Metabolic syndrome at 6 weeks after delivery in a cohort of pre-eclamptic and normotensive women.

BACKGROUND: The association between pre-eclampsia and the subsequent development of metabolic syndrome has not been well documented in low- and middle-income countries. OBJECTIVES: To compare the prevalence of metabolic syndrome at 6 weeks after delivery among women with pregnancies complicated by pre-eclampsia with that in a normotensive, low-risk control group in an urban South African (SA) setting. METHODS: This was a prospective cohort study at two tertiary-level hospitals and one district-level hospital in Pretoria, SA. Women were recruited after delivery and were followed up 6 weeks later to confirm or exclude the diagnosis of metabolic syndrome. RESULTS: Metabolic syndrome was diagnosed in 48/150 women with pregnancies complicated by pre-eclampsia (32.0%), compared with 33/150 (22.0%) of the control group (p=0.05). CONCLUSIONS: Women who developed pre-eclampsia during pregnancy had an increased chance of metabolic syndrome being diagnosed 6 weeks after delivery. Guidelines should be developed to identify women with cardiometabolic risk, so that interventions may be implemented to modify this risk before and after pregnancy.

The prevalence of abnormal Doppler's of the umbilical artery in a low-risk pregnant population in South Africa.

BACKGROUND: The assessment of fetal blood flow using Doppler waveform can be used to identify placental insufficiency, and hence is a tool to identify fetuses at risk of stillbirth due to fetal growth restriction (FGR). In South Africa the largest category of perinatal deaths is 'unexplained intrauterine death'. The majority of the mothers are clinically healthy women. This study was performed to determine the prevalence of abnormal umbilical resistance indices (abnormal RI) to see if screening a low-risk pregnant population is worthwhile. METHODS: A descriptive study across 9 sites in 8 provinces of South Africa was performed to determine the prevalence of abnormal RI of the umbilical artery in women classified as having a low-risk pregnancy. The study was conducted from 1st September 2017- February 2020.The pregnant women classified were screened using a continuous wave Doppler ultrasound apparatus (Umbiflow™) between 28 and 34 weeks' gestation. Women with fetuses with an abnormal RI were referred to a high-risk clinic and were managed according to standard protocol. The outcomes of all the deliveries were recorded. FINDINGS: Umbiflow™ screening of the umbilical artery was performed in 7088 women across nine sites; 919 (13·0%) fetuses had an abnormal RI. Absent end diastolic flow (AEDF) was found in 87 (1·2%) fetuses. The prevalence of small for gestational ages (SGA) babies was 23·1% in the normal RI group and was significantly higher in the abnormal RI group 32·1% (p<0·0001). There was a statistical difference in the perinatal mortality rate between the normal RI (9.8/1000) and abnormal RI group (21.4/1000) [RR 0·046; 95% CI -0·06-0·98]. INTERPRETATION: The prevalence of abnormal RI and AEDF in this screened low-risk population was about ten times higher than that previously recorded in high income countries. Continuous wave Doppler ultrasound screening detected previously undiagnosed growth restricted babies. The prevalence of AEDF warrants continuous wave Doppler ultrasound screening of the low-risk pregnant population in South Africa. FUNDING: This study was funded by the South African Medical Research Council (SAMRC) and the Council for Scientific and Industrial Research (CSIR).

Safety, tolerability, and pharmacokinetics of once-daily trazodone extended-release caplets in healthy subjects.

OBJECTIVE: To characterize the pharmacokinetics, safety, and tolerability of an extended-release formulation of trazodone hydrochloride (HCl), Trazodone Contramid® Once-a-Day (TzCOAD) developed as scored 150-mg and 300-mg caplets for oncedaily administration. METHODS: Relative bioavailability studies compared the pharmacokinetics of TzCOAD and trazodone immediate-release (TzIR) tablets following single- and multiple-dose administration. In addition, the effect of food on the pharmacokinetics of TzCOAD was assessed. RESULTS: After single-dose administration of 300 mg TzCOAD, trazodone AUC and C(max) were approximately 20% and 60% lower, respectively, than for TzIR 100-mg tablets administered as 3 doses, 8 h apart. After multipledose administration of 300 mg daily for 7 days, TzCOAD given once daily and TzIR given 3 times a day were equivalent with respect to AUC, while C(max) was 43% lower for TzCOAD. Trazodone AUC following single-dose administration of TzCOAD was similar to AUC at steady state, suggesting that steady-state exposure can be predicted from single-dose data. When TzCOAD was taken shortly after ingestion of a high-fat meal, C(max) increased 86% compared with fasting conditions. However, AUC and t(max) were not affected by food. CONCLUSION: Administration of TzCOAD 300 mg once daily provides equivalent steady-state exposure to, with a lower C(max) than, TzIR 100 mg given 3 times a day. A high-fat meal results in an increase in C(max), but there is no substantial effect on AUC.

Comparative bioavailability of two once-daily tramadol HCl 200 mg extended-release products in healthy volunteers.

An open-label, randomized, 2-way crossover study was conducted to compare the pharmacokinetics of Tramadol Contramid OAD 200 mg tablets and Monocrixo L.P. 200 mg capsules following single-dose administration under fasting conditions in 30 healthy adult volunteers. Serial blood samples were collected at predefined time points over 48 hours post-dose and racemic tramadol and O-desmethyltramadol concentrations in plasma were determined using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using noncompartmental methods. Results were compared using an analysis of variance (ANOVA) and the bioequivalence determination was based on the 90% confidence intervals for C(max), AUC(0-t) and AUC(0-infinity). Although the two products were determined to be bioequivalent with respect to C(max) and AUC, the time to reach peak tramadol concentrations was significantly earlier for Tramadol Contramid OAD (6 hours vs. 10 hours). A mean tramadol concentration of 100 ng/ml was attained within 1 hour for Tramadol Contramid OAD compared with > 4 hours for Monocrixo L.P. Both products were well tolerated.