The Obstetrical Care and Delivery Experience of Women with Epilepsy in the MONEAD Study.

OBJECTIVE: We examined mode of delivery among pregnant women with epilepsy (PWWE) versus pregnant controls (PC). We hypothesize that PWWE are more likely to deliver by cesarean. STUDY DESIGN: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an observational, prospective, multicenter investigation of pregnancy outcomes funded by the National Institute of Health (NIH). MONEAD enrolled patients from December 2012 through January 2016. PWWE were matched to PC in a case:control ratio of 3:1. This analysis had 80% power to detect a 36% increase in cesarean frequency assuming a baseline rate of 30% among PC at an α = 0.05. RESULTS: This report analyzed 331 PWWE (76%) and 102 PC (24%) who gave birth while enrolled in the study. PWWE and PC had similar rates of cesarean delivery (34.7 vs. 28.6%; p = 0.27). Of women with cesarean, rates of cesarean without labor were similar between groups for those delivering in recruitment hospitals (48.2 vs. 50.0%) but in nonrecruitment hospitals, cesarean rates without labor were over two-fold higher among PWWE than those of PC (68.8 vs. 30.8%; p = 0.023). Receipt of a cesarean after labor did not differ for PWWE compared to PC or by type of antiepileptic drug among the PWWE. CONCLUSION: These findings suggest that the obstetrical experiences of PWWE and PC are similar. An interesting deviation from this observation was the mode of delivery with higher unlabored cesarean rates occurring among PWWE in nonrecruitment hospitals. As the study recruitment hospitals were tertiary academic centers and nonrecruitment hospitals tended to be community-based institutions, differences in perinatal expertise might contribute to this difference. KEY POINTS: · Unlabored cesarean rates higher among women with epilepsy.. · Provider preference may influence delivery mode among women with epilepsy.. · Type and amount of antiepileptic drug was not associated with mode of delivery..

Augmentation of cellular and humoral immune responses to HPV16 and HPV18 E6 and E7 antigens by VGX-3100.

We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV)16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFN)γ production, tumor necrosis factor (TNF)α production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR) sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth "booster" dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100.

Misoprostol vaginal insert for successful labor induction: a randomized controlled trial.

OBJECTIVE: To compare three doses of misoprostol vaginal insert for successful labor induction measured by the proportion of vaginal deliveries within 24 hours. METHODS: A total of 374 women with modified Bishop scores of 4 or lower before induction of labor were randomly assigned to receive misoprostol vaginal insert (MVI) 100 (n=118), MVI 150 (n=125), or MVI 200 (n=131) micrograms. The insert was removed for onset of active labor or adverse event. The primary outcome was proportion of vaginal deliveries within 24 hours. The comparison group was MVI 100. Safety was assessed by comparing rates of cesarean deliveries and adverse events. RESULTS: Twenty-four percent of women receiving MVI 200 failed to achieve vaginal delivery within 24 hours compared with 36.3% of those receiving MVI 100 (P=.057, relative risk [RR] 0.66, 95% confidence interval [CI] 0.42-1.04). Compared with MVI 100, MVI 200 reduced median time to vaginal delivery (1,181 compared with 1,744 minutes, P=.02) and need for oxytocin (48.9% compared with 70.9%, P<.001, RR 0.70, 95% CI 0.56-0.85). The cesarean rates for women assigned to MVI 200 and 100 were 22.9% (30/131) and 31.4% (37/118) (P=.15, RR 0.73, 95% CI 0.48-1.10). Misoprostol vaginal insert 200 was associated with an increased rate of tachysystole (41.2%) compared with MVI 100 (19.5%) (P<.001, RR 2.11, 95% CI 1.39-3.22). CONCLUSION: Compared with MVI 100, MVI 200 was associated with a significant reduction in time to vaginal delivery, but did not improve proportion with vaginal delivery by 24 hours. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00828711.

Transdermal contraception: evaluation of three transdermal norelgestromin/ethinyl estradiol doses in a randomized, multicenter, dose-response study.

OBJECTIVE: The objective of this study was to identify the dose for a contraceptive patch that provides a predetermined level of ovulation suppression and cycle control and that is well tolerated. STUDY DESIGN: In this randomized study, 610 subjects received 10-, 15-, or 20-cm(2) patch dose sizes (20-cm(2), Ortho Evra/Evra) (Janssen Pharmaceutica, NV Belgium) or Ortho-Cyclen/Cilest (Janssen Pharmaceutica, NV Belgium) for up to 4 cycles. As with Ortho-Cyclen, patch regimens included 21 dosing days (3 consecutive 7-day patches) followed by 1 dose-free week. RESULTS: The patch regimens demonstrated a dose-response for ovulation suppression and cycle control. Presumed ovulation, determined on the basis of serum progesterone concentrations > or = 3 ng/mL in cycles 1 and 3, occurred in 6.2% (Ortho Evra) and 7.2% (Ortho-Cyclen) of subjects. At cycle 3, breakthrough bleeding/spotting was reported by 10.5% and 15.0% of subjects, respectively. Compliance with each patch was superior to that with Ortho-Cyclen (all P <.001). All regimens had safety profiles typical of oral contraceptives. CONCLUSION: The 20-cm(2) patch (Ortho Evra) provided ovulation suppression, cycle control, and safety similar to that of Ortho-Cyclen, with significantly better compliance.