Tranexamic acid for the treatment of postpartum hemorrhage: a cost-effectiveness analysis.

BACKGROUND: Postpartum hemorrhage is a leading cause of pregnancy-related morbidity and mortality. Recent data have demonstrated that tranexamic acid reduces death because of bleeding when used as a treatment for postpartum hemorrhage. The World Health Organization now recommends tranexamic acid as a first-line treatment for postpartum hemorrhage; however, data are not yet available on the frequency of use in the United States, where tranexamic acid is currently recognized as an adjunct treatment for postpartum hemorrhage. OBJECTIVE: We aimed to strengthen the current evidence that tranexamic acid should be recognized as a first-line treatment for postpartum hemorrhage, even in high-resource countries. Furthermore, we aimed to determine whether early administration of tranexamic acid (within 3 hours of diagnosis) is a cost-effective strategy for reducing maternal morbidity and mortality from postpartum hemorrhage in the United States. STUDY DESIGN: A decision-analytical model was designed to compare the outcomes and costs of the administration of tranexamic acid in the treatment of postpartum hemorrhage. Moreover, this model was used to compare outcomes for early administration with those of routine use. The interventions compared were 1 g of intravenous tranexamic acid or matching placebo. The risks analyzed in the model were death because of hemorrhage and laparotomy to control bleeding. Probabilities, utilities, and costs were derived from literature. Quality-adjusted life-years were calculated using a discounted life expectancy rate of 3%. Cost-effectiveness was determined on the basis of a willingness-to-pay threshold of $100,000 per quality-adjusted life year. RESULTS: The administration of tranexamic acid to a theoretical cohort of 100,000 women would prevent 11 maternal deaths, 6 postpartum laparotomies after vaginal delivery, and 112 reoperations after cesarean delivery. This would lead to an increase in 329 quality-adjusted life years and a total cost savings of $15.39 million. Furthermore, if tranexamic acid were administered early (within 3 hours of postpartum hemorrhage diagnosis) to the same theoretical cohort, 16 maternal deaths owing to hemorrhage, 9 laparotomies, and 155 reoperations would be prevented. This amounts to an increase in 438 quality-adjusted life years and an annual cost savings of $23.15 million. A sensitivity analysis showed that the administration of tranexamic acid was the dominant strategy at all probabilities of maternal death owing to hemorrhage >0.00002. When the cost of tranexamic acid was varied, the administration of tranexamic acid remained dominant up to a cost of $267 per administration in the United States if given within the first 3 hours. Furthermore, in a Monte Carlo probabilistic sensitivity analysis, the early administration of tranexamic acid remained the dominant strategy (both lowered costs and improved outcomes) in 99.8% of models. CONCLUSION: Early administration of tranexamic acid was a cost-effective strategy for reducing maternal morbidity and mortality owing to postpartum hemorrhage in the United States.

Circulating MicroRNAs: Association with Lung Function in Asthma.

BACKGROUND: MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated. OBJECTIVE: We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients. METHODS: We 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. RESULTS: Of 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. CONCLUSIONS: Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity.

Heterochromatin position effects on circularized sex chromosomes cause filicidal embryonic lethality in Drosophila melanogaster.

Some circularized X-Y chromosomes in Drosophila melanogaster are mitotically unstable and induce early embryonic lethality, but the genetic basis is unknown. Our experiments suggest that a large region of X-linked satellite DNA causes anaphase bridges and lethality when placed into a new heterochromatic environment within certain circularized X-Y chromosomes. These results reveal that repetitive sequences can be incompatible with one another in cis. The lethal phenotype also bears a remarkable resemblance to a case of interspecific hybrid lethality.