Thrombin-activatable fibrinolysis inhibitor and sex modulate thrombus stability and pulmonary embolism burden in a murine model.

BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) levels are positively correlated with the risk of thrombosis. The mechanism of how TAFI affects venous thromboembolism (VTE) remains uncertain. In addition, the role of sex on the risk of VTE has also been studied. However, their association also remains unclear. OBJECTIVES: To investigate how TAFI and/or sex affect venous thrombus stability and consequent pulmonary embolism (PE). METHODS: Ferric chloride-induced thrombi were formed within the femoral veins of male and female wild-type (WT) or TAFI-knockout (Cpb2-/-) mice. Thrombi were imaged over 2 hours using intravital videomicroscopy to quantify embolization and thrombus size over time. Lungs were examined by immunohistochemistry to quantify (a) emboli and (b) fibrin composition of these emboli. RESULTS: Embolization events in female mice were higher than in males (7.9-fold in WT and 3.1-fold in Cpb2-/- mice). Although the maximal thrombus sizes were not different across groups, Cpb2-/- mice had thrombi that were, on average, 24% smaller at the end of the 2-hour experiment than WT mice. Loss of TAFI led to a 4.0- and 2.8-fold increase in PE burden in males and females, respectively, while sex had no influence. Pulmonary emboli in Cpb2-/- mice had higher fibrin composition compared with WT mice. CONCLUSION: Female mice had less stable venous thrombi than male mice, suggesting a higher risk of PE in females with deep vein thrombosis. Mice lacking TAFI had more thrombus degradation and higher PE burden than WT mice. These results confirm the role of TAFI in venous thrombosis.

Emergency department care experiences among people who use substances: a qualitative study.

BACKGROUND: People who use substances (PWUS) encounter significant barriers to accessing care for their complex health needs. As a result, emergency departments (EDs) often become the first point of healthcare access for many PWUS and are a crucial setting for the study of health inequities. This study aimed to understand the ED healthcare experiences of PWUS with the intent of informing ways of improving the delivery of equitable care. METHODS: This qualitative study was part of a larger cross-sectional, mixed-methods study that examined ED experiences among diverse underserved and equity-deserving groups (EDGs) within Kingston, Ontario, Canada. Participants shared and self-interpreted a story about a memorable ED or UCC visit within the preceding 24 months. Data from participants who self-identified as having substance use experiences was analyzed through inductive thematic analysis. RESULTS: Of the 1973 unique participants who completed the survey, 246 participants self-identified as PWUS and were included in the analysis. Most participants were < 45 years of age (61%), male (53%), and white/European (57%). 45% identified as a person with a disability and 39% frequently struggled to make ends meet. Themes were determined at the patient, provider, and system levels. PATIENT: history of substance use and experience of intersectionality negatively influenced participants' anticipation and perception of care. Provider: negative experiences were linked to assumption making, feelings of stigma and discrimination, and negative perceptions of provider care. Whereas positive experiences were linked to positive perceptions of provider care. System: timeliness of care and the perception of inadequate mental health resources negatively impacted participants' care experience. Overall, these themes shaped participants' trust of ED staff, their desire to seek care, and their perception of the care quality received. CONCLUSIONS: PWUS face significant challenges when seeking care in the ED. Given that EDs are a main site of healthcare utilization, there is an urgent need to better support staff in the ED to improve care experiences among PWUS. Based on the findings, three recommendations are proposed: (1) Integration of an equity-oriented approach into the ED, (2) Widespread training on substance use, and (3) Investment in expert resources and services to support PWUS.