The use of drones for the delivery of diagnostic test kits and medical supplies to remote First Nations communities during Covid-19.

BACKGROUND: Health care inequity in remote and rural Indigenous communities often involves difficulty accessing health care services and supplies. Remotely Piloted Aircraft Systems, or drones, offer a potentially cost-effective method for reducing inequity by removing geographic barriers, increasing timeliness, and improving accessibility of supplies, equipment, and remote care. METHODS: We assessed the feasibility of drones for delivery of supplies, medical equipment, and medical treatment across multiple platforms, including drone fleet development and testing; payload system integration (custom fixed-mount, winch, and parachute); and medical delivery simulations (COVID-19 test kit delivery and return, delivery of personal protective equipment, and remote ultrasound delivery and testing). RESULTS: Drone operational development has led to a finalized, scalable fleet of small to large drones with functional standard operating procedures across a range of scenarios, and custom payload systems including a fixed-mount, winch-based and parachute-based system. Simulation scenarios were successful, with COVID-19 test swabs returned to the lab with no signal degradation and a remote ultrasound successfully delivered and remotely guided in the field. DISCUSSION/CONCLUSIONS: Drone-based medical delivery models offer an innovative approach to addressing longstanding issues of health care access and equity and are particularly relevant in the context of SARS-CoV-2.

Factors influencing emergency department observation time following anaphylaxis: a systematic review.

OBJECTIVE: Anaphylaxis is a condition that warrants an observation period after symptoms resolution to detect rare but life-threatening delayed complications. There is a need for evidence to identify patients who would benefit from prolonged observation time. The purpose of this review was to identify factors that may influence the need for longer observation in the emergency department. METHODS: PubMed, Embase, EBM Review, and Cochrane Library were searched using controlled vocabulary and keywords to cover all relevant data. Titles, abstract, and full text were reviewed for inclusion and exclusion criteria. Data were extracted from the included articles regarding case definitions, prognosis, treatment and time factors, and recommended observation time. Factors linked to observation time or complications were tabulated and compared between studies. RESULTS: The search retrieved 2443 citations of which 49 were included. Twenty-one were primary studies and were used to identify factors influencing observation time or complications. Biphasic anaphylaxis was the only adverse event that warranted prolonged observation. The five risk factors often associated with biphasic reactions were time to first epinephrine, history of anaphylaxis, symptom severity, number of epinephrine doses, and unknown trigger. Biphasic reactions happened mostly within the first 72 h with most severe reactions occurring earlier than the milder ones. Heterogeneity in the definition of biphasic anaphylaxis made comparisons challenging. CONCLUSIONS: Observation time should be based on the provider's best estimation of the risk of biphasic anaphylaxis, although no single factor can predict their occurrence. The identified factors will allow the development of an early discharge screening tool.

RéSUMé: OBJECTIF: L'anaphylaxie est une condition qui mérite une période d'observation après la disparition des symptômes pour détecter des complications retardées rares, mais potentiellement mortelles. Il est nécessaire de trouver des preuves pour identifier les patients qui bénéficieraient d'une période d'observation prolongée. Le but de cet examen était d'identifier les facteurs qui pourraient influencer la nécessité d'une période d'observation plus longue aux urgences. MéTHODES: PubMed, Embase, EBM Review et Cochrane Library ont été recherchés au moyen d'un vocabulaire contrôlé et des mots-clés pour couvrir toutes les données pertinentes. Les titres, le résumé et le texte intégral ont été examinés pour les critères d'inclusion et d'exclusion. Les données concernant les définitions de cas, le pronostic, le traitement et la durée de traitement, et la période d'observation recommandée ont été extraites des articles inclus. Les facteurs liés à la période d'observation ou aux complications ont été présentés sous forme de tableau et comparés entre les études. RéSULTATS: La recherche a permis de récupérer 2443 citations dont 49 ont été incluses. Vingt et un étaient des études primaires et ont été utilisées pour identifier les facteurs influençant la période d'observation ou les complications. L'anaphylaxie biphasique était le seul événement indésirable qui méritait une observation prolongée. Les cinq facteurs de risque souvent associés aux réactions biphasiques étaient le délai de la première épinéphrine, les antécédents d'anaphylaxie, la gravité des symptômes, le nombre de doses d'épinéphrine et le déclencheur inconnu. Les réactions biphasiques se sont produites principalement dans les 72 premières heures avec les réactions les plus graves se présentant plus tôt que les réactions plus légères. L'hétérogénéité de la définition de l'anaphylaxie biphasique a rendu les comparaisons difficiles. CONCLUSIONS: La période d'observation doit être basée sur la meilleure estimation du risque d'anaphylaxie biphasique fournie par le professionnel de la santé, bien qu'aucun facteur unique ne puisse prédire son apparition. Les facteurs identifiés permettront le développement d'un outil de dépistage pour les sorties précoces de l'hôpital.

Implementing a specialty pharmacy course within a professional pharmacy curriculum.

BACKGROUND AND PURPOSE: Specialty pharmacy is an important area of pharmacy practice where patients who are prescribed a growing number of specialty drugs receive specialized care, including: benefits investigation, financial support, side effect management, and adherence assessment. As these specialty medications continue to emerge, it is important for pharmacy students to have knowledge of this specialized practice and awareness of the opportunities that exist in this area. The objective is to describe the development of a specialty pharmacy elective course to meet this educational need. EDUCATIONAL ACTIVITY AND SETTING: A one-credit specialty pharmacy elective course was created for second and third-year pharmacy students. Content experts with a variety of clinical and administrative specialty pharmacy expertise led student lectures and topic discussions. Students were assessed for baseline specialty pharmacy knowledge, knowledge at the completion of the course, and satisfaction with the course. FINDINGS: Student knowledge of specialty pharmacy practice increased 27.7% when comparing baseline to post-course test scores. Students evaluated the new course positively with recommendations that the course could benefit by being expanded by an additional credit. SUMMARY: The development of a specialty pharmacy elective course within a college of pharmacy curriculum improved student knowledge of specialty pharmacy practice and was well-received by students who enrolled in the course. Given the complexity and growing importance of specialty pharmacy in practice, this type of course should be considered by other colleges of pharmacy.

Effect of chemotherapy and heat on biomechanical properties of absorbable sutures.

BACKGROUND: The quality of tissue repairs depends on tissue integrity, surgical technique, and material properties of the sutures used. Currently, there is no clear consensus on which is the best suture to use during cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. The aim of this study was to evaluate the impact of heat and chemotherapy on sutures' biomechanical properties. METHODS: Six different 3.0 absorbable sutures (Biosyn, Dexon II, Maxon, Monocryl, PDS II, and Vicryl Plus) were tested. All suture strands were incubated for a 24-h period in saline, mitomycin-c, and oxaliplatin at 37 and 45°C. Suture loops were then loaded to failure using a servohydraulic testing machine. Data for tensile breaking force (TBF) and elongation rate were collected for all samples. RESULTS: Under basal condition, Maxon was the strongest of all sutures with a TBF of 59.6 ± 4.3 N (P < 0.01), and no significant difference in TBF was observed between other sutures. Heat alone had no impact on sutures' biomechanical parameters. Exposition to mitomycin-c at 45°C did not significantly affect sutures' basal tensile properties, with Maxon remaining the strongest suture. When incubated in oxaliplatin at 45°C, the six suture types had a similar TBF. In all experimental conditions, multifilament sutures had a significantly lower elongation rate than monofilament sutures, and no correlations were demonstrated between elongation rate and the TBF of sutures. CONCLUSIONS: This study showed that exposition to heated chemotherapy did not significantly affect absorbable sutures biomechanical properties.

Group V secreted phospholipase A2 contributes to LPS-induced leukocyte recruitment.

Secreted phospholipases A(2) (sPLA(2)s) are well known for their contribution in the biosynthesis of inflammatory eicosanoids. These enzymes also participate in the inflammatory process by regulating chemokine production and protein expression of adhesion molecules. The majority of sPLA(2) isoforms are up-regulated by proinflammatory stimuli such as bacterial lipopolysaccharide (LPS), which predominantly increases the expression of group V sPLA(2) (sPLA(2)-V). Furthermore, it has recently been shown that sPLA(2)-V is a critical messenger in the regulation of cell migration during allergic airway responsiveness. Herein, we investigated the effect of sPLA(2)-V on LPS-mediated leukocyte recruitment and its capacity to modulate adhesion molecule expression. We conducted our study in the murine air pouch model, using sPLA(2)-V null mice (sPLA(2)-V(-/-)) and control wild-type (WT) littermates. We observed that LPS (1 microg/ml)-mediated leukocyte emigration in sPLA(2)-V(-/-) was attenuated by 52% and 86% upon 6 and 12 h of treatment respectively, as compared to WT mice. In WT mice, treatment with the cell-permeable sPLA(2) inhibitor (12-epi-scalaradial; SLD) reduced LPS-mediated leukocyte recruitment by 67%, but had no additional inhibitory effect in sPLA(2)-V(-/-) mice. Protein analyses from the air pouch skin were carried out upon LPS-challenge, and the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were both significantly reduced in sPLA(2)-V(-/-) mice as compared to control WT mice. Together, our data demonstrate the role of sPLA(2)-V in LPS-induced ICAM-1 and VCAM-1 protein overexpression and leukocyte recruitment, supporting the contribution of sPLA(2)-V in the development of inflammatory innate immune responses.

Quetiapine blocks cocaine-induced enhancement of brain stimulation reward.

Quetiapine is an effective atypical antipsychotic medication that was reported to reduce substance use and craving in patients with schizophrenia. This clinical effect of quetiapine is hypothesized to be due to its low affinity for dopamine receptors and its weak attenuation of central reward functions. The present study was designed to determine the magnitude of the reward attenuation induced by different doses of quetiapine and its effectiveness at reducing the effect of cocaine. Experiments were performed on male Sprague-Dawley rats that were trained to produce operant responses to receive rewarding stimulations to the medial forebrain bundle. In a first study, we tested the effects of three doses of quetiapine (5, 10, 20 mg/kg) on brain stimulation reward using a within-subject design and the curve-shift method. In a second study, we tested the effectiveness of a low and high dose of quetiapine (5 and 20 mg/kg) at blocking the reward enhancing effect of cocaine (4 mg/kg) in different groups of animals. Quetiapine produced a weak (20%) but significant attenuation of reward. Cocaine enhanced reward by 20% and the combination of cocaine with the high dose of quetiapine lead to cancellation of each drug effect. The low dose of quetiapine did not alter baseline reward but completely blocked the effect of cocaine. The magnitude of the reward attenuation induced by quetiapine is consistent with its low affinity for dopamine receptors. Its actions on dopamine and non-dopamine neurotransmission are likely to account for its effectiveness at blocking the enhancement of reward by cocaine.

Discovery and pharmacological characterization of a small-molecule antagonist at neuromedin U receptor NMUR2.

Neuromedin U (NMU), through its cognate receptor NMUR2 in the central nervous system, regulates several important physiological functions, including energy balance, stress response, and nociception. By random screening of our corporate compound collection with a ligand binding assay, we discovered (R)-5'-(phenylaminocarbonylamino)spiro[1-azabicyclo[2.2.2]octane-3,2'(3'H)-furo[2,3-b]pyridine] (R-PSOP), a highly potent and selective NMUR2 antagonist. R-PSOP is a nonpeptidic small-molecule with the chemical composition C(20)N(4)O(2)H(22). In competition binding experiments, this compound was found to bind to NMUR2 with high affinity; the K(i) values were determined to be 52 and 32 nM for the human and rat NMUR2, respectively. Moreover, in functional assays measuring phosphoinositide turnover or intracellular calcium mobilization, R-PSOP strongly inhibited the responses stimulated by peptide agonists NMU-25, NMU-23, and NMU-8 in human embryonic kidney 293 cells expressing NMUR2. From Schild analyses, the functional K(b) values for R-PSOP were determined to be 92 and 155 nM at human and rat NMUR2, respectively. Highly selective for NMUR2, R-PSOP exhibited low affinity to the other subtype of NMU receptor, NMUR1, with a K(i) value >10 microM. R-PSOP in vivo attenuated NMU-23-evoked nociceptive responses in a rat spinal reflex preparation. To our knowledge, this is the first antagonist ever reported for NMU receptors. This compound could serve as a valuable tool for further understanding the physiological and pathophysiological roles of NMU system, while providing a chemical starting point that may lead to development of new therapeutics for treatment of eating disorders, obesity, pain, and stress-related disorders.

HIF2 alpha reduces growth rate but promotes angiogenesis in a mouse model of neuroblastoma.

BACKGROUND: HIF2alpha/EPAS1 is a hypoxia-inducible transcription factor involved in catecholamine homeostasis, vascular remodelling, physiological angiogenesis and adipogenesis. It is overexpressed in many cancerous tissues, but its exact role in tumour progression remains to be clarified. METHODS: In order to better establish its function in tumourigenesis and tumour angiogenesis, we have stably transfected mouse neuroblastoma N1E-115 cells with the native form of HIF2alpha or with its dominant negative mutant, HIF2alpha (1-485) and studied their phenotype in vitro and in vivo. RESULTS: In vitro studies reveal that HIF2alpha induces neuroblastoma cells hypertrophy and decreases their proliferation rate, while its inactivation by the HIF2alpha (1-485) mutant leads to a reduced cell size, associated with an accelerated proliferation. However, our in vivo experiments show that subcutaneous injection of cells overexpressing HIF2alpha into syngenic mice, leads to the formation of tumour nodules that grow slower than controls, but that are well structured and highly vascularized. In contrast, HIF2alpha (1-485)-expressing neuroblastomas grow fast, but are poorly vascularized and quickly tend to extended necrosis. CONCLUSION: Together, our data reveal an unexpected combination between an antiproliferative and a pro-angiogenic function of HIF2alpha that actually seems to be favourable to the establishment of neuroblastomas in vivo.

Angiopoietins-1 and -2 are both capable of mediating endothelial PAF synthesis: intracellular signalling pathways.

Vascular endothelial growth factor (VEGF) is the only angiogenic growth factor capable of inducing an inflammatory response and we have recently demonstrated that its inflammatory effect is mediated by the endothelial synthesis of platelet-activating factor (PAF). Recently discovered, Ang1 and Ang2, upon binding to Tie2 receptor, modulate vascular permeability and integrity, contributing to angiogenesis. Ang1 was initially identified as a Tie2 agonist whereas Ang2 can behave as a context-dependent Tie2 agonist or antagonist. We sought to determine if Ang1 and/or Ang2 could modulate PAF synthesis in bovine aortic endothelial cells (BAEC) and if so, through which intracellular signalling pathways. Herein, we report that Ang1 and Ang2 (1 nM) are both capable of mediating a rapid Tie2 phosphorylation and a rapid, progressive and sustained endothelial PAF synthesis maximal within 4 h (1695% and 851% increase, respectively). Angiopoietin-mediated endothelial PAF synthesis requires the activation of the p38 and p42/44 MAPKs, PI3K intracellular signalling pathways, and a secreted phospholipase A(2) (sPLA(2)-V). Furthermore, angiopoietin-mediated PAF synthesis is partly driven by a relocalization of endogenous VEGF to the cell surface membrane. Our results demonstrate that the angiopoietins constitute another class of angiogenic factors capable of mediating PAF synthesis which may contribute to proinflammatory activities.