Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin–antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC). In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution.

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BackgroundEvidence suggests that pharmacists integrated into primary care can improve patient outcomes and satisfaction, but their impact on healthcare systems is unclear.AimTo identify the key impacts of pharmacists’ integration into primary care on health system indicators, such as healthcare utilisation and costs.Design and settingA systematic review of literature.MethodEmbase, MEDLINE, Scopus, the Health Management Information Consortium, CINAHL, and the Cochrane Central Register of Controlled Trials databases were examined, along with reference lists of relevant studies. Randomised controlled trials (RCTs) and observational studies published up until June 2018, which considered health system outcomes of the integration of pharmacists into primary care, were included. The Cochrane risk of bias quality assessment tool was used to assess risk of bias for RCTs; the National Institute of Health National Heart, Lung, and Blood Institute quality assessment tool was used for observational studies. Data were extracted from published reports and findings synthesised.ResultsSearches identified 3058 studies, of which 28 met the inclusion criteria. Most included studies were of fair quality. Pharmacists in primary care resulted in reduced use of GP appointments and reduced emergency department (ED) attendance, but increased overall primary care use. There was no impact on hospitalisations, but some evidence of savings in overall health system and medication costs.ConclusionIntegrating pharmacists into primary care may reduce GP workload and ED attendance. However, further higher quality studies are needed, including research to clarify the cost-effectiveness of the intervention and the long-term impact on health system outcomes.

Our results suggest knowledge translation (KT) of HRQL results would improve if the clinical trial HRQL data were easily accessible to clinicians, and presented in a comprehensible and clinically applicable format, which includes discussion of the relevance of the measurement domains and implications of the findings. We recommend that standards of clinical trial HRQL reporting be implemented in clinical journals.

Background Massive open online courses (MOOCs) have the potential to make a broader educational impact because many learners undertake these courses. Despite their reach, there is a lack of knowledge about which methods are used for evaluating these courses. Objective The aim of this review was to identify current MOOC evaluation methods to inform future study designs. Methods We systematically searched the following databases for studies published from January 2008 to October 2018: (1) Scopus, (2) Education Resources Information Center, (3) IEEE (Institute of Electrical and Electronic Engineers) Xplore, (4) PubMed, (5) Web of Science, (6) British Education Index, and (7) Google Scholar search engine. Two reviewers independently screened the abstracts and titles of the studies. Published studies in the English language that evaluated MOOCs were included. The study design of the evaluations, the underlying motivation for the evaluation studies, data collection, and data analysis methods were quantitatively and qualitatively analyzed. The quality of the included studies was appraised using the Cochrane Collaboration Risk of Bias Tool for randomized controlled trials (RCTs) and the National Institutes of Health—National Heart, Lung, and Blood Institute quality assessment tool for cohort observational studies and for before-after (pre-post) studies with no control group. Results The initial search resulted in 3275 studies, and 33 eligible studies were included in this review. In total, 16 studies used a quantitative study design, 11 used a qualitative design, and 6 used a mixed methods study design. In all, 16 studies evaluated learner characteristics and behavior, and 20 studies evaluated learning outcomes and experiences. A total of 12 studies used 1 data source, 11 used 2 data sources, 7 used 3 data sources, 4 used 2 data sources, and 1 used 5 data sources. Overall, 3 studies used more than 3 data sources in their evaluation. In terms of the data analysis methods, quantitative methods were most prominent with descriptive and inferential statistics, which were the top 2 preferred methods. In all, 26 studies with a cross-sectional design had a low-quality assessment, whereas RCTs and quasi-experimental studies received a high-quality assessment. Conclusions The MOOC evaluation data collection and data analysis methods should be determined carefully on the basis of the aim of the evaluation. The MOOC evaluations are subject to bias, which could be reduced using pre-MOOC measures for comparison or by controlling for confounding variables. Future MOOC evaluations should consider using more diverse data sources and data analysis methods. International Registered Report Identifier (IRRID) RR2-10.2196/12087