Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Quantifying Bias in Hierarchical Category Systems

Code for the paper: Warburton, K., Kemp, C., Xu, Y., & Frermann, L. (2024). Quantifying Bias in Hierarchical Category Systems. Open Mind: Discoveries in Cognitive Science. Advance publication. https:// doi.org/10.1162/opmi_a_0012

Talking to children about their HIV diagnosis: a discussion rooted in different global perspectives

An online meeting was arranged with four professionals representing four countries to debate current practices and future steps in naming HIV to children (disclosing HIV status). This article considers the evidence and reports on the commentary and debate from the meeting. Naming HIV to children remains a challenge. Although studies identify some of the facilitators and barriers to informing children of their HIV diagnosis, further review of practice is required. This article presents a global perspective of naming practices from different settings. The article comprises commentary and a report of the online debate, along with supporting evidence. The four participating authors concluded that health professionals must work in collaboration with families to support early naming of HIV to children or having an open discussion about HIV in clinics. Naming when a child is younger reduces self-stigma and empowers children and young people to adhere to their medication, make informed decisions and share their own diagnosis appropriately. The authors concluded that health professionals play a key role in educating colleagues and the public to reduce stigma and discrimination. Professionals working with children and families living with HIV require support and resources to instil confidence in naming and facilitate naming of HIV status to a child

Quantifying Bias in Library Classification Systems

Categorization is ubiquitous in human cognition and society, and impacts how we perceive and understand the world. In reflecting the needs and perspectives of their creators, no categorization system is entirely objective, and inbuilt biases can have harmful social consequences. Here, we propose methods for quantifying three kinds of category biases in hierarchical category systems. We present a study on two widely used library classification systems (the DDC and LCC) as large-scale examples of human categorization, and use our methods to quantify bias towards content associated with western (vs non-western) concepts in topic areas including history and religion. We find consistent evidence for western bias and show that the DDC tends to exhibit more western bias than the LCC. Our methods are general, and can be used to survey biases across topic areas, bias attributes, and hierarchical category systems

Alcohol-related harm in emergency departments: a prospective, multi-centre study

Background and aims Emergency department (ED) alcohol-related presentation data are not routinely collected in Australia and New Zealand. It is likely that previous research has underestimated the numbers of patients presenting with alcohol-related conditions. This study aimed to quantify the level of alcohol harm presenting to EDs in Australia and New Zealand [Correction added on 23 Jan 2018, after first online publication: The 'aims' section was missing and is updated in this version]. Design Multi-centre, prospective study. Patients were screened prospectively for alcohol-related presentations during a 7-day period in December 2014. Part 1 involved screening to determine alcohol-positive ED presentations and data collection of patient demographic and clinical information. Part 2 involved a consent-based survey conducted with patients aged 14 years to perform Alcohol Use Disorders Identification Test (AUDIT) scores. Setting Eight EDs in Australia and New Zealand, representing differing hospital role delineations. Participants A total of 8652 patients aged 14 years attended and 8435 (97.5%) were screened. Measurements The main outcome measure was the proportion of patients who had an alcohol-related presentation termed 'alcohol-positive', using pre-defined criteria. It included injuries, intoxication, medical conditions and injuries caused by an alcohol-affected third party. Secondary outcomes included demographic and clinical information, the type of alcohol-related presentations and AUDIT scores. Findings A total of 801 [9.5%; 95% confidence interval (CI) = 8.9-10.1%] presentations were identified as alcohol-positive, ranging between 4.9 and 15.2% throughout sites. Compared with alcohol-negative patients, alcohol-positive patients were more likely to be male [odds ratio (OR) = 1.90, 95% CI = 1.63-2.21], younger (median age 37 versus 46 years, P < 0.0001), arrive by ambulance (OR = 1.94, 95% CI = 1.68-2.25) or police/correctional vehicle (OR = 4.56, 95% CI = 3.05-6.81) and require immediate treatment (OR = 3.20, 95% CI = 2.03-05.06). The median AUDIT score was 16 (interquartile range = 10-24). Conclusions Almost one in 10 presentations to emergency departments in Australia and New Zealand are alcohol related.This study was funded by the Australian Government Department of Health