Rates of pediatric emergency department visits vary according to neighborhood marginalization in Ottawa, Canada.

OBJECTIVES: To determine the association between neighborhood marginalization and rates of pediatric ED visits in Ottawa, Ontario. Secondary objectives investigated if the association between neighborhood marginalization and rates varied by year, acuity, and distance to hospital. METHODS: We calculated rates of pediatric ED visits per 1000 person-years for census dissemination areas within 100 km of the Children's Hospital of Eastern Ontario for patients < 18 years old from January 2018 through December 2020. The 2016 Ontario Marginalization Index categorized neighborhoods along quintiles of residential instability, material deprivation, ethnic concentration, and dependency. Generalized mixed-effects models determined the incidence rate ratios of pediatric ED visits for each quintile of marginalization; multivariate models were used to control for year of presentation and distance to hospital. Analysis was repeated for low versus high acuity ED visits. RESULTS: There were 154,146 ED visits from patients in 2055 census dissemination areas within 100 km of CHEO from 2018 to 2020. After controlling for year and distance from hospital in multivariate analyses, there were higher rates of pediatric ED visits for dissemination areas with high residential instability, high material deprivation, and low ethnic concentration. These findings did not change according to visit acuity. CONCLUSIONS: Neighborhood residential instability and material deprivation should be considered when locating alternatives to emergency care.

RéSUMé: OBJECTIFS: Déterminer l'association entre la marginalisation du quartier et les taux de visites aux urgences pédiatriques à Ottawa, en Ontario. Les objectifs secondaires visaient à déterminer si l'association entre la marginalisation du quartier et les taux variait selon l'année, l'acuité et la distance à l'hôpital. MéTHODES: Nous avons calculé les taux de visites aux urgences pédiatriques par tranche de 1000 années-personnes dans les aires de diffusion du recensement à moins de 100 km du Centre hospitalier pour enfants de l'est de l'Ontario pour les patients de moins de 18 ans de janvier 2018 à décembre 2020. L'Indice de marginalisation de l'Ontario de 2016 classait les quartiers selon des quintiles d'instabilité résidentielle, de privation matérielle, de concentration ethnique et de dépendance. Les modèles à effets mixtes généralisés ont déterminé les ratios des taux d'incidence des visites aux urgences pédiatriques pour chaque quintile de marginalisation; des modèles multivariés ont été utilisés pour contrôler l'année de présentation et la distance à l'hôpital. L'analyse a été répétée pour les visites à l'urgence de faible acuité par rapport à haute acuité. RéSULTATS: Il y a eu 154 146 visites aux urgences de patients dans 2 055 aires de diffusion du recensement à moins de 100 km du CHEO de 2018 à 2020. Après avoir tenu compte de l'année et de la distance par rapport à l'hôpital dans les analyses multivariées, on a constaté des taux plus élevés de visites aux urgences pédiatriques dans les zones de diffusion présentant une instabilité résidentielle élevée, une privation matérielle élevée et une faible concentration ethnique. Ces résultats n'ont pas changé selon l'acuité de la visite. CONCLUSIONS: L'instabilité résidentielle du quartier et la privation matérielle doivent être prises en compte lors de la recherche de solutions de rechange aux soins d'urgence.

Cost analysis and economic evaluation of a virtual pediatric emergency department pilot program.

OBJECTIVES: The Children's Hospital of Eastern Ontario launched Canada's first virtual pediatric emergency department (ED) from May 2020 through November 2021 to deliver accessible care during the COVID-19 pandemic. The objective of this study was to (i) conduct a cost analysis of the virtual pediatric ED, and (ii) compare the virtual costs to in-person ED costs to inform future resource allocation decisions. METHODS: We calculated costs from a health system perspective in 2021 Canadian dollars. Using a decision tree model, we compared expected costs with and without the virtual pediatric ED, and calculated overall and per patient cost savings of implementing the virtual ED. RESULTS: The virtual ED provided care to 7394 patients. In the base case, virtual care saved $890,000 ($120 per patient). One-way sensitivity analyses suggest overall cost savings were most sensitive to the proportion of virtual care patients who would have received in-person care had the virtual option not been available (range $300,000-$1,700,000), followed by ED overhead costs (range $640,000-$1,140,000). Multivariate sensitivity analyses demonstrated robust cost savings of $920,000 (95% CI 850,000-990,000) in a scenario using billing codes to calculate costs, and savings of $1,040,000 (95% CI 960,000-1,120,000) if physician salaries were used instead. CONCLUSIONS: These findings suggest the virtual pediatric ED reduced costs per patient. Virtual care may represent a financially valuable pediatric emergency department service.

ABSTRAIT: OBJECTIFS: Le Centre hospitalier pour enfants de l'Est de l'Ontario a lancé le premier service d'urgence pédiatrique (SU) virtuel du Canada de mai 2020 à novembre 2021 pour offrir des soins accessibles pendant la pandémie de COVID-19. L'objectif de cette étude est de i) effectuer une analyse des coûts du DE pédiatrique virtuel et ii) comparer les coûts virtuels aux coûts du DE, en personne pour éclairer les décisions futures en matière d'affectation des ressources. MéTHODES: Nous avons calculé les coûts du point de vue du système de santé en dollars canadiens de 2021. À l'aide d'un modèle d'arbre décisionnel, nous avons comparé les coûts prévus avec et sans le service d'urgence pédiatrique virtuel et calculé les économies globales et par patient découlant de la mise en œuvre du service d'urgence virtuel. RéSULTATS: Le service d'urgence virtuel a fourni des soins à 7 394 patients. Dans le cas de base, les soins virtuels ont permis d'économiser 890 000 $ (120 $ par patient). Les analyses de sensibilité unidirectionnelles donnent à penser que les économies de coûts globales étaient plus sensibles à la proportion de patients en soins virtuels qui auraient reçu des soins en personne si l'option virtuelle n'avait pas été disponible (fourchette de 300 000 $ à 1 700 000 $), suivie des frais généraux du SU (fourchette de 640 000 $ à 1 140 000 $). Les analyses de sensibilité à variables multiples ont démontré de solides économies de coûts de 920 000 $ (IC à 95 %, 850 000 à 990 000) dans un scénario utilisant des codes de facturation pour calculer les coûts, et des économies de 1 040 000 $ (IC à 95 %, 960 000 à 1 120 000) si les salaires des médecins étaient utilisés à la place. CONCLUSIONS: Ces résultats suggèrent que le SU pédiatrique virtuel a réduit les coûts par patient. Les soins virtuels peuvent représenter un service d'urgence pédiatrique financièrement utile.

Cannabis-related emergency department visits by youths and their outcomes in Ontario: a trend analysis.

BACKGROUND: Cannabis-related emergency department visits can be an entry point for youths to mental health and substance use care systems. We aimed to examine trends in cannabis-related emergency department visits as a function of youths' age and sex. METHODS: Using administrative data, we examined all visits to emergency departments in Ontario, Canada, from 2003 to 2017, by youth aged 10-24 years (grouped as 10-13, 14-18 and 19-24 yr) to determine trends in cannabis-related emergency department visits. Cannabis-related visits were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for cannabis poisoning and mental disorders due to cannabinoids. We categorized presentations as "less severe" versus "more severe" using scores assigned by nurses at triage. RESULTS: We examined 14 697 778 emergency department visits. Cannabis-related visits increased from 3.8 per 10 000 youths (95% confidence interval [CI] 3.5-4.0) in 2003 to 17.9 (95% CI 17.4-18.4) in 2017, a 4.8-fold increase (95% CI 4.4-5.1). Rates increased for both sexes and each age group. Males were more likely to have a visit than females (rate ratios ≥ 1.5 in 2003 and 2017). The number of cannabis-related visits in 2017 was 25.0 per 10 000 (95% CI 24.0-25.9) among youth aged 19-24 years, 21.9 per 10 000 (95% CI 20.9-22.9) among those aged 14-18 years, and 0.8 per 10 000 (95% CI 0.5-1.0) among those aged 10-13 years. In 2017, 88.2% (95% CI 87.3%-89.0%) of cannabis-related visits and 58.1% (95% CI 58.0%-58.2%) of non-cannabis-related visits were triaged as "more severe," (rate ratio 1.52, 95% CI 1.50-1.53). Similarly, in 2017, 19.0% (95% CI 18.0%-20.1%) of cannabis-related visits and 5.8% (95% CI 5.7%-5.8%) of non-cannabis-related visits resulted in hospital admission (rate ratio 3.3, 95% CI 3.1-3.5). INTERPRETATION: Rates of cannabis-related emergency department visit by youths aged 10-24 years increased almost fivefold from 2003 to 2017, with increases in visit severity and hospital admissions. These trends describe an emerging public health problem, and research is needed to identify the causes of this increase and the health and social consequences of cannabis-related visits for these youths.

Psychosocial and Psychological Vulnerability in Adolescents with Gender Dysphoria: A "Proof of Principle" Study.

For adolescents with gender dysphoria, it has become common to be offered hormonal treatment to either delay or suppress pubertal development and/or to masculinize or feminize the body. At the same time, it has been our clinical impression that the psychological vulnerability of at least some of these youth has been overlooked. Fifty consecutive referrals of adolescents with a DSM-IV-TR diagnosis of gender identity disorder (GID) constituted the sample. Information obtained at intake was coded for the presence or absence of 15 psychosocial and psychological vulnerability factors. The mean number of psychosocial/psychological vulnerability factors coded as present was 5.56 (range, 0-13). Over half of the sample had six or more of the vulnerability factors. The number of factors coded as present was significantly correlated with behavioral and emotional problems on the Youth Self-Report Form and the Child Behavior Checklist, but not with demographic variables or IQ. The findings supported the clinical impression that a large percentage of adolescents referred for gender dysphoria have a substantial co-occurring history of psychosocial and psychological vulnerability, thus supporting a "proof of principle" for the importance of a comprehensive psychologic/psychiatric assessment that goes beyond an evaluation of gender dysphoria per se.

Procedural pain and patient-reported side effects with weekly injections of subcutaneous methotrexate in children with rheumatic disorders.

BACKGROUND: Despite the widespread use of subcutaneous methotrexate in treating pediatric rheumatic disorders, the amount of pain associated with the injections has not been quantified. Our study aims 1) to quantify the amount of pain associated with subcutaneous injections of methotrexate, 2) to explore predictors of pain, 3) to determine the frequency of patient-reported clinical adverse effects of methotrexate, and 4) identify coping strategies of patients and caregivers. METHODS: Patients aged 4-17 years with rheumatologic diseases who were receiving weekly subcutaneous methotrexate injections for at least 4 weeks were invited to participate in this prospective cohort study. They were trained to use the Faces Pain Scale-Revised (FPS-R) and Faces, Legs, Arms, Cry, Consolability (FLACC) tools to rate pain associated with the injections. All patients underwent focused interviews exploring their experiences with methotrexate injections. RESULTS: Forty-one patients consented to the study. The mean age was 11.2 years (SD = 3.9 years) and 68% were female. Most patients were diagnosed with JIA (73%). Mean duration of methotrexate therapy was 2.5 years (SD = 2.1 yrs). All but one of the patients used methotrexate 25 mg/ml solution for injection in 1 cc or 3 cc syringe with 30 gauge ½" needle. Median amount of pain was 2/10 on the FPS-R and 1/10 on the FLACC. Higher intensity of pain was significantly associated with presence of side effects (p = 0.004), but not duration of therapy (p = 0.20) or age (p = 0.24). Most participants (61%) experienced at least one adverse effect; nausea (56%) and vomiting (34%) were the most common symptoms reported. Patients and caregivers reported using ice (34%), comfort positions (51%), rewards (49%), reassurance (54%), distraction (51%), and analgesic medications (22%) to cope with the injections. CONCLUSION: Subcutaneous injections of methotrexate are associated with a mild amount of pain. Presence of side effects may amplify the amount of perceived pain. Clinicians can apply this knowledge when counseling patients and family members about methotrexate therapy.

Early versus late-phase consolidation of opiate reward memories requires distinct molecular and temporal mechanisms in the amygdala-prefrontal cortical pathway.

The consolidation of newly acquired memories involves the temporal transition from a recent, less stable trace to a more permanent consolidated form. Opiates possess potent rewarding effects and produce powerful associative memories. The activation of these memories is associated with opiate abuse relapse phenomena and the persistence of compulsive opiate dependence. However, the neuronal, molecular and temporal mechanisms by which associative opiate reward memories are consolidated are not currently understood. We report that the consolidation of associative opiate reward memories involves a temporal and molecular switch between the basolateral nucleus of the amygdala (BLA) (early consolidation phase) to the medial prefrontal cortex (mPFC) (late consolidation phase). We demonstrate at the molecular, behavioral and neuronal levels that the consolidation of a recently acquired opiate reward memory involves an extracellular signal-related kinase (ERK)-dependent phosphorylation process within the BLA. In contrast, later-stage consolidation of a newly acquired memory is dependent upon a calcium-calmodulin-dependent (CaMKII), ERK-independent, mechanism in the mPFC, over a 12 hr temporal gradient. In addition, using in vivo multi-unit neuronal recordings in the mPFC, we report that protein synthesis within the BLA modulates the consolidation of opiate-reward memory in neuronal mPFC sub-populations, via the same temporal dynamic.

Supra-normal stimulation of dopamine D1 receptors in the prelimbic cortex blocks behavioral expression of both aversive and rewarding associative memories through a cyclic-AMP-dependent signaling pathway.

Dopamine (DA) receptor transmission through either D(1) or D(2)-like subtypes is involved critically in the processing of emotional information within the medial prefrontal cortex (mPFC). However the functional role of specific DA D(1)-like receptor transmission in the expression of emotionally salient associative memories (either aversive or rewarding) is not currently understood. Here we demonstrate that specific activation of DA D(1) receptors in the prelimbic (PLC) division of the mPFC causes a transient block in the behavioral expression of both aversive and rewarding associative memories. We report that intra-PLC microinfusions of a selective D(1) receptor agonist block the spontaneous expression of an associative olfactory fear memory, without altering the stability of the original memory trace. Furthermore, using an unbiased place conditioning procedure (CPP), intra-PLC D(1) receptor activation blocks the spontaneous expression of an associative morphine (5 mg/kg; i.p.) reward memory, while leaving morphine-primed memory expression intact. Interestingly, both intra-PLC D(1)-receptor mediated block of either fear-related or reward-related associative memories were dependent upon downstream cyclic-AMP (cAMP) signaling as both effects were rescued by co-administration of a cAMP signaling inhibitor. The blockade of both rewarding and aversive associative memories is mediated through a D(1)-specific signaling pathway, as neither forms of spontaneous memory expression were blocked by intra-PLC microinfusions of a D(2)-like receptor agonist. Our results demonstrate that the spontaneous expression of either rewarding or aversive emotionally salient memories shares a common, D(1)-receptor mediated substrate within the mPFC.

Cannabinoid transmission in the basolateral amygdala modulates fear memory formation via functional inputs to the prelimbic cortex.

The cannabinoid CB1 receptor system is critically involved in the control of associative fear memory formation within the amygdala-prefrontal cortical pathway. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the prelimbic division (PLC) of the medial prefrontal cortex (mPFC). However, the precise role of CB1 receptor transmission within the BLA during the processing of fear memory is not fully understood. We examined the potential role of BLA CB1 receptor transmission during an olfactory fear-conditioning procedure in rats by pharmacologically modulating CB1 cannabinoid transmission directly within the BLA. We report that blockade of BLA CB1 receptor transmission prevents the acquisition of associative fear memory, while having no effect on the recall or consolidation of these memories. In contrast, intra-BLA activation of CB1 receptor transmission or blockade of endocannabinoid reuptake strongly potentiated the emotional salience of normally subthreshold fear-conditioning stimuli. In addition, pharmacological inactivation of the mPFC before intra-BLA CB1 activation blocked CB1-receptor-mediated potentiation of fear memory formation. In vivo single-unit electrophysiological recordings within the PLC revealed that modulation of BLA CB1 receptor transmission strongly influences neuronal activity within subpopulations of PLC neurons, with blockade of intra-BLA CB1 receptor transmission inhibiting spontaneous PLC neuronal activity and activation of CB1 receptors producing robust activation, in terms of neuronal firing frequency and bursting activity. Thus, cannabinoid transmission within the BLA strongly modulates the processing of associative fear memory via functional interactions with PLC neuronal populations.

NMDA receptor hypofunction in the prelimbic cortex increases sensitivity to the rewarding properties of opiates via dopaminergic and amygdalar substrates.

The medial prefrontal cortex (mPFC) plays a significant role in associative learning and memory formation during the opiate addiction process. Various lines of evidence demonstrate that glutamatergic (GLUT) transmission through the N-methyl D-aspartate (NMDA) receptor can modulate neuronal network activity within the mPFC and influence dopaminergic signaling within the mesocorticolimbic pathway. However, little is known about how modulation of NMDA receptor signaling within the mPFC may regulate associative opiate reward learning and memory formation. Using a conditioned place preference (CPP) procedure, we examined the effects of selective NMDA receptor blockade directly within the prelimbic cortex (PLC) during the acquisition of associative opiate reward learning. NMDA receptor blockade specifically within the PLC caused a strong potentiation in the rewarding effects of either systemic or intra-ventral tegmental area (intra-VTA) morphine administration. This reward potentiation was dose dependently blocked by coadministration of dopamine D1 or D2 receptor antagonists and by blockade of presynaptic GLUT release. In addition, pharmacological inactivation of the basolateral amygdala (BLA) also prevented intra-PLC NMDA receptor blockade-induced potentiation of opiate reward signals, demonstrating a functional interaction between inputs from the VTA and BLA within the PLC, during the encoding and modulation of associative opiate reward information.

Integrated cannabinoid CB1 receptor transmission within the amygdala-prefrontal cortical pathway modulates neuronal plasticity and emotional memory encoding.

The cannabinoid CB1 receptor system is functionally involved in the processing and encoding of emotionally salient sensory information, learning and memory. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC). In addition, synaptic plasticity in the form of long-term potentiation (LTP) within the BLA > mPFC pathway is an established correlate of exposure to emotionally salient events. We performed a series of in vivo LTP studies by applying tetanic stimulation to the BLA combined with recordings of local field potentials within prelimbic cortical (PLC) region of the rat mPFC. Systemic pretreatment with AM-251 dose dependently blocked LTP along the BLA-PLC pathway and also the behavioral acquisition of conditioned fear memories. We next performed a series of microinfusion experiments wherein CB1 receptor transmission within the BLA > PLC circuit was pharmacologically blocked. Asymmetrical, interhemispheric blockade of CB1 receptor transmission along the BLA > PLC pathway prevented the acquisition of emotionally salient associative memory. Our results indicate that coordinated CB1 receptor transmission within the BLA > PLC pathway is critically involved in the encoding of emotional fear memories and modulates neural plasticity related to the encoding of emotionally salient associative learning.