Enantioselective determination of ondansetron and 8-hydroxyondansetron in human plasma from recovered surgery patients by liquid chromatography-tandem mass spectrometry

A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization for quantification of ondansetron and its main metabolite 8-hydroxyondansetron in human plasma was presented. The enantiomeric separation was achieved on a Chiralcel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate). The validation data were within the required limits. The assay was successfully applied to authentic plasma samples. Quantitative results from postoperative patients receiving ondansetron demonstrated a great interindividual variability in postoperative plasma drug concentrations, the metabolites were not detected in their unconjugated form. A wide variation in the S-(+)-/R-(-)-ondansetron concentration ratio between 0.14 and 7.18 is indicative for a stereoselective disposition or metabolism. In further studies CYP2D6 and CYP3A4 genotype dependent metabolism of ondansetron enantiomers as well as of co-administered drugs and clinical efficacy of the medication should be tested.

Impact of single nucleotide polymorphisms and of clinical risk factors on new-onset diabetes mellitus in HIV-infected individuals

Background. Metabolic complications, including cardiovascular events and diabetes mellitus (DM), are a major long-term concern in human immunodeficienc virus (HIV)-infected individuals. Recent genome-wide association studies have reliably associated multiple single nucleotide polymorphisms (SNPs) to DM in the general population. Methods. We evaluated the contribution of 22 SNPs identifie in genome-wide association studies and of longitudinally measured clinical factors to DM. We genotyped all 94 white participants in the Swiss HIV Cohort Study who developed DM from 1 January 1999 through 31 August 2009 and 550 participants without DM. Analyses were based on 6054 person-years of follow-up and 13,922 measurements of plasma glucose. Results. The contribution to DM risk explained by SNPs (14% of DM variability) was larger than the contribution to DM risk explained by current or cumulative exposure to different antiretroviral therapy combinations (3% of DM variability). Participants with the most unfavorable genetic score (representing 12% and 19% of the study population, respectively, when applying 2 different genetic scores) had incidence rate ratios for DM of 3.80 (95% confidenc interval [CI], 2.05–7.06) and 2.74 (95% CI, 1.53–4.88), respectively, compared with participants with a favorable genetic score. However, addition of genetic data to clinical risk factors that included body mass index only slightly improved DM prediction. Conclusions. In white HIV-infected persons treated with antiretroviral therapy, the DM effect of genetic variants was larger than the potential toxic effects of antiretroviral therapy. SNPs contributed significantl to DM risk, but their addition to a clinical model improved DM prediction only slightly, similar to studies in the general population.

Long-term antibiotic treatment for Crohn's disease: systematic review and meta-analysis of placebo-controlled trials

We investigated the effectiveness of long-term antibiotic treatment in patients with Crohn's disease.

The role of reinfection and partner notification in the efficacy of Chlamydia screening programs

Repeated Chlamydia trachomatis infections after treatment are common. One reason is reinfection from untreated partners in ongoing sexual partnerships. Mathematical models that are used to predict the impact of screening on reducing chlamydia prevalence often do not incorporate reinfection and might overestimate the expected impact. We describe a pair compartmental model that explicitly incorporates sexual partnership duration and reinfection. The pair model predicts a weaker impact of screening when compared directly with a model that does not accommodate partnerships. Effective management of sex partners to prevent reinfection might need to be strengthened in chlamydia control programs.

Screening and treatment to prevent sequelae in women with Chlamydia trachomatis genital infection: how much do we know?

Background. An important question for chlamydia control programs is the extent to which finding and treating prevalent, asymptomatic Chlamydia trachomatis genital infection reduces reproductive sequelae in infected women. Methods. We reviewed the literature to critically evaluate evidence on the effect of chlamydia screening on development of sequelae in infected women. Results. Two randomized controlled trials of 1-time screening for chlamydial infection—in a Seattle-area health maintenance organization and a Danish school district—revealed that screening was associated with an ∼50% reduction in the incidence of pelvic inflammatory disease over the following year. However, both of these trials had methodological issues that may have affected the magnitude of observed screening benefits and might limit generalizability to other populations. A large, nonrandomized cohort of chlamydia screening among US Army recruits, although limited by lack of outpatient data, did not find a benefit of similar magnitude to the randomized trials. Methodological limitations restrict valid conclusions about individual benefits of screening using data from historical cohorts and ecological studies. We identified no trials directly evaluating the effect of chlamydia screening on subclinical tubal inflammation or damage, ectopic pregnancy, or tubal factor infertility and no studies addressing the effects of >1 round of screening, the optimal frequency of screening, or the benefits of screening for repeat infections. Conclusions. Additional studies of the effectiveness of chlamydia screening would be valuable; feasible study designs may depend on the degree to which screening programs are already established. In addition, better natural history data on the timing of tubal inflammation and damage after C. trachomatis infection and development of more accurate, noninvasive tools to assess chlamydial sequelae are essential to informing chlamydia control efforts.