CP-465,022, a selective noncompetitive AMPA receptor antagonist, blocks AMPA receptors but is not neuroprotective in vivo.

BACKGROUND AND PURPOSE: Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition has been hypothesized to provide neuroprotective efficacy after cerebral ischemia on the basis of the activity in experimental ischemia models of a variety of compounds with varying selectivity for AMPA over other glutamate receptor subtypes. CP-465,022 is a new, potent, and selective noncompetitive AMPA receptor antagonist. The present study investigated the ability of this compound to reduce neuronal loss after experimental cerebral ischemia to probe the neuroprotective potential of AMPA receptor inhibition. METHODS: To demonstrate that CP-465,022 gains access to the brain, the effects of systemic administration of CP-465,022 were investigated on AMPA receptor-mediated electrophysiological responses in hippocampus and on chemically induced seizures in rats. The compound was then investigated for neuroprotective efficacy in rat global and focal ischemia models at doses demonstrated to be maximally effective in the electrophysiology and seizure models. RESULTS: CP-465,022 potently and efficaciously inhibited AMPA receptor-mediated hippocampal synaptic transmission and the induction of seizures. However, at comparable doses, CP-465,022 failed to prevent CA1 neuron loss after brief global ischemia or to reduce infarct volume after temporary middle cerebral artery occlusion. CONCLUSIONS: Given the high selectivity of CP-465,022 for AMPA over kainate and N-methyl-D-aspartate subtypes of glutamate receptors, the lack of neuroprotective efficacy of the compound calls into question the neuroprotective efficacy of AMPA receptor inhibition after ischemia

Sharing the Lessons: the 10-year Journey of a Safe Patient Movement Program

In 2005, an 850-bed acute care, level-one trauma center, academic Magnet® hospital in southeastern Pennsylvania developed and implemented a safe patient movement (SPM) program to mitigate occupationally acquired injuries to bedside clinicians. The initial directive included the provision of highly accessible and appropriate patient handling equipment in patient care areas identified as high-risk for occupational-related manual patient handling injuries. A 6-month equipment pilot outcome demonstrated a 38% reduction in employee injuries caused by manual patient handling tasks. Ongoing program growth included the expansion of highly accessible lift technology, the establishment of a SPM committee, the adoption of a dedicated program educator, and the ongoing enculturation of a SPM philosophy into employee and patient safety endeavors. The evolution from the initial execution of the program has demonstrated a network-wide ongoing and sustained downward reduction in manual patient handling injuries throughout the first 10 years of the program’s existence