Lacosamide, a novel anti-convulsant drug, shows efficacy with a wide safety margin in rodent models for epilepsy.

This paper comprises a series of experiments in rodent models of partial and generalized epilepsy which were designed to describe the anti-convulsant profile of the functionalized amino acid lacosamide. Lacosamide was effective against sound-induced seizures in the genetically susceptible Frings mouse, against maximal electroshock test (MES)-induced seizures in rats and mice, in the rat hippocampal kindling model of partial seizures, and in the 6Hz model of psychomotor seizures in mice. The activity in the MES test in both mice (4.5mg/kg i.p.) and rats (3.9 mg/kg p.o.) fell within the ranges previously reported for most clinically available anti-epileptic drugs. At both the median effective dose for MES protection, as well as the median toxic dose for rotorod impairment, lacosamide elevated the seizure threshold in the i.v. pentylenetetrazol seizure test, suggesting that it is unlikely to be pro-convulsant at high doses. Lacosamide was inactive against clonic seizures induced by subcutaneous administration of the chemoconvulsants pentylenetetrazol, bicuculline, and picrotoxin, but it did inhibit NMDA-induced seizures in mice and showed full efficacy in the homocysteine model of epilepsy. In summary, the overall anti-convulsant profile of lacosamide appeared to be unique, and the drug displayed a good margin of safety in those tests in which it was effective. These results suggest that lacosamide may have the potential to be clinically useful for at least the treatment of generalized tonic-clonic and partial-onset epilepsies, and support ongoing clinical trials in these indications.

Optimizing antibiotic prescribing for acute respiratory tract infections in an urban urgent care clinic.

OBJECTIVE: To decrease unnecessary antibiotic use for acute respiratory tract infections in adults in a point-of-service health care setting. DESIGN: Prospective, nonrandomized controlled trial. SETTING: An urban urgent care clinic associated with the major indigent care hospital in Denver, Colorado between October 2000 and April 2001. PATIENTS/PARTICIPANTS: Adults diagnosed with acute respiratory tract infections (bronchitis, sinusitis, pharyngitis, and nonspecific upper respiratory infection). A total of 554 adults were included in the baseline period (October to December 2000) and 964 adults were included in the study period (January to April 2001). INTERVENTIONS: A provider educational session on recommendations for appropriate antibiotic use recently published by the Centers for Disease Control and Prevention, and placement of examination room posters were performed during the last week of December 2000. Study period patients who completed a brief, interactive computerized education (ICE) module were classified as being exposed to the full intervention, whereas study period patients who did not complete the ICE module were classified as being exposed to the limited intervention. MEASUREMENTS AND MAIN RESULTS: The proportion of patients diagnosed with acute bronchitis who received antibiotics decreased from 58% during the baseline period to 30% and 24% among patients exposed to the limited and full intervention, respectively (P <.001 for intervention groups vs baseline). Antibiotic prescriptions for nonspecific upper respiratory tract infections decreased from 14% to 3% and 1% in the limited- and full-intervention groups, respectively (P <.001 for intervention groups vs baseline). CONCLUSION: Antibiotic use for adults diagnosed with acute respiratory tract infections can be reduced in a point-of-service health care setting using a combination of patient and provider educational interventions.