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Aim: Xen2174 is a synthetic 13-amino acid peptide that binds specifically to the norepinephrine transporter, which results in inhibition of norepinephrine uptake. It is being developed as a possible treatment for moderate to severe pain and is delivered intrathecally. The current study was performed to assess the pharmacodynamics (PD) and the cerebrospinal fluid (CSF) pharmacokinetics (PK) of Xen2174 in healthy subjects., Methods: This was a randomized, blinded, placebo-controlled study in healthy subjects. The study was divided into three treatment arms. Each group consisted of eight subjects on active treatment and two or three subjects on placebo. The CSF was sampled for 32 h using an intrathecal catheter. PD assessments were performed using a battery of nociceptive tasks (electrical pain, pressure pain and cold pressor tasks)., Results: Twenty-five subjects were administered Xen2174. CSF PK analysis showed a higher area under the CSF concentration-time curve of Xen2174 in the highest dose group than allowed by the predefined safety margin based on nonclinical data. The most common adverse event was post-lumbar puncture syndrome, with no difference in incidence between treatment groups. Although no statistically significant differences were observed in the PD assessments between the different dosages of Xen2174 and placebo, pain tolerability in the highest dose group was higher than in the placebo group [contrast least squares mean pressure pain tolerance threshold of Xen2174 2.5 mg-placebo (95% confidence interval), 22.2% (-5.0%, 57.1%); P = 0.1131]., Conclusions: At the Xen2174 dose level of 2.5 mg, CSF concentrations exceeded the prespecified exposure limit based on the nonclinical safety margin. No statistically significant effects on evoked pain tests were observed., (© 2016 The British Pharmacological Society.)

Objective: To determine percentages of domestic cats and dogs vaccinated against rabies, identify barriers to vaccination, and assess knowledge about rabies in a semirural New Mexico community after a skunk rabies outbreak., Design: Cross-sectional, door-to-door, bilingual, community-based participatory survey., Sample: 366 residential properties in Eddy County, NM., Procedures: The New Mexico Department of Health and CDC administered surveys and analyzed data., Results: Individuals at 247 of the 366 residential properties participated in the survey. One hundred eighty of the 247 (73%) households owned a dog (n = 292) or cat (163). Cats were more likely than dogs to not have an up-to-date rabies vaccination status (prevalence ratio, 3.2; 95% confidence interval, 2.3 to 4.4). Cost and time or scheduling were the most frequently identified barriers to vaccination. One hundred sixty (65%) respondents did not know livestock can transmit rabies, 78 (32%) did not know rabies is fatal, and 89 (36%) did not know a bat scratching a person can be an exposure. Only 187 (76%) respondents indicated they would contact animal control if they saw a sick skunk, and only 166 (67%) indicated they would contact animal control if bitten by a dog they did not own., Conclusions and Clinical Relevance: Findings indicated that rabies vaccination prevalence among pet dogs and cats was low, despite the fact that the region had experienced a skunk rabies outbreak during the previous 2 years. In addition, substantial percentages of respondents did not have correct knowledge of rabies or rabies exposure.

Teaching wilderness medicine to medical students comes alive when nontraditional methods are used. In our wilderness medicine elective at the University of Massachusetts Medical School, the teaching is primarily experientially based. The following anecdote illustrates the magic that can happen when teaching is done via the scenario-debriefing method.