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Purpose: In order to spread competence in vaginal breech deliveries, it is necessary to develop new and easily applicable tools for birth progression and safety evaluation. Ultrasound is a useful and ubiquitously available tool with already documented value for birth progression observation. In deliveries out of breech presentation, an established ultrasound examination is missing. We determined the descent of the fetal buttocks in relation to the maternal pelvic inlet using intrapartum ultrasound. We evaluated these results in comparison to the clinical vaginal examination with the aim to establish an easily applicable method for birth outcome prediction. Therefore, we analyzed the predictive value of our examinations on birth outcome parameters, such as cesarean section rate, as well as fetal and maternal outcome parameters. Methods: We performed a prospective blinded study on 106 mothers with vaginally intended breech delivery. At beginning of stage two in labor, the descent of the fetal buttocks into the mother's pelvic inlet was detected with transabdominal ultrasound and vaginal examination by different observers. Primary outcome variable: Cesarean section rate. Secondary outcome variables: rate of manual assistance in vaginal deliveries, birth duration, 5′ APGAR score, umbilical arterial pH, maternal blood loss, and perineal injury. For non-parametric values, Wilcoxon's χ2 test was performed. In order to analyze the predictive value of our examination, lack-of-fit analysis was conducted. Reliability evaluation of the sonographic examination was done with a matched-pair analysis. Results: Women with positive intrapartum ultrasound breech engagement sign (+ IPUBES) had a significantly lower rate of cesarean section in comparison with those with negative IPUBES (5/67; 7.5% vs. 18/39; 46.2%; p < 0.0001). The area under the ROC curve for the prediction of CS for negative IPUBES was 0.765 with a sensitivity of 78.3% and a specificity of 74.7%. Sonographic examination showed an excellent reliability in a matched-pair analysis comparing vaginal and sonographic examinations with a mean difference of 0.012 (SD ± 0.027, 95% CI − 0.014 to 0.065). Mean birth duration was significantly longer in deliveries with negative IPUBES (533 min vs. 440 min; p = 0.0011). Fetal and maternal outcome parameters were not significantly different between deliveries with positive and negative IPUBES. Conclusions: Sonographic evaluation of the fetal descent in relation to the mother's pelvic inlet screens reliably for emergency cesarean section. This newly presented method for birth progression observation might be a powerful tool for distribution of expertise in vaginal breech delivery and is able to give reference for clinical vaginal examination by obstetricians in training. Trail registry: Clinical trial. Date of registration: 13.03.2019; Date of initial participant enrollment: 20.03.2019; DRKS00016885; https://www.drks.de; German clinical trials register. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the dose and concentration dependency of CYP3A inhibition by ritonavir using the established limited sampling strategy with midazolam for CYP3A activity. Methods: An open, fixed-sequence study was carried out in 12 healthy subjects. Single ascending doses of ritonavir (0.1-300 mg) were evaluated for CYP3A inhibition in two cohorts using midazolam as a marker substance. Results: Ritonavir administered as a single oral dose produced a dose-dependent CYP3A inhibition with an ID of 3.4 mg. Using the measured ritonavir concentrations an exposure-inhibition effect curve was established with an IC of 600 h pmol/L (AUC). Over the ritonavir dose range studied non-linear exposure of ritonavir was observed. Conclusions: Ritonavir shows a dose and concentration effect relationship of CYP3A inhibition. In addition, a proposed auto-inhibition of ritonavir metabolism resulted in a non-linear exposure of ritonavir with sub-proportional concentrations at low doses. A time-dependent CYP3A activity may result when inhibitors of CYP3A with short elimination half-lives are used. [ABSTRACT FROM AUTHOR]