Background: Patients with atrial fibrillation generally require anticoagulant therapy and, at times, therapy with additional platelet aggregation inhibitors. Data are scarce on bleeding rates in high-risk groups receiving combination therapy, such as the elderly or patients with a high CHA 2 DS 2 -VASc score. Methods: We conducted a nationwide cohort study of Danish patients with atrial fibrillation ≥50 years of age. Treatments were ascertained from a prescription database. These included no anticoagulant treatment, and treatment with vitamin K antagonists, direct oral anticoagulants, platelet inhibitors, and combinations of antithrombotic drugs. Incidence rates (IRs) of major bleeding and hazard ratios were estimated overall, and also stratified by treatment modality, age, CHA 2 DS 2 -VASc score, and comorbidity. Major bleeding was defined as bleeding requiring hospitalization or causing death. Results: We identified 272 315 patients with atrial fibrillation. Median age was 75 years (interquartile range, 67–83) and 47% were women. Over a total follow-up period of 1 373 131 patient-years (PYs), 31 459 major bleeds occurred (IR 2.3/100 PYs; 95% CI, 2.3–2.3/100 PYs). In comparison with vitamin K antagonist monotherapy, adjusted hazard ratios of major bleeding were 1.13 (95% CI, 1.06–1.19) for dual antiplatelet therapy, 1.82 (95% CI, 1.76–1.89) for therapy with a vitamin K antagonist and an antiplatelet drug, 1.28 (95% CI, 1.13–1.44) for therapy of a direct oral anticoagulant with an antiplatelet drug, 3.73 (95% CI, 3.23–4.31) for vitamin K antagonist triple therapy, and 2.28 (95% CI, 1.67–3.12) for direct oral anticoagulant triple therapy. Subgroup analyses showed similar patterns. The IR for major bleeding was 10.2/100 PYs among patients receiving triple therapy. Very high major bleeding rates occurred among patients on triple therapy aged >90 years (IR 22.8/100 PYs) or with a CHA 2 DS 2 -VASc score >6 (IR 17.6/100 PYs) or with a history of major bleeding (IR 17.5/100 PYs). Conclusions: Patients with atrial fibrillation on triple therapy experienced high rates of major bleeding in comparison with patients on dual therapy or monotherapy. The high bleeding rates observed in patients on triple therapy >90 years of age or with a CHA 2 DS 2 -VASc score >6 or with a history of a major bleeding warrants careful consideration of such therapy in these patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Some psychotropic medications (e.g. benzodiazepines, sedative antidepressants, etc.) can impair cognitive and psychomotor functions and, therefore, endanger traffic safety. • There is a lack of knowledge concerning the role in traffic safety of first and new generations of psychotropic medications, new and chronic users, young and old drivers, and polypharmacy. WHAT THIS STUDY ADDS • There is an increased risk of having a traffic accident after being exposed to some psychotropic medicine classes and, in particular, to SSRIs. • Health care professionals and patients should be properly informed about the potential effects of some psychoactive medications on driving abilities. • The role of SSRIs in traffic safety has to be investigated further. AIM To examine the association between the use of commonly prescribed psychotropic medications and road traffic accident risk. METHODS A record‐linkage database was used to perform a case–control study in the Netherlands. The data came from three sources: pharmacy prescription data, police traffic accident data and driving licence data. Cases were defined as drivers, who had a traffic accident that required medical assistance between 2000 and 2007. Controls were defined as adults, who had a driving licence and had no traffic accident during the study period. Four controls were matched for each case. The following psychotropic medicine groups were examined: antipsychotics, anxiolytics, hypnotics and sedatives, and antidepressants stratified in the two groups, SSRIs and other antidepressants. Various variables, such as age, gender, medicine half‐life and alcohol use, were considered for the analysis. RESULTS Three thousand nine hundred and sixty‐three cases and 18 828 controls were included in the case–control analysis. A significant association was found between traffic accident risk and exposure to anxiolytics (OR = 1.54, 95% CI 1.11, 2.15), and SSRIs (OR = 2.03, 95% CI 1.31, 3.14). A statistically significant increased risk was also seen in chronic anxiolytic users, females and young users (18 to 29 years old), chronic SSRI users, females and middle‐aged users (30 to 59 years old), and intermediate half‐life hypnotic users. CONCLUSIONS The results of this study support previous findings and confirm that psychoactive medications can constitute a problem in traffic safety. Both health care providers and patients should be properly informed of the potential risks associated with the use of these medicines.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: In contrast to vitamin K antagonists (VKA), direct oral anticoagulants (DOAC's) are not strictly monitored and dose titrated by anticoagulation clinics in the Netherlands. This may affect drug persistence of atrial fibrillation (AF) patients, whom often require lifelong treatment.Objectives: To assess persistence of DOACs and of VKAs in patients with AF.

Nearly half of HCPs in private pharmacies do not refer TB suspects, possibly contributing to delays in diagnosis and treatment. Knowledge about free NTP treatment predicted better performance of HCPs.

Background The association between socioeconomic status and arterial cardiovascular disease is well established. However, despite its high burden of disability-adjusted life years, little research has been carried out to determine whether socioeconomic status is associated with venous thromboembolism. Objective To determine if neighborhood socioeconomic status is associated with venous thromboembolism in a population-based study from the Netherlands. Methods We identified all patients aged 15 years and older with a first event of venous thromboembolism from inhabitants who lived in the urban districts of The Hague, Leiden and Utrecht in the Netherlands in 2008-2012. Neighborhood socioeconomic status was based on the status score, which combines educational level, income and unemployment on a four-digit postal code level. Incidence rate ratios of venous thromboembolism were calculated for different levels of neighborhood socioeconomic status, with adjustments for age and sex. Results A total of 7373 patients with a first venous thromboembolism (median age 61 years; 50% deep vein thrombosis) were identified among more than 1.4 million inhabitants. Higher neighborhood SES was associated with lower incidence of VTE. In the two highest status score groups (i.e. the 95-99th and > 99th percentile), the adjusted incidence rate ratios were 0.91 (95% confidence interval [CI], 0.84-1.00) and 0.80 (95% CI, 0.69-0.93), respectively, compared with the reference status score group (i.e. 30-70th percentile). Conclusions High neighborhood socioeconomic status is associated with a lower risk of first venous thromboembolism.

Statins are said to protect against a wide range of diseases. We studied to what extent potential bias influences the results of studies on beneficial side effects of statins. We selected 8,188 atrial fibrillation patients who started treatment with anticoagulants at the Leiden Anticoagulation Clinic in the Netherlands between 2003 and 2009 and experienced 1,683 minor and 451 major bleeds during 18,105 person-years of follow-up. Statins were associated with a risk reduction of 9% for bleeds (hazard ratio = 0.91, 95% confidence interval: 0.82, 1.00). Additionally, analyses were stratified by age, incident users (patients who started statins during follow-up, i.e., an inception cohort), and prevalent statin users (statin users at baseline), as restriction to incident users avoids overoptimistic risk estimates. After stratification, the protective associations disappeared or reversed (range of hazard ratios = 0.99-3.22), except for patients aged 75 years or older. This remaining association could be due to another bias as, according to guidelines, in the elderly, statins should be prescribed only to those with a reasonable life expectancy. This could have resulted in a comparison of fit statin users with less fit nonstatin users (healthy user effect). The apparent protective association of statins on bleeds may be due to bias. We recommend stratification by age and incident and prevalent statin use when studying associations of statins with disease outcomes to avoid overoptimistic risk estimates.

Because practice-based data on the usage of idarucizumab for urgent dabigatran reversal is unavailable, we evaluated the appropriateness of idarucizumab usage, its haemostatic effectiveness and clinical outcomes.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. In a review of the pharmacologic literature we showed that antidepressant exposure might disturb the development of the enteric nervous system. WHAT THIS STUDY ADDS • In utero exposure to selective serotonin re‐uptake inhibitors (SSRIs) in the second and third trimester or to tricyclic antidepressants (TCAs) in the first trimester leads to a significant increase in laxative use compared with non‐exposed children. SSRI exposure was not associated with significant increased antidiarrhoeal medication use, but TCA exposure was. AIMS Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS The pharmacy prescription database IADB.nl was used for a cohort study in which laxative and antidiarrhoeal medication use in children after in utero exposure to antidepressants (TCA, SSRI, fluoxetine or paroxetine exposed) was compared with no antidepressant exposure. Laxatives and antidiarrhoeal medication use were applied as a proxy for constipation and diarrhoea respectively, which may be associated with disturbed enteric nervous system (ENS) development. RESULTS Children exposed in utero to SSRIs (mainly fluoxetine and paroxetine) in the second and third trimester or to TCAs in the first trimester, more often received laxatives. Combined exposure to TCAs and SSRIs in pregnancy was associated with a 10‐fold increase in laxative use. In utero exposure to SSRIs is not associated with antidiarrhoeal medication use compared with non‐exposed children. In contrast, antidiarrhoeal medication use was significantly higher in children exposed to TCAs anytime in pregnancy. CONCLUSIONS The increased laxative use after second and third trimester exposure to SSRIs might be explained through the inhibitory effect of the serotonin re‐uptake transporter (SERT) and because of selectivity for the 5‐HT2B receptor which affects the ENS. TCA exposure during the first trimester leads to increased laxative use probably through inhibition of the norepinephrine transporter (NET). Exposure of TCAs anytime in pregnancy leads to increase diarrhoeal use possibly through down‐regulation of α2‐adrenoceptors or up‐regulation of the pore forming α1c subunit.