Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis.

OBJECTIVE: To examine and compare the safety and efficacy of extended treatment with dabigatran, apixaban, rivaroxaban and warfarin in patients with unprovoked venous thromboembolism. METHODS: PubMed and Embase were searched for randomized clinical trials reporting on the use of direct oral anticoagulants (DOACs) and warfarin for the extended treatment of VTE. Meta-analysis was performed on studies reporting similar study design and comparator. RESULTS: A total of 729 articles were identified and 5 studies covering 6 randomized clinical trials met the eligibility criteria and were included in the study. 5 studies were included in the meta-analysis. Results from the meta-analysis showed that the extended use of DOACs and warfarin significantly decreased the risk of recurrent VTE with 83 % when compared placebo. Warfarin (RR: 0.03, CI: 0.00-0.49) and dabigatran (RR: 0.08, CI: 0.03-0.27) showed the largest relative risk reduction followed by apixaban 2.5mg (RR: 0.19, CI: 0.11-0.33), rivaroxaban (RR:0.19, CI: 0.09-0.40) and apixaban 5mg (RR: 0.20, CI: 0.11-0.34). No significant increased risk of major bleeding was observed with the extended use of any DOACs and warfarin compared to placebo (1.15, CI: 0.40-3.31), but an overall increased risk of non-major clinically relevant bleeding (NMCRB) was observed (RR: 2.12, CI: 1.55-2.90). Apixaban 2.5mg and warfarin was not individually associated with an increased risk of NMCRB. Furthermore, it was found from a study not included in the meta-analysis that dabigatran was non-inferior to VKA for the prevention of recurrent VTE (HR: 1.44, CI: 0.78-2.64, p=0.01 for noninferiority) and decreased the risk of NMCRB compared to VKA (RR: 0.58, CI: 0.43-0.77). CONCLUSION: Extended treatment with both warfarin and DOACs are effective in preventing recurrent VTE and does not increase the risk of major bleeding, but increases the risk of NMCRB.

Validation of the Danish translation of the Medicine Knowledge Questionnaire among elementary school children.

BACKGROUND: There is a lack of instruments which can be used to quantitatively assess school children's knowledge about medicine in different countries. OBJECTIVES: The aim of this study was to validate the Danish translation of a school children's medicine knowledge questionnaire developed in Finland. METHODS: A total of 685 children from 37 Danish elementary schools, aged 10-14 years, participated in a validation study. Test-retest and inter-rater reliability, as well as known-group-validity of the translated instrument were investigated. Significance level was set at P ≤ 0.05. RESULTS: For test-retest reliability, Spearman r correlation coefficients for correct knowledge score between the two rounds was 0.433, P < 0.001. For inter-rater reliability, kappa for agreement in correct knowledge score ratings between the two raters was 0.202. For known-group validity, a multivariate linear regression model was run for correct knowledge scores, and it significantly explained 9.2% of variance (R square 0.092, P < 0.001). Gender, school grade and use of medicine for asthma were significant predictors in the model. CONCLUSIONS: The translated questionnaire showed a fair test-retest and inter-rater reliability, as well as acceptable known-group validity. In order to be reliably used in further studies to evaluate school children's knowledge about medicine in Denmark, the methodic of knowledge scoring in the instrument is warranted.