Efficacy Results of a Trial of a Herpes Simplex Vaccine

Two previous studies of a herpes simplex virus type 2 (HSV-2) subunit vaccine containing glycoprotein D in HSV-discordant couples revealed 73% and 74% efficacy against genital disease in women who were negative for both HSV type 1 (HSV-1) and HSV-2 antibodies. Efficacy was not observed in men or HSV-1 seropositive women

Residual Diagnostic Methods for Bayesian Structural Equation Models

Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Biostatistics and Computational Biology, 2009.Often environmental epidemiological studies focus on estimating eects of highly correlated exposures on a health condition measured with multiple outcomes. Adjusting for all exposures as separate covariates in a multiple linear regression model can cause multicollinearity. Furthermore, tting separate models for each exposure and outcome combination leads to problems of multiple comparisons and may introduce confounding with the exposures left out of the model. Structural equation modeling (SEM) alleviates these issues by assuming a latent variable structure underlying the observed exposures and outcomes. Bayesian methods for estimating the parameters in SEM treat the latent variables as missing data and impute them as part of a Markov Chain Monte Carlo (MCMC) sampler, resulting in the full posterior distribution for both the parameters and the latent variables. Bayesian SEM is reviewed and illustrated with a model analyzing the eects of phthalate exposure on human semen quality. Although methods exist for checking overall goodness-of-t in SEM, little attention has been given to testing specic model assumptions. Individual-level residuals are easy to estimate in the Bayesian SEM and are used to dene posterior predictive checks for model assumptions. The empirical cumulative distribution function of the residuals is used to test the assumption that the residual error is normally distributed. Cumulative sums of the residuals are used to check the assumption that the predictors have a linear relationship to the dependent variables in the model equations. The validity of the posterior predictive checks is examined through simulation studies, and the tests are applied to the example data set

A longitudinal trial comparing chloroquine as monotherapy or in combination with artesunate, azithromycin or atovaquone-proguanil to treat malaria.

The predominance of chloroquine-susceptible falciparum malaria in Malawi more than a decade after chloroquine's withdrawal permits contemplation of re-introducing chloroquine for targeted uses. We aimed to compare the ability of different partner drugs to preserve chloroquine efficacy and prevent the re-emergence of resistance.Children with uncomplicated malaria were enrolled at a government health center in Blantyre, Malawi. Participants were randomized to receive chloroquine alone or combined with artesunate, azithromycin or atovaquone-proguanil for all episodes of uncomplicated malaria for one year. The primary outcome was incidence of clinical malaria. Secondary endpoints included treatment efficacy, and incidence of the chloroquine resistance marker pfcrt T76 and of anemia. Of the 640 children enrolled, 628 were included in the intention-to-treat analysis. Malaria incidence (95% confidence interval) was 0.59 (.46-.74), .61 (.49-.76), .63 (.50-.79) and .68 (.54-.86) episodes/person-year for group randomized to receive chloroquine alone or in combination with artesunate, azithromycin or atovaquone-proguanil respectively and the differences were not statistically significant. Treatment efficacy for first episodes was 100% for chloroquine monotherapy and 97.9% for subsequent episodes of malaria. Similar results were seen in each of the chloroquine combination groups. The incidence of pfcrt T76 in pure form was 0%; mixed infections with both K76 and T76 were found in two out of 911 infections. Young children treated with chloroquine-azithromycin had higher hemoglobin concentrations at the study's end than did those in the chloroquine monotherapy group.Sustained chloroquine efficacy with repeated treatment supports the eventual re-introduction of chloroquine combinations for targeted uses such as intermittent preventive treatment.ClinicalTrials.gov NCT00379821

Demographics and Clinical Characteristics of Initial Malaria Episode.

*<p>7 subjects missing baseline weight and stature measurements.</p>††<p>Peak malaria season is defined as 01 Dec through 31 March.</p

Mean and 95% confidence interval for hemoglobin measured at baseline and routine study follow-up visits.

<p>Mean and 95% confidence interval for hemoglobin measured at baseline and routine study follow-up visits.</p

Malaria Incidence per Year of Follow-up.

<p>Incidence and relative risk estimated from a Poisson regression model with follow-up time as offset term.</p>*<p>Intention-to-treat analysis uses all evaluable subjects. All malaria episodes subsequent to initial treatment, including non-P. <i>falciparum</i> infections and episodes diagnosed outside of the study clinic, are included, and follow-up time is days from enrollment to date of last contact.</p>†<p>Per-protocol analysis excludes subjects who did not receive full course of treatment, and includes only malaria episodes subsequent to initial treatment caused by P. <i>falciparum</i> mono-infection and diagnosed at the study clinic. Follow-up time is days from enrollment to date of last contact, or receipt of off-study anti-malarial medication.</p

Malaria-free survival from initial episode to first subsequent episode.

<p>CQ, Chloroquine.</p

Consort Diagram.

<p>Consort Diagram.</p

Summary of 28-Day Treatment Outcomes^*.

*<p>WHO 2004 treatment outcome definitions. No subjects experienced late parasitological failure without fever at any episode.</p