A fresh look at the role of spiramycin in preventing a neglected disease: meta-analyses of observational studies.

PURPOSE: We aimed to investigate the effect of antepartum treatment with spiramycin with or without subsequent pyrimethamine-sulfonamide-folinic acid, compared to no treatment, on the rate of mother-to-child transmission (MTCT) of Toxoplasma gondii (T. gondii) and incidence/severity of sequelae in the offspring. METHODS: Embase and PubMed were searched for literature on spiramycin in pregnant women suspected/diagnosed with T. gondii infection. Meta-analyses were performed using random-effects model. RESULTS: Thirty-three studies (32 cohorts and 1 cross-sectional study), with a total of 15,406 mothers and 15,250 offspring, were pooled for analyses. The MTCT rate for all treated patients was significantly lower than the untreated [19.5% (95% CI 14-25.5%) versus 50.7% (95% CI 31.2-70%), p < 0.001]. The transmission rate in patients on spiramycin monotherapy was also significantly lower than untreated [17.6% (95% CI 9.9-26.8%) versus 50.7% (95% CI 31.2-70%), p < 0.001]. CONCLUSION: Results indicate significant reduction in MTCT rates following spiramycin treatment of suspected/diagnosed maternal T. gondii infection.

End points in hospital-acquired pneumonia and/or ventilator-associated pneumonia clinical trials: food and drug administration perspective.

Identification of reliable, reproducible, and precise end points for future studies of hospital-acquired and ventilator-associated pneumonia is of paramount importance for approval of new therapeutic agents. As required by the Code of Federal Regulations 21 CFR 314.126, the methods of assessment of a subject's response (ie, end points) must be well defined and reliable. The study protocol and results should explain the variables measured, the methods of observation, and criteria used to assess response. Meeting these requirements has proven to be problematic in clinical trials for the evaluation of new products for the treatment of hospital-acquired and ventilator-associated pneumonia because of the subjectivity of assessing a clinical response end point. There are multiple issues and caveats to consider when selecting appropriate end points for these trials.