Time-series analysis of ondansetron use in pediatric gastroenteritis.

OBJECTIVE: Emergency department use of ondansetron in children with gastroenteritis is increasing; however, its effect on clinical outcomes is unknown. We aimed to determine whether increasing ondansetron usage is associated with improved outcomes in children with gastroenteritis. METHODS: A retrospective cohort study was conducted at The Hospital for Sick Children, Toronto, Canada. Eligible children included those younger than 18 years old with gastroenteritis who presented to an emergency department between 2003 and 2008. There were 22,125 potentially eligible visits; 20% were selected at random for chart review. The primary outcome measure, the intravenous rehydration rate, was evaluated using an interrupted time-series analysis with segmented logistic regression. Secondary outcomes included emergency department revisits, hospitalization, and length of stay. RESULTS: A total of 3508 patient visits were included in the final analysis. During the study period, there was a significant reduction in intravenous rehydration usage (27%-13%; P < 0.001) and an increase in ondansetron administration (1%-18%; P < 0.001). Time-series analysis demonstrated a level break (P = 0.03) following the introduction of ondansetron. The mean length of stay for children declined from 8.6 ±â€Š3.4 to 5.9 ±â€Š2.8 hours, P = 0.03. During the week following the index visit, there was a reduction in return visits (18%-13%; P = 0.008) and need for intravenous rehydration (7%-4%; P = 0.02). CONCLUSIONS: Ondansetron use has increased significantly and is associated with reductions in the use of intravenous rehydration, emergency department revisits, and length of stay. The selective use of ondansetron is associated with improved clinical outcomes.

Resistance of presynaptic CaV2.2 channels to voltage-dependent inactivation: dynamic palmitoylation and voltage sensitivity.

Presynaptic CaV2.2 (N type) calcium channels gate the influx of calcium ions to trigger transmitter release. We have previously demonstrated at the chick ciliary ganglion presynaptic calyx terminal that the bulk of these channels are highly resistant to voltage dependent inactivation [E.F. Stanley, G. Goping, Characterization of a calcium current in a vertebrate cholinergic presynaptic nerve terminal, J. Neurosci. 11 (1991) 985-993; E.F. Stanley, Syntaxin I modulation of presynaptic calcium channel inactivation revealed by botulinum toxin C1, Eur. J. Neurosci. 17 (2003) 1303-1305; E.F. Stanley, R.R. Mirotznik, Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium channels, Nature (Lond.) 385 (1997) 340-343]. Recent studies have suggested that CaV2.2 can be rendered inactivation resistant when expressed with the palmitoylated beta2A subunit and that this effect can be eliminated by tunicamycin, a general inhibitor of dynamic palmitoylation [J.H. Hurley, A.L. Cahill, K.P. Currie, A.P. Fox, The role of dynamic palmitoylation in Ca(2+) channel inactivation, Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 9293-9298]. We find that while tunicamycin treatment had no effect on CaV2.2 current in the inactivation-sensitive isolated chick dorsal root ganglion (DRG) neuron, it caused a 10mV hyperpolarized shift in the profile of the inactivation-resistant presynaptic CaV2.2 population. This shift occurred without any effect on the voltage sensitivity of the inactivation process, as measured by a Boltzmann slope factor. Our findings suggest that dynamic palmitoylation contributes to the hyperpolarized steady inactivation profile of presynaptic CaV2.2. However, some other factor must also contribute since its inhibition does is not restore the inactivation profile to that of channels in the cell soma.