Medication use in pregnancy: a cross-sectional, multinational web-based study

Objectives: Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. his study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. Design: Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. Setting: Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. Participants: Pregnant women and new mothers with children less than 1 year of age. Primary and secondary outcome measures: Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. Results: The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of ute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than nonimmigrants. Conclusions: In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used

Micro-Engineered Heart Tissues On-Chip with Heterotypic Cell Composition Display Self-Organization and Improved Cardiac Function

Advanced in vitro models that recapitulate the structural organization and function of the human heart are highly needed for accurate disease modeling, more predictable drug screening, and safety pharmacology. Conventional 3D Engineered Heart Tissues (EHTs) lack heterotypic cell complexity and culture under flow, whereas microfluidic Heart-on-Chip (HoC) models in general lack the 3D configuration and accurate contractile readouts. In this study, an innovative and user-friendly HoC model is developed to overcome these limitations, by culturing human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs), endothelial (ECs)- and smooth muscle cells (SMCs), together with human cardiac fibroblasts (FBs), underflow, leading to self-organized miniaturized micro-EHTs (µEHTs) with a CM-EC interface reminiscent of the physiological capillary lining. µEHTs cultured under flow display enhanced contractile performance and conduction velocity. In addition, the presence of the EC layer altered drug responses in µEHT contraction. This observation suggests a potential barrier-like function of ECs, which may affect the availability of drugs to the CMs. These cardiac models with increased physiological complexity, will pave the way to screen for therapeutic targets and predict drug efficacy.</p

Vaccine Willingness and Impact of the COVID-19 Pandemic on Women's Perinatal Experiences and Practices-A Multinational, Cross-Sectional Study Covering the First Wave of the Pandemic.

The COVID-19 pandemic may be of particular concern for pregnant and breastfeeding women. We aimed to explore their beliefs about the coronavirus and COVID-19 vaccine willingness and to assess the impact of the pandemic on perinatal experiences and practices. A multinational, cross-sectional, web-based study was performed in six European countries between April and July 2020. The anonymous survey was promoted via social media. In total, 16,063 women participated (including 6661 pregnant and 9402 breastfeeding women). Most responses were collected from Belgium (44%), Norway (18%) and the Netherlands (16%), followed by Switzerland (11%), Ireland (10%) and the UK (3%). Despite differences between countries, COVID-19 vaccine hesitancy was identified among 40-50% of the respondents at the end of the first wave of the pandemic and was higher among pregnant women. Education level and employment status were associated with vaccine hesitancy. The first wave had an adverse impact on pregnancy experiences and disrupted access to health services and breastfeeding support for many women. In the future, access to health care and support should be maintained at all times. Evidence-based and tailored information on COVID-19 vaccines should also be provided to pregnant and breastfeeding women to avoid unfounded concerns about the vaccines and to support shared decision making in this population

Comparison between EQ-5D-5L and PROMIS-10 to evaluate health-related quality of life 3 months after stroke:a cross-sectional multicenter study

BACKGROUND: Although the use of patient-reported outcome measures to assess Health-Related Quality of Life (HRQoL) has been advocated, it is still open to debate which patient-reported outcome measure should be preferred to evaluate HRQoL after stroke.AIM: To compare the measurement properties (including concurrent validity and discriminant ability) between the 5-dimensional 5-level Euro-Qol (EQ-5D-5L) and the Patient-Reported Outcomes Measurement Information System 10-Question Global Health Short Form (PROMIS-10) to evaluate HRQoL 3 months after stroke.DESIGN: Cross-sectional study.SETTING: Neurology outpatient clinics in 6 Dutch hospitals.POPULATION: The participants 360 consecutive individuals with stroke. Their median age was 71 years, 143 (39.7%) were female and 335 (93.0%) had suffered an ischemic stroke.METHODS: The EQ-5D-5L, PROMIS-10, modified Rankin Scale and two items on experienced decrease in health and activities post-stroke were administered by a stroke nurse or nurse practitioner through a telephone interview 3 months after stroke. The internal consistency, distribution, floor/ceiling effects, inter-correlations and discriminant ability (using the modified Rankin Scale and experienced decrease in health and in activities post-stroke as external anchors) were calculated for both the EQ-5D-5L and PROMIS-10.RESULTS: Ninety-six percent of the participants were living at home and 50.9% experienced minimal or no disabilities (modified Rankin Scale 0-1) 3 months after stroke. A ceiling effect and a non-normal left skewed distribution were observed in the EQ-5D-5L. The PROMIS-10 showed higher internal consistency (alpha=0.90) compared to the EQ-5D-5L (alpha=0.75). Both the EQ-5D-5L and the PROMIS-10 were strongly correlated with the modified Rankin Scale (r=0.62 and 0.60 respectively). The PROMIS-10 showed better discriminant ability in less affected individuals with stroke, whereas the EQ-5D-5L showed slightly better discriminant ability in more affected individuals with stroke.CONCLUSIONS: Both EQ-5D-5L and PROMIS-10 prove to be useful instruments to evaluate HRQoL in patients who are living at home 3 months after stroke.CLINICAL REHABILITATION IMPACT: The clinical rehabilitation impact depended on the setting and underlying goal which patient-reported outcome measure is preferred to evaluate HRQoL 3 months after stroke. The PROMIS-10 should be preferred to detect differences in less affected stroke patients, whereas the EQ-5D-5L provides slightly more information in more affected stroke patients.Paroxysmal Cerebral Disorder

Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology

Drugs targeting atrial-specific ion channels, K(v)1.5 or K(ir)3.1/3.4, are being developed as new therapeutic strategies for atrial fibrillation. However, current preclinical studies carried out in non-cardiac cell lines or animal models may not accurately represent the physiology of a human cardiomyocyte (CM). In the current study, we tested whether human embryonic stem cell (hESC)-derived atrial CMs could predict atrial selectivity of pharmacological compounds. By modulating retinoic acid signaling during hESC differentiation, we generated atrial-like (hESC-atrial) and ventricular-like (hESC-ventricular) CMs. We found the expression of atrial-specific ion channel genes, KCNA5 (encoding Kv1.5) and KCNJ3 (encoding K-ir 3.1), in hESC-atrial CMs and further demonstrated that these ion channel genes are regulated by COUP-TF transcription factors. Moreover, in response to multiple ion channel blocker, vernakalant, and K(v)1.5 blocker, XEN-D0101, hESC-atrial but not hESC-ventricular CMs showed action potential (AP) prolongation due to a reduction in early repolarization. In hESC-atrial CMs, XEN-R0703, a novel K(ir)3.1/3.4 blocker restored the AP shortening caused by CCh. Neither CCh nor XEN-R0703 had an effect on hESC-ventricular CMs. In summary, we demonstrate that hESC-atrial CMs are a robust model for pre-clinical testing to assess atrial selectivity of novel antiarrhythmic drugs

A COUP-TFII Human Embryonic Stem Cell Reporter Line to Identify and Select Atrial Cardiomyocytes

Stem cells & developmental biolog

Cardiovascular development: towards biomedical applicability: Regulation of cardiomyocyte differentiation of embryonic stem cells by extracellular signalling

Investigating the signalling pathways that regulate heart development is essential if stem cells are to become an effective source of cardiomyocytes that can be used for studying cardiac physiology and pharmacology and eventually developing cell-based therapies for heart repair. Here, we briefly describe current understanding of heart development in vertebrates and review the signalling pathways thought to be involved in cardiomyogenesis in multiple species. We discuss how this might be applied to stem cells currently thought to have cardiomyogenic potential by considering the factors relevant for each differentiation step from the undifferentiated cell to nascent mesoderm, cardiac progenitors and finally a fully determined cardiomyocyte. We focus particularly on how this is being applied to human embryonic stem cells and provide recent examples from both our own work and that of others

Novel, multiphasic gene-activated matrices for gradient based multi-gene delivery

Univ Fed Sao Paulo, Dept Med, Sao Paulo, BrazilUniversidade Federal de São Paulo (UNIFESP), Dept Med, Sao Paulo, BrazilWeb of Scienc