Understanding tensions and identifying clinician agreement on improvements to early-stage chronic kidney disease monitoring in primary care : a qualitative study

Funding This article presents independent research funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR) (reference:120). JE was also supported by the NIHR Programme Grants for Applied Research programme (Reference: RP-PG-1210-12012). DSL and LL are supported by the NIHR Oxford Biomedical Research CentrePeer reviewedPublisher PD

UPBEAT-UK::a programme of research into the relationship between coronary heart disease and depression in primary care patients

Many people with coronary heart disease (CHD) are depressed and research on people who have had a heart attack found that depression increases the chance of further heart attacks. The UPBEAT-UK team conducted research with people on general practitioner CHD registers in 33 south London practices to: examine any link between CHD, depression and worse future heart disease; and develop case\ud management by practice nurses for people with CHD and depression. We followed 803 people with CHD for up to 3 years, assessing them for depression, chest pain and\ud worsening of heart disease, and also measured care costs. We asked patients, GPs and nurses how people with CHD and depression should be treated. From this, we developed care designed for each person called ‘personalised care’ (PC). We tested it in 41 people (while 40 people received their usual care from GPs)\ud with chest pain and depression, to assess how acceptable it is, whether or not it helps and what the costs would be. PC was acceptable to people, and those who received it reported less chest pain 6 and 12 months later. Costs were lower following PC but the difference was not statistically significant. Just under half of those with CHD had chest pain. Depression was frequent, but anxiety was more\ud common and increased the chances of both heart attacks and death. We conclude that further research is needed to understand the links between anxiety, chest pain and heart\ud disease, and to further develop our promising findings that PC can be helpful in reducing chest pain in\ud general practice

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales. Archives of Virology (2021) 166:3567–3579. https://doi.org/10.1007/s00705-021-05266-wIn March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. This work was also supported in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. 75N91019D00024, Task Order No. 75N91019F00130 to I.C., who was supported by the Clinical Monitoring Research Program Directorate, Frederick National Lab for Cancer Research. This work was also funded in part by Contract No. HSHQDC-15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges partial support from the Special Research Initiative of Mississippi Agricultural and Forestry Experiment Station (MAFES), Mississippi State University, and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project 1021494. Part of this work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001030), the UK Medical Research Council (FC001030), and the Wellcome Trust (FC001030).S

"Sometimes we can't fix things": A qualitative study of health care professionals' perceptions of end of life care for patients with heart failure

Background Although heart failure has a worse prognosis than some cancers, patients often have restricted access to well-developed end of life (EoL) models of care. Studies show that patients with advanced heart failure may have a poor understanding of their condition and its outcome and, therefore, miss opportunities to discuss their wishes for EoL care and preferred place of death. We aimed to explore the perceptions and experiences of health care professionals (HCPs) working with patients with heart failure around EoL care. Design A qualitative in-depth interview study nested in a wider ethnographic study of unplanned admissions in patients with heart failure (HoldFAST). We interviewed 24 HCPs across primary, secondary and community care in three locations in England, UK – the Midlands, South Central and South West. Results The study revealed three issues impacting on EoL care for heart failure patients. Firstly, HCPs discussed approaches to communicating with patients about death and highlighted the challenges involved. HCPs would like to have conversations with patients and families about death and dying but are aware that patient preferences are not easy to predict. Secondly, professionals acknowledged difficulties recognising when patients have reached the end of their life. Lack of communication between patients and professionals can result in situations where inappropriate treatment takes place at the end of patients’ lives. Thirdly, HCPs discussed the struggle to find alternatives to hospital admission for patients at the end of their life. Patients may be hospitalised because of a lack of planning which would enable them to die at home, if they so wished. Conclusions The HCPs regarded opportunities for patients with heart failure to have ongoing discussions about their EoL care with clinicians they know as essential. These key professionals can help co-ordinate care and support in the terminal phase of the condition. Links between heart failure teams and specialist palliative care services appear to benefit patients, and further sharing of expertise between teams is recommended. Further research is needed to develop prognostic models to indicate when a transition to palliation is required and to evaluate specialist palliative care services where heart failure patients are included

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Patients' perceptions of depression and coronary heart disease:a qualitative UPBEAT-UK study

BACKGROUND: The prevalence of depression in people with coronary heart disease (CHD) is high but little is known about patients’ own perceptions and experiences of this. This study aimed to explore (i) primary care (PC) patients’ perceptions of links between their physical condition and mental health, (ii) their experiences of living with depression and CHD and (iii) their own self-help strategies and attitudes to current PC interventions for depression. METHOD: Qualitative study using consecutive sampling, in-depth interviews and thematic analysis using a process of constant comparison. 30 participants from the UPBEAT-UK cohort study, with CHD and symptoms of depression. All participants were registered on the General Practitioner (GP) primary care, coronary register. RESULTS: A personal and social story of loss underpinned participants’ accounts of their lives, both before and after their experience of having CHD. This theme included two interrelated domains: interpersonal loss and loss centred upon health/control issues. Strong links were made between CHD and depression by men who felt emasculated by CHD. Weaker links were made by participants who had experienced distressing life events such as divorce and bereavement or were living with additional chronic health conditions (i.e. multimorbidity). Participants also felt ‘depressed’ by the ‘medicalisation’ of their lives, loneliness and the experience of ageing and ill health. Just under half the sample had consulted their GP about their low mood and participants were somewhat ambivalent about accessing primary care interventions for depression believing the GP would not be able to help them with complex health and social issues. Talking therapies and interventions providing the opportunity for social interaction, support and exercise, such as Cardiac Rehabilitation, were thought to be helpful whereas anti-depressants were not favoured. CONCLUSIONS: The experiences and needs of patients with CHD and depression are diverse and include psycho-social issues involving interpersonal and health/control losses. In view of the varying social and health needs of patients with CHD and depression the adoption of a holistic, case management approach to care is recommended together with personalised support providing the opportunity for patients to develop and achieve life and health goals, where appropriate