Nonexpandable lung is a recognized phenomenon that can create management challenges in patients with mesothelioma. Its prevalence and clinical importance are unknown. Objectives: The aim of this study was to describe the prevalence of nonexpandable lung and to evaluate whether there was any association between nonexpandable lung and survival in a clinical cohort of patients with mesothelioma. Methods: This was a prospective, observational cohort study of patients with mesothelioma who were seen in a single center between March 1, 2008, and August 3, 2017. Baseline characteristics were collected at diagnosis. Serial chest radiographs were assessed for the presence of pleural effusions and nonexpandable lung (defined as a lack of lung expansion after pleural aspiration or drainage). Patients were followed until they died or were censored on March 14, 2019. Results: Of 229 patients, 192 (82.7%) had a pleural effusion at presentation, and nonexpandable lung was observed in 64 of these 192 patients (33.3%). Breathlessness and cough were more frequent in patients with pleural effusions, especially in those with underlying nonexpandable lung, whereas chest pain was more prevalent in patients without effusions. Patients with pleural effusions, both with and without underlying nonexpandable lung, were more likely to have epithelioid or early-stage disease and to receive chemotherapy than patients with no pleural effusion. Nonexpandable lung was an independent risk factor for short survival, with a hazard ratio for mortality of 1.80 (95% confidence interval, 1.16-2.80) compared with patients without nonexpandable lung. The presence of a pleural effusion did not appear to be associated with a worse prognosis compared with patients with an effusion (adjusted hazard ratio, 1.86; 95% confidence interval, 0.93-3.72). Conclusions: This is the first study to describe the prevalence and clinical implications of nonexpandable lung in mesothelioma. It demonstrates that nonexpandable lung is a relatively common phenomenon that is associated with significant symptomatology and shorter survival. Keywords: mesothelioma; nonexpandable lung; pleural effusion.