Plasma and synovial fluid extracellular vesicles display altered microRNA profiles in horses with naturally occurring post-traumatic osteoarthritis: an exploratory study.

ObjectiveThe objective of this study was to characterize extracellular vesicles (EVs) in plasma and synovial fluid obtained from horses with and without naturally occurring post-traumatic osteoarthritis (PTOA).AnimalsEVs were isolated from plasma and synovial fluid from horses with (n = 6) and without (n = 6) PTOA.MethodsPlasma and synovial fluid EVs were characterized with respect to quantity, size, and surface markers. Small RNA sequencing was performed, and differentially expressed microRNAs (miRNAs) underwent bioinformatic analysis to identify putative targets and to explore potential associations with specific biological processes.ResultsPlasma and synovial fluid samples from horses with PTOA had a significantly higher proportion of exosomes and a lower proportion of microvesicles compared to horses without PTOA. Small RNA sequencing revealed several differentially expressed miRNAs, including miR-144, miR-219-3p, and miR-199a-3l in plasma and miR-199a-3p, miR-214, and miR-9094 in synovial fluid EVs. Bioinformatics analysis of the differentially expressed miRNAs highlighted their potential role in fibrosis, differentiation of chondrocytes, apoptosis, and inflammation pathways in PTOA.Clinical relevanceWe have identified dynamic molecular changes in the small noncoding signatures of plasma and synovial fluid EVs in horses with naturally occurring PTOA. These findings could serve to identify promising biomarkers in the pathogenesis of PTOA, to facilitate the development of targeted therapies, and to aid in establishing appropriate translational models of PTOA

The injustice of unfit clinical practice guidelines in low-resource realities

To end the international crisis of preventable deaths in low-income and middle-income countries, evidence-informed and cost-efficient health care is urgently needed, and contextualised clinical practice guidelines are pivotal. However, as exposed by indirect consequences of poorly adapted COVID-19 guidelines, fundamental gaps continue to be reported between international recommendations and realistic best practice. To address this long-standing injustice of leaving health providers without useful guidance, we draw on examples from maternal health and the COVID-19 pandemic. We propose a framework for how global guideline developers can more effectively stratify recommendations for low-resource settings and account for predictable contextual barriers of implementation (eg, human resources) as well as gains and losses (eg, cost-efficiency). Such development of more realistic clinical practice guidelines at the global level will pave the way for simpler and achievable adaptation at local levels. We also urge the development and adaptation of high-quality clinical practice guidelines at national and subnational levels in low-income and middle income countries through co-creation with end-users, and we encourage global sharing of these experiences.Research into fetal development and medicin

Cost-effectiveness of first-trimester screening with early preventative use of aspirin in women at high risk of early-onset pre-eclampsia

Objective: Pre-eclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. A first-trimester screening algorithm predicting the risk of early-onset PE has been developed and validated. Early prediction coupled with initiation of aspirin at 11–13 weeks in women identified as high risk is effective at reducing the prevalence of early-onset PE. The aim of this study was to evaluate the cost-effectiveness of this first-trimester screening program coupled with early use of low-dose aspirin in women at high risk of developing early-onset PE, in comparison to current practice in Canada. Methods: A decision analysis was performed based on a theoretical population of 387 516 live births in Canada in 1 year. The clinical and financial impact of early preventative screening using the Fetal Medicine Foundation algorithm for prediction of early-onset PE coupled with early (< 16 weeks) use of low-dose aspirin in those at high risk was simulated and compared with current practice using decision-tree analysis. The probabilities at each decision point and associated costs of utilized resources were calculated based on published literature and public databases. Results: Of the theoretical 387 516 births per year, the estimated prevalence of early PE based on first-trimester screening and aspirin use was 705 vs 1801 cases based on the current practice. This was associated with an estimated total cost of C$9.52 million with the first-trimester screening program compared with C$23.91 million with current practice for the diagnosis and management of women with early-onset PE. This equals an annual cost saving to the Canadian healthcare system of approximately C$14.39 million. Conclusions: The implementation of a first-trimester screening program for PE and early intervention with aspirin in women identified as high risk for early PE has the potential to prevent a significant number of early-onset PE cases with a substantial associated cost saving to the healthcare system in Canada