Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning

ObjectiveClinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce.MethodMeasures of Complement Activation and inflammation in patientS with CoronAvirus DisEase 2019 (CASCADE) patients (n = 72), (clinicaltrials.gov: NCT04453527), classified as mild, moderate, or severe (by support needed to maintain SpO2 > 93%), and healthy controls (HC, n = 20), were bioprofiled using 76 immunological biomarkers and compared using ANOVA. Spearman correlation analysis on biomarker pairs was visualised via heatmaps. Linear Discriminant Analysis (LDA) models were generated to identify patients likely to deteriorate. An X-Gradient-boost (XGB) model trained on CASCADE data to triage patients as mild, moderate, and severe was retrospectively employed to classify COROnavirus Nomacopan Emergency Treatment for covid 19 infected patients with early signs of respiratory distress (CORONET) patients (n = 7) treated with nomacopan.ResultsThe LDA models distinctly discriminated between deteriorators, nondeteriorators, and HC, with IL-27, IP-10, MDC, ferritin, C5, and sC5b-9 among the key predictor variables during deterioration. C3a and C5 were elevated in all severity classes vs. HC (p < 0.05). sC5b-9 was elevated in the “moderate” and “severe” categories vs. HC (p < 0.001). Heatmap analysis shows a pairwise increase of negatively correlated pairs with IL-27. The XGB model indicated sC5b-9, IL-8, MCP1, and prothrombin F1 and F2 were key discriminators in nomacopan-treated patients (CORONET study).ConclusionDistinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery

Interaction between cannabis consumption and childhood abuse in psychotic disorders:preliminary findings on the role of different patterns of cannabis use

Aim: Several studies have suggested that lifetime cannabis consumption and childhood abuse synergistically contribute to the risk for psychotic disorders. This study aimed to extend existing findings regarding an additive interaction between childhood abuse and lifetime cannabis use by investigating the moderating role of type and frequency of cannabis use. Methods: Up to 231 individuals presenting for the first time to mental health services with psychotic disorders and 214 unaffected population controls from South London, United Kingdom, were recruited as part of the Genetics and Psychosis study. Information about history of cannabis use was collected using the Cannabis Experiences Questionnaire. Childhood physical and sexual abuse was assessed using the Childhood Experience of Care and Abuse Questionnaire. Results: Neither lifetime cannabis use nor reported exposure to childhood abuse was associated with psychotic disorder when the other environmental variable was taken into account. Although the combination of the two risk factors raised the odds for psychosis by nearly three times (adjusted OR = 2.94, 95% CI: 1.44–6.02, P = 0.003), no evidence of interaction was found (adjusted OR = 1.46, 95% CI: −0.54 to 3.46, P = 0.152). Furthermore, the association of high-potency cannabis and daily consumption with psychosis was at least partially independent of the effect of childhood abuse. Conclusions: The heavy use of high-potency cannabis increases the risk of psychosis but, in addition, smoking of traditional resin (hash) and less than daily cannabis use may increase the risk for psychosis when combined with exposure to severe childhood abuse.</p

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Climate and population biology of trochids along the English Channel: are impacts of the cold winter of 2005/2006 detectable.

Intertidal species are useful indicators of marine biodiversity response to climate change. The trochid species Gibbula umbilicalis and Osilinus lineatus were studied at their eastern limit in the English Channel to determine the factors setting distribution limit and if climatic controls can be detected. The abundance of trochids on rocky shores was measured using a catch per unit effort method of repeated three minute counts. Limitations in this method have been identified and a new method to estimate population abundance of trochids on rocky shores has been proposed (see appendix 1). Trochid populations have extended their range eastwards along the English Channel. Populations of G. umbilicalis now inhabit as far east as Beachy Head, east Sussex. This is thought to be the result of sea defence structures at Elmer, Sussex increasing the connectivity of suitable habitat between the Isle of Wight and Sussex. The 0. lineatus population at Portland Harbour, Dorset has increased in abundance and is potentially the main source of recruits at White Nothe and Osmington Mills, Dorset. The gonad development in trochid populations in the western basin of the Channel (milder winter temperatures) is larger than in the eastern basin (lower winter temperatures), suggesting some temperature/ climatic control. Regression analysis revealed that there is a strong relationship between the population density and shell size of G. umbilicalis, but not in O. lineatus. Changes in the reproductive cycle of trochids after the 2005/6 winter were detected but it is not clear if reproductive success was affected.Faculty of Scienc

Measurement of Vital Signs by Lifelight Software in Comparison to Standard of Care Multisite Development (VISION-MD): Protocol for an Observational Study

BackgroundMeasuring vital signs (VS) is an important aspect of clinical care but is time-consuming and requires multiple pieces of equipment and trained staff. Interest in the contactless measurement of VS has grown since the COVID-19 pandemic, including in nonclinical situations. Lifelight is an app being developed as a medical device for the contactless measurement of VS using remote photoplethysmography (rPPG) via the camera on smart devices. The VISION-D (Measurement of Vital Signs by Lifelight Software in Comparison to the Standard of Care—Development) and VISION-V (Validation) studies demonstrated the accuracy of Lifelight compared with standard-of-care measurement of blood pressure, pulse rate, and respiratory rate, supporting the certification of Lifelight as a class I Conformité Européenne (CE) medical device. ObjectiveTo support further development of the Lifelight app, the observational VISION Multisite Development (VISION-MD) study is collecting high-quality data from a broad range of patients, including those with VS measurements outside the normal healthy range and patients who are critically ill. MethodsThe study is recruiting adults (aged ≥16 years) who are inpatients (some critically ill), outpatients, and healthy volunteers, aiming to cover a broad range of normal and clinically relevant VS values; there are no exclusion criteria. High-resolution 60-second videos of the face are recorded by the Lifelight app while simultaneously measuring VS using standard-of-care methods (automated sphygmomanometer for blood pressure; finger clip sensor for pulse rate and oxygen saturation; manual counting of respiratory rate). Feedback from patients and nurses who use Lifelight is collected via a questionnaire. Data to estimate the cost-effectiveness of Lifelight compared with standard-of-care VS measurement are also being collected. A new method for rPPG signal processing is currently being developed, based on the identification of small areas of high-quality signals in each individual. Anticipated recruitment is 1950 participants, with the expectation that data from approximately 1700 will be used for software development. Data from 250 participants will be retained to test the performance of Lifelight against predefined performance targets. ResultsRecruitment began in May 2021 but was hindered by the restrictions instigated during the COVID-19 pandemic. The development of data processing methodology is in progress. The data for analysis will become available from September 2022, and the algorithms will be refined continuously to improve clinical accuracy. The performance of Lifelight compared with that of the standard-of-care measurement of VS will then be tested. Recruitment will resume if further data are required. The analyses are expected to be completed in early 2023. ConclusionsThis study will support the refinement of data collection and processing toward the development of a robust app that is suitable for routine clinical use. Trial RegistrationClinicalTrials.gov NCT04763746; https://clinicaltrials.gov/ct2/show/NCT04763746 International Registered Report Identifier (IRRID)DERR1-10.2196/4153

Neuropsychological, clinical and cognitive insight predictors of outcome in a first episode psychosis study

The outcome of first episode psychosis (FEP) is highly variable and difficult to predict. We studied prospectively the impact of poor insight and neuropsychological deficits on outcomes in a longitudinal cohort of 127 FEP patients. Participants were assessed on 5 domains of cognitive function and 2 domains of insight (clinical and cognitive). At 12. months, patients were assessed again for symptom severity and psychosocial function. Regression analyses revealed that cognitive insight (a measure of self-reflectiveness and self-certainty) was the best baseline predictor of overall psychopathology at 12. months whereas executive function performance at admission to the study indicated later severity of negative symptoms. Other neuropsychological and insight measures were poor predictors of psychosocial function at 1. year. The results suggest that specific neuropsychological and insight factors have separate predictive capacities indicating that they are distinct psychological processes in psychosis. Cognitive insight proved to be a useful prognostic indicator, and should be considered for future studies and as a potential focus for treatment. \ua9 2013 Elsevier B.V