10 research outputs found

    Serum microRNA profiles in athyroid patients on and off levothyroxine therapy

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    Background Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone. Objective To study if serum miRNA profiles are changed in different thyroid states. Design and methods We studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification. Results Mean age of the subjects was 44.0 years (range 20–61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 μg/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment

    Delivery or expectant management for prevention of adverse maternal and neonatal outcomes in hypertensive disorders of pregnancy:an individual participant data meta-analysis

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    Objective Hypertensive disorders affect 3-10% of pregnancies. Delayed delivery carries maternal risks, while early delivery increases fetal risk, so appropriate timing is important. The aim of this study was to compare immediate delivery with expectant management for prevention of adverse maternal and neonatal outcomes in women with hypertensive disease in pregnancy. Methods CENTRAL, PubMed, MEDLINE and Clinical Trials.gov were searched for randomized controlled trials comparing immediate delivery to expectant management in women presenting with gestational hypertension or pre-eclampsia without severe features from 34 weeks of gestation. The primary neonatal outcome was respiratory distress syndrome (RDS) and the primary maternal outcome was a composite of HELLP syndrome and eclampsia. The PRISMA-IPD guideline was followed and a two-stage meta-analysis approach was used. Relative risks (RR) and numbers needed to treat or harm (NNT/NNH) with 95% CI were calculated to evaluate the effect of the intervention. Results Main outcomes were available for 1724 eligible women. Compared with expectant management, immediate delivery reduced the composite risk of HELLP syndrome and eclampsia in all women (0.8% vs 2.8%; RR, 0.33 (95% CI, 0.15-0.73); I-2 = 0%; NNT, 51 (95% CI, 31.1-139.3)) as well as in the pre-eclampsia subgroup (1.1% vs 3.5%; RR, 0.39 (95% CI, 0.15-0.98); I-2 = 0%). Immediate delivery increased RDS risk (3.4% vs 1.6%; RR, 1.94 (95% CI 1.05-3.6); I-2 = 24%; NNH, 58 (95% CI, 31.1-363.1)), but depended upon gestational age. Immediate delivery in the 35th week of gestation increased RDS risk (5.1% vs 0.6%; RR, 5.5 (95% CI, 1.0-29.6); I-2 = 0%), but immediate delivery in the 36th week did not (1.5% vs 0.4%; RR, 3.4 (95% CI, 0.4-30.3); I-2 not applicable). Conclusion In women with hypertension in pregnancy, immediate delivery reduces the risk of maternal complications, whilst the effect on the neonate depends on gestational age. Specifically, women with a-priori higher risk of progression to HELLP, such as those already presenting with pre-eclampsia instead of gestational hypertension, were shown to benefit from earlier delivery. (c) 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

    Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor

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    OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd

    Fetal MRI of the heart and brain in congenital heart disease

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    Antenatal assessment of congenital heart disease and associated anomalies by ultrasound has improved perinatal care. Fetal cardiovascular MRI and fetal brain MRI are rapidly evolving for fetal diagnostic testing of congenital heart disease. We give an overview on the use of fetal cardiovascular MRI and fetal brain MRI in congenital heart disease, focusing on the current applications and diagnostic yield of structural and functional imaging during pregnancy. Fetal cardiovascular MRI in congenital heart disease is a promising supplementary imaging method to echocardiography for the diagnosis of antenatal congenital heart disease in weeks 30–40 of pregnancy. Concomitant fetal brain MRI is superior to brain ultrasound to show the complex relationship between fetal haemodynamics in congenital heart disease and brain development.</p

    A systematic approach for the adequacy analysis of a set of experimental databases: application in the framework of the ATRIUM activity

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    International audienceIn the Best-Estimate Plus Uncertainty (BEPU) framework, the use of best-estimate code requires to go through a Verification, Validation and Uncertainty Quantification process (VVUQ). The relevance of the experimental data in relation to the physical phenomena of interest in the VVUQ process is crucial. Adequacy analysis of selected experimental databases addresses this problem. The outcomes of the analysis can be used to select a subset of relevant experimental data, to encourage designing new experiments or to drop some experiments from a database because of their substantial lack of adequacy. The development of a specific transparent and reproducible approach to analyze the relevance of experimental data for VVUQ still remains open and is the topic of this contribution.In this paper, the concept of adequacy initially introduced in the OECD/NEA SAPIUM (Systematic APproach for model Input Uncertainty quantification Methodology) project is formalized. It is defined through two key properties, called representativeness and completeness, that allows considering the multifactorial dimension of the adequacy problem. A new systematic approach is then proposed to analyze the adequacy of a set of experimental databases. It relies on the introduction of two sets of criteria to characterize representativeness and completeness and on the use of multi-criteria decision analysis method to perform the analysis. Finally, the approach is applied in the framework of the new OECD/NEA ATRIUM project which includes a set of practical IUQ exercises in thermal-hydraulics to test the SAPIUM guideline in determining input uncertainties and forward propagating them on an application case . It allows evaluating the adequacy of eight experimental databases coming from the Super Moby-dick, Sozzi-Sutherland and Marviken experiments and identifying the most adequate ones

    Molecular basis of the establishment and functioning of a N2-fixing root nodule

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