Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study.

Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.).

Organic and elemental carbon filter sets: preparation method and interlaboratory results.

Carbonaceous aerosols play an important role in climate, visibility, air quality, and human health effects, and they have been routinely monitored in workplace and environmental settings. Different thermal analysis methods have been applied to determine the carbon content of carbonaceous aerosols. Good agreement between results for total carbon (TC) generally has been found, but the organic and elemental carbon (OC and EC) fractions determined by different methods often disagree. Measurement uncertainty is mainly due to pyrolysis and charring of OC sample components. Lack of reference materials has impeded progress on method standardization and understanding method biases. A relatively simple method for generating matched filter sets having known OC-EC contents is reported. After generation and analysis of each set to confirm agreement between filters, the filter sets were distributed to six laboratories for an interlaboratory comparison. Analytical results indicate a uniform carbon distribution for the filter sets and good agreement between the participating laboratories. Relative standard deviations (RSDs) for mean TC (OC + EC), OC, and EC results for seven laboratories were <10, 11, and 12% (respectively). Except for one EC result (RSD = 16%), RSDs reported by individual laboratories for TC, OC, and EC were <12%. The method of filter generation is generally applicable and reproducible. Depending on the application, different filter loadings and types of OC materials can be employed. Matched filter sets prepared by the described approach can be used for determining the accuracy of OC-EC methods and thereby contribute to method standardization.

Symptom-based, algorithmic approach for handling the initial encounter with victims of a potential terrorist attack.

OBJECTIVES: This study intended to create symptom-based triage algorithms for the initial encounter with terror-attack victims. The goals of the triage algorithms include: (1) early recognition; (2) avoiding contamination; (3) early use of antidotes; (4) appropriate handling of unstable, contaminated victims; and (5) provisions of force protection. The algorithms also address industrial accidents and emerging infections, which have similar clinical presentations and risks for contamination as weapons of mass destruction (WMD). METHODS: The algorithms were developed using references from military and civilian sources. They were tested and adjusted using a series of theoretical patients from a CD-ROM chemical, biological, radiological/nuclear, and explosive victim simulator. Then, the algorithms were placed into a card format and sent to experts in relevant fields for academic review. RESULTS: Six inter-connected algorithms were created, described, and presented in figure form. The "attack" algorithm, for example, begins by differentiating between overt and covert attack victims (A covert attack is defined by epidemiological criteria adapted from the Centers for Disease Control and Prevention (CDC) recommendations). The attack algorithm then categorizes patients either as stable or unstable. Unstable patients flow to the "Dirty Resuscitation" algorithm, whereas, stable patients flow to the "Chemical Agent" and "Biological Agent" algorithms. The two remaining algorithms include the "Suicide Bomb/Blast/Explosion" and the "Radiation Dispersal Device" algorithms, which are inter-connected through the overt pathway in the "Attack" algorithm. CONCLUSION: A civilian, symptom-based, algorithmic approach to the initial encounter with victims of terrorist attacks, industrial accidents, or emerging infections was created. Future studies will address the usability of the algorithms with theoretical cases and utility in prospective, announced and unannounced, field drills. Additionally, future studies will assess the effectiveness of teaching modalities used to reinforce the algorithmic approach.