Cohort profile of the Biomarkers of Acute Serious Illness in Children (BASIC) study: a prospective multicentre cohort study in critically ill children

Yael Feinstein, Jennifer Claire Walker, Mark J Peters, Simon Nadel, Nazima Pathan, Naomi Edmonds, Jethro Herberg, Myrsini Kaforou, Victoria Wright, Michael Levin, Padmanabhan Ramnarayan, Yael Feinstein, Jennifer Claire Walker, Mark J Peters, Simon Nadel, Nazima Pathan, Naomi Edmonds, Jethro Herberg, Myrsini Kaforou, Victoria Wright, Michael Levin, Padmanabhan Ramnarayan

Abstract

Purpose: Despite significant progress, challenges remain in the management of critically ill children, including early identification of infection and organ failure and robust early risk stratification to predict poor outcome. The Biomarkers of Acute Serious Illness in Children study aims to identify genetic and biological pathways underlying the development of critical illness in infections and organ failure and those leading to poor outcome (death or severe disability) in children requiring emergency intensive care.

Participants: We recruited a prospective cohort of critically ill children undergoing emergency transport to four paediatric intensive care units (PICUs) in Southeast England between April 2014 and December 2016.

Findings to date: During the study period, 1017 patients were recruited by the regional PICU transport team, and blood and urine samples were obtained at/around first contact with the patient by the transport team. Consent for participation in the study was deferred until after PICU admission and 674 parents/carers were consented. Further samples (blood, urine, stool and throat swabs) were collected after consent. Samples were processed and stored for genomic, transcriptomic, proteomic and metabolomic analyses. Demographic, clinical and laboratory data at first contact, during PICU stay and at discharge, were collected, as were detailed data regarding infectious or non-infectious aetiology. In addition, 115 families have completed 12-month validated follow-up questionnaires to assess quality of life and child behaviour.The first phase of sample analyses (transcriptomic profiling) is currently in progress.

Future plans: Stored samples will be analysed using genomic, proteomic and metabolic profiling. Advanced bioinformatics techniques will be used to identify biomarkers for early diagnosis of infection, identification of organ failure and risk stratification to predict poor outcome (death/severe disability).

Trial registration number: NCT03238040.

Keywords: biomarkers; children; multi-omics; retreival.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flow chart of recruitment to the Biomarkers of Acute Serious Illness in Children study.

References

    1. Paediatric Intensive Care Network (PICANet). National report of the Paediatric Intensive Care Audit Network, January 2011–December 2013. Leeds 2014.
    1. Namachivayam P, Shann F, Shekerdemian L, et al. . Three decades of pediatric intensive care: Who was admitted, what happened in intensive care, and what happened afterward. Pediatr Crit Care Med 2010;11:549–55. 10.1097/PCC.0b013e3181ce7427
    1. Ramnarayan P, Thiru K, Parslow RC, et al. . Effect of specialist retrieval teams on outcomes in children admitted to paediatric intensive care units in England and Wales: a retrospective cohort study. Lancet 2010;376:698–704. 10.1016/S0140-6736(10)61113-0
    1. Agbeko RS, Burns JP, Peters MJ. Tools for revealing uncomfortable truths? Measuring child-centred health-related quality of life after paediatric intensive care. Intensive Care Med 2015;41:1330–2. 10.1007/s00134-015-3873-3
    1. Thompson MJ, Van den Bruel A. Diagnosing serious bacterial infection in young febrile children. BMJ 2010;340:c2062 10.1136/bmj.c2062
    1. Brent AJ, Lakhanpaul M, Thompson M, et al. . Risk score to stratify children with suspected serious bacterial infection: observational cohort study. Arch Dis Child 2011;96:361–7. 10.1136/adc.2010.183111
    1. Ostrowsky B, Banerjee R, Bonomo RA, et al. . Infectious diseases physicians: Leading the way in antimicrobial stewardship. Clin Infect Dis 2018;66:995–1003. 10.1093/cid/cix1093
    1. Le Doare K, Nichols AL, Payne H, et al. . Very low rates of culture-confirmed invasive bacterial infections in a prospective 3-year population-based surveillance in Southwest London. Arch Dis Child 2014;99:526–31. 10.1136/archdischild-2013-305565
    1. Leteurtre S, Martinot A, Duhamel A, et al. . Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet 2003;362:192–7. 10.1016/S0140-6736(03)13908-6
    1. Sweney JS, Poss WB, Grissom CK, et al. . Comparison of severity of illness scores to physician clinical judgment for potential use in pediatric critical care triage. Disaster Med Public Health Prep 2012;6:126–30. 10.1001/dmp.2012.17
    1. Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a pediatric sequential organ failure assessment score and evaluation of the sepsis-3 definitions in critically ill children. JAMA Pediatr 2017;171:e172352 10.1001/jamapediatrics.2017.2352
    1. Straney L, Clements A, Parslow RC, et al. . Paediatric index of mortality 3: an updated model for predicting mortality in pediatric intensive care*. Pediatr Crit Care Med 2013;14:673–81. 10.1097/PCC.0b013e31829760cf
    1. Pollack MM, Patel KM, Ruttimann UE. The pediatric risk of mortality III–Acute Physiology Score (PRISM III-APS): a method of assessing physiologic instability for pediatric intensive care unit patients. J Pediatr 1997;131:575–81. 10.1016/S0022-3476(97)70065-9
    1. Wong HR, Cvijanovich NZ, Anas N, et al. . Improved risk stratification in pediatric septic shock using both protein and mRNA biomarkers. PERSEVERE-XP. Am J Respir Crit Care Med 2017;196:494–501. 10.1164/rccm.201701-0066OC
    1. Mickiewicz B, Vogel HJ, Wong HR, et al. . Metabolomics as a novel approach for early diagnosis of pediatric septic shock and its mortality. Am J Respir Crit Care Med 2013;187:967–76. 10.1164/rccm.201209-1726OC
    1. Correia GD, Wooi Ng K, Wijeyesekera A, et al. . Metabolic profiling of children undergoing surgery for congenital heart disease. Crit Care Med 2015;43:1467–76. 10.1097/CCM.0000000000000982
    1. Sweeney TE, Azad TD, Donato M, et al. . Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters. Crit Care Med 2018;46:915–25. 10.1097/CCM.0000000000003084
    1. Valenzuela-Sánchez F, Valenzuela-Méndez B, Rodríguez-Gutiérrez JF, et al. . Personalized medicine in severe influenza. Eur J Clin Microbiol Infect Dis 2016;35:893–7. 10.1007/s10096-016-2611-2
    1. Friggeri A, Cazalis MA, Pachot A, et al. . Decreased CX3CR1 messenger RNA expression is an independent molecular biomarker of early and late mortality in critically ill patients. Crit Care 2016;20:204 10.1186/s13054-016-1362-x
    1. Herberg JA, Kaforou M, Wright VJ, et al. . Diagnostic test accuracy of a 2-transcript Host RNA signature for discriminating bacterial vs viral infection in febrile children. JAMA 2016;316:835–45. 10.1001/jama.2016.11236
    1. Kaforou M, Herberg JA, Wright VJ, et al. . Diagnosis of bacterial infection using a 2-transcript host RNA signature in febrile infants 60 days or younger. JAMA 2017;317:1577–8. 10.1001/jama.2017.1365
    1. Woolfall K, Frith L, Dawson A, et al. . Fifteen-minute consultation: an evidence-based approach to research without prior consent (deferred consent) in neonatal and paediatric critical care trials. Arch Dis Child Educ Pract Ed 2016;101:49–53. 10.1136/archdischild-2015-309245
    1. Woolfall K, Frith L, Gamble C, et al. . How experience makes a difference: practitioners' views on the use of deferred consent in paediatric and neonatal emergency care trials. BMC Med Ethics 2013;14:45 10.1186/1472-6939-14-45
    1. Harron K, Woolfall K, Dwan K, et al. . Deferred consent for randomized controlled trials in emergency care settings. Pediatrics 2015;136:e1316–e1322. 10.1542/peds.2015-0512
    1. Elliott P, Peakman TC. The UK Biobank sample handling and storage protocol for the collection, processing and archiving of human blood and urine. Int J Epidemiol 2008;37:234–44. 10.1093/ije/dym276
    1. Peakman TC, Elliott P. The UK Biobank sample handling and storage validation studies. Int J Epidemiol 2008;37:i2–6. 10.1093/ije/dyn019
    1. Herberg JA, Kaforou M, Wright VJ, et al. . Diagnostic test accuracy of a 2-Transcript Host RNA signature for discriminating bacterial vs viral infection in febrile children. JAMA 2016;316:835–45. 10.1001/jama.2016.11236

Source: PubMed

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