Readiness of emergency departments for pediatric patients and pediatric mortality: a systematic review.

BACKGROUND: Most children who need emergency care visit general emergency departments and urgent care centres; the weighted pediatric readiness score (WPRS) is currently used to evaluate emergency departments' readiness for pediatric patients. The aim of this study was to determine whether a higher WPRS was associated with decreased mortality and improved health care outcomes and utilization. METHODS: We conducted a systematic review of cohort and cross-sectional studies on emergency departments that care for children (age ≤ 21 yr). We searched MEDLINE (Ovid), Embase (Ovid), the Cochrane Library (Wiley), CINAHL (EBSCO), Global Health (Ovid) and Scopus from inception until July 29, 2022. Articles identified were screened for inclusion by 2 independent reviewers. The primary outcome was mortality, and the secondary outcomes were health care outcomes and utilization. We used the Newcastle-Ottawa Scale to assess for quality and bias of the included studies. The I 2 statistic was calculated to quantify study heterogeneity. RESULTS: We identified 1789 articles. Eight articles were included in the final analysis. Three studies showed an inverse association between highest WPRS quartile and pediatric mortality (pooled odds ratio [OR] 0.45, 95% confidence interval [CI] 0.26 to 0.78; I 2 = 89%, low certainty of evidence) in random-effects meta-analysis. Likewise, 1 study not included in the meta-analysis also reported an inverse association with a 1-point increase in WPRS (OR 0.93, 95% CI 0.88 to 0.98). One study reported that the highest WPRS quartile was associated with shorter length of stay in hospital (ß -0.36 days, 95% CI -0.61 to -0.10). Three studies concluded that the highest WPRS quartile was associated with fewer interfacility transfers. The certainty of evidence is low for mortality and moderate for the studied health care outcomes and utilization. INTERPRETATION: The data suggest a potential inverse association between the WPRS of emergency departments and mortality risk in children. More studies are needed to refute or confirm these findings. PROTOCOL REGISTRATION: PROSPERO-CRD42020191149.

Oxidized Phosphatidylcholines Trigger TRPA1 and Ryanodine Receptor-dependent Airway Smooth Muscle Contraction.

Asthma pathobiology includes oxidative stress that modifies cell membranes and extracellular phospholipids. Oxidized phosphatidylcholines (OxPCs) in lung lavage from allergen-challenged human participants correlate with airway hyperresponsiveness and induce bronchial narrowing in murine thin-cut lung slices. OxPCs activate many signaling pathways, but mechanisms for these responses are unclear. We hypothesize that OxPCs stimulate intracellular free Ca2+ flux to trigger airway smooth muscle contraction. Intracellular Ca2+ flux was assessed in Fura-2-loaded, cultured human airway smooth muscle cells. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) induced an approximately threefold increase in 20 kD myosin light chain phosphorylation. This correlated with a rapid peak in intracellular cytoplasmic Ca2+ concentration ([Ca2+]i) (143 nM) and a sustained plateau that included slow oscillations in [Ca2+]i. Sustained [Ca2+]i elevation was ablated in Ca2+-free buffer and by TRPA1 inhibition. Conversely, OxPAPC-induced peak [Ca2+]i was unaffected in Ca2+-free buffer, by TRPA1 inhibition, or by inositol 1,4,5-triphosphate receptor inhibition. Peak [Ca2+]i was ablated by pharmacologic inhibition of ryanodine receptor (RyR) Ca2+ release from the sarcoplasmic reticulum. Inhibiting the upstream RyR activator cyclic adenosine diphosphate ribose with 8-bromo-cyclic adenosine diphosphate ribose was sufficient to abolish OxPAPC-induced cytoplasmic Ca2+ flux. OxPAPC induced ∼15% bronchial narrowing in thin-cut lung slices that could be prevented by pharmacologic inhibition of either TRPA1 or RyR, which similarly inhibited OxPC-induced myosin light chain phosphorylation in cultured human airway smooth muscle cells. In summary, OxPC mediates airway narrowing by triggering TRPA1 and RyR-mediated mobilization of intracellular and extracellular Ca2+ in airway smooth muscle. These data suggest that OxPC in the airways of allergen-challenged subjects and subjects with asthma may contribute to airway hyperresponsiveness.

Call to action: equity, diversity, and inclusion in emergency medicine resident physician selection.

OBJECTIVES: This call to action seeks to improve emergency care in Canada for equity-deserving communities, enabled by equitable representation among emergency physicians nationally. Specifically, this work describes current resident selection processes and makes recommendations to enhance the equity, diversity, and inclusion (EDI) of resident physician selection in Canadian emergency medicine (EM) residency programs. METHODS: A diverse panel of EM residency program directors, attending and resident physicians, medical students, and community representatives met monthly from September 2021 to May 2022 via videoconference to coordinate a scoping literature review, two surveys, and structured interviews. This work informed the development of recommendations for incorporating EDI into Canadian EM resident physician selection. At the 2022 Canadian Association of Emergency Physicians (CAEP) Academic Symposium, these recommendations were presented to symposium attendees composed of national EM community leaders, members, and learners. Attendees were divided into small working groups to discuss the recommendations and address three conversation-facilitating questions. RESULTS: Symposium feedback informed a final set of eight recommendations to promote EDI practices during the resident selection process that address recruitment, retention, mitigating inequities and biases, and education. Each recommendation is accompanied by specific, actionable sub-items to guide programs toward a more equitable selection process. The small working groups also described perceived barriers to the implementation of these recommendations and outlined strategies for success that are incorporated into the recommendations. CONCLUSION: We call on Canadian EM training programs to implement these eight recommendations to strengthen EDI practices in EM resident physician selection and, in doing so, help to improve the care that patients from equity-deserving groups receive in Canada's emergency departments (EDs).

ABSTRAIT: OBJECTIFS: Cet appel à l'action vise à améliorer les soins d'urgence au Canada pour les collectivités méritant l'équité, grâce à une représentation équitable parmi les médecins d'urgence à l'échelle nationale. Plus précisément, ce travail décrit les processus actuels de sélection des médecins résidents et formule des recommandations pour améliorer l'équité, la diversité et l'inclusion (EDI) de la sélection des médecins résidents dans les programmes de résidence en médecine d'urgence (SE) du Canada. MéTHODES: Un groupe diversifié de directeurs du programme de résidence en GU, de médecins résidents, d'étudiants en médecine et de représentants communautaires se sont réunis mensuellement de septembre 2021 à mai 2022 par vidéoconférence pour coordonner une analyse documentaire, deux sondages et des entrevues structurées. Ces travaux ont orienté l'élaboration de recommandations pour l'intégration de l'IDE dans la sélection des médecins résidents en SE au Canada. À l'occasion du Symposium universitaire 2022 de l'Association canadienne des médecins d'urgence (ACMU), ces recommandations ont été présentées aux participants au symposium composé de dirigeants, de membres et d'apprenants de la communauté nationale de la GU. Les participants ont été divisés en petits groupes de travail pour discuter des recommandations et aborder trois questions facilitant la conversation. RéSULTATS: Les commentaires recueillis lors du symposium ont servi à formuler une dernière série de huit recommandations visant à promouvoir les pratiques de l'IDE au cours du processus de sélection des résidents qui traitent du recrutement, du maintien en poste, de l'atténuation des inégalités et des préjugés, et de l'éducation. Chaque recommandation est accompagnée de sous-éléments précis et réalisables pour orienter les programmes vers un processus de sélection plus équitable. Les petits groupes de travail ont également décrit les obstacles perçus à la mise en œuvre de ces recommandations et décrit les stratégies de réussite qui sont intégrées aux recommandations. CONCLUSION: Nous demandons aux programmes canadiens de formation en GU de mettre en œuvre ces huit recommandations afin de renforcer les pratiques d'IDE dans la sélection des médecins résidents en GU et, ce faisant, d'aider à améliorer les soins que les patients des groupes méritant l'équité reçoivent dans les services d'urgence du Canada.

Glucocorticoids for croup in children.

BACKGROUND: Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018. OBJECTIVES: To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below. SEARCH METHODS: We searched the Cochrane Library, which includes the Cochrane Central Register of Controlled Trials (CENTRAL; 2022 Issue 9), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 4 March 2022), Embase (Ovid) (1974 to 4 March 2022). We also searched the WHO ICTRP and ClinicalTrials.gov on 4 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children (aged 18 years and below) with croup. We assessed the effect of glucocorticoids compared to the following: placebo, any other pharmacologic agents, any other glucocorticoids, any combination of other glucocorticoids, given by different modes of administration, or given in different doses. The included studies must have assessed at least one of our primary outcomes (defined as the change in croup score or return visits, (re)admissions to the hospital or both) or secondary outcomes (defined as the length of stay in hospital or emergency departments, patient improvement, use of additional treatments, or adverse events). DATA COLLECTION AND ANALYSIS: Review authors independently extracted data, with another review author verified. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed studies for risk of bias using the Cochrane risk of bias tool. Two review authors assessed the certainty of the evidence for the primary outcomes using the GRADE approach. MAIN RESULTS: This updated review includes 45 RCTs with a total of 5888 children, an increase of two RCTs with 1323 children since the last update. We also identified one ongoing study and one study awaiting classification. We assessed most studies (98%) as at high or unclear risk of bias.  Any glucocorticoid compared to placebo  Compared to placebo, glucocorticoids may result in greater reductions in croup score after two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs, 426 children; low-certainty evidence); six hours (SMD -0.76, 95% CI -1.12 to -0.40; 11 RCTs, 959 children; low-certainty evidence); and 12 hours (SMD -1.03, 95% CI -1.53 to -0.53; 8 RCTs, 571 children; low-certainty evidence). The evidence for change in croup score after 24 hours is very uncertain (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs, 351 children; very low-certainty evidence).  One glucocorticoid compared to another glucocorticoid There was little to no difference between prednisolone and dexamethasone for reduction in croup score at two-hour post-baseline score (SMD 0.06, 95% CI -0.06 to 0.18; 1 RCT, 1231 children; high-certainty evidence). There was likely little to no difference between prednisolone and dexamethasone for reduction in croup score at six-hour post-baseline score (SMD 0.21, 95% CI -0.21 to 0.62; 1 RCT, 99 children; moderate-certainty evidence). However, dexamethasone probably reduced the return visits or (re)admissions for croup by almost half (risk ratio (RR) 0.55, 95% CI 0.28 to 1.11; 4 RCTs, 1537 children; moderate-certainty evidence), and showed a 28% reduction in the use of supplemental glucocorticoids as an additional treatment (RR 0.72, 95% CI 0.53 to 0.97; 2 RCTs, 926 children).  Dexamethasone given in different doses Compared to 0.15 mg/kg, 0.60 mg/kg dexamethasone probably reduced the severity of croup as assessed by the croup scoring scale at 24-hour postbaseline score (SMD 0.63, 95% CI 0.16 to 1.10; 1 RCT, 72 children; moderate-certainty evidence); however, this was not the case at two hours (SMD -0.27, 95% CI -0.76 to 0.22; 2 RCTs, 861 children; high-certainty evidence). There was probably no reduction at six hours (SMD -0.45, 95% CI -1.26 to 0.35; 3 RCTs, 178 children; moderate-certainty evidence), and the evidence at 12 hours is very uncertain (SMD -0.60, 95% CI -4.39 to 3.19; 2 RCTs, 113 children; very low-certainty evidence). There was little to no difference between doses of dexamethasone in return visits or (re)admissions of children or both (RR 0.91, 95% CI 0.71 to 1.17; 3 RCTs, 949 children; high-certainty evidence) or length of stay in the hospital or emergency department (mean difference 0.12, 95% CI -0.32 to 0.56; 2 RCTs, 892 children). The need for additional treatments, such as epinephrine (RR 0.78, 95% CI 0.34 to 1.75; 2 RCTs, 885 children); intubation (risk difference 0.00, 95% CI -0.00 to 0.00; 2 RCTs, 861 children); or use of supplemental glucocorticoids (RR 0.77, 95% CI 0.51 to 1.15; 2 RCTs, 617 children), also did not differ between doses of dexamethasone.  There were moderate to high levels of heterogeneity in the analyses for most comparisons. Adverse events were observed for some of the comparisons reported in the review. AUTHORS' CONCLUSIONS: The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low-dose dexamethasone at 0.15 mg/kg to treat croup.

Allergen inhalation generates pro-inflammatory oxidised phosphatidylcholine associated with airway dysfunction.

Oxidised phosphatidylcholines (OxPCs) are produced under conditions of elevated oxidative stress and can contribute to human disease pathobiology. However, their role in allergic asthma is unexplored. The aim of this study was to characterise the OxPC profile in the airways after allergen challenge of people with airway hyperresponsiveness (AHR) or mild asthma. The capacity of OxPCs to contribute to pathobiology associated with asthma was also to be determined.Using bronchoalveolar lavage fluid from two human cohorts, OxPC species were quantified using ultra-high performance liquid chromatography-tandem mass spectrometry. Murine thin-cut lung slices were used to measure airway narrowing caused by OxPCs. Human airway smooth muscle (HASM) cells were exposed to OxPCs to assess concentration-associated changes in inflammatory phenotype and activation of signalling networks.OxPC profiles in the airways were different between people with and without AHR and correlated with methacholine responsiveness. Exposing patients with mild asthma to allergens produced unique OxPC signatures that associated with the severity of the late asthma response. OxPCs dose-dependently induced 15% airway narrowing in murine thin-cut lung slices. In HASM cells, OxPCs dose-dependently increased the biosynthesis of cyclooxygenase-2, interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor and the production of oxylipins via protein kinase C-dependent pathways.Data from human cohorts and primary HASM cell culture show that OxPCs are present in the airways, increase after allergen challenge and correlate with metrics of airway dysfunction. Furthermore, OxPCs may contribute to asthma pathobiology by promoting airway narrowing and inducing a pro-inflammatory phenotype and contraction of airway smooth muscle. OxPCs represent a potential novel target for treating oxidative stress-associated pathobiology in asthma.