Recent Chemical Exposures and Blood Volatile Organic Compound Levels in a Large Population-Based Sample

Little is known about factors that influence blood levels of volatile organic compounds in nonoccupationally exposed populations. The authors examined the possible relationship between recent self-reported chemical exposures and elevated blood volatile organic compound levels among 982 adult participants in the Third National Health and Nutrition Examination Survey. A strong dose-response effect was indicated (p < .001) for increasing lifetime pack-years of cigarettes smoked for elevated levels of toluene, styrene, and benzene. A positive dose-response effect was indicated for daily alcohol consumption with respect to elevated blood levels of 2-butanone and acetone. For volatile organic compounds typically found in 10-75% of the population, the establishment of a link with specific environmental exposures is relatively easy because there is less effect of confounding in this group. Some volatile organic compounds, however, are seen in less than 10% of the general population; finding these compounds at any level may warrant a search for a particular exposure.     

Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies

Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMOplus) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates in previous studies. AVI-6002 (a combination of AVI-7537 and AVI-7539) or AVI-6003 (a combination of AVI-7287 and AVI-7288) were administered as sequential intravenous (i.v.) infusions of a 1:1 fixed dose ratio of the two subcomponents. In each study, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in six-dose escalation cohorts of five subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg/kg per component) or placebo in a 4:1 ratio. Both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied. A maximum tolerated dose was not observed in either study. The four chemically similar PMOplus components exhibited generally similar PK profiles. The mean peak plasma concentration and area under the concentration-time curve values of the four components exhibited dose-proportional PK. The estimated plasma half-life of all four components was 2 to 5 h. The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence.     

Change in self‐reported oral health in relation to use of dental services over 2 yr

To investigate change in oral health in relation to use of dental services, a random sample of 45‐ to 54‐yr‐old subjects from Adelaide, South Australia, was surveyed in 2004–2005 (n = 986, response rate = 44.4%). Service use and a global oral‐health transition (GOHT) statement were collected over 2 yr. Worsening in oral health was reported from the GOHT statement by 25% of persons, while improvement was reported by 30%. Prevalence ratios (PRs, 95% CI), adjusted for sex, education, health card status, and toothbrushing, showed that worsening oral health was inversely associated with dental visiting (PR = 0.5, 0.4–0.7) and with scaling and cleaning services (PR = 0.6, 0.4–0.9), whereas extractions (PR = 2.3, 1.6–3.4) and dentures (PR = 2.2, 1.3–3.7) were associated with a higher prevalence of worsening. Scaling and cleaning services were associated with improvement in oral health (PR = 1.5, 1.01–2.3), while endodontic services were inversely associated with improvement (PR = 0.3, 0.1–0.9). Worsening in oral health was associated with extractions and dentures and was inversely associated with visiting and preventive care. Improvement in oral health was associated with preventive care and was inversely associated with endodontic treatment.     

Ceftaroline fosamil as first-line versus second-line treatment for acute bacterial skin and skin structure infections (ABSSSI) or community-acquired bacterial pneumonia (CABP)

The Clinical Assessment Program and Teflaro^® Utilization Registry (CAPTURE) is a multicenter registry study of acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) patients treated with ceftaroline fosamil in the US. Data for this analysis were collected between August 2011 and February 2013 at US study centres by randomly ordered chart review. Clinical success rates among ABSSSI patients were >81% when ceftaroline fosamil was used as first- or second-line therapy, including monotherapy and concurrent therapy. Among CABP patients, clinical success rates were >77% among first-line and second-line patients and patients who received first-line concurrent therapy or second line monotherapy or concurrent therapy. For CABP patients treated with ceftaroline fosamil as first-line monotherapy, the clinical success rate was 70%. Ceftaroline fosamil is an effective treatment option for patients with ABSSSI or CABP with similar clinical success rates when used as first-line or second-line treatment.