No abstract

Background Exercise training is beneficial in health and disease. Part of the training effect materialises in the brainstem due to the exercise-associated somatosensory nerve traffic. Because active music making also involves somatosensory nerve traffic, we hypothesised that this will have training effects resembling those of physical exercise. Methods We compared two groups of healthy, young subjects between 18 and 30 years: 25 music students (13/12 male/ female, group M) and 28 controls (12/16 male/female, group C), peers, who were non-musicians. Measurement sessions to determine resting heart rate, resting blood pressure and baroreflex sensitivity (BRS) were held during morning hours.

Background The benefit of periprocedural bridging with low-molecular-weight heparin (LMWH) in patients with atrial fibrillation has been contested by the publication of the BRIDGE trial. Objective This article determines whether publication of the BRIDGE trial has led to less bridging procedures and better patient outcomes (i.e., a composite of thromboembolism, major bleeding, and death) in patients undergoing invasive procedures at the Leiden Anticoagulation Clinic, the Netherlands. Methods We identified all procedures that required vitamin K antagonist interruption. Procedures were divided in a period before (2014–2016; 22 months) and after the publication of the BRIDGE trial (2016–2017; 22 months). Cumulative incidences 30 days postprocedure and relative risks of thromboembolic events, major bleeding, and mortality were calculated. Results A total of 4,892 and 4,237 eligible procedures were performed in 2014 to 2016 and 2016 to 2017, respectively. The cumulative incidence of thromboembolism was 0.5% in 2014 to 2016 compared with 0.3% in 2016 to 2017; adjusted odds ratio (OR) 0.60 (95% confidence interval [CI] 0.30–1.21). The cumulative incidence of major bleeding was 1.0% in the 2014 to 2016 period as compared with 1.3% in the 2016 to 2017 period; adjusted OR was 1.27 (95% CI 0.85–1.90). The adjusted OR of the composite endpoint was 1.05 (95% CI 0.74–1.48). The frequency of bridging with LMWH (14.8% in 2014–2016 vs. 16.6% in 2016–2017) as well as mean CHA2DS2-VASc scores of patients receiving bridging did not change after publication of the BRIDGE trial. Conclusion We showed that despite publication of the BRIDGE trial, the frequency of bridging with LMWH and patient outcomes regarding bleeding complications did not change.

Background: Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of major bleeding by decreasing platelet function or decreasing vitamin K antagonist (VKA) metabolism via cytochrome P450 (CYP) inhibition. Aims: To determine whether SSRIs are associated with major bleeding during VKA treatment and investigate the possible mechanisms. Methods: In this cohort study, information on SSRI use and bleeding complications was obtained from patient records of VKA initiators between 2006 and 2018 from two anticoagulation clinics. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRI users. The adjusted hazard ratio of major bleeding was 1.22 (95%CI 0.99-1.50) in all SSRI users and 1.31 (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRI users compared to non-users. Conclusion: SSRI use is associated with an increased risk of high INR and might be associated with major bleeding. The risk of a high INR was slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting there might be a pharmacokinetic interaction (by CYP2C9 inhibition) next to a pharmacodynamic effect of SSRIs on platelet activation.

Aims: To determine whether Selective serotonin reuptake inhibitors (SSRIs) cause major bleeding during vitamin K antagonist (VKA) treatment and investigate the possible mechanisms behind this interaction. Methods: Information on SSRI use and bleeding complications was obtained from patient records at the Anticoagulation Clinics of Leiden and Rotterdam of VKA initiators between 2006 and 2018. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRIs. SSRI use versus non-use was associated with a 1.22-fold (95%CI 0.99-1.50) increased risk for major bleeding in all SSRI users, which was 1.31-fold (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRIs compared to non-users. Conclusion: SSRIs are associated with an increased risk of high INR and major bleeding. These risks were slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting that this was due to a pharmacokinetic interaction (by CYP2C9 inhibition) as well as a pharmacodynamic effect of SSRIs on platelet activation.