Safety of Dronedarone in Routine Clinical Care

ObjectivesThe aim of this study was to examine mortality and liver disease among patients exposed to dronedarone.BackgroundThere has been concern about the safety of dronedarone, especially for patients with heart failure and permanent atrial fibrillation (AF). There have also been suspicions about liver toxicity.MethodsAll 174,995 patients with a diagnosis of AF during 2010 to 2012 were identified in the Swedish Patient Register. Of these, 4,856 patients had received dronedarone according to the Swedish Drug Register, and 170,139 patients who had not were used as a control population. Mean follow-up was 1.6 years, with a minimal follow-up of 6 months.ResultsPatients prescribed dronedarone were younger (age 65.5 years vs. 75.7 years, p < 0.0001) and healthier than control patients. The annual mortality rate among patients who received dronedarone was 1.3% compared with 14.0% in the control population. There were no sudden cardiac deaths and no deaths related to liver failure among patients who received treatment with dronedarone. After propensity score matching and adjustment for cofactors, patients who received dronedarone had lower mortality than other AF patients (hazard ratio [HR]: 0.41; 95% confidence interval [CI]: 0.33 to 0.51). Dronedarone patients with heart failure had lower mortality than other heart failure patients (HR: 0.40; 95% CI: 0.30 to 0.53). They also had lower mortality than expected from the general population (standardized mortality ratio: 0.67; 95% CI: 0.55 to 0.78), which indicates the selection of low-risk patients. The risk of liver disease was not increased (HR: 0.57; 95% CI: 0.34 to 0.92).ConclusionsDronedarone, as prescribed to AF patients in Sweden, has not exposed patients to increased risks of death or liver disease

Assessment of female sex as a risk factor in atrial fibrillation in Sweden: nationwide retrospective cohort study

Objective To determine whether women with atrial fibrillation have a higher risk of stroke than men

High-Energy-Physics Event Generation with PYTHIA 6.1

PYTHIA version 6 represents a merger of the PYTHIA 5, JETSET 7 and SPYTHIA programs, with many improvements. It can be used to generate high-energy-physics `events', i.e. sets of outgoing particles produced in the interactions between two incoming particles. The objective is to provide as accurate as possible a representation of event properties in a wide range of reactions. The underlying physics is not understood well enough to give an exact description; the programs therefore contain a combination of analytical results and various models. The emphasis in this article is on new aspects, but a few words of general introduction are included. Further documentation is available on the web.Comment: 1 + 27 pages, submitted to Computer Physics Communication

From sonnet to dream text : Gunnar Björling’s road to Modernism

The subject of this dissertation is the Finland-Swedish author Gunnar Björling (1887-1960) and his journey towards Modernism. The principle thesis of this dissertation, the idea that Björling’s distinctive language cannot be understood without an underlying modernistic current, is outlined in Chapter I. It also discusses the idea that Modernism cannot be reduced to a matter of style, but encompasses particular values, ideological stances and practical matters, such as the forming of alliances, writing manifestos and publishing journals. Chapter II examines how and why Björling came to be regarded as a modernist. A strongly contributing factor was Björling’s language, which from the very first violated prevailing ideas on acceptable forms of expression. The fact that he published his first book through the modernist publishing firm Daimon, and contributed to its journal Ultra, further confirmed his modernistic placing. Chapter III focuses on Björling’s unpublished juvenilia from the 1910’s. The young Björling wrote traditional rhyming verse but was also influenced by writings of a more symbolistic and modern character. The chapter concludes with a study of bizarrerierna, Björling’s dream notes, originally written during the 1910’s but first published in 1928. With their bold enjambments and highly compressed form, these notes came to influence the continued development of his lyrical imagery. Chapter IV deals with his debut Vilande dag (Resting day) (1922) and its symbolistically coloured language problematic. Björling struggled to find a language that would convey his experience of the limitlessness of being, a language striving to transcend words, leaving space for silence. This struggle for the right words continues in the later Korset och löftet (The cross and the promise) (1925) and Chapter V demonstrates how this is connected with the quest for God. In the wake of German Expressionism and Dadaism, Björling adopts a more disjointed syntax and a bolder and more dissonant lyrical imagery. There also occurs a thematic expansion, giving greater prominence to the daily life of the metropolis, a life transformed by media. In accordance with modernistic patterns, Björling chose to end his book with a theoretical epilogue, which is a distinctive collation of life philosophy, anti-clericalism, passionate religiousness, moral-philosophical discussions and aesthetic expositions

Paroxysmal atrial fibrillation : Prognostic implications

p>This thesis is based on data from the Stockholm Cohort on Atrial Fibrillation (SCAF). This cohort consists of all 2912 patients with atrial fibrillation or flutter who were treated as in or outpatients at South Hospital in Stockholm or at Gustavsberg Primary Care Centre during 2002. The patients have been followed prospectively through medical records complemented by information from national registers of hospitalisations and mortality. In Study I we evaluated the incidence of ischaemic and haemorrhagic stroke in 855 patients with paroxysmal atrial fibrillation (PxAF). We found that the stroke incidence was approximately twice as high as in the general population and similar to that of permanent atrial fibrillation (PermAF). Warfarin prophylaxis appeared to be as efficient in Px AF as in PermAF. The incidence of cerebral bleedings was low and not higher in patients using warfarin than in patients using aspirin. In Study II we investigated the mortality among patients with PxAF and found it to be higher than expected from age and sex adjusted specific rates in the general population. The standardized mortality ratio (SMR) was 1.6. Patients with PxAF died more often than expected from myocardial infarction (SMR 2.4), heart failure (SMR 2.6) and cardiovascular disease in general (SMR 2.1). The increased mortality in PxAF appears to be present mainly in subjects with concomitant cardiovascular co-morbidity. Treatment with warfarin was found to be associated with improved survival in PxAF patients. In Study III we studied how current guideline recommendations are translated into clinical practice. We found that approximately half of the patients who ought to have warfarin also had received such treatment. Undertreatment was particularly common in patients with PxAF and in patients aged >80 years. Important risk factors for stroke did not increase the likelihood of warfarin treatment. In Study IV we investigated whether patients who remain in sinus rhythm after DCcardioversion obtain any prognostic benefit from having normal sinus rhythm restored. From the SCAF-cohort 361 patients who had been DC-cardioverted were studied. Patients without known relapse to atrial fibrillation within three months after cardioversion had a lower incidence of all-cause mortality (HR 0.5, 95% C.I. 0.3-1.0) as well as a lower incidence of the composite end point consisting of death, ischaemic stroke, myocardial infarction or hospitalization for heart failure (HR 0.5, 95% C.I. 0.3-0.8) after multivariable adjustment. Conclusions PxAF is associated with increased morbidity and mortality which is similar to that of PermAF. Underlying cardiovascular disease seems to account for most of this. Therefore it is essential to diagnose and treat any underlying cardiovascular disease in PxAF-patients. Warfarin seems to be helpful, not only against stroke but also against premature cardiovascular death. Therefore it is essential to provide PxAF-patients with adequate anticoagulant treatment unless there are clear contraindications for such therapy. Our results suggest that restoration and maintenance of sinus rhythm may improve the prognosis in patients with atrial fibrillation. Therefore, we propose that eligible patients should be given an opportunity to be restored to sinus rhythm before atrial fibrillation is accepted as permanent

Efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with warfarin in patients with atrial fibrillation

AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) were in pivotal randomised controlled trials at least non-inferior to warfarin for stroke prevention in atrial fibrillation, but time in therapeutic range (TTR) for warfarin was lower (mean 55%-65%) than in Swedish general care where TTR is &gt;70%. We compared efficacy and safety of NOACs and warfarin treatment for stroke prevention in Sweden. METHODS: Retrospective cohort study of all non-selected oral anticoagulation naïve atrial fibrillation patients with first prescription for NOACs or warfarin between December 2011 and December 2014, excluding patients with mitral stenosis or mechanical valvular prosthesis. Data were obtained from cross-linked national registers, propensity scores were used as continuous covariates, and associations between treatment and outcomes were evaluated by multivariable Cox regressions. RESULTS: -VASc points (mean) 3.38 vs 3.24, p&lt;0.001, in NOAC and warfarin groups, respectively. HRs (95% CI) for NOACs versus warfarin were 1.04 (0.91-1.19) for all-cause stroke or systemic embolism, 1.16 (1.00-1.35) for ischaemic stroke, 0.85 (0.76-0.96) for major bleeding, 1.22 (1.01-1.46) for gastrointestinal bleeding, 0.60 (0.47-0.76) for intracranial haemorrhage and 0.89 (0.81-0.96) for all-cause mortality. CONCLUSION: In this large non-selected anticoagulation naïve Swedish atrial fibrillation cohort, the risks for all-cause stroke or systemic embolism were similar with NOACs and warfarin, but NOACs were associated with significantly lower risks of all-cause mortality, major bleeding and intracranial haemorrhage but higher risk of gastrointestinal bleeding. Better safety suggests NOACs as preferred treatment for patients with atrial fibrillation starting oral anticoagulation