ICU Care Team's Perception of Clinical Research in the ICU: A Cross-Sectional Study.

OBJECTIVES: Adequate recruitment is essential for successful clinical research. ICU nurses play a crucial role in identifying eligible patients, introducing research teams, facilitating informed consent, and caring for enrolled patients. However, a larger group of multidisciplinary healthcare professionals (the ICU care team) is equally important in promoting clinical research participation.To describe the ICU care team's experiences in ongoing clinical research, identifying perceived barriers and enablers to their participation, and apply a behavior framework to enhance research engagement. DESIGN: Cross-sectional survey study. SETTING: Four adult ICUs and one PICU between June 2021 and March 2023. SUBJECTS: We recruited nurses, physicians, nurse practitioners, allied health professionals, and unit clerks. MEASUREMENT AND MAIN RESULTS: We developed and validated a cross-sectional survey based on the Capability, Opportunity, Motivation, Behavior model. This survey included: 1) demographic questions (n = 7); 2) research experience questions (n = 6), 3) capability questions (n = 8); 4) opportunity questions (n = 11); 5) and motivation questions (n = 13).A total of 172 ICU care team members completed the survey. Results showed differences in capabilities, opportunities, and motivations among ICU care team members. For example, fellow/attending physicians and nurse practitioners reported higher confidence in discussing research with patients/families, while registered nurses and allied health professionals expressed less confidence. CONCLUSIONS: ICU care team members face multiple barriers that impact their involvement with the conduct of ICU research. To effectively engage healthcare professionals in this process, it is essential to address their capabilities (research knowledge and skills to communicate research with patients/families), create opportunities (collaboration/communication with research team, discuss research during multidisciplinary rounds), and motivate them (recognize their help and share the results of the research being conducted at their site) to improve ICU care team engagement in the conduct of ICU research.

Measuring evidence-based clinical guideline compliance in the paediatric intensive care unit.

BACKGROUND: Evidence-based clinical care guidelines improve medical treatment by reducing error, improving outcomes and possibly lowering healthcare costs. While some data exist on individual guideline compliance, no data exist on overall compliance to multiple nuanced guidelines in a paediatric intensive care setting. METHODS: Guideline compliance was observed and measured with a prospective cohort at a tertiary academic paediatric medical-surgical intensive care unit. Adherence to 19 evidence-based clinical care guidelines was evaluated in 814 patients, and reasons for non-compliance were noted along with other associated outcomes. MEASUREMENTS AND MAIN RESULTS: Overall facility compliance was unexpectedly high at 77.8% over 4512 compliance events, involving 826 admissions. Compliance varied widely between guidelines. Guidelines with the highest compliance were stress ulcer prophylaxis (97.1%) and transfusion administration such as fresh frozen plasma (97.4%) and platelets (94.8%); guidelines with the lowest compliance were ventilator-associated pneumonia prevention (28.7%) and vitamin K administration (34.8%). There was no significant change in compliance over time with observation. Guidelines with binary decision branch points or single-page decision flow diagrams had a higher average compliance of 90.6%. Poor compliance was more often observed with poor perception of guideline trustworthiness and time limitations. CONCLUSIONS: Measuring guideline compliance, though onerous, allowed for evaluation of current clinical practices and identified actionable areas for institutional improvement.

Gene Expression Profiling in Pediatric Appendicitis.

Importance: Appendicitis is the most common indication for urgent surgery in the pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) and perforated appendicitis (PA) on presentation may help direct further diagnostic workup and appropriate therapy selection, including antibiotic choice and timing of surgery. Objective: To provide a mechanistic understanding of the differences in disease severity of appendicitis with the objective of developing improved diagnostics and treatments, specifically for the pediatric population. Design, Setting, and Participants: The Gene Expression Profiling of Pediatric Appendicitis (GEPPA) study was a single-center prospective exploratory diagnostic study with transcriptomic profiling of peripheral blood collected from a cohort of children aged 5 to 17 years with abdominal pain and suspected appendicitis between November 2016 and April 2017 at the Alberta Children's Hospital in Calgary, Alberta, Canada, with data analysis reported in August 2023. There was no patient follow-up in this study. Exposure: SA, PA, or nonappendicitis abdominal pain. Main Outcomes and Measures: Blood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics. Results: Seventy-one children (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) presenting to the emergency department with abdominal pain and suspected appendicitis were investigated using whole-blood transcriptomics. A central role for immune system pathways was revealed in PA, including a dampening of major innate interferon responses. Gene expression changes in patients with PA were consistent with downregulation of immune response and inflammation pathways and shared similarities with gene expression signatures derived from patients with sepsis, including the most severe sepsis endotypes. Despite the challenges in identifying early biomarkers of severe appendicitis, a 4-gene signature that was predictive of PA compared to SA, with an accuracy of 85.7% (95% CI, 72.8-94.1) was identified. Conclusions: This study found that PA was complicated by a dysregulated immune response. This finding should inform improved diagnostics of severity, early management strategies, and prevention of further postsurgical complications.

Organ Donation in Canadian PICUs: A Cross-Sectional Survey, 2021-2022.

OBJECTIVES: To understand contemporary pediatric organ donation programs in Canadian PICUs, including: policies and practices, data collection and reporting, and system and process barriers. DESIGN: A cross-sectional survey carried out 2021-2022. SETTING: Canadian PICUs affiliated with a donor physician network. SUBJECTS: Pediatric intensivists identified as the donation program lead, or most knowledgeable about donation for their institution. MEASUREMENTS AND MAIN RESULTS: A 19-item survey was developed through collaboration with stakeholders from the organ donation and transplantation community within Canada. Domains and items were generated and reduced iteratively during an in-person workshop. Pretesting and pilot testing were completed to ensure readability, flow, clinical sensibility, and construct validity. Fifteen of 16 (94%) invited Canadian PICUs from seven provinces completed the survey representing 88% (15/18) of all noncardiac Canadian PICUs. Surveys were completed between June 2021 and September 2022. All units support donation after death by neurologic criteria (DNC); 14 of 15 indicated donation policies were in place and 1 of 15 indicated no policy but the ability to facilitate donation. Thirteen of 15 units (87%) support donation after death by circulatory criteria (DCC) with policies in place, with 11 of 13 of these indicating routine support of donation opportunities. The majority (13/15) of units identified a donation champion. Of the 16 identified champions across these centers, 13 were physicians and were registered nurses or nurse practitioners. Eight of 13 units (62%) with donation champions had positions supported financially, of which 5 units came from the Organ Donation Organization and the other 3 came from the provincial health authority. Finally, only 3 of 15 PICU donation programs have a pediatric donation committee with family involvement. Variability exists in identification (including determination of death practices), referral, and approach for donation between units. CONCLUSIONS: Although all Canadian PICUs support donation after DNC donation, and most support donation after DCC, variability exists in the identification, referral, and approach of potential donors. There is a notable lack of family involvement in pediatric donation programs. There are many opportunities for standardization of PICU donation programs which may result in improved rates of pediatric organ donation in Canada.

Assent in Pediatric Critical Care Research: A Cross-Sectional Stakeholder Survey of Canadian Research Ethics Boards, Research Coordinators, Pediatric Critical Care Researchers, and Nurses.

OBJECTIVES: Survey of four stakeholder groups involved in defining and obtaining assent for research in Canadian PICUs to better understand their perspectives and perceived barriers to assent. DESIGN: Cross-sectional survey. SETTING: Fourteen tertiary-care pediatric hospitals in Canada. PARTICIPANTS: Research Ethics Board Chairs, pediatric critical care nurses, research coordinators, and researchers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 193 participants responded. Thirty-seven percent (59/159) thought it was "Never/Almost Never" (59/159, 37%) feasible to obtain assent during the first 48 hours of PICU admission, and 112 of 170 (66%) indicated there are unique barriers to assent at the time of enrollment in PICU studies. Asking children for assent was most frequently rated as Important/Very Important for interviews/focus groups with the child (138/180, 77%), blood sample collection with a needle poke for research (137/178, 77%), and studies involving genetic testing with results communicated to the child/legal guardian (134/180, 74%). In two scenarios where a child and legal guardian disagreed about study participation, most respondents indicated that whether the child should still be enrolled would depend on the patient's age (34-36%), and/or the risk of the study (24-28%). There was a lack of consensus over how the assent process should be operationalized, and when and for how long children should be followed to seek assent for ongoing study participation. Most stakeholders (117/158, 74%) thought that children should have the opportunity to decide if their samples could stay in a biobank once they are old enough to do so. CONCLUSIONS: There was an overall lack of consensus on the feasibility of, and challenges associated with, obtaining assent at the time of study enrollment and on how key aspects of the assent process should be operationalized in the PICU. This highlights the need for guidelines to clarify the assent process in pediatric critical care research.

Metabolomics and Inflammatory Mediator Profiling for the Differentiation of Life-Threatening and Non-Severe Appendicitis in the Pediatric Population.

While children with appendicitis often have excellent clinical outcomes, some develop life-threatening complications including sepsis and organ dysfunction requiring pediatric intensive care unit (PICU) support. Our study applied a metabolomics and inflammatory protein mediator (IPM) profiling approach to determine the bio-profiles of children who developed severe appendicitis compared with those that did not. We performed a prospective case-control study of children aged 0-17 years with a diagnosis of appendicitis. Cases had severe disease resulting in PICU admission. Primary controls had moderate appendicitis (perforation without PICU); secondary controls had mild appendicitis (non-perforated). Serum samples were analyzed using Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy and Gas Chromatography-Mass Spectrometry (GC-MS); IPM analysis was performed using plasma bead-based multiplex profiling. Comparisons were made using multivariate data statistical analysis. Fifty-three children were included (15 severe, 38 non-severe). Separation between severe and moderate appendicitis demonstrated excellent sensitivity and specificity (100%, 88%; 14 compounds), separation between severe and mild appendicitis also showed excellent sensitivity and specificity (91%, 90%; 16 compounds). Biomarker patterns derived from metabolomics and IPM profiling are capable of distinguishing children with severe appendicitis from those with less severe disease. These findings provide an important first step towards developing non-invasive diagnostic tools for clinicians in early identification of children who are at a high risk of developing severe appendicitis.

Comfort-holding in critically ill children: a scoping review.

PURPOSE: To understand and summarize the breadth of knowledge on comfort-holding in pediatric intensive care units (PICUs). SOURCES: This scoping review was conducted using PRISMA methodology. A literature search was conducted in MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane CENTRAL Register of Controlled Trials. Search strategies were developed with a medical librarian and revised through a peer review of electronic search strategies. All databases were searched from inception to 14 April 2020. Only full-text articles available in English were included. All identified articles were reviewed independently and in duplicate using predetermined criteria. All study designs were eligible if they reported on comfort-holding in a PICU. Data were extracted independently and in duplicate. PRINCIPAL FINDINGS: Of 13,326 studies identified, 13 were included. Comfort-holding was studied in the context of end-of-life care, developmental care, mobilization, and as a unique intervention. Comfort-holding is common during end-of-life care with 77.8% of children held, but rare during acute management (51% of children < three years, < 5% of children ≥ three years). Commonly reported outcomes included child outcomes (e.g., physiologic measurements), safety outcomes (e.g., accidental line removal), parent outcomes (e.g., psychological symptoms), and frequency of holding. CONCLUSION: There is a paucity of literature on comfort-holding in PICUs. This scoping review identifies significant gaps in the literature, including assessment of child-based outcomes of comfort-holding or safety assessment of comfort-holding, and highlights core outcomes to consider in future evaluations of this intervention including child-based outcomes, parent-based outcomes, and safety of the intervention.

RéSUMé: OBJECTIF: Comprendre et résumer l'étendue des connaissances sur la pratique des étreintes de réconfort dans les unités de soins intensifs pédiatriques (USIP). SOURCES: Cette étude de portée a été réalisée en utilisant la méthodologie PRISMA. Une recherche de la littérature a été menée dans les bases de données MEDLINE, EMBASE, PsycINFO, CINAHL et dans le registre Cochrane CENTRAL d'études contrôlées. Les stratégies de recherche ont été élaborées avec un bibliothécaire médical et révisées au moyen d'un examen par les pairs des stratégies de recherche électronique. Toutes les bases de données ont été passées en revue de leur création au 14 avril 2020. Seuls les articles en texte intégral disponibles en anglais ont été inclus. Tous les articles identifiés ont été révisés indépendamment et en double à l'aide de critères prédéterminés. Tous les types de plans d'étude étaient admissibles s'ils abordaient le thème des étreintes de réconfort dans une USIP. Les données ont été extraites indépendamment et en double. CONSTATATIONS PRINCIPALES: Sur les 13 326 études identifiées, 13 ont été incluses. Les étreintes de réconfort ont été étudiées dans le contexte des soins de fin de vie, des soins développementaux, de la mobilisation et en tant qu'intervention unique. Les étreintes de réconfort sont une approche courante dans le cadre de soins de fin de vie, durant lesquels 77,8 % des enfants sont étreints, mais plus rares pendant la prise en charge aiguë (51 % des enfants < trois ans, < 5 % des enfants ≥ trois ans). Les résultats couramment rapportés comprenaient les issues pour les enfants (p. ex. mesures physiologiques), les issues en matière de sécurité (p. ex. retrait accidentel d'une ligne), les issues pour les parents (p. ex. symptômes psychologiques) et la fréquence des étreintes. CONCLUSION: Il n'existe que très peu de littérature s'intéressant aux étreintes de réconfort dans les USIP. Cette étude de portée identifie d'importantes lacunes dans la littérature, notamment l'évaluation des issues pour l'enfant suite à une étreinte de réconfort ou l'évaluation de la sécurité de telles étreintes, et met en évidence les issues principales dont il faudra tenir compte dans les évaluations futures de cette intervention, y compris les issues axées sur l'enfant, les issues basées sur les parents et la sécurité de l'intervention.

Magnetic Resonance Imaging Provides Useful Diagnostic Information Following Equivocal Ultrasound in Children With Suspected Appendicitis [Formula: see text].

PURPOSE: In Canada, ultrasonography is the primary imaging modality for children with suspected appendicitis, yet equivocal studies are common. Magnetic resonance imaging provides promise as an adjunct imaging strategy. The primary objective of this study was to determine the proportion of children with suspected appendicitis and equivocal ultrasound where magnetic resonance imaging determined a diagnosis. METHODS: A prospective consecutive cohort of children aged 5-17 years presenting to a tertiary pediatric Emergency Department with suspected appendicitis were enrolled. Participants underwent diagnostic and management strategies according to our local suspected appendicitis pathway, followed by magnetic resonance (Siemens Avanto 1.5 Tesla) imaging. Sub-specialty pediatric radiologists reported all images. RESULTS: Magnetic resonance imaging was performed in 101 children with suspected appendicitis. The mean age was 11.9 (SD 3.4) years and median Pediatric Appendicitis Score was 6 [IQR 4,8]. Ultrasonography was completed in 98/101 (97.0%). Of 53/98 (54.1%) with equivocal ultrasound, magnetic resonance imaging provided further diagnostic information in 41 (77.4%; 10 positive, 31 negative; 12 remained equivocal). Secondary findings of appendicitis on magnetic resonance imaging in children with equivocal ultrasound included abdominal free fluid (24, 45.3%), peri-appendiceal fluid (12, 22.6%), intraluminal appendiceal fluid (9, 17.0%), fat stranding (8, 15.1%), appendicolith (2, 3.8%), and peri-appendiceal abscess (1, 1.9%). The observed agreement between magnetic resonance imaging results and final diagnosis was 94.9% (kappa = 0.89).

Quality of clinical care provided during simulated pediatric cardiac arrest: a simulation-based study.

PURPOSE: We sought to assess compliance to resuscitation guidelines during pediatric simulated cardiac arrests in a pediatric intensive care unit (PICU) and to identify performance gaps to target with future training. METHODS: In a prospective observational study in a PICU, ten cardiac arrest scenarios were developed for resuscitation training and video recorded. The video recordings were examined for times to start cardiopulmonary resuscitation (CPR), delivery of first shock, CPR quality (rate, depth), length of pauses, chest compression fraction (CCF), ventilation, pulse/rhythm assessment, compressors' rotation, and leader's behaviours. The primary outcome was percentage of events compliant to Pediatric Advance Life Support guidelines. RESULTS: Compliance to guidelines was poor in the 23 simulation events studied. The median [interquartile range] time to start CPR was 29 [16-76] sec and 320 [245-421] sec to deliver the first shock. A total of 306 30-sec epochs of CPR were analyzed; excellent CPR (≥ 90% compressions in target for rate and depth) was achieved in 22 (7%) epochs. More than a quarter of the CPR pauses lasted > 10 seconds (33/127, 26%) with just one task performed in most of them; CCF was ≥ 80% in 19/23 (82.6%) events. Ventilation rate for intubated patients was greater than 10 breaths·min-1 in 15/27 (56%) of one-minute epochs observed. CONCLUSIONS: Review of simulated resuscitation events found suboptimal compliance with resuscitation guidelines, particularly the times to starting CPR and delivering the first shock, as well as compression rate and depth.

RéSUMé: OBJECTIF: Nous avons tenté d'évaluer l'observance des directives de réanimation pendant les arrêts cardiaques pédiatriques simulés dans une unité de soins intensifs pédiatriques (USIP) et d'identifier les écarts de performance afin d'aiguiller la formation future. MéTHODE: Dans une étude observationnelle prospective réalisée au sein d'une USIP, dix scénarios d'arrêt cardiaque ont été élaborés à des fins de formation en réanimation et enregistrés sur vidéo. Les enregistrements vidéo ont été étudiés pour évaluer le délai d'initiation de la réanimation cardiorespiratoire (RCR) et d'administration du premier choc, ainsi que la qualité de la RCR (fréquence, profondeur), la durée des pauses, la fraction des compressions thoraciques (FCT), la ventilation, l'évaluation du pouls/rythme, la rotation des compresseurs et les comportements du leader. Le critère d'évaluation principal était le pourcentage d'événements conformes aux directives de Soins avancés en réanimation pédiatrique (SARP). RéSULTATS: L'observance des directives était faible dans les 23 sessions étudiées. Le temps médian [écart interquartile] était de 29 [16­76] sec avant d'amorcer la RCR et de 320 [245­421] sec avant d'administrer le premier choc. Au total, 306 séquences de 30 sec de RCR ont été analysées; une RCR excellente (≥ 90 % des compressions situées dans la cible de fréquence et de profondeur) a été réalisée dans 22 (7 %) séquences. Plus d'un quart des pauses de RCR ont duré > dix secondes (33/127, 26 %), avec une seule tâche réalisée dans la plupart; la FCT était de ≥ 80 % dans 19/23 (82,6 %) sessions. Chez les patients intubés, la fréquence de ventilation était supérieure à 10 respirations·min-1 dans 15/27 (56 %) des séquences d'une minute observées. CONCLUSION: Le passage en revue des événements de réanimation simulés a décelé une observance sous-optimale des directives de réanimation, particulièrement en ce qui touche au délai de l'initiation de la RCR et du premier choc, ainsi qu'à la fréquence et à la profondeur des compressions.

Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators.

OBJECTIVES: We aimed to demonstrate the potential of precision medicine to describe the inflammatory landscape present in children with suspected appendicitis. Our primary objective was to determine levels of seven inflammatory protein mediators previously associated with intra-abdominal inflammation (C-reactive protein-CRP, procalcitonin-PCT, interleukin-6 (IL), IL-8, IL-10, monocyte chemoattractant protein-1-MCP-1, and serum amyloid A-SAA) in a cohort of children with suspected appendicitis. Subsequently, using a multiplex proteomics approach, we examined an expansive array of novel candidate cytokine and chemokines within this population. METHODS: We performed a secondary analysis of targeted proteomics data from Alberta Sepsis Network studies. Plasma mediator levels, analyzed by Luminex multiplex assays, were evaluated in children aged 5-17 years with nonappendicitis abdominal pain (NAAP), acute appendicitis (AA), and nonappendicitis sepsis (NAS). We used multivariate regression analysis to evaluate the seven target proteins, followed by decision tree and heat mapping analyses for all proteins evaluated. RESULTS: 185 children were included: 83 with NAAP, 79 AA, and 23 NAS. Plasma levels of IL-6, CRP, MCP-1, PCT, and SAA were significantly different in children with AA compared to those with NAAP (p < 0.001). Expansive proteomic analysis demonstrated 6 patterns in inflammatory mediator profiles based on severity of illness. A decision tree incorporating the proteins CRP, ferritin, SAA, regulated on activation normal T-cell expressed and secreted (RANTES), monokine induced by gamma interferon (MIG), and PCT demonstrated excellent specificity (0.920) and negative predictive value (0.882) for children with appendicitis. CONCLUSIONS: Multiplex proteomic analyses described the inflammatory landscape of children presenting to the ED with suspected appendicitis. We have demonstrated the feasibility of this approach to identify potential novel candidate cytokines/chemokine patterns associated with a specific illness (appendicitis) amongst those with a broad ED presentation (abdominal pain). This approach can be modelled for future research initiatives in pediatric emergency medicine.

Bedside chest compression skills: Performance and skills retention in in-hospital trained pediatric providers. A simulation study.

PURPOSE: To assess the effects of a real-time feedback device and refresher sessions in acquiring and retaining chest compression skills. METHODS: Healthcare providers participated in refresher sessions at 3-time points (blocks) over 1-year. At each block, chest compression (CC) skills were assessed on an infant and adult task trainer, in one 2-min trial without feedback (blinded), and up to three 2-min trials with feedback (unblinded). Skills retention over time was explored at three time lags: 1-3, 3-6, >6 months. Data collected included chest compression rate (100-120/min), depth (4 cm for infants and 5 cm for adults), and recoil between compressions. RESULTS: Among 194 participants, achievement of excellent CC (≥90% of adequate compressions for all parameters) increased with feedback. Linear mixed models found significant (p < 0.05) improvement in rate, depth, and recoil. Performance between last unblinded trial in block 1 with the following blinded trial in block 2 significantly decayed in rate on both task trainers irrespective of time passed, while depth and recoil performance were maintained only for infants. CONCLUSIONS: A real-time visual feedback device improved CC skills with better results in infants. Skills decayed over time despite two refresher sessions with feedback.

Ability to Assent in Pediatric Critical Care Research: A Prospective Environmental Scan of Two Canadian PICUs.

OBJECTIVES: To determine the number of patients considered not appropriate to approach for assent within the first 24 hours of PICU admission. DESIGN: Exploratory prospective 1-month environmental scan. SETTING: Two tertiary Canadian PICUs. PATIENTS: Ninety patients age newborn to 17 years old admitted to the PICU during September 2016 (Site 1) or May 2017 (Site 2). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At PICU admission, 81% of patients were deemed not appropriate to approach for assent most commonly due to age, influence of psychotropic medications, and/or mechanical ventilation. At PICU discharge, 74% of patients were considered not appropriate to approach, most commonly due to age and/or developmental delay. There was moderate to good agreement between the research team and care team assessments of appropriateness for assent. Only 8% of patients considered not approachable at admission become appropriate to approach for assent by PICU discharge. CONCLUSIONS: Very few patients were considered approachable for assent during the first 24 hours of PICU admission. Those who were considered appropriate to approach were less ill, spent less time in PICU, and were unlikely to be considered for enrollment in pediatric critical care research.

The Use of Metabolomics and Inflammatory Mediator Profiling Provides a Novel Approach to Identifying Pediatric Appendicitis in the Emergency Department.

Multiplexed profiling approaches including various 'omics' platforms are becoming a new standard of biomarker development for disease diagnosis and prognosis. The present study applied an integrated metabolomics and cytokine profiling approach as a potential aid to the identification of pediatric appendicitis. Metabolic analysis using serum (n = 121) and urine (n = 102) samples, and cytokine analysis using plasma (n = 121) samples from children presenting to the Emergency Department with abdominal pain were performed. Comparisons between children with appendicitis vs. non-appendicitis abdominal pain, and with perforated vs. non-perforated appendicitis were made using multivariate statistics. Serum and urine biomarker patterns were statistically significantly different between groups. The combined serum metabolomics and inflammatory mediator model revealed clear separation between appendicitis and non-appendicitis abdominal pain (AUROC: 0.92 ± 0.03) as well as for perforated and non-perforated appendicitis (AUROC: 0.88 ± 0.05). Urine metabolic analysis also demonstrated distinction between the groups appendicitis and non-appendicitis abdominal pain (AUROC: 0.85 ± 0.04), and perforated and non-perforated appendicitis (AUROC: 0.98 ± 0.02). In children presenting to the Emergency Department with abdominal pain, metabolomics and inflammatory mediator profiling are capable of distinguishing children with appendicitis from those without. The approach also differentiates between severities of disease. These results provide an important first step towards a potential aid for improving appendicitis identification.

Metabolomic and inflammatory mediator based biomarker profiling as a potential novel method to aid pediatric appendicitis identification.

Various limitations hinder the timely and accurate diagnosis of appendicitis in pediatric patients. The present study aims to investigate the potential of metabolomics and cytokine profiling for improving the diagnosis of pediatric appendicitis. Serum and plasma samples were collected from pediatric patients for metabolic and inflammatory mediator analyses respectively. Targeted metabolic profiling was performed using Proton Nuclear Magnetic Resonance Spectroscopy and Flow Injection Analysis Mass Spectrometry/Mass Spectrometry and targeted cytokine/chemokine profiling was completed using a multiplex platform to compare children with and without appendicitis. Twenty-three children with appendicitis and 35 control children without appendicitis from the Alberta Sepsis Network pediatric cohorts were included. Metabolomic profiling revealed clear separation between the two groups with very good sensitivity (80%), specificity (97%), and AUROC (0.93 ± 0.05) values. Inflammatory mediator analysis also distinguished the two groups with high sensitivity (82%), specificity (100%), and AUROC (0.97 ± 0.02) values. A biopattern comprised of 9 metabolites and 7 inflammatory compounds was detected to be significant for the separation between appendicitis and control groups. Integration of these 16 significant compounds resulted in a combined metabolic and cytokine profile that also demonstrated strong separation between the two groups with 81% sensitivity, 100% specificity and AUROC value of 0.96 ± 0.03. The study demonstrated that metabolomics and cytokine mediator profiling is capable of distinguishing children with appendicitis from those without. These results suggest a potential new approach for improving the identification of appendicitis in children.

Test characteristics of common appendicitis scores with and without laboratory investigations: a prospective observational study.

BACKGROUND: Despite the poor independent test characteristics of the white blood cell count (WBC) and neutrophil count (NC) in identifying appendicitis, common clinical decision supports including the Pediatric Appendicitis Score (PAS) and Alvarado Score (AS), require the WBC and NC values. Moreover, blood tests cause discomfort/pain to children and require time for processing results. Scores based on clinical information alone may be of benefit in the pediatric population. The objective of our study was to determine the test characteristics of the PAS and the AS with and without laboratory investigations (mPAS, mAS respectively) as well as the Lintula Score. METHODS: A prospective cohort study of children aged 5-17 years presenting to a pediatric ED with suspected appendicitis. Clinical care of the patient was left to the managing physician. At risk for appendicitis was defined by PAS ≥6; AS ≥5; LS ≥16, as originally described; modified cutoffs were defined as mPAS ≥4; mAS ≥4. Appendicitis was defined as acute inflammation, rupture or abscess of the appendix on pathologic evaluation. Test characteristics for each of the 5 scores were calculated. RESULTS: Of the 180 eligible children, 102 (56.7 %) were female. The average age was 11.2 years (SD 3.1). Appendectomy was performed in 58 (32.2 %) of children, 55 (94.8 %) were positive. For the PAS and mPAS, sensitivity and negative predictive values were similar (80.0 %, 86.4 % vs 87.3 %, 85.1 % respectively). For the AS and mAS, sensitivity and negative predictive values were also similar (85.5 %, 87.1 % vs 83.6 %, 83.3 % respectively). Specificities in the PAS, mPAS, AS and mAS were low (56.0 %, 32.0 %, 43.2 %, 63.0 % respectively). Test characteristics of the LS were poor (59.3 %, 79.2 %, 55.2 %, 81.8 %). CONCLUSIONS: A modified Alvarado and PAS can be used to screen for children at low risk of appendicitis who may be carefully observed at home without the need for laboratory investigation. Translation to primary care settings should evaluate generalizability and determine impact on referral patterns.