A novel method for identification of patients at risk of deterioration using FACS

Facial displays are used by health professionals to assess the wellbeing of patients at risk of deterioration. Surprisingly, there is not a single early warning system based on the assessment of facial expressions. There is ample literature that supports the study of face expressions by means of anatomical based score systems, such as FACS (1). Preliminary studies suggested that outreach nurses identified mostly sadness and fear in patients at risk of deterioration (2). As part of a pilot study on analysing facial expressions in critical illness, this research has compared Action Units (AU in FACS terminology) from patients at risk of deterioration against AU inferred from 20 facial images of patients deemed to die

What faces reveal : a novel method to identify patients at risk of deterioration using facial expressions

Objectives: To identify facial expressions occurring in patients at risk of deterioration in hospital wards. Design: Prospective observational feasibility study. Setting: General ward patients in a London Community Hospital, United Kingdom. Patients: Thirty-four patients at risk of clinical deterioration. Interventions: A 5-minute video (25 frames/s; 7,500 images) was recorded, encrypted, and subsequently analyzed for action units by a trained facial action coding system psychologist blinded to outcome. Measurements and Main Results: Action units of the upper face, head position, eyes position, lips and jaw position, and lower face were analyzed in conjunction with clinical measures collected within the National Early Warning Score. The most frequently detected action units were action unit 43 (73%) for upper face, action unit 51 (11.7%) for head position, action unit 62 (5.8%) for eyes position, action unit 25 (44.1%) for lips and jaw, and action unit 15 (67.6%) for lower face. The presence of certain combined face displays was increased in patients requiring admission to intensive care, namely, action units 43 + 15 + 25 (face display 1, p < 0.013), action units 43 + 15 + 51/52 (face display 2, p < 0.003), and action units 43 + 15 + 51 + 25 (face display 3, p < 0.002). Having face display 1, face display 2, and face display 3 increased the risk of being admitted to intensive care eight-fold, 18-fold, and as a sure event, respectively. A logistic regression model with face display 1, face display 2, face display 3, and National Early Warning Score as independent covariates described admission to intensive care with an average concordance statistic (C-index) of 0.71 (p = 0.009). Conclusions: Patterned facial expressions can be identified in deteriorating general ward patients. This tool may potentially augment risk prediction of current scoring systems

Do temporal changes in facial expressions help identify patients at risk of deterioration in hospital wards? A post hoc analysis of the Visual Early Warning Score study

Objectives: To determine whether time-series analysis and Shannon information entropy of facial expressions predict acute clinical deterioration in patients on general hospital wards. Design: Post hoc analysis of a prospective observational feasibility study (Visual Early Warning Score study). Setting: General ward patients in a community hospital. Patients: Thirty-four patients at risk of clinical deterioration. Interventions: A 3-minute video (153,000 frames) for each of the patients enrolled into the Visual Early Warning Score study database was analyzed by a trained psychologist for facial expressions measured as action units using the Facial Action Coding System. Measurements and Main Results: Three-thousand six-hundred eighty-eight action unit were analyzed over the 34 3-minute study periods. The action unit time variables considered were onset, apex, offset, and total time duration. A generalized linear regression model and time-series analyses were performed. Shannon information entropy (Hn) and diversity (Dn) were calculated from the frequency and repertoire of facial expressions. Patients subsequently admitted to critical care displayed a reduced frequency rate (95% CI moving average of the mean: 9.5–10.9 vs 26.1–28.9 in those not admitted), a higher Shannon information entropy (0.30 ± 0.06 vs 0.26 ± 0.05; p = 0.019) and diversity index (1.36 ± 0.08 vs 1.30 ± 0.07; p = 0.020) and a prolonged action unit reaction time (23.5 vs 9.4 s) compared with patients not admitted to ICU. The number of action unit identified per window within the time-series analysis predicted admission to critical care with an area under the curve of 0.88. The area under the curve for National Early Warning Score alone, Hn alone, National Early Warning Score plus Hn, and National Early Warning Score plus Hn plus Dn were 0.53, 0.75, 0.76, and 0.81, respectively. Conclusions: Patients who will be admitted to intensive care have a decrease in the number of facial expressions per unit of time and an increase in their diversity

An improved classifier for mortality prediction in adult critical care admissions

Introduction: Over the last 25 years there has been significant work carried out in producing risk prediction models for patients admitted to critical care units. The most recent of these models is the Intensive Care National Audit and Research Centre (ICNARC) model developed in 2007 (1) which uses data from 231,930 admissions to 163 critical care units to develop and validate a UK based model outperforming other approaches (with an average c index of 0.863). Aims: This research aims to present an artificial neural network based model for critical care admissions that improves over the ICNARC model in terms of the discrimination across the data set used in this study. Results: Figure 1 shows a comparison between the receiver operator characteristics (ROC) curve for our artificial neural network (ANN) model and the ICNARC model presented in (1). This figure shows the ROC curve and point-wise confidence intervals for the true positive values of both our model (in blue) and the ICNARC model (in red). In comparison, our artificial neural network classification model produces an average c value of 0.8983 in 10 fold cross validation of our data compared to a c value of 0.8306 for the ICNARC model using the same data set (consisting of 642 patients admitted to North Middlesex Hospital critical care unit over a 28 month period. Data excludes 432 patients where data was incomplete). Conclusion: Our classification model provides a percentage risk score that outperforms the ICNARC model. This classification model does suffer from some of same issues surrounding the ICNARC model – for instance, the influence of some of the parameters within both models can be unclear to clinicians trying to predict the survival of individual patients. However, further work is ongoing to improve the transparency of this mode

Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients

A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia

The polygenic basis of relapse after a first episode of schizophrenia

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11–0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe