Screening for factors influencing parental psychological vulnerability during a child’s PICU admission

OBJECTIVES: To identify the risks of developing post-traumatic stress disorder (PTSD) and/or depression in parents following their child’s PICU admission using a brief screening instrument and to examine the associations with these risks.  DESIGN: A cross-sectional parental survey.  SETTING: A general 13-bed PICU at a large teaching hospital.  SUBJECTS: One hundred and seven parents of 75 children admitted to the PICU.    INTERVENTIONS: None.  MEASUREMENTS AND MAIN RESULTS: All parents completed the 10-item Posttraumatic Adjustment Screen (PAS) before discharge. The PAS assesses risk factors known to be associated with poorer psychological outcome, including psychosocial variables pretrauma and peritrauma, and acute stress. Parents’ scores on the PAS indicated that 64 (60%) were at risk of developing PTSD and 80 (75%) were at risk of developing depression following their child’s admission. Univariate analyses suggested that psychosocial variables, such as preexisting stressors and a history of previous mental health problems, were more strongly associated with PAS risk scores for PTSD and depression than medical or sociodemographic factors. In logistic regression analyses, a history of previous mental health problems was significantly associated with risk of developing PTSD and depression (p < 0.001) explaining 28% and 43% of the variance in these outcomes.  CONCLUSIONS: This study suggests that a significant number of parents on PICU are potentially at risk of developing PTSD and/or depression postdischarge and that psychosocial factors, pretrauma and peritrauma, are stronger determinants of this risk, and of acute distress, than other variables. Identification of vulnerable parents during admission, using a measure such as the PAS, could facilitate the targeting of support and monitoring, acutely and postdischarge, at those who might be most likely to benefit

A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era

Background In the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making. Methods An online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe and Australasia with a total of 755 members. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array. Results Seventy-two survey responses were received; most responses were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within 6 h for stable patients and within 1 h for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team. Conclusions Diagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial. Trial registration Clinicaltrials.gov, NCT04233268. Registered on 18 January 2020

Rapid Assay for Sick Children with Acute Lung infection Study (RASCALS): diagnostic cohort study protocol.

INTRODUCTION: Lower respiratory tract infection (LRTI) is the most commonly treated infection in critically ill children. Pathogens are infrequently identified on routine respiratory culture, and this is a time-consuming process. A syndromic approach to rapid molecular testing that includes a wide range of bacterial and fungal targets has the potential to aid clinical decision making and reduce unnecessary broad spectrum antimicrobial prescribing. Here, we describe a single-centre prospective cohort study investigating the use of a 52-pathogen TaqMan array card (TAC) for LRTI in the paediatric intensive care unit (PICU). METHODS AND ANALYSIS: Critically ill children with suspected LRTI will be enrolled to this 100 patient single-centre prospective observational study in a PICU in the East of England. Samples will be obtained via routine non-bronchoscopic bronchoalveolar lavage which will be sent for standard microbiology culture in addition to TAC. A blood draw will be obtained via any existing vascular access device. The primary outcomes of the study will be (1) concordance of TAC result with routine culture and 16S rRNA gene sequencing and (2) time of diagnostic result from TAC versus routine culture. Secondary outcomes will include impact of the test on total antimicrobial prescriptions, a description of the inflammatory profile of the lung and blood in response to pneumonia and a description of the clinical experience of medical and nursing staff using TAC. ETHICS AND DISSEMINATION: This study has been approved by the Yorkshire and the Humber-Bradford Leeds Research Ethics Committee (REC reference 20/YH/0089). Informed consent will be obtained from all participants. Results will be published in peer-reviewed publications and international conferences. TRIAL REGISTRATION NUMBER: NCT04233268

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Rapid Detection of Antimicrobial Resistance Genes in Critically Ill Children Using a Custom TaqMan Array Card

Bacteria are identified in only 22% of critically ill children with respiratory infections treated with antimicrobial therapy. Once an organism is isolated, antimicrobial susceptibility results (pheno-typic testing) can take another day. A rapid diagnostic test identifying antimicrobial resistance (AMR) genes could help clinicians make earlier, informed antimicrobial decisions. Here we aimed to validate a custom AMR gene TaqMan Array Card (AMR-TAC) for the first time and assess its feasibility as a screening tool in critically ill children. An AMR-TAC was developed using a com-bination of commercial and bespoke targets capable of detecting 23 AMR genes. This was vali-dated using isolates with known phenotypic resistance. The card was then tested on lower respir-atory tract and faecal samples obtained from mechanically ventilated children in a single-centre observational study of respiratory infection. There were 82 children with samples available, with a median age of 1.2 years. Major comorbidity was present in 29 (35%) children. A bacterial res-piratory pathogen was identified in 13/82 (16%) of children, of which 4/13 (31%) had phenotypic AMR. One AMR gene was detected in 49/82 (60%), and multiple AMR genes were detected in 14/82 (17%) children. Most AMR gene detections were not associated with the identification of pheno-typic AMR. AMR genes are commonly detected in samples collected from mechanically ventilated children with suspected respiratory infections. AMR-TAC may have a role as an adjunct test in se-lected children in whom there is a high suspicion of antimicrobial treatment failure

Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics (STARSHIP): protocol to study cerebral autoregulation in a prospective multicentre observational research database study.

IntroductionStudying cerebral autoregulation, particularly PRx (Pressure Reactivity Index), is commonly employed in adult traumatic brain injury (TBI) and gives real-time information about intracranial pathophysiology, which can help in patient management. Experience in paediatric TBI (PTBI) is limited to single-centre studies despite disproportionately higher incidence of morbidity and mortality in PTBI than in adult TBI.ProjectWe describe the protocol to study cerebral autoregulation using PRx in PTBI. The project called Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics is a multicentre prospective ethics approved research database study from 10 centres across the UK. Recruitment started in July 2018 with financial support from local/national charities (Action Medical Research for Children, UK).Methods and analysisThe first phase of the project is powered to detect optimal thresholds of PRx associated with favourable outcome in PTBI by recruiting 135 patients (initial target of 3 years which has changed to 5 years due to delays related to COVID-19 pandemic) from 10 centres in the UK with outcome follow-up to 1-year postictus. The secondary objectives are to characterise patterns of optimal cerebral perfusion pressure in PTBI and compare the fluctuations in these measured parameters with outcome. The goal is to create a comprehensive research database of a basic set of high-resolution (full waveforms resolution) neuromonitoring data in PTBI for scientific use.Ethics and disseminationFavourable ethical approval has been provided by Health Research Authority, Southwest-Central Bristol Research Ethics Committee (Ref: 18/SW/0053). Results will be disseminated via publications in peer-reviewed medical journals and presentations at national and international conferences.Trial registration numberNCT05688462

Rapid Detection of Antimicrobial Resistance Genes in Critically Ill Children Using a Custom TaqMan Array Card

Peer reviewed: TrueAcknowledgements: We express our deepest thanks to the families who volunteered to participate in the study. This study could not have taken place without the support of all the Paediatric Intensive Care Unit staff and Addenbrooke’s Hospital, Cambridge. We also wish to acknowledge physiotherapists Helen Starace and Colin Hamilton for assisting with developing the mini-BAL sampling procedure and scientist Claire Jenkins for assisting with sample workflow.Publication status: PublishedFunder: NIHR Cambridge Biomedical Research CentreBacteria are identified in only 22% of critically ill children with respiratory infections treated with antimicrobial therapy. Once an organism is isolated, antimicrobial susceptibility results (phenotypic testing) can take another day. A rapid diagnostic test identifying antimicrobial resistance (AMR) genes could help clinicians make earlier, informed antimicrobial decisions. Here we aimed to validate a custom AMR gene TaqMan Array Card (AMR-TAC) for the first time and assess its feasibility as a screening tool in critically ill children. An AMR-TAC was developed using a combination of commercial and bespoke targets capable of detecting 23 AMR genes. This was validated using isolates with known phenotypic resistance. The card was then tested on lower respiratory tract and faecal samples obtained from mechanically ventilated children in a single-centre observational study of respiratory infection. There were 82 children with samples available, with a median age of 1.2 years. Major comorbidity was present in 29 (35%) children. A bacterial respiratory pathogen was identified in 13/82 (16%) of children, of which 4/13 (31%) had phenotypic AMR. One AMR gene was detected in 49/82 (60%), and multiple AMR genes were detected in 14/82 (17%) children. Most AMR gene detections were not associated with the identification of phenotypic AMR. AMR genes are commonly detected in samples collected from mechanically ventilated children with suspected respiratory infections. AMR-TAC may have a role as an adjunct test in selected children in whom there is a high suspicion of antimicrobial treatment failure

Low diagnostic yield and time to diagnostic confirmation results in prolonged use of antimicrobials in critically ill children [version 2; peer review: 2 approved, 1 approved with reservations]

Funder: Action Medical Research; Grant(s):Funder: Academy of Medical Sciences; Grant(s):Funder: NIHR Cambridge Biomedical Research Centre; Grant(s):Funder: Gates Cambridge Trust; Grant(s):Background: Broad-spectrum antimicrobial therapy is a key driver of antimicrobial resistance. Here, we aimed to review indications for antimicrobial therapy, determine the proportion of suspected bacterial infections that are confirmed by culture, and assess the time taken for microbiology test results to become available in the paediatric intensive care unit (PICU). Methods: A single-centre prospective observational cohort study of 100 consecutive general PICU admissions from 30 October 2019 to 19 February 2020. Data were collected from the hospital medical record and entered into a study database prior to statistical analysis using standard methods. Results: Of all episodes of suspected infection, 22% of lower respiratory tract infection, 43% of bloodstream and 0% of central nervous system infection were associated with growth on microbiology culture. 90% of children received antimicrobial therapy. Hospital-acquired infection occurred less commonly than primary infection, but an organism was grown in a greater proportion (64%) of cultures. Final laboratory reports for negative cultures were issued at a median of 120.3 hours for blood cultures and 55.5 hours for endotracheal tube aspirate cultures. Conclusions: Despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. Novel molecular diagnostics may improve rationalisation of treatment in this population

A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era.

Acknowledgements: We thank all the prescribers locally and abroad for participating in our survey. We also thank the paediatric intensive care unit staff at Addenbrooke’s Hospital, Cambridge, for participating in the interviews, and Ms Carmel Delzoppo, Royal Children’s Hospital Melbourne for assisting with survey distribution in Australasia. We are grateful for the expert study methodology advice of Dr Alexandra Freeman, Dr. Gabriel Recchia and Ms Alice Lawrence, Winton Centre for Risk and Evidence Communication, Centre for Mathematical Sciences at the University of Cambridge.Funder: NIHR Cambridge Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100018956Funder: Academy of Medical Sciences; doi: http://dx.doi.org/10.13039/501100000691Funder: Health Foundation Clinical Scientist FellowshipBACKGROUND: In the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making. METHODS: An online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe and Australasia with a total of 755 members. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array. RESULTS: Seventy-two survey responses were received; most responses were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within 6 h for stable patients and within 1 h for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team. CONCLUSIONS: Diagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04233268. Registered on 18 January 2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44253-023-00008-z

Short-duration selective decontamination of the digestive tract infection control does not contribute to increased antimicrobial resistance burden in a pilot cluster randomised trial (the ARCTIC Study)

Peer reviewed: TrueAcknowledgements: The authors would like to thank the NIHR for their assistance in running the PICnIC trial, and ICNARC for their oversight of trial data.Objective: Selective decontamination of the digestive tract (SDD) is a well-studied but hotly contested medical intervention of enhanced infection control. Here, we aim to characterise the changes to the microbiome and antimicrobial resistance (AMR) gene profiles in critically ill children treated with SDD-enhanced infection control compared with conventional infection control. Design: We conducted shotgun metagenomic microbiome and resistome analysis on serial oropharyngeal and faecal samples collected from critically ill, mechanically ventilated patients in a pilot multicentre cluster randomised trial of SDD. The microbiome and AMR profiles were compared for longitudinal and intergroup changes. Of consented patients, faecal microbiome baseline samples were obtained in 89 critically ill children. Additionally, samples collected during and after critical illness were collected in 17 children treated with SDD-enhanced infection control and 19 children who received standard care. Results: SDD affected the alpha and beta diversity of critically ill children to a greater degree than standard care. At cessation of treatment, the microbiome of SDD patients was dominated by Actinomycetota, specifically Bifidobacterium, at the end of mechanical ventilation. Altered gut microbiota was evident in a subset of SDD-treated children who returned late longitudinal samples compared with children receiving standard care. Clinically relevant AMR gene burden was unaffected by the administration of SDD-enhanced infection control compared with standard care. SDD did not affect the composition of the oral microbiome compared with standard treatment. Conclusion: Short interventions of SDD caused a shift in the microbiome but not of the AMR gene pool in critically ill children at the end mechanical ventilation, compared with standard antimicrobial therapy