Changing trends in the use of seizure prophylaxis after traumatic brain injury: a shift from phenytoin to levetiracetam.

PURPOSE: Current guidelines for traumatic brain injury (TBI) recommend antiepileptic drugs (AEDs) for 7 days after injury to decrease posttraumatic seizure risk. Phenytoin decreases seizure risk 73% vs placebo during this time. Levetiracetam (LEV) is an alternative; however, no published data validate comparable efficacy. Our objective was to evaluate seizure incidence 7 days after TBI in patients treated with phenytoin (PHT) vs LEV and to characterize practice of AED selection. METHODS: A retrospective observational study was conducted using a Trauma Registry (Collector Trauma Registry; Digital Innovation, Inc, Forrest Hill, Md) to evaluate patients with TBI. Patients with an initial Head/Neck Abbreviated Injury Scale score of 3 or higher and a Glasgow Coma Scale of 8 or less were included. RESULTS: Of 109 patients, 89 received PHT, and 20, LEV. Two patients experienced posttraumatic seizure, 1 in each group. Sixty-eight patients survived to hospital discharge; 65% received prophylactic AED greater than 7 days. Ninety-eight percent of 81 patients admitted between 2000 and 2007 received PHT, whereas 64% of 28 patients admitted between 2008 and 2010 received LEV. CONCLUSION: Only 2 patients experienced posttraumatic seizure after receiving AED, indicating low incidence. Most surviving to hospital discharge received AED prophylaxis greater than 7 days despite guideline recommendations. After approval of intravenous LEV, a trend favoring LEV was observed.

Cancer immunotherapy using Sindbis virus replicon particles encoding a VP22-antigen fusion.

Alphavirus vectors have emerged as a strategy for the development of cancer vaccines and gene therapy applications. The availability of a new packaging cell line (PCL), which is capable of generating alphavirus replicon particles without contamination from replication-competent virus, has advanced the field of vaccine development. This replication-defective vaccine vector has potential advantages over naked nucleic acid vaccines, such as increased efficiency of gene delivery and large-scale production. We have developed a new strategy to enhance nucleic acid vaccine potency by linking VP22, a herpes simplex virus type 1 (HSV-1) tegument protein, to a model antigen. This strategy facilitated the spread of linked E7 antigen to neighboring cells. In this study, we created a recombinant Sindbis virus (SIN)-based replicon particle encoding VP22 linked to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, using a stable SIN PCL. The linkage of VP22 to E7 in these SIN replicon particles resulted in a significant increase in the number of E7-specific CD8(+) T cell precursors and a strong antitumor effect against E7-expressing tumors in vaccinated C57BL/6 mice relative to wild-type E7 SIN replicon particles. Furthermore, a head-to-head comparison of VP22-E7-containing naked DNA, naked RNA replicons, or RNA replicon particle vaccines indicated that SINrep5-VP22/E7 replicon particles generated the most potent therapeutic antitumor effect. Our results indicated that the VP22 strategy used in the context of SIN replicon particles may facilitate the generation of a highly effective vaccine for widespread immunization.