Memantine Improves Recovery After Spreading Depolarization in Brain Slices and can be Considered for Future Clinical Trials.

BACKGROUND: Spreading depolarization (SD) has been identified as a key mediator of secondary lesion progression after acute brain injuries, and clinical studies are beginning to pharmacologically target SDs. Although initial work has focused on the N-Methyl-D-aspartate receptor antagonist ketamine, there is also interest in alternatives that may be better tolerated. We recently showed that ketamine can inhibit mechanisms linked to deleterious consequences of SD in brain slices. The present study tested the hypothesis that memantine improves recovery of brain slices after SD and explored the effects of memantine in a clinical case targeting SD. METHODS: For mechanistic studies, electrophysiological and optical recordings were made from hippocampal area CA1 in acutely prepared brain slices from mice. SDs were initiated by localized microinjection of K+ in conditions of either normal or reduced metabolic substrate availability. Memantine effects were assessed from intrinsic optical signals and extracellular potential recordings. For the clinical report, a subdural strip electrode was used for continuous electrocorticographic recording after the surgical evacuation of a chronic subdural hematoma. RESULTS: In brain slice studies, memantine (10-300 µM) did not prevent the initiation of SD, but impaired SD propagation rate and recovery from SD. Memantine reduced direct current (DC) shift duration and improved recovery of synaptic potentials after SD. In brain slices with reduced metabolic substrate availability, memantine reduced the evidence of structural disruption after the passage of SD. In our clinical case, memantine did not noticeably immediately suppress SD; however, it was associated with a significant reduction of SD duration and a reduction in the electrocorticographic (ECoG) suppression that occurs after SD. SD was completely suppressed, with improvement in neurological examination with the addition of a brief course of ketamine. CONCLUSIONS: These data extend recent work showing that N-Methyl-D-aspartate receptor antagonists can improve recovery from SD. These results suggest that memantine could be considered for future clinical trials targeting SD, and in some cases as an adjunct or alternative to ketamine.

Optimizing resident physician use of clinical pharmacy services.

BACKGROUND AND OBJECTIVES: Clinical pharmacists provide pharmacy services in family medicine residency programs across the nation. Currently, clinical pharmacy services are not optimally used by most residents. The objective of this study was to design strategies to educate family medicine resident physicians on optimal use of clinical pharmacy services. METHODS: Between April 2009 and May 2010, surveys and focus groups were conducted to develop educational strategies tailored to physician residents' needs. Strategies included visual reminders and one-on-one time between pharmacists and residents. Data on pharmacy services use was collected before and after implementing the educational strategies and analyzed to assess the effectiveness of the strategies. RESULTS: Clinical pharmacy services use by resident physicians increased after the intervention (51.5% to 57.2%). Reasons providers used pharmacy services changed after the intervention, with increases in drug information (66.2% to 69.4%) and patient education services (2.5% to 7.2%) and a decrease in patient care services (31.2% to 23.3%). Pharmacists saw fewer uncomplicated patients (59.1% to 53.9%) and more complicated patients (19.7% to 38.5%) after the intervention. CONCLUSIONS: Educating resident physicians on optimal use of pharmacy services required clarification of the pharmacist's role on the care team and in the educational process. The educational strategies defined the pharmacist role to include that of a preceptor and not just patient care provider, a distinction that is congruent with the medical teaching model. These strategies could be applied at other training sites to optimize use of clinical pharmacy services in physician residency training programs.