Postoperative Tonsillectomy Hemorrhage Wall, Jessica J; Tay, Khoon-Yen
Emergency medicine clinics of North America,
05/2018, Volume:
36, Issue:
2
Journal Article
Peer reviewed
Post-tonsillectomy hemorrhage represents a potentially life-threatening condition that occurs in up to 5% of pediatric patients. Minor bleeding often precedes severe hemorrhage. Patients with minor ...or self-resolving bleeding should be observed in the emergency department or admitted for monitoring. Patients with severe bleeding should be immediately assessed for airway and hemodynamic stability. Management of severe bleeding includes immediate surgical consultation or initiation of the transfer process to a center with surgical capabilities, direct pressure to the site of hemorrhage with or without the additional of a hemostatic agent, possible rapid sequence intubation, and management of hemodynamic instability with volume resuscitation.
Here, we describe the characterization of a radioligand selective for GluN2B-containing NMDA receptors, 3-
H 1-(azetidin-1-yl)-2-(6-(4-fluoro-3-methyl-phenyl)pyrrolo3,2-bpyridin-1-yl)ethanone (
...H-JNJ- GluN2B-5). In rat cortical membranes, the compound bound to a single site, and the following kinetic parameters were measured; association rate constant K
= 0.0066 ± 0.0006 min
nM
, dissociation rate constant K
= 0.0210 ± 0.0001 min
indicating calculated K
= K
/K
= 3.3 ± 0.4 nM, (mean ± SEM, n = 3). The equilibrium dissociation constant determined from saturation binding experiments in rat cortex was K
of 2.6 ± 0.3 nM (mean ± SEM, n = 3). In contrast to the widely used GluN2B radioligand
H-Ro 25-6981, whose affinity K
for sigma 1 and sigma 2 receptors are 2 and 189 nM, respectively,
H-JNJ-GluN2B-5 exhibits no measurable affinity for sigma 1 and sigma 2 receptors (K
> 10 μM for both) providing distinct selectivity advantages. Anatomical distribution of
H-JNJ-GluN2B-5 binding sites in rat, mouse, dog, monkey, and human brain tissue was studied using in vitro autoradiography, which showed high specific binding in the hippocampus and cortex and negligible binding in the cerebellum. Enhanced selectivity for GluN2B-containing receptors translated to a good signal-to-noise ratio in both in vitro radioligand binding and in vitro autoradiography assays. In conclusion,
H-JNJ-GluN2B-5 is a high-affinity GluN2B radioligand with excellent signal-to-noise ratio and unprecedented selectivity.
Michelson et al respond to Wall and Naim's comments regarding on residual confounding of the relationship between ED type and survival. To confound this association, a risk factor for survival in ...cardiac arrest would also have to be associated with ED type. They are not aware of evidence suggesting that prehospital interventions such as bystander CPR are associated with ED type, although this is theoretically possible. They believe their study's limitations are outweighed by its representativeness and inclusion of EDs that do not typically participate in cardiac arrest outcomes research.
Herein, we describe a series of substituted 1H-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. Exploration of several five- and six-membered heterocycles ...led to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound 18, and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. The comprehensive investigation of substitution on the pyrimidine moiety of the 1H-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound 31, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. Compound 31 was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED50 of 1.7 mg/kg.
Herein, we describe a series of substituted 1
-((1,2,3-triazol-4-yl)methoxy)pyrimidines as potent GluN2B negative allosteric modulators. Exploration of several five- and six-membered heterocycles led ...to the identification of O-linked pyrimidine analogues that possessed a balance of potency and desirable ADME profiles. Due to initial observations of metabolic saturation, early metabolite identification studies were conducted on compound
and the results drove further iterative optimization efforts to avoid the formation of undesired saturating metabolites. The comprehensive investigation of substitution on the pyrimidine moiety of the 1
-1,2,3-triazol-4-yl)methoxy)pyrimidines allowed for the identification of compound
, which demonstrated high GluN2B receptor affinity, improved solubility, and a clean cardiovascular profile. Compound
was profiled in an ex vivo target engagement study in rats at a 10 mg/kg oral dose and achieved an ED
of 1.7 mg/kg.
Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for ...children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.
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The synthesis, SAR, and preclinical characterization of a series of substituted 6,7-dihydro1,2,4triazolo4,3pyrazin-8(5H)-one P2X7 receptor antagonists are described. Optimized leads ...from this series comprise some of the most potent human P2X7R antagonists reported to date (IC50s<1nM). They also exhibit sufficient potency and oral bioavailability in rat to enable extensive in vivo profiling. Although many of the disclosed compounds are peripherally restricted, compound 11d is brain penetrant and upon oral administration demonstrated dose-dependent target engagement in rat hippocampus as determined by ex vivo receptor occupancy with radiotracer 5 (ED50=0.8mg/kg).
Cannabis is the most used recreational drug in the United States, and its use is increasing among children and adolescents. With the increase in legalized use, there have been increases in ...intentional and accidental cannabis exposure in the pediatric population. There is also minimized perceived risk. We review the current use of cannabis and its derivatives, the drug effects and clinical presentation, common misconceptions, pharmacology, and epidemiology. Finally, we review some long‐term consequences of cannabis use.
Pediatric heart disease is a large and diverse field with an overall prevalence estimated at 6 to 13 per 1,000 live births. This document discusses appropriateness of advanced imaging for a broad ...range of variants. Diseases covered include tetralogy of Fallot, transposition of great arteries, congenital or acquired pediatric coronary artery abnormality, single ventricle, aortopathy, anomalous pulmonary venous return, aortopathy and aortic coarctation, with indications for advanced imaging spanning the entire natural history of the disease in children and adults, including initial diagnosis, treatment planning, treatment monitoring, and early detection of complications. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
To achieve high‐quality emergency care for pediatric patients nationwide, it is necessary to define the key elements for pediatric emergency medicine (PEM) education and scholarship that would: 1) ...close the gaps in fundamental PEM education and 2) promote systems and standards that assure an ongoing communication of best practices between tertiary pediatric institutions, general (nonchildren's) hospital emergency departments, and urgent care centers. A working group of medical educators was formed to review the literature, develop a framework for consensus discussion at the breakout session, and then translate their findings into recommendations for future research and scholarship. The breakout session consensus discussion yielded many recommendations. The group concluded that future progress depends on multicenter collaborations as a PEM education research network and a unified vision for PEM education that bridges organizations, providers, and institutions to assure the best possible outcomes for acutely ill or injured children.
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