Nausea and Vomiting of Pregnancy and its Management with the Dual-Release Formulation of Doxylamine and Pyridoxine.

Nausea and vomiting of pregnancy (NVP) is among the most common conditions that pregnant women encounter in the early stages of pregnancy. It can affect up to 85% of pregnant women, thus representing a significant public health concern. NVP results in substantial negative physical, emotional, and financial consequences. Despite its prevalence, the pathogenesis remains elusive. Few guidelines have been published; however, several interventions exist for the symptomatic treatment of NVP. The aim of this review is to provide an overview of modern treatment strategies of NVP with a special focus on the recently approved dual-release formulation of the doxylamine and pyridoxine combination. This combination was approved by the Food and Drug Administration (FDA) in November 2016 for the treatment of NVP when conservative management fails, and it has been introduced to the American market in April 2018. The maximum plasma concentration (T max ) of doxylamine and pyridoxal-5-phosphate is reached 3.5 h and 15 h, respectively, after administration of one tablet twice daily, or 4.5 h and 0.5 h, respectively, when one tablet is administered just once daily. In addition, the delayed-release combination allows sufficient levels of doxylamine and the active metabolite pyridoxal-5-phosphate in the systemic circulation, providing symptoms relief in the subsequent morning. Hence, the dual-release formulation can improve the quality of life of pregnant women suffering from NVP. Additionally, large epidemiological trials have shown no increased risk of adverse effects to newborns, demonstrating that its use is not teratogenic.

Safety aspects of Chinese herbal medicine in pregnancy-re-evaluation of experimental data of two animal studies and the clinical experience.

INTRODUCTION: Chinese herbal medicine is an increasingly popular worldwide medical therapy which also has an impact in pregnancy. However, the question of its drug safety during pregnancy remains unresolved. Potential problems include teratogenicity, abortion, perinatal toxicity, pre- and postnatal developmental abnormalities, and eventually an increased risk for carcinomas in the offspring. Standard Materia Medica textbooks contain unreliable information when it comes to risks during pregnancy. Wang and co-workers conducted an experimental study (WS) on mice in which they investigated the effects of 17 Chinese medicinals regarding embryotoxicity and fetotoxicity. All these drugs seemed to exhibit multiple significant toxic effects. Another study by Li and co-workers (LS) investigated the reproductive toxicity of Atractylodis macrocephalae Rhizoma in mice, rats and rabbits. They described an increased pre- and postnatal mortality and, at high doses, congenital malformations. In an attempt to identify the risks of the tested medicinals during pregnancy, we analysed these two experimental studies and compared their results with possible safety data for humans from two reviews of clinical studies on threatened miscarriage (AR and CR). METHODS: We re-evaluated WS and LS in relation to accordance with internationally accepted rules, equivalence to human dose, biometric accuracy, plausibility, and coherence. Eligible studies of the two reviews on threatened miscarriage were evaluated for specific pregnancy risks concerning the 17 medicinals tested in WS and LS. RESULTS: We found that WS does not conform to international ICH guidelines and includes many inconsistencies, implausibilities and several severe biometrical flaws. It reported a total of 364 significant events out of which 145 false significant results are expected. The data-handling pointed to irregularities. Analysis of LS exhibited also many inconsistencies. The results regarding congenital malformations were statistically insignificant and are based on small case numbers. Insofar as the safety data of the 17 medicinals were documented by eligible studies of the two reviews, there was no indication of an increased abortion rate in humans. Fetal growth retardation was not observed in the human studies. For neonatal health and postnatal development, there were sufficient safety data only for a few medicinals in the human studies. As for teratogenicity, only small case numbers (0 to 109) were available from the human data. CONCLUSION: WS and LS are not reliable data sources for deriving pregnancy risks in humans for the tested Chinese medicinals. In addition, the results appear to contradict the outcomes observed in the treatment of humans. Regarding teratogenicity, for most Chinese medicinals, neither the safety nor the risk during pregnancy can be definitively ascertained. Further studies on the risks of Chinese medicinals during pregnancy are urgently needed.

Effectiveness of additional self-care acupressure for women with menstrual pain compared to usual care alone: using stakeholder engagement to design a pragmatic randomized trial and study protocol.

BACKGROUND: Self-care acupressure might be successful in treating menstrual pain, which is common among young women. There is a need for comparative effectiveness research with stakeholder engagement in all phases seeking to address the needs of decision-makers. Our aim was to design a study on the effectiveness of additional self-care acupressure for menstrual pain comparing usual care alone using different methods of stakeholder engagement. METHODS: The study was designed using multiple mixed methods for stakeholder engagement. Based on the results of a survey and focus group discussion, a stakeholder advisory group developed the study design. RESULTS: Stakeholder engagement resulted in a two-arm pragmatic randomized trial. Two hundred and twenty women aged 18 to 25 years with menstrual pain will be included in the study. Outcome measurement will be done using electronic questionnaires provided by a study specific mobile application (App). Primary outcome will be the mean pain intensity at the days of pain during the third menstruation after therapy start. CONCLUSION: Stakeholder engagement helped to develop a study design that better serves the needs of decision makers, including an App as a modern tool for both intervention and data collection in a young target group. TRIAL REGISTRATION: Clinicaltrials.gov identifier http://NCT01582724.