The Impact of an Accelerated Diagnostic Protocol Using Conventional Troponin I for Patients With Cardiac Chest Pain in the Emergency Department.

Background: This study strove to assess the impact of the implementation of an accelerated diagnostic protocol (ADP), using shortened serial-testing intervals and a conventional troponin I (c-TnI) test, on emergency department (ED) length of stay (LOS). Methods: This retrospective cohort study included adults (aged ≥ 18 years) presenting to a Canadian ED with a primary complaint of cardiac chest pain between January 14, 2017 and January 15, 2019. For non-high-risk patients, the troponin delta timing decreased from 6 hours to 3 hours, and a different conventional troponin I level cut-point was implemented on January 15, 2018. The primary outcome was ED LOS. Secondary outcomes included disposition status, consultation proportions, and major adverse cardiac events within 30 days. Results: A total of 3133 patient interactions were included. Although the overall decrease in median ED LOS was not significant (P = 0.074), a significant reduction occurred in ED LOS (-33 minutes; 95% confidence interval: -53.6 to -12.4 minutes) among patients who were discharged in the post-ADP group. Consultations were unchanged between groups (36.1% before vs 33.8% after; P = 0.17). The major adverse cardiac events outcomes were unchanged across cohorts (15.9% vs 15.3%; P = 0.62). Conclusions: The implementation of an ADP, with a conventional troponin I test, for cardiac chest pain in a Canadian ED was not associated with a significant reduction of LOS for all patients; however, a significant reduction occurred for patients who were discharged, and the strategy appears safe.

Contexte: Cette étude visait à évaluer les répercussions de la mise en œuvre d'un protocole de diagnostic accéléré avec intervalles plus courts entre les épreuves séquentielles et dosage classique de la troponine I sur la durée du séjour à l'urgence. Méthodologie: Cette étude de cohortes rétrospective a été menée chez des adultes (âgés de 18 ans ou plus) qui se sont présentés à l'urgence d'un hôpital canadien principalement pour une douleur thoracique cardiaque entre le 14 janvier 2017 et le 15 janvier 2019. Chez les patients qui n'étaient pas exposés à un risque élevé, l'intervalle de dosage de la troponine (delta) est passé de 6 heures à 3 heures, et une nouvelle valeur seuil a été utilisée pour le dosage classique de la troponine I à compter du 15 janvier 2018. Le critère d'évaluation principal était la durée du séjour à l'urgence. Les critères d'évaluation secondaires comprenaient le statut au moment de la sortie, les proportions de consultation et les événements cardiovasculaires indésirables majeurs dans les 30 jours. Résultats: Au total, 3 133 interactions avec des patients ont été incluses. Bien que la diminution globale de la durée médiane du séjour à l'urgence n'ait pas été significative (p = 0,074), une réduction significative du séjour à l'urgence (-33 minutes; intervalle de confiance à 95 % : -53,6 à -12,4 minutes) a été observée chez les patients ayant reçu leur congé appartenant au groupe dans lequel le protocole de diagnostic accéléré a été mis en œuvre. Les consultations étaient inchangées entre les groupes (36,1 % avant vs 33,8 % après; p = 0,17). Les résultats relatifs aux événements cardiovasculaires indésirables majeurs sont demeurés inchangés dans les cohortes (15,9 % vs 15,3 %; p = 0,62). Conclusions: La mise en œuvre d'un protocole de diagnostic accéléré, avec un dosage classique de la troponine I, en cas de douleur thoracique d'origine cardiaque, à l'urgence d'un établissement canadien ne s'est pas traduite par une réduction significative du séjour à l'urgence chez tous les patients. Une réduction significative a néanmoins été observée chez les patients qui ont reçu leur congé, et la stratégie s'est avérée sûre.

Effect of a High-Sensitivity Troponin I and Associated Diagnostic Protocol on Emergency Department Length of Stay: A Retrospective Cohort Study.

Background: The objective of this study was to assess the introduction of a high-sensitivity troponin I (hs-TnI) assay and its associated accelerated protocol on emergency department (ED) length of stay (LOS) for patients presenting with chest pain, compared to an accelerated diagnostic protocol using conventional troponin (TnI) testing. Methods: We conducted a retrospective cohort study of all adults with a primary presenting complaint of chest pain of cardiac origin and a Canadian Triage and Acuity Scale score of 2 or 3, between November 8, 2019 and November 9, 2021, to a tertiary-care urban Canadian ED. The primary outcome was ED LOS. Secondary outcomes included consultation proportions and major adverse cardiac events within 30 days of the index ED visit. Results: A total of 2640 patients presenting with chest pain were included, with 1333 in the TnI group and 1307 in the hs-TnI group. Median ED LOS decreased significantly, from 392 minutes for the TnI group, and 371 minutes for the hs-TnI group (median difference = 21 minutes; 95% confidence interval: 5.3, 36.7). The numbers of consultations and admissions were not statistically different between study periods. The major adverse cardiac events outcomes did not change following the implementation of the hs-TnI test (13.6% vs 13.1%; P = 0.71). Conclusions: The implementation of an accelerated chest pain protocol using an hs-TnI assay in a tertiary-care Canadian ED was associated with a modest reduction of LOS for all patients, and a substantial reduction of LOS for patients undergoing serial troponin testing. This strategy was safe, with no increase in adverse outcomes.

Contexte: Cette étude visait à évaluer l'introduction du dosage de la troponine I de haute sensibilité (hs-TnI) et le protocole accéléré qui lui est associé sur la durée des séjours aux urgences dans le cas des patients qui consultent pour une douleur thoracique, comparativement à un protocole diagnostique accéléré faisant appel à un test de troponine classique (TnI). Méthodologie: Nous avons mené une étude de cohorte rétrospective portant sur tous les adultes qui se sont présentés aux urgences d'un établissement urbain de soins tertiaires canadien entre le 8 novembre 2019 et le 9 novembre 2021 principalement pour une douleur thoracique d'origine cardiaque et dont le score était de 2 ou 3 à l'Échelle canadienne de triage et de gravité (ETG). Le principal critère d'évaluation était la durée du séjour au service des urgences. Les critères d'évaluation secondaires comprenaient la fréquence des consultations et les événements cardiaques indésirables majeurs dans les 30 jours ayant suivi la visite de référence aux urgences. Résultats: Au total, 2640 patients qui s'étaient présentés aux urgences pour une douleur thoracique ont été inclus, 1333 se trouvant dans le groupe TnI et 1307 dans le groupe hs-TnI. La durée médiane du séjour aux urgences a diminué considérablement, passant de 392 minutes dans le groupe TnI à 371 minutes dans le groupe hs-TnI (différence médiane de 21 minutes; intervalle de confiance [IC] à 95 % : 5,3-36,7). Les consultations et les admissions n'ont pas affiché de différence statistique entre les périodes de l'étude. Les événements cardiaques indésirables majeurs n'ont pas varié après l'introduction du dosage de la hs-TnI (13,6 % vs 13,1 %; p = 0,71). Conclusions: L'adoption d'un protocole accéléré pour la douleur thoracique à l'aide du dosage de la hs-TnI au service des urgences d'un établissement de soins tertiaires canadien a été associée à une légère réduction de la durée du séjour pour l'ensemble des patients et à une réduction substantielle de cette durée pour les patients soumis à des analyses de la troponine en série. De plus, cette stratégie était sûre sans hausse des événements indésirables.

Ketorolac in the treatment of acute migraine: a systematic review.

This systematic review examined the effectiveness of parenteral ketorolac (KET) in acute migraine. Acute migraine headaches are common emergency department presentations, and despite evidence for various treatments, there is conflicting evidence regarding the use of KET. Searches of MEDLINE, EMBASE, Cochrane, CINAHL, and gray literature sources were conducted. Included studies were randomized controlled trials in which KET alone or in combination with abortive therapy was compared with placebo or other standard therapy in adult patients with acute migraine. Two reviewers assessed relevance, inclusion, and study quality independently, and agreement was measured using kappa (k). Weighted mean differences (WMD) and relative risks are reported with 95% confidence intervals (CIs). Overall, the computerized search identified 418 citations and 1414 gray literature citations. From a list of 34 potentially relevant studies (k = 0.915), 8 trials were included, involving over 321 (141 KET) patients. The median quality scores were 3 (interquartile range: 2-4), and two used concealed allocation. There were no baseline differences in 10-point pain scores (WMD = 0.07; 95% CI: -0.39, 0.54). KET and meperidine resulted in similar pain scores at 60 minutes (WMD = 0.31; -0.68, 1.29); however, KET was more effective than intranasal sumatriptan (WMD = -4.07; 95% CI: -6.02 to -2.12). While there was no difference in pain relief at 60 minutes between KET and phenothiazine agents (WMD = 0.82; 95% CI: -1.33 to 2.98), heterogeneity was high (I(2) = 70%). Side effect profiles were similar between KET and comparison groups. Overall, KET is an effective alternative agent for the relief of acute migraine headache in the emergency department. KET results in similar pain relief, and is less potentially addictive than meperidine and more effective than sumatriptan; however, it may not be as effective as metoclopramide/phenothiazine agents.

A novel form of presynaptic CaMKII-dependent short-term potentiation between Lymnaea neurons.

Short-term plasticity is thought to form the basis for working memory, the cellular mechanisms of which are the least understood in the nervous system. In this study, using in vitro reconstructed synapses between the identified Lymnaea neuron visceral dorsal 4 (VD4) and left pedal dorsal 1 (LPeD1), we demonstrate a novel form of short-term potentiation (STP) which is 'use'- but not time-dependent, unlike most previously defined forms of short-term synaptic plasticity. Using a triple-cell configuration we demonstrate for the first time that a single presynaptic neuron can reliably potentiate both inhibitory and excitatory synapses. We further demonstrate that, unlike previously described forms of STP, the synaptic potentiation between Lymnaea neurons does not involve postsynaptic receptor sensitization or presynaptic residual calcium. Finally, we provide evidence that STP at the VD4-LPeD1 synapse requires presynaptic calcium/calmodulin dependent kinase II (CaMKII). Taken together, our study identifies a novel form of STP which may provide the basis for both short- and long-term potentiation, in the absence of any protein synthesis-dependent steps, and involve CaMKII activity exclusively in the presynaptic cell.

Integrative biology of an embryonic respiratory behaviour in pond snails: the 'embryo stir-bar hypothesis'.

Embryos of freshwater snails undergo direct development from single cell to juvenile inside egg masses that are deposited on vegetation and other substratum in pond, lake and stream habitats. Helisoma trivolvis, a member of the Planorbidae family of basommatophoran snails, has served as a model for studying the developmental and physiological roles for neurotransmitters during embryogenesis. Early studies revealed that H. trivolvis embryos from stage E15 to E30, the period between gastrulation and the trochophore-juvenile transition, display a cilia-driven behaviour consisting of slow basal rotation and transient periods of rapid rotation. The discovery of a bilateral pair of early serotonergic neurons, named ENC1, which project an apical process to the embryo surface and basal neurites to ciliated cells, prompted the hypothesis that each ENC1 is a dual-function sensory and motor neuron mediating a physiological embryonic response. This article reviews our past and present studies and addresses questions concerning this hypothesis, including the following. (1) What environmental signal regulates ENC1 activity and rotational behaviour? (2) Does ENC1 function as both a primary sensory and motor neuron underlying the rotational behaviour? (3) What are the sensory transduction mechanisms? (4) How does ENC1 regulate ciliary beating? (5) Do other basommatophoran species have similar neural-ciliary pathways and behavioural responses? (6) How is the behaviour manifest in the dynamic natural environment? In this review, we introduce the ;embryo stir-bar hypothesis', which proposes that embryonic rotation is a hypoxia-sensitive respiratory behaviour responsible for mixing the egg capsule fluid, thereby enhancing delivery of environmental oxygen to the embryo.

Roles of Ca2+ and protein kinase C in the excitatory response to serotonin in embryonic molluscan ciliary cells.

We examined the roles of Ca2+ and protein kinase C (PKC) in the cilio-excitatory response to serotonin in pedal ciliary cells from Helisoma trivolvis embryos. Serotonin (5-hydroxytryptamine; 5-HT; 100 micromol/L) induced an increase in ciliary beat frequency (CBF) was abolished by microinjected BAPTA (50 mmol/L), but was only partially inhibited by the phospholipase C inhibitor U-73122 (10 micromol/L). The diacylglycerol analogs 1-oleoyl-2-acetyl-sn-glycerol (100 micromol/L) and 1,2-dioctanoyl-sn-glycerol (100 micromol/L) caused increases in [Ca2+]i that were smaller than those induced by serotonin. In the absence of extracellular Ca2+, 1,2-dioctanoyl-sn-glycerol (100 micromol/L) failed to elicit an increase in both CBF and [Ca2+]i. In contrast, the serotonin-induced increase in CBF persisted in the absence of extracellular Ca2+, although the increase in [Ca2+]i was abolished. PKC inhibitors bisindolylmaleimide (10 and 100 nmol/L) and calphostin C (10 nmol/L) partially inhibited the serotonin-induced increase in CBF, but didn't affect the serotonin-induced change in [Ca2+]i. These findings suggest that an intracellular store-dependent increase in [Ca2+]i mediates the cilio-excitatory response to serotonin. Furthermore, although PKC is able to cause an increase in [Ca2+]i through calcium influx, it contributes to the cilio-excitatory response to 5-HT through a different mechanism.

Effect of serotonin on ciliary beating and intracellular calcium concentration in identified populations of embryonic ciliary cells.

Embryos of the pond snail Helisoma trivolvis express three known subtypes of ciliary cells on the surface of the embryo early in development: pedal, dorsolateral and scattered single ciliary cells (SSCCs). The pedal and dorsolateral ciliary cells are innervated by a pair of serotonergic sensory-motor neurons and are responsible for generating the earliest whole-animal behavior, rotation within the egg capsule. Previous cell culture studies on unidentified ciliary cells revealed that serotonin (5-hydroxytryptamine; 5-HT) produces a significant increase in the ciliary beat frequency (CBF) in a large proportion of ciliary cells. Both Ca2+ influx and a unique isoform of protein kinase C (PKC) were implicated in the signal transduction pathway underlying the cilio-excitatory response to 5-HT. The goal of the present study was to characterize the anatomical and physiological differences between the three known populations of superficial ciliary cells. The pedal and dorsolateral ciliary cells shared common structural characteristics, including flat morphology, dense cilia and lateral accessory ciliary rootlets. By contrast, the SSCCs had a cuboidal morphology, reduced number of cilia, increased ciliary length and absence of lateral accessory rootlets. In cultures containing unidentified ciliary cells, the calcium/calmodulin-dependent enzyme inhibitor calmidazolium (2 micromol l(-1)) blocked the stimulatory effect of 5-HT (100 micromol l(-1)) on CBF. In addition, 50% of unidentified cultured cells responded to 5-HT (100 micromol l(-1)) with an increase in [Ca2+]i. To facilitate the functional analyses of the individual populations, we developed a method to culture identified ciliary subtypes and characterized their ciliary and calcium responses to 5-HT. In cultures containing either pedal or dorsolateral ciliary cells, 5-HT (100 micromol l(-1)) produced a rapid increase in CBF and a slower increase in [Ca2+]i in all cells examined. By contrast, the CBF and [Ca2+]i of SSCCs were not affected by 100 micromol l(-1) 5-HT. Immunohistochemistry for two putative 5-HT receptors recently cloned from Helisoma revealed that pedal and dorsolateral ciliary cells consistently express the 5-HT(1Hel) protein. Intense 5-HT(7Hel) immunoreactivity was observed in only a subset of pedal and dorsolateral ciliary cells. Cells neighboring the SSCCs, but not the ciliary cells themselves, expressed 5-HT(1Hel) and 5-HT(7Hel) immunoreactivity. These data suggest that the pedal and dorsolateral ciliary cells, but not the SSCCs are a homogeneous physiological subtype that will be useful for elucidating the signal transduction mechanisms underlying 5-HT induced cilio-excitation.

Constitutive and permissive roles of nitric oxide activity in embryonic ciliary cells.

Embryos of Helisoma trivolvis exhibit cilia-driven rotation within the egg capsule during development. In this study we examined whether nitric oxide (NO) is a physiological regulator of ciliary beating in cultured ciliary cells. The NO donor S-nitroso-N-acetylpenicillamine (SNAP; 1-1,000 microM) produced a dose-dependent increase in ciliary beat frequency (CBF). In contrast, the nitric oxide synthase (NOS) inhibitor 7-nitroindazole (10 and 100 microM) inhibited the basal CBF and blocked the stimulatory effects of serotonin (100 microM). NO production in response to serotonin was investigated with 4,5-diaminofluorescein diacetate imaging. Although SNAP (100 microM) produced a rise in NO levels in all cells, only 22% of cells responded to serotonin with a moderate increase. The cGMP analog 8-bromo-cGMP (8-Br-cGMP; 0.2 and 2 mM) increased CBF, and the soluble guanylate cyclase inhibitor LY-83583 (10 microM) blocked the cilioexcitatory effects of SNAP and serotonin. These data suggest that NO has a constitutive cilioexcitatory effect in Helisoma embryos and that the stimulatory effects of serotonin and NO work through a cGMP pathway. It appears that in Helisoma cilia, NO activity is necessary, but not sufficient, to fully mediate the cilioexcitatory action of serotonin.

Coordinated development of identified serotonergic neurons and their target ciliary cells in Helisoma trivolvis embryos.

Embryonic neuron C1s (ENC1s) are bilateral serotonergic neurons that function as cilioexcitatory motor neurons in embryonic development of the pond snail, Helisoma trivolvis. Recent experiments demonstrated that these neurons stimulate cilia-driven embryo rotation in response to hypoxia. In the present study, a comprehensive anatomic analysis of these cells and their target ciliary structures was done to address the following questions: (1) Does ENC1 have a morphology consistent with an oxygen-sensitive sensory cell; (2) Is the development of ENC1's neurite outgrowth pathway coordinated with the development of its target effectors, the pedal and dorsolateral ciliary bands; and (3) What is the anatomic basis of ENC1-ciliary communication? By using an array of microscopic techniques on live and serotonin-immunostained embryos, we found that each ENC1 possessed an apical dendrite that was capped with an integral dendritic knob penetrating the embryo surface. The dendritic knobs contained both microvilli and nonmotile cilia that suggested a sensory transduction role. Each ENC1 also possessed a descending projection, whose development was characterized by the rapid formation of the primary neurite pathway between stages E13 and E15, with the primary neurite of the right ENC1 developing in advance of its contralateral homologue. Secondary neurite branches formed between stages E15 and E30 in a spatiotemporal pattern that closely matched the development of the dorsolateral and pedal bands of cilia. Both dorsolateral and pedal ciliated cells formed basal processes that contacted ENC1 neurites. Finally, gap junction profiles were observed at neurite-neurite, neurite-ciliary cell, and ciliary cell-ciliary cell apposition sites, whereas putative chemical synaptic profiles were observed at neurite-neurite and neurite-ciliary cell apposition sites.

Serotonergic sensory-motor neurons mediate a behavioral response to hypoxia in pond snail embryos.

Oxygen (O(2)) is one of the most important environmental factors that affects both physiological processes and development of aerobic animals, yet little is known about the neural mechanism of O(2) sensing and adaptive responses to low O(2) (hypoxia) during development. In the pond snail, Helisoma trivolvis, the first embryonic neurons (ENC1s) to develop are a pair of serotonergic sensory-motor cells that regulate a cilia-driven rotational behavior. Here, we report that the ENC1-ciliary cell circuit mediates an adaptive behavioral response to hypoxia. Exposure of egg masses to hypoxia elicited a dose-dependent and reversible acceleration of embryonic rotation that mixed capsular fluid, thereby facilitating O(2) diffusion to the embryo. The O(2) partial pressures (Po(2)) for threshold, half-maximal, and maximal rotational response were 60, 28, and 13 mm Hg, respectively. During hypoxia, embryos relocated to the periphery of the egg masses where higher Po(2) levels occurred. Furthermore, intermittent hypoxia treatments induced a sensitization of the rotational response. In isolated ciliary cells, ciliary beating was unaffected by hypoxia, suggesting that in the embryo, O(2) sensing occurs upstream of the motile cilia. The rotational response of embryos to hypoxia was attenuated by application of the serotonin receptor antagonist, mianserin, correlated to the development of ENC1-ciliary cell circuit, and abolished by laser-ablation of ENC1s. Together, these data suggest that ENC1s are unique oxygen sensors that may provide a good single cell model for the examination of mechanistic, developmental, and evolutionary aspects of O(2) sensing.