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.

Comparing mortality among adult, general intensive care units in England with varying intensivist cover patterns: a retrospective cohort study.

INTRODUCTION: Research has demonstrated that intensivist-led care of the critically ill is associated with reduced intensive care unit (ICU) and hospital mortality. The objective of this study was to evaluate whether a relation exists between intensivist cover pattern (for example, number of days of continuous cover) and patient outcomes among adult general ICUs in England. METHODS: We conducted a retrospective cohort study by using data from a pooled case mix and outcome database of adult general critical care units participating in the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme. Consecutive admissions to participating units for the years 2010 to 2011 were linked to a survey of intensivist cover practices. Our primary outcome of interest was mortality at ultimate discharge from acute-care hospital. RESULTS: The analysis included 80,122 patients admitted to 130 ICUs in 128 hospitals. Multivariable logistic regression analysis was used to assess the relation between intensivist cover patterns (days of continuous cover, grade of physician staffing at nighttime, and frequency of daily handovers) and acute hospital mortality, adjusting for patient case mix. No relation was seen between days of continuous cover by a single intensivist or grade of physician staffing at nighttime and acute hospital mortality. Acute hospital mortality and ICU length of stay were not associated with intensivist characteristics, intensivist full-time equivalents per bed, or years of clinical experience. Intensivist participation in handover was associated with increased mortality (odds ratio, 1.27; 95% confidence interval, 1.04 to 1.55); however, only nine units reported no intensivist participation. CONCLUSIONS: We found no relation between days of continuous cover by a single intensivist or grade of physician staffing at nighttime and patient outcomes in adult, general ICUs in England. Intensivist participation in handover was associated with increased mortality; further research to confirm or refute this finding is required.

The increasing burden of alcoholic liver disease on United Kingdom critical care units: secondary analysis of a high quality clinical database.

OBJECTIVES: To investigate the effect of increasing alcohol consumption on the number of admissions to adult, general critical/intensive care units (ICUs) in England and Wales with alcoholic liver disease, their case mix, mortality, and impact on critical care and hospital activity by extrapolating from admissions to ICUs over the last 10 years. METHODS: Secondary analysis of a high quality clinical database from a national clinical audit using data from 385,429 admissions to174 ICUs in England and Wales between December 1995 and July 2005, of which 4219 (1.1%) had alcoholic liver disease. The extrapolated total number of admissions with alcoholic liver disease and total number of ICU bed-days occupied were calculated. Changes over time in the case mix (age, sex and APACHE II and ICNARC risk prediction models), mortality at ultimate discharge from acute hospital, and length of stay in ICU and in hospital were explored. RESULTS: The percentage of ICU admissions with alcoholic liver disease increased from 0.65% in 1996 to 1.35% in 2005, but the case mix remained similar. Mortality decreased and length of stay increased over this period. The extrapolated total number of admissions to all 229 adult, general critical care units in England and Wales increased from 550 in 1996 to 1513 in 2005, and the extrapolated total number of bed-days occupied by these admissions increased from around 3100 to over 10,000. CONCLUSIONS: Admissions to ICUs in England and Wales with alcoholic liver disease tripled over the 10-year period from 1996 to 2005. The continuing increase in alcohol consumption means that this trend is likely to continue.

A new risk prediction model for critical care: the Intensive Care National Audit & Research Centre (ICNARC) model.

OBJECTIVE: To develop a new model to improve risk prediction for admissions to adult critical care units in the UK. DESIGN: Prospective cohort study. SETTING: The setting was 163 adult, general critical care units in England, Wales, and Northern Ireland, December 1995 to August 2003. PATIENTS: Patients were 216,626 critical care admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The performance of different approaches to modeling physiologic measurements was evaluated, and the best methods were selected to produce a new physiology score. This physiology score was combined with other information relating to the critical care admission-age, diagnostic category, source of admission, and cardiopulmonary resuscitation before admission-to develop a risk prediction model. Modeling interactions between diagnostic category and physiology score enabled the inclusion of groups of admissions that are frequently excluded from risk prediction models. The new model showed good discrimination (mean c index 0.870) and fit (mean Shapiro's R 0.665, mean Brier's score 0.132) in 200 repeated validation samples and performed well when compared with recalibrated versions of existing published risk prediction models in the cohort of patients eligible for all models. The hypothesis of perfect fit was rejected for all models, including the Intensive Care National Audit & Research Centre (ICNARC) model, as is to be expected in such a large cohort. CONCLUSIONS: The ICNARC model demonstrated better discrimination and overall fit than existing risk prediction models, even following recalibration of these models. We recommend it be used to replace previously published models for risk adjustment in the UK.

The Acute Care Undergraduate TEaching (ACUTE) Initiative: consensus development of core competencies in acute care for undergraduates in the United Kingdom.

BACKGROUND: The care of the acutely ill patient in hospital is often sub-optimal. Poor recognition of critical illness combined with a lack of knowledge, failure to appreciate the clinical urgency of a situation, a lack of supervision, failure to seek advice and poor communication have been identified as contributory factors. At present the training of medical students in these important skills is fragmented. The aim of this study was to use consensus techniques to identify the core competencies in the care of acutely ill or arrested adult patients that medical students should possess at the point of graduation. DESIGN: Healthcare professionals were invited to contribute suggestions for competencies to a website as part of a modified Delphi survey. The competency proposals were grouped into themes and rated by a nominal group comprised of physicians, nurses and students from the UK. The nominal group rated the importance of each competency using a 5-point Likert scale. RESULTS: A total of 359 healthcare professionals contributed 2,629 competency suggestions during the Delphi survey. These were reduced to 88 representative themes covering: airway and oxygenation; breathing and ventilation; circulation; confusion and coma; drugs, therapeutics and protocols; clinical examination; monitoring and investigations; team-working, organisation and communication; patient and societal needs; trauma; equipment; pre-hospital care; infection and inflammation. The nominal group identified 71 essential and 16 optional competencies which students should possess at the point of graduation. CONCLUSIONS: We propose these competencies form a core set for undergraduate training in resuscitation and acute care.