Out-of-hospital cardiac arrest survival in international airports

Background  The highest achievable survival rate following out-of-hospital cardiac arrest is unknown. Data from airports serving international destinations (international airports) provide the opportunity to evaluate the success of pre-hospital resuscitation in a relatively controlled but real-life environment.  Methods  This retrospective cohort study included all cases of out-of-hospital cardiac arrest at international airports with resuscitation attempted between January 1st, 2013 and December 31st, 2015. Crude incidence, patient, event characteristics and survival to hospital discharge/survival to 30 days (survival) were calculated. Mixed effect logistic regression analyses were performed to identify predictors of survival. Variability in survival between airports/countries was quantified using the median odds ratio.  Results  There were 800 cases identified, with an average of 40 per airport. Incidence was 0.024/100,000 passengers per year. Percentage survival for all patients was 32%, and 58% for patients with an initial shockable heart rhythm.  In adjusted analyses, initial shockable heart rhythm was the strongest predictor of survival (odds ratio, 36.7; 95% confidence interval [CI], 15.5 to 87.0). In the bystander-witnessed subgroup, delivery of a defibrillation shock by a bystander was a strong predictor of survival (odds ratio 4.8; 95% CI, 3.0 to 7.8). Grouping of cases was significant at country level and survival varied between countries.  Conclusions  In international airports, there was 32% of patients survived an out-of-hospital cardiac arrest, substantially more than in the general population. Our analysis suggested similarity between airports within countries, but differences between countries. Systematic data collection and reporting is essential to ensure international airports continually maximise activities to increase survival

Outcome of Conventional Bystander Cardiopulmonary Resuscitation in Cardiac Arrest Following Drowning

INTRODUCTION: The concept of compressions only cardiopulmonary resuscitation (CO-CPR) evolved from a perception that lay rescuers may be less likely to perform mouth-to-mouth ventilations during an emergency. This study hopes to describe the efficacy of bystander compressions and ventilations cardiopulmonary resuscitation (CV-CPR) in cardiac arrest following drowning. HYPOTHESIS/PROBLEM: The aim of this investigation is to test the hypothesis that bystander cardiopulmonary resuscitation (CPR) utilizing compressions and ventilations results in improved survival for cases of cardiac arrest following drowning compared to CPR involving compressions only. METHODS: The Cardiac Arrest Registry for Enhanced Survival (CARES) was queried for patients who suffered cardiac arrest following drowning from January 1, 2013 through December 31, 2017, and in whom data were available on type of bystander CPR delivered (ie, CV-CPR CO-CPR). The primary outcome of interest was neurologically favorable survival, as defined by cerebral performance category (CPC). RESULTS: Neurologically favorable survival was statistically significantly associated with CV-CPR in pediatric patients aged five to 15 years (aOR = 2.68; 95% CI, 1.10-6.77; P = .03), as well as all age group survival to hospital discharge (aOR = 1.54; 95% CI, 1.01-2.36; P = .046). There was a trend with CV-CPR toward neurologically favorable survival in all age groups (aOR = 1.35; 95% CI, 0.86-2.10; P = .19) and all age group survival to hospital admission (aOR = 1.29; 95% CI, 0.91-1.84; P = .157). CONCLUSION: In cases of cardiac arrest following drowning, bystander CV-CPR was statistically significantly associated with neurologically favorable survival in children aged five to 15 years and survival to hospital discharge

Quinazolin-4-one derivatives:A novel class of noncompetitive NR2C/D subunit-selective N-methyl-D-aspartate receptor antagonists

We describe a new class of subunit-selective antagonists of N-methyl D-Aspartate (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2-styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor function induced by these quinazolin-4-one derivatives is non-competitive and voltage-independent, suggesting that this family of compounds does not exert action on the agonist binding site of the receptor or block the channel pore. The compounds described here resemble CP-465,022 ((S)-3-(2-chlorophenyl)-2-[2-(6-diethylaminomethyl-pyridin-2-yl)-vinyl]-6-fluoro-3H-quinazolin-4-one), a non-competitive antagonist of AMPA-selective glutamate receptors. However, modification of ring substituents resulted in analogues with greater than 100-fold selectivity for recombinant NMDA receptors over AMPA and kainate receptors. Furthermore, within this series of compounds, analogues were identified with 50-fold selectivity for recombinant NR2C/D-containing receptors over NR2A/B containing receptors. These compounds represent a new class of non-competitive subunit-selective NMDA receptor antagonists

Implementation of a Fluorescence-Based Screening Assay Identifies Histamine H3 Receptor Antagonists Clobenpropit and Iodophenpropit as Subunit-Selective N-Methyl-d-Aspartate Receptor Antagonists

N-Methyl-d-aspartate (NMDA) receptors are ligand-gated ion channels that mediate a slow, Ca2+-permeable component of excitatory synaptic transmission in the central nervous system and play a pivotal role in synaptic plasticity, neuronal development, and several neurological diseases. We describe a fluorescence-based assay that measures NMDA receptor-mediated changes in intracellular calcium in a BHK-21 cell line stably expressing NMDA receptor NR2D with NR1 under the control of a tetracycline-inducible promoter (Tet-On). The assay selectively identifies allosteric modulators by using supramaximal concentrations of glutamate and glycine to minimize detection of competitive antagonists. The assay is validated by successfully identifying known noncompetitive, but not competitive NMDA receptor antagonists among 1800 screened compounds from two small focused libraries, including the commercially available library of pharmacologically active compounds. Hits from the primary screen are validated through a secondary screen that used two-electrode voltage-clamp recordings on recombinant NMDA receptors expressed in Xenopus laevis oocytes. This strategy identified several novel modulators of NMDA receptor function, including the histamine H3 receptor antagonists clobenpropit and iodophenpropit, as well as the vanilloid receptor transient receptor potential cation channel, subfamily V, member 1 (TRPV1) antagonist capsazepine. These compounds are noncompetitive antagonists and the histamine H3 receptor ligand showed submicromolar potency at NR1/NR2B NMDA receptors, which raises the possibility that compounds can be developed that act with high potency on both glutamate and histamine receptor systems simultaneously. Furthermore, it is possible that some actions attributed to histamine H3 receptor inhibition in vivo may also involve NMDA receptor antagonism