ABSTRACT
INTRODUCTION: Emergencies in the pediatric primary care office are high-risk, low-frequency events that offices may be ill-prepared to manage. We developed an intervention to improve pediatric primary care office emergency preparedness involving a baseline measurement, a customized report out with action plans for improvement (based on baseline measures), and a plan to repeat measurement at 6 months. This article reports on the baseline measurement. METHODS: This baseline measurement consisted of 2 components: preparedness checklists and in situ simulations. The preparedness checklists were completed in person to measure compliance with the American Academy of Pediatrics Policy Statement: preparation for emergencies in the offices of pediatricians and pediatric primary care providers, in the domains of equipment, supplies, medication, and guidelines. Two in situ simulations, a child in respiratory distress and a child with a seizure, were conducted with the offices' interprofessional teams; performance was scored using checklists. RESULTS: Baseline measurements were conducted in 12 pediatric offices from October to December 2018. Wide variability was noted for compliance with the American Academy of Pediatrics recommendations (range = 47%-87%) and performance during in situ simulations (range = 43%-100%). CONCLUSIONS: Pediatric primary care office emergency preparedness was found to be variable. Simulation can be used to augment existing measures of emergency preparedness, such as checklists. By using simulation to measure office emergency preparedness, areas of knowledge deficit and latent safety threats were identified and are being addressed through ongoing collaboration.
Subject(s)
Emergencies , Patient Care Team/organization & administration , Pediatrics/organization & administration , Primary Health Care/organization & administration , Quality Improvement/organization & administration , Simulation Training/organization & administration , Equipment and Supplies/standards , Humans , Patient Care Team/standards , Pediatrics/standards , Primary Health Care/standards , Respiratory Distress Syndrome/therapy , Seizures/therapy , United StatesABSTRACT
Oxindole alkaloids in the paraherquamide/marcfortine family exhibit broad-spectrum anthelmintic activity that includes drug-resistant strains of nematodes. Paraherquamide (PHQ), 2-deoxoparaherquamide (2DPHQ), and close structural analogs of these compounds rapidly induce flaccid paralysis in parasitic nematodes in vitro, without affecting adenosine triphosphate (ATP) levels. The mechanism of action of this anthelmintic class was investigated using muscle tension and microelectrode recording techniques in isolated body wall segments of Ascaris suum. None of the compounds altered A. suum muscle tension or membrane potential. However, PHQ blocked (when applied before) or reversed (when applied after) depolarizing contractions induced by acetylcholine (ACh) and the nicotinic agonists levamisole and morantel. These effects were mimicked by the nicotinic ganglionic blocker mecamylamine, suggesting that the anthelmintic activity of PHQ and marcfortines is due to blockade of cholinergic neuromuscular transmission. The effects of these compounds were also examined on subtypes of human nicotinic ACh receptors expressed in mammalian cells with a Ca2+ flux assay. 2DPHQ blocked nicotinic stimulation of cells expressing alpha3 ganglionic (IC50 approximately 9 microm) and muscle-type (IC50 approximately 3 microm) nicotinic cholinergic receptors, but was inactive at 100 microm vs. the alpha7 CNS subtype. PHQ anthelmintics are nicotinic cholinergic antagonists in both nematodes and mammals, and this mechanism appears to underlie both their efficacy and toxicity.
Subject(s)
Anthelmintics , Cholinergic Antagonists , Indolizines , Receptors, Cholinergic/drug effects , Spiro Compounds , Animals , Anthelmintics/chemistry , Anthelmintics/toxicity , Ascaris suum , Cholinergic Antagonists/chemistry , Cholinergic Antagonists/toxicity , Female , Indolizines/chemistry , Indolizines/toxicity , Membrane Potentials/drug effects , Muscles/drug effects , Nematoda , Spiro Compounds/chemistry , Spiro Compounds/toxicity , Structure-Activity RelationshipABSTRACT
N-Methyloctadepsipeptides attached to an oxime resin were cyclized by heating them in refluxing ethyl acetate for 2 days to give cyclodepsipeptide PF1022A analogues. By using this method, we generated a small library of PF 1022A analogues (2), several of which possessed anthelmintic activity, based on an in vitro assay.
