The effect of blood pressure on mortality following out-of-hospital cardiac arrest : a retrospective cohort study of the United Kingdom Intensive Care National Audit and Research Centre database

Correction: Volume27, Issue 1 Article Number:169 DOI: 10.1186/s13054-023-04458-x Published: MAY 4 2023Background: Hypotension following out-of-hospital cardiac arrest (OHCA) may cause secondary brain injury and increase mortality rates. Current guidelines recommend avoiding hypotension. However, the optimal blood pressure following OHCA is unknown. We hypothesised that exposure to hypotension and hypertension in the first 24 h in ICU would be associated with mortality following OHCA. Methods: We conducted a retrospective analysis of OHCA patients included in the Intensive Care National Audit and Research Centre Case Mix Programme from 1 January 2010 to 31 December 2019. Restricted cubic splines were created following adjustment for important prognostic variables. We report the adjusted odds ratio for associations between lowest and highest mean arterial pressure (MAP) and systolic blood pressure (SBP) in the first 24 h of ICU care and hospital mortality. Results: A total of 32,349 patients were included in the analysis. Hospital mortality was 56.2%. The median lowest and highest MAP and SBP were similar in survivors and non-survivors. Both hypotension and hypertension were associated with increased mortality. Patients who had a lowest recorded MAP in the range 60-63 mmHg had the lowest associated mortality. Patients who had a highest recorded MAP in the range 95-104 mmHg had the lowest associated mortality. The association between SBP and mortality followed a similar pattern to MAP. Conclusions: We found an association between hypotension and hypertension in the first 24 h in ICU and mortality following OHCA. The inability to distinguish between the median blood pressure of survivors and non-survivors indicates the need for research into individualised blood pressure targets for survivors following OHCA.Peer reviewe

The association between time of in hospital cardiac arrest and mortality:a retrospective analysis of two UK databases

Aims: The incidence of in hospital cardiac arrest (IHCA) varies throughout the day. This study aimed to report the variation in incidence of IHCA, presenting rhythm and outcome based on the hour in which IHCA occurred. Methods: We conducted a retrospective analysis of the National Cardiac Arrest Audit (NCAA) including patients who suffered an IHCA from 1st April 2011 to 31st December 2019. We then linked the NCAA and intensive care Case Mix Programme databases to explore the effect of time of IHCA on hospital survival in the subgroup of patients admitted to intensive care following IHCA. Results: We identified 115,690 eligible patients in the NCAA database. Pulseless electrical activity was the commonest presenting rhythm (54.8%). 66,885 patients died in the immediate post resuscitation period. Overall, hospital survival in the NCAA cohort was 21.3%. We identified 13,858 patients with linked ICU admissions in the Case Mix Programme database; 37.0% survived to hospital discharge. The incidence of IHCA peaked at 06.00. Rates of return of spontaneous circulation, survival to hospital discharge and good neurological outcome were lowest between 05.00 and 07.00. Among those admitted to ICU, no clear diurnal variation in hospital survival was seen in the unadjusted or adjusted analysis. This pattern was consistent across all presenting rhythms. Conclusions: We observed higher rates of IHCA, and poorer outcomes at night. However, in those admitted to ICU, this variation was absent. This suggests patient factors and processes of care issues contribute to the variation in IHCA seen throughout the day

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma

Priority Needs for Conducting Pandemic-Relevant Clinical Research With Children in Europe : A Consensus Study With Pediatric Clinician-Researchers

Background: Infectious disease pandemics (IDP) pose a considerable global threat and can disproportionately affect vulnerable populations including children. Pediatric clinical research in pandemics is essential to improve children’s healthcare and minimize risks of harm by interventions that lack an adequate evidence base for this population. The unique features of IDPs require consideration of special processes to facilitate clinical research. We aimed to obtain consensus on pediatric clinician-researchers’ perceptions of the priorities to feasibly conduct clinical pediatric pandemic research in Europe.Methods: Mixed method study in 2 stages, recruiting pediatric clinician-researchers with experience of conducting pediatric infectious disease (ID) research in clinical settings in Europe. Stage one was an expert stakeholder workshop and interviews. Discussions focused on participant’s experience of conducting pediatric ID research and processes to facilitate pandemic research. Information informed stage two; an on-line consensus survey to identify pediatric clinician-researchers priorities to enable IDP research.Results: Twenty-three pediatric clinician-researchers attended the workshop and thirty-nine completed the survey. Priorities were primarily focused on structural and operational requirements of research design and regulation: 1) Clarity within the European Clinical Trials Directive for pediatric pandemic research; 2) Simplified regulatory processes for research involving clinical samples and data; and 3) Improved relationships between regulatory bodies and researchers.Conclusions: Results suggest that changes need to be made to the current regulatory environment to facilitate and improve pediatric research in the pandemic context. These findings can provide expert evidence to research policy decision makers and regulators and to develop a strategy to lobby for change.</p

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A)

The Phoenix stream : a cold stream in the southern hemisphere

We report the discovery of a stellar stream in the Dark Energy Survey Year 1 (Y1A1) data. The discovery was made through simple color–magnitude filters and visual inspection of the Y1A1 data. We refer to this new object as the Phoenix stream, after its resident constellation. After subtraction of the background stellar population we detect a clear signal of a simple stellar population. By fitting the ridge line of the stream in color–magnitude space, we find that a stellar population with age τ=11.5±0.5 Gyr and [Fe/H]<−1.6, located 17.5±0.9 kpc from the Sun, gives an adequate description of the stream stellar population. The stream is detected over an extension of 8°.1 (2.5 kpc) and has a width of ∼54 pc assuming a Gaussian profile, indicating that a globular cluster (GC) is a probable progenitor. There is no known GC within 5 kpc that is compatible with being the progenitor of the stream, assuming that the stream traces its orbit. We examined overdensities (ODs) along the stream, however, no obvious counterpart-bound stellar system is visible in the coadded images. We also find ODs along the stream that appear to be symmetrically distributed—consistent with the epicyclic OD scenario for the formation of cold streams—as well as a misalignment between the northern and southern part of stream. Despite the close proximity we find no evidence that this stream and the halo cluster NGC 1261 have a common accretion origin linked to the recently found EriPhe OD

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical Covid-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalisation2-4 following SARS-CoV-2 infection. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from critically-ill cases with population controls in order to find underlying disease mechanisms. Here, we use whole genome sequencing in 7,491 critically-ill cases compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical Covid-19. We identify 16 new independent associations, including variants within genes involved in interferon signalling (IL10RB, PLSCR1), leucocyte differentiation (BCL11A), and blood type antigen secretor status (FUT2). Using transcriptome-wide association and colocalisation to infer the effect of gene expression on disease severity, we find evidence implicating multiple genes, including reduced expression of a membrane flippase (ATP11A), and increased mucin expression (MUC1), in critical disease. Mendelian randomisation provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5, CD209) and coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of Covid-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication, or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between critically-ill cases and population controls is highly efficient for detection of therapeutically-relevant mechanisms of disease

Host galaxy identification for supernova surveys

Host galaxy identification is a crucial step for modern supernova (SN) surveys such as the Dark Energy Survey (DES) and the Large Synoptic Survey Telescope (LSST), which will discover SNe by the thousands. Spectroscopic resources are limited, so in the absence of real-time SN spectra these surveys must rely on host galaxy spectra to obtain accurate redshifts for the Hubble diagram and to improve photometric classification of SNe. In addition, SN luminosities are known to correlate with host-galaxy properties. Therefore, reliable identification of host galaxies is essential for cosmology and SN science. We simulate SN events and their locations within their host galaxies to develop and test methods for matching SNe to their hosts. We use both real and simulated galaxy catalog data from the Advanced Camera for Surveys General Catalog and MICECATv2.0, respectively. We also incorporate "hostless" SNe residing in undetected faint hosts into our analysis, with an assumed hostless rate of 5%. Our fully automated algorithm is run on catalog data and matches SNe to their hosts with 91% accuracy. We find that including a machine learning component, run after the initial matching algorithm, improves the accuracy (purity) of the matching to 97% with a 2% cost in efficiency (true positive rate). Although the exact results are dependent on the details of the survey and the galaxy catalogs used, the method of identifying host galaxies we outline here can be applied to any transient survey