Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

Cluster analysis of European Union states using social and economical indicators

Dissertation follows up cluster analysis of European Union states using social and economical indicators. In the first part all the social and economical indicators are defined. In the second part of the dissertation all these indicators in time of economical and financial and later debt crisis in years from 2007 to 2012 in European Union states are analysed. In the third part the cluster analysis is applicated for the social and economical indicators of the European Union states. Five clusters were identified using cluster analysis. Structure of these clusters was changing during years 2007 and 2012. First cluster contained developed Western European countries (Belgium, Denmark, Germany, Ireland, France, Netherlands, Austria, Finland, Sweden and United Kingdom). The second cluster was created from countries, that entered to European Union after year 2004 (Bulgaria, Estonia, Croatia, Latvia, Lithuania, Hungary, Poland, Romania and Slovakia). The third cluster contained Czech Republic, Estonia, Greece, Lithuania, Portugal, Slovakia and Slovenia. In the fourth cluster were Southern European countries Greece, Spain, Italy, Cyprus and Malta and the fifth cluster contained only Luxembourg

Steroid metabolome and multiple pregnancy

Steroid hormones can be divided into 2 groups - intracellular and extracellular, depending on location of their activity. Intracellular ones influence expression of genes while acting as transcription factors. This so-called genomic effect is very slow. Extracellular (non-genomic) steroids bind to neurotransmitter receptors located on the cytoplasmic cell membrane and thus affect ionic channels permeability. Their effect is faster. We refer to them as neuroactive steroids (produced in different body tissues or administered externally) or neurosteroids (synthetized in nervous system cells). Some neuroactive steroids and their metabolites (e.g. progesterone) are crucial in stabilizing the pregnancy. Other steroid disorders play their role in wide spectre of pregnancy complications, such as preterm labor, preeclampsia, intrahepatic cholestasis in pregnancy etc. Our scientific interest in collaboration with the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague is focused on investigation of multiple pregnancies in term of steroid metabolome. Studies conducted so far have not provided a comprehensive analysis of steroidome within mothers and fetuses of multiple pregnancies. The aim of our research is to clarify the relationship between fetuses and mother from the point..

Evolution and mutual relations between demographic indicators

This Bachelor's thesis focuses on the analysis and evolution of demographic indicators through world's regions and states. It searches for a relation between demographic indicators and finds connections between economical, political and demographics evolution. The first part of the thesis defines the demographic indicators and shows the evolution from the period 1960-2008. Especially the evolution of the Czech Republic and those states where changes were the greatest in the mentioned period is shown there. The second part of the thesis focuses on the analysis of the economical and medical factors that influence demographic indicators. The purpose is to quantify this influence and measure its intensity. For this purpose regression analysis and analysis of variance is used. The biggest reduction in mortality rate was in Yemen in the mentioned period, on the other hand the biggest increase was noted in Ukraine. The smallest values of the infant mortality rate are detected in Scandinavia which positively influences the life expectancy at birth in these states. Infant mortality rate dropped most in the states of Southern Europe and Egypt while in Zimbabwe and Democratic Republic of the Congo the improvement was the smallest. The evolution of these indicators dramatically influenced life expectancy at birth in these particular states. The main factors that influence life expectancy at birth include GDP per capita in PPP, the number of physicians, health expenditure, alcohol consumption and immunization

Evolution and mutual relations between demographic indicators

Bakalářská práce je zaměřena na analýzu a vývoj demografických ukazatelů v rámci světových regionů a států. Zkoumá vztahy mezi demografickými ukazateli a nachází souvislosti mezi ekonomickým, politickým a demografickým vývojem. První část práce definuje demografické ukazatele a zobrazuje jejich vývoj od roku 1960 až 2008. Důraz je kladen především na zobrazení vývoje v České republice a v zemích, ve kterých došlo k nejvýraznějším změnám. Druhá část práce je zaměřena na zkoumání ekonomických a zdravotnických faktorů, které ovlivňují demografické ukazatele. Cílem je tento vliv kvantifikovat a změřit jeho intenzitu. K tomu jsou použity metody regresní analýzy a analýzy rozptylu. K nejvýraznějšímu poklesu obecné míry úmrtnosti došlo ve sledovaném období v Jemenu, naopak na Ukrajině došlo k navýšení. Nejnižší hodnoty kojenecké úmrtnosti jsou dlouhodobě měřeny ve státech skandinávského poloostrova, což také pozitivně ovlivňuje střední délku života při narození v těchto zemích. Ve státech jižní Evropy a Egyptě klesl kvocient kojenecké úmrtnosti nejvíce, zatímco v Zimbabwe a Demokratické republice Kongo došlo pouze k nevýraznému snížení. Vývoj těchto ukazatelů značně ovlivnil střední délku života při narození v jednotlivých zemích. Mezi hlavní faktory, ovlivňující střední délku života při narození, patří HDP na obyvatele v PPS, počet doktorů, výdaje ve zdravotnictví, spotřeba alkoholu či rozšíření očkování.This Bachelor's thesis focuses on the analysis and evolution of demographic indicators through world's regions and states. It searches for a relation between demographic indicators and finds connections between economical, political and demographics evolution. The first part of the thesis defines the demographic indicators and shows the evolution from the period 1960-2008. Especially the evolution of the Czech Republic and those states where changes were the greatest in the mentioned period is shown there. The second part of the thesis focuses on the analysis of the economical and medical factors that influence demographic indicators. The purpose is to quantify this influence and measure its intensity. For this purpose regression analysis and analysis of variance is used. The biggest reduction in mortality rate was in Yemen in the mentioned period, on the other hand the biggest increase was noted in Ukraine. The smallest values of the infant mortality rate are detected in Scandinavia which positively influences the life expectancy at birth in these states. Infant mortality rate dropped most in the states of Southern Europe and Egypt while in Zimbabwe and Democratic Republic of the Congo the improvement was the smallest. The evolution of these indicators dramatically influenced life expectancy at birth in these particular states. The main factors that influence life expectancy at birth include GDP per capita in PPP, the number of physicians, health expenditure, alcohol consumption and immunization

A case of pulmonary thromboembolism with synchronous and metachronous paradoxical embolism through the patent foramen ovale—A case report

AbstractA rare case is presented in this article—namely consecutive and synchronous embolizations in the pulmonary artery and paradoxical embolizations in the systemic circulation. Although paradoxical embolizations represent a relatively rare cause of acute ischemic attack of any localization, this nosological unit should always be considered in cases where the source of thrombembolism is unclear, and particularly where pulmonary embolism in the premorbid history or limb phlebothrombosis verified by sonography is present in the history. In the acute phase of treatment it is essential to ensure surgical or endovascular reperfusion of the ischemic organ and then at the next time to prevent further such events especially by occlusion of patent foramen ovale

A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic Cholestasis of Pregnancy

<div><p>Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.</p></div

Steroids quantified in the circulation of women with ICP and controls.

<p>Steroids quantified in the circulation of women with ICP and controls.</p