Prognostic association of routinely measured biomarkers in patients admitted to critical care: a systematic review.

PURPOSE: To examine reported prognostic associations of routine blood measurements in the intensive care unit. MATERIALS AND METHODS: We searched PubMed, EMBASE through 28th May 2020 to identify all studies in adult critical care investigating associations between parameters measured routinely in whole blood, plasma or serum, and length of stay or mortality. Registration: PROSPERO; CRD42019122058. RESULTS: A total of 128 studies, reporting 28 different putative prognostic biomarkers, met eligibility criteria. Those most frequently examined were red cell distribution width, neutrophil-to-lymphocyte ratio, C-reactive protein, and platelet count. A higher red cell distribution width, a lower platelet count, and a higher neutrophil-to-lymphocyte ratio were consistently associated with both increased mortality and length of stay. A lower level of albumin was consistently associated with greater mortality. C-reactive protein was inconsistent. Most studies (n = 110) used regression modelling with wide variation in variable selection and covariate-adjustment; none externally validated the proposed predictive models. CONCLUSIONS: Simple regression models have so far proved inadequate for the complexity of data available from routine blood sampling in critical care. Adoption of a direct causal framework may help better assess mechanistic processes, aid design of future studies, and guide clinical decision making using routine data.

Genotype-Specific Evolution of Hepatitis E Virus.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis globally. HEV comprises four genotypes with different geographic distributions and host ranges. We utilize this natural case-control study for investigating the evolution of zoonotic viruses compared to single-host viruses, using 244 near-full-length HEV genomes. Genome-wide estimates of the ratio of nonsynonymous to synonymous evolutionary changes (dN/dS ratio) located a region of overlapping reading frames, which is subject to positive selection in genotypes 3 and 4. The open reading frames (ORFs) involved have functions related to host-pathogen interaction, so genotype-specific evolution of these regions may reflect their fitness. Bayesian inference of evolutionary rates shows that genotypes 3 and 4 have significantly higher rates than genotype 1 across all ORFs. Reconstruction of the phylogenies of zoonotic genotypes demonstrates significant intermingling of isolates between hosts. We speculate that the genotype-specific differences may result from cyclical adaptation to different hosts in genotypes 3 and 4.IMPORTANCE Hepatitis E virus (HEV) is increasingly recognized as a pathogen that affects both the developing and the developed world. While most often clinically mild, HEV can be severe or fatal in certain demographics, such as expectant mothers. Like many other viral pathogens, HEV has been classified into several distinct genotypes. We show that most of the HEV genome is evolutionarily constrained. One locus of positive selection is unusual in that it encodes two distinct protein products. We are the first to detect positive selection in this overlap region. Genotype 1, which infects humans only, appears to be evolving differently from genotypes 3 and 4, which infect multiple species, possibly because genotypes 3 and 4 are unable to achieve the same fitness due to repeated host jumps.

Long-term healthcare use after postoperative complications: an analysis of linked primary and secondary care routine data.

Background: Postoperative complications are associated with reduced long-term survival. We characterise healthcare use changes after sentinel postoperative complications. Methods: We linked primary and secondary care records of patients undergoing elective surgery at four East London hospitals (2012-7) with at least 90 days follow-up. Complication codes (wound infection, urinary tract infection, pneumonia, new stroke, and new myocardial infarction) recorded within 90 days of surgery were identified from primary or secondary care. Outcomes were change in healthcare contact days in the 2 yr before and after surgery, and 2 yr mortality. We report rate ratios (RaR) with 95% confidence intervals and adjusted for baseline healthcare use and confounders using negative binomial regression. Results: We included 49 913 patients (median age 49 yr [inter-quartile range {IQR}: 34-64]), 27 958 (56.0%) were female. Amongst 3883 (7.8%) patients with complications (median age 58 [IQR: 43-72]), there were 18.4 days per year in contact with healthcare before surgery and 25.3 days after surgery (RaR: 1.38 [1.37-1.39]). Patients without complications (median age 48 [IQR: 33-63]) had 12.3 days per year in contact with healthcare before surgery and 14.0 days after surgery (RaR: 1.14 [1.14-1.15]). The adjusted incidence rate ratio of days in contact with healthcare associated with complications was 1.67 (1.49-1.87). More patients (391; 10.1%) with complications died within 2 yr than those without (1428; 3.1%). Conclusions: Patients with postoperative complications are older with greater healthcare use before surgery. However, their absolute and relative increases in healthcare use after surgery are greater than patients without complications.

Critical care drowning admissions in Southwest England 2009-2020, a retrospective study.

Aim: In the United Kingdom (UK), 600 deaths per annum are attributable to drowning. Despite this there is scarce critical care data on drowning patients globally. We describe drowning cases admitted to critical care units with a focus on functional outcomes. Materials and Methods: Medical records for critical care admissions following a drowning event were retrospectively reviewed across six hospitals in Southwest England for cases presenting in the period between 2009 and 2020. Data was collected according to the Utstein international consensus guidelines on drowning. Results: Forty-nine patients were included, 36 males and 13 females, including seven children. Median submersion duration was 2.5 min 20 cases were in cardiac arrest when rescued. At discharge 22 patients had preserved functional status, 10 patients had a reduced functional status. 17 patients died in hospital. Conclusion: Admission to critical care following drowning is uncommon and associated with high rates of mortality and poor functional outcomes. We find that 31% of those who survived a drowning event subsequently required an increased level of assistance with their activities of daily living.