Prognostic value of National Early Warning Scores (NEWS2) and component physiology in hospitalised patients with COVID-19:a multicentre study

BACKGROUND: National Early Warning Scores (NEWS2) are used to detect all-cause deterioration. While studies have looked at NEWS2, the use of virtual consultation and remote monitoring of patients with COVID-19 mean there is a need to know which physiological observations are important. AIM: To investigate the relationship between outcome and NEWS2, change in NEWS2 and component physiology in COVID-19 inpatients. METHODS: A multi-centre retrospective study of electronically recorded, routinely collected physiological measurements between March and June 2020. First and maximum NEWS2, component scores and outcomes were recorded. Areas under the curve (AUCs) for 2-day, 7-day and 30-day mortality were calculated. RESULTS: Of 1263 patients, 26% died, 7% were admitted to intensive care units (ICUs) before discharge and 67% were discharged without ICU. Of 1071 patients with initial NEWS2, most values were low: 50% NEWS2=0–2, 27% NEWS2=3–4, 14% NEWS2=5–6 and 9% NEWS2=7+. Maximum scores were: 14% NEWS2=0–2, 22% NEWS2=3–4, 17% NEWS2=5–6 and 47% NEWS2=7+. Higher first and maximum scores were predictive of mortality, ICU admission and longer length of stay. AUCs based on 2-day, 7-day, 30-day and any hospital mortality were 0.77 (95% CI 0.70 to 0.84), 0.70 (0.65 to 0.74), 0.65 (0.61 to 0.68) and 0.65 (0.61 to 0.68), respectively. The AUCs for 2-day mortality were 0.71 (0.65 to 0.77) for supplemental oxygen, 0.65 (0.56 to 0.73) oxygen saturation and 0.64 (0.56 to 0.73) respiratory rate. CONCLUSION: While respiratory parameters were most predictive, no individual parameter was as good as a full NEWS2, which is an acceptable predictor of short-term mortality in patients with COVID-19. This supports recommendation to use NEWS2 alongside clinical judgement to assess patients with COVID-19

Using the Recommended Summary Plan for Emergency care and Treatment (ReSPECT) in care homes:a qualitative interview study

BACKGROUND: The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) is an advance care planning process designed to facilitate discussion and documentation of preferences for care in a medical emergency. Advance care planning is important in residential and nursing homes. AIM: To explore the views and experiences of GPs and care home staff of the role of ReSPECT in: (i) supporting, and documenting, conversations about care home residents’ preferences for emergency care situations, and (ii) supporting decision-making in clinical emergencies. SETTING/PARTICIPANTS: Sixteen GPs providing clinical care for care home residents and 11 care home staff in the West of England. METHODS: A qualitative research design using semi-structured interviews. RESULTS: Participants’ accounts described the ReSPECT process as facilitating person-centred conversations about residents’ preferences for care in emergency situations. The creation of personalised scenarios supported residents to consider their preferences. However, using ReSPECT was complex, requiring interactional work to identify and incorporate resident or relative preferences. Subsequent translation of preferences into action during emergency situations also proved difficult in some cases. Care staff played an important role in facilitating and supporting ReSPECT conversations and in translating it into action. CONCLUSIONS: The ReSPECT process in care homes was positive for GPs and care home staff. We highlight challenges with the process, communication of preferences in emergency situations and the importance of balancing detail with clarity. This study highlights the potential for a multi-disciplinary approach engaging care staff more in the process

The impact of digital educational interventions to support parents caring for acutely ill children at home and factors that affect their use: systematic review protocol

Background: Emergency and urgent care healthcare services are overburdened and the use of these services by acutely ill infants and children is increasing. A large proportion of these visits could be sufficiently addressed by other healthcare professionals. Uncertainty about the severity of a child’s symptoms is one of many factors that play a role in parents’ decisions to take their children to emergency services, demonstrating the need for improved support for health literacy. Digital interventions are a potential tool to improve parents’ knowledge, confidence, and self-efficacy at managing acute childhood illness. However, existing systematic reviews related to this topic need to be updated and expanded to provide a contemporary review of the impact, usability, and limitations of these solutions. Objective: The purpose of this systematic review protocol is to present the method for an evaluation of the impact, usability, and limitations of different types of digital educational interventions to support parents caring for acutely ill children at home. Methods: The review will be structured using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) and Population, Intervention, Comparator, and Outcome (PICO) frameworks. Five databases will be systematically searched for studies published in English during and after 2014: Medline, EMBASE, CINAHL, APA PsycNet, and Web of Science. Two reviewers will independently screen references’ titles and abstracts, select studies for inclusion based on the eligibility criteria, and extract the data into a standardized form. Any disagreements will be discussed and resolved by a third reviewer if necessary. Risk of bias of all studies will be assessed using the Mixed-Methods Appraisal Tool (MMAT) and a descriptive analysis will be used to evaluate the outcomes reported.Results: The systematic review will commence during 2021. Conclusions: This systematic review will summarize the impact, usability, and limitations of digital interventions for parents with acutely ill children. It will provide an overview of the field, identify reported impacts on health and behavioural outcomes; parental knowledge, satisfaction, and decision making; and the factors that affect use to help inform the development of more effective and sustainable interventions.<br/

Impact of Digital Educational Interventions to Support Parents Caring for Acutely Ill Children at Home and Factors That Affect Their Use: Protocol for a Systematic Review

BACKGROUND: Urgent and emergency care health services are overburdened, and the use of these services by acutely ill infants and children is increasing. A large proportion of these visits could be sufficiently addressed by other health care professionals. Uncertainty about the severity of a child's symptoms is one of many factors that play a role in parents' decisions to take their children to emergency services, demonstrating the need for improved support for health literacy. Digital interventions are a potential tool to improve parents' knowledge, confidence, and self-efficacy at managing acute childhood illness. However, existing systematic reviews related to this topic need to be updated and expanded to provide a contemporary review of the impact, usability, and limitations of these solutions. OBJECTIVE: The purpose of this systematic review protocol is to present the method for an evaluation of the impact, usability, and limitations of different types of digital educational interventions to support parents caring for acutely ill children at home. METHODS: The review will be structured using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) and Population, Intervention, Comparator, and Outcome (PICO) frameworks. Five databases will be systematically searched for studies published in English during and after 2014: Medline, EMBASE, CINAHL, APA PsycNet, and Web of Science. Two reviewers will independently screen references' titles and abstracts, select studies for inclusion based on the eligibility criteria, and extract the data into a standardized form. Any disagreements will be discussed and resolved by a third reviewer if necessary. Risk of bias of all studies will be assessed using the Mixed-Methods Appraisal Tool (MMAT), and a descriptive analysis will be used to evaluate the outcomes reported. RESULTS: The systematic review will commence during 2021. CONCLUSIONS: This systematic review will summarize the impact, usability, and limitations of digital interventions for parents with acutely ill children. It will provide an overview of the field; identify reported impacts on health and behavioral outcomes as well as parental knowledge, satisfaction, and decision making; and identify the factors that affect use to help inform the development of more effective and sustainable interventions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/27504

Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses

Abstract: IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and this is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R. We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3 and ZNF341, genes encoding different components of the IL-6 signalling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.J.E.D.T. is supported by the MRC (RG95376 and MR/L006197/1). KB is supported by the European Research Council (ERC StG 310857) and the Austrian Science Fund (P29951-B30). This work is supported, in part, by the intramural research program of the NIAID, NIH. A.J.T. is supported by the Wellcome Trust (104807/Z/14/Z) and the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. KGCS is supported by the Medical Research Council (program grant MR/L019027) and is a Wellcome Investigator. M.G. and S.T. are supported in part by Cancer Research UK. RCA and MT are supported by a DOC fellowship of the Austrian Academy of Sciences. This research was made possible through access to the data and findings generated by two pilot studies for the 100,000 Genomes Project. The enrolment for one pilot study was coordinated by the NIHR BioResource (preprint from doi: https://doi.org/10.1101/507244) and the other by Genomics England Limited (GEL), a wholly owned company of the Department of Health in the UK. Over 90% of participants in the pilot studies have been enrolled in the NIHR BioResource. These pilot studies were mainly funded by grants from the National Institute for Health Research (NIHR) in England to the University of Cambridge and GEL, respectively. Additional funding was provided by the BHF, MRC, NHS England, the Wellcome Trust, amongst many other funders. The pilot studies use data provided by patients and their close relatives and collected by the NHS and other healthcare providers as part of their care and support. We thank all volunteers for their participation, and also gratefully acknowledge NIHR Biomedical Research Centres, NIHR BioResource Centres, NHS Trust Hospitals, NHS Blood and Transplant and staff for their contribution. ST is on the scientific advisory board for Ipsen, and is a consultant for Kallyope Inc. The authors declare no competing financial interests

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies