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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. [ABSTRACT FROM AUTHOR]

Background: Ondansetron is often used in the emergency department (ED) to promote oral rehydration in children with acute gastroenteritis (AGE), yet medication solutions administered orally may be poorly tolerated in this population.Objectives: We compared the tolerability of ondansetron oral dissolve tab (ODT) to oral solution (OS) in children presenting to the ED with AGE.Methods: Using alternate-day controlled clinical trial design, children aged 3 months to 10 years received either ondansetron ODT or OS. Our primary outcome was early vomiting (within 15 min of drug administration). The secondary outcome was intravenous (i.v.) fluid administration.Results: There were 462/534 eligible children who met study criteria. Demographics, severity, and duration of illness were similar between groups. Using intention-to-treat analysis, early vomiting occurred in 8/209 ODT vs. 19/253 OS children (3.8% vs. 7.5%; odds ratio [OR] 0.49; 95% confidence interval [CI] 0.18-1.21). Using as-treated analysis, 6/222 (2.7%) children receiving ODT experienced early vomiting, compared with 21/221 (9.5%) of the OS group (OR 0.26; 95% CI 0.09-0.70). The proportion of children discharged without i.v. fluids was not different (intention-to-treat: ODT = 91.4% (191/209), OS = 94.1% (238/253), OR 1.49, 95% CI 0.69-3.28; as-treated: ODT = 92.3% (205/222), OS = 93.2% (206/221), OR 0.88, 95% CI 0.40-1.93).Conclusions: Using a conservative intention-to-treat analysis, we found that children presenting to an ED with AGE did not have statistically less early vomiting with ondansetron ODT as compared with OS. However, our as-treated analysis demonstrates that children receiving ondansetron ODT experienced early vomiting approximately one-third as often as those receiving OS. The rate of i.v. fluid administration was no different between groups regardless of the type of analysis used. [ABSTRACT FROM AUTHOR]

Background: Pediatric sepsis remains a leading cause of morbidity and mortality. Understanding current practice patterns and challenges is essential to inform future research and education strategies.Objective: Our aim was to describe the practice patterns of pediatric emergency physicians (PEPs) in the recognition and management of sepsis in children and to identify perceived priorities for future research and education.Methods: We conducted a cross-sectional, internet-based survey of members of the American Academy of Pediatrics, Section on Emergency Medicine and Pediatric Emergency Research Canada. The survey was internally derived, externally validated, and distributed using a modified Dillman methodology. Rank scores (RS) were calculated for responses using Likert-assigned frequency values.Results: Tachycardia, mental-status changes, and abnormal temperature (RS = 83.7, 80.6, and 79.6) were the highest ranked clinical measures for diagnosing sepsis; white blood cell count, lactate, and band count (RS = 73.5, 70.9, and 69.1) were the highest ranked laboratory investigations. The resuscitation fluid of choice (85.5%) was normal saline. Dopamine was the first-line vasoactive medication (VAM) for cold (57.1%) and warm (42.2%) shock with epinephrine (18.5%) and norepinephrine (25.1%) as second-line VAMs (cold and warm, respectively). Steroid administration increased with complexity of presentation (all-comers 3.8%, VAM-resistant shock 54.5%, chronic steroid users 72.0%). Local ED-specific clinical pathways, national emergency department (ED)-specific guidelines, and identification of clinical biomarkers were described as future priorities.Conclusions: While practice variability exists among clinicians, PEPs continue to rely heavily on clinical metrics for recognizing sepsis. Improved recognition through clinical biomarkers and standardization of care were perceived as priorities. Our results provide a strong framework to guide future research and education strategies in pediatric sepsis. [ABSTRACT FROM AUTHOR]

The article describes the cases of a right-handed 14-year-old boy and a right-handed four-year-old girl with recurring tremor. The 14-year-old boy had a family history of tremor. The four-year-old girl was presented with a progressive intention tremor on her right side. An effective treatment plan for each patient may be formulated based on the accurately determined signs, symptoms and causes of the tremor on the patient.

• 37% of caregivers opposed vaccine mandates at all school levels. • Only 20% of caregivers agreed with immediate vaccine mandates. • Vaccine safety was the most important concern regarding vaccine mandates. • 26% of caregivers would remove their child from school if vaccines became mandated. Caregiver attitudes toward mandating COVID-19 vaccines for their children are poorly understood. We aimed to determine caregiver acceptability of COVID-19 vaccine mandates for schools/daycares and assess if opposition to mandates would result in removal of children from the educational system. Perform a cross-sectional, anonymous survey of adult caregivers with children ≤ 18 years presenting to 21 pediatric emergency departments in the United States, Canada, Israel, and Switzerland, November 1st through December 31st, 2021. The primary outcome was caregiver acceptance rates for school vaccine mandates, and the secondary outcomes included factors associated with mandate acceptance and caregiver intention to remove the child from school. Of 4,393 completed surveys, 37% of caregivers were opposed to any school vaccine mandate. Caregiver acceptance was lowest for daycare settings (33%) and increased as the child's level of education increased, college (55%). 26% of caregivers report a high likelihood (score of 8–10 on 0–10 scale) to remove their child from school if the vaccine became mandatory. Child safety was caregivers' greatest concern over vaccine mandates. A multivariable model demonstrated intent to vaccinate their child for COVID-19 (OR = 8.9, 95% CI 7.3 to 10.8; P < 0.001) and prior COVID-19 vaccination for the caregiver (OR = 3.8, 95% CI 3.0 to 4.9; P < 0.001) had the greatest odds of increasing mandate acceptance for any school level. Many caregivers are resistant to COVID-19 vaccine mandates for schools, and acceptance varies with school level. One-fourth of caregivers plan to remove their child from the educational system if vaccines become mandated. [ABSTRACT FROM AUTHOR]

Background/aims: Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock.Methods: The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under "exception from informed consent" in the USA or "deferred consent" in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed.Discussion: PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings.Trial Registration: PRoMPT BOLUS was first registered at ClinicalTrials.gov ( NCT04102371 ) on September 25, 2019. Enrollment started on August 25, 2020. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the prevalence of invasive bacterial infections (IBIs) and adverse events in afebrile infants with acute otitis media (AOM). METHODS: We conducted a 33-site cross-sectional study of afebrile infants #90 days of age with AOM seen in emergency departments from 2007 to 2017. Eligible infants were identified using emergency department diagnosis codes and confirmed by chart review. IBIs (bacteremia and meningitis) were determined by the growth of pathogenic bacteria in blood or cerebrospinal fluid (CSF) culture. Adverse events were defined as substantial complications resulting from or potentially associated with AOM. We used generalized linear mixed-effects models to identify factors associated with IBI diagnostic testing, controlling for site-level clustering effect. RESULTS: Of 5270 infants screened, 1637 met study criteria. None of the 278 (0%; 95% confidence interval [CI]: 0%-1.4%) infants with blood cultures had bacteremia; 0 of 102 (0%; 95% CI: 0%-3.6%) with CSF cultures had bacterial meningitis; 2 of 645 (0.3%; 95% CI: 0.1%-1.1%) infants with 30-day follow-up had adverse events, including lymphadenitis (1) and culture-negative sepsis (1). Diagnostic testing for IBI varied across sites and by age; overall, 278 (17.0%) had blood cultures, and 102 (6.2%) had CSF cultures obtained. Compared with infants 0 to 28 days old, older infants were less likely to have blood cultures (P < .001) or CSF cultures (P < .001) obtained. CONCLUSION: Afebrile infants with clinician-diagnosed AOM have a low prevalence of IBIs and adverse events; therefore, outpatient management without diagnostic testing may be reasonable. [ABSTRACT FROM AUTHOR]

This study determined the predictors of caregivers' willingness to accept an accelerated regulatory process for the development of vaccines against coronavirus disease 2019 (COVID-19). An international cross-sectional survey was administered to 2557 caregivers of children in 17 pediatric emergency departments (EDs) across 6 countries from March 26, 2020, to June 30, 2020. Caregivers were asked to select 1 of 4 choices with which they most agreed regarding a proposed COVID-19 vaccine–approval process, in addition to questions regarding demographic characteristics, the ED visit, and attitudes about COVID-19. Univariate analyses were conducted using the Mann–Whitney U test for comparing non–normally distributed continuous variables, an independent t test for comparing normally distributed continuous variables, and a χ2 or Fisher exact test for categorical variables. Multivariate logistic regression analysis was used for determining independent factors associated with caregivers' willingness to accept abridged development of a COVID-19 vaccine. A P value of <0.05 was considered significant. Almost half (1101/2557; 43%) of caregivers reported that they were willing to accept less rigorous testing and postresearch approval of a new COVID-19 vaccine. Independent factors associated with caregivers' willingness to accept expedited COVID-19 vaccine research included having children who were up to date on the vaccination schedule (odds ratio [OR] = 1.72; 95% CI, 1.29–2.31), caregivers' concern about having had COVID-19 themselves at the time of survey completion in the ED (OR = 1.1; 95% CI, 1.05–1.16), and caregivers' intent to have their children vaccinated against COVID-19 if a vaccine were to become available (OR = 1.84; 95% CI, 1.54–2.21). Compared with fathers, mothers completing the survey were less likely to approve of changes in the vaccine-development process (OR = 0.641; 95% CI, 0.529–0.775). Less than half of caregivers in this worldwide sample were willing to accept abbreviated COVID-19 vaccine testing. As a part of an effort to increase acceptance and uptake of a new vaccine, especially in order to protect children, public health strategies and individual providers should understand caregivers' attitudes toward the approval of a vaccine and consult them appropriately. • Half of caregivers accept an abridged process for rapid COVID-19 vaccine approval. • Seeking fast approval associated with caregiver's gender, intent to vaccinate child. • Concern about own COVID-19 infection associated with preferring expedited approval. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Evidence exists that analgesics are underutilized, delayed, and insufficiently dosed for emergency department (ED) patients with acute abdominal pain. For physicians practicing in a Canadian paediatric ED setting, we (1) explored theoretical practice variation in the provision of analgesia to children with acute abdominal pain; (2) identified reasons for withholding analgesia; and (3) evaluated the relationship between providing analgesia and surgical consultation. Methods: Physician members of Paediatric Emergency Research Canada (PERC) were prospectively surveyed and presented with three scenarios of undifferentiated acute abdominal pain to assess management. A modified Dillman's Tailored Design method was used to distribute the survey from June to July 2014. Results: Overall response rate was 74.5% (149/200); 51.7% of respondents were female and mean age was 44 (SD 8.4) years. The reported rates of providing analgesia for case scenarios representative of renal colic, appendicitis, and intussusception, were 100%, 92.1%, and 83.4%, respectively, while rates of providing intravenous opioids were 85.2%, 58.6%, and 12.4%, respectively. In all 60 responses where the respondent indicated they would obtain a surgical consultation, analgesia would be provided. In the 35 responses where analgesia would be withheld, 21 (60%) believed pain was not severe enough, while 5 (14.3%) indicated it would obscure a surgical condition. Conclusions: Pediatric emergency physicians self-reported rates of providing analgesia for acute abdominal pain scenarios were higher than previously reported, and appeared unrelated to request for surgical consultation. However, an unwillingness to provide opioid analgesia, belief that analgesia can obscure a surgical condition, and failure to take self-reported pain at face value remain, suggesting that the need exists for further knowledge translation efforts. [ABSTRACT FROM AUTHOR]