BackgroundMicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated.ObjectiveWe hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients.MethodsWe isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan microRNA array containing 754 microRNA primers, we tested for the presence of known asthma microRNAs, and assessed the association of the individual microRNAs with lung function as measured by FEV1/FVC, FEV1% and FVC%. We further tested the subset of FEV1/FVC microRNAs for sex-specific and lung developmental associations.ResultsOf the 108 well-detected circulating microRNAs, 74 (68.5%) had previously been linked to asthma susceptibility. We found 22 (20.3%), 4 (3.7%) and 8 (7.4%) microRNAs to be associated with FEV1/FVC, FEV1% and FVC%, respectively. 8 (of 22) FEV1/FVC, 3 (of 4) FEV1% and 1 (of 8) FVC% microRNAs had functionally validated target genes that have been linked via genome wide association studies to asthma and FEV1 change. Among the 22 FEV1/FVC microRNAs, 9 (40.9%) remain associated with FEV1/FVC in boys alone in a sex-stratified analysis (compared with 3 FEV1/FVC microRNAs in girls alone), 7 (31.8%) were associated with fetal lung development, and 3 (13.6%) in both. Ontology analyses revealed enrichment for pathways integral to asthma, including PPAR signaling, G-protein coupled signaling, actin and myosin binding, and respiratory system development.ConclusionsCirculating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity.
INTRODUCTION: Postpartum hemorrhage (PPH) is a leading cause of pregnancy-related morbidity and mortality worldwide. Recent data has demonstrated that tranexamic acid (TXA), an antifibrinolytic agent, reduces death due to bleeding when used as a treatment for PPH. Our objective was to determine whether the routine use of TXA in the setting of PPH is cost-effective. METHODS: A decision analytic model was designed using TreeAge software in order to compare the outcomes and costs of TXA use in the treatment of PPH. RESULTS: Administration of TXA to a theoretical cohort of 100,000 women receiving usual care for PPH would prevent 403 maternal deaths due to hemorrhage and 457 laparotomies to control bleeding. This improvement in outcomes would result in an increase in 11,000 QALYs and a cost savings of $596 million. Furthermore, if TXA were administered early (within 3 hours) to the same theoretical cohort, 568 maternal deaths due to hemorrhage and 635 laparotomies would be prevented. This amounts to an increase in 16,000 QALYs and a cost savings of $842 million. Sensitivity analysis showed that the administration of TXA was the dominant strategy (lower costs, better outcomes) at all probabilities of maternal death due to hemorrhage. When the cost of TXA was varied, TXA use remained dominant up to a cost of $6,000 per administration and was cost-effective up to $16,555 (assumed cost = $50.40 per administration). CONCLUSION: Early administration of TXA is a cost-effective strategy for reducing maternal morbidity and mortality due to PPH.
INTRODUCTION: Postpartum hemorrhage (PPH) is a leading cause of pregnancy-related morbidity and mortality. Tranexamic acid (TXA), an antifibrinolytic agent, has been shown to reduce morbidity and mortality as a treatment for active hemorrhage. However, the incidence of postpartum hemorrhage varies widely and is heavily influenced by a number of risk factors. Our objective was to determine the rate of postpartum hemorrhage at which the use of prophylactic TXA becomes cost-effective. METHODS: A decision analytic model was designed using TreeAge software in order to compare the outcomes and costs of TXA use in the prevention of PPH associated morbidity and mortality. The outcomes analyzed in the model were death due to hemorrhage and need for surgical intervention to control bleeding. Probabilities, utilities, and costs were derived from the literature. RESULTS: A one-way sensitivity analysis was done to look at the cost-effectiveness of TXA prophylaxis based on risk of postpartum hemorrhage. TXA prophylaxis was shown to be cost effective at risks of 0.0034 or greater based on a willingness-to-pay threshold of $100,000 per QALY. Additionally, in women at high risk of PPH due to morbidly adherent placenta, prophylactic TXA administration in a theoretical cohort of 100,000 women would prevent 270 maternal deaths due to hemorrhage. This amounts to an increase in 7,332 QALYs at a cost/QALY of $458. CONCLUSION: Prophylactic administration of TXA is a cost-effective strategy for reducing maternal morbidity and mortality in women at increased risk of PPH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.