Temporal trends of cause-specific mortality after diagnosis of atrial fibrillation.

BACKGROUND AND AIMS: Reports of outcomes after atrial fibrillation (AF) diagnosis are conflicting. The aim of this study was to investigate mortality and hospitalisation rates following AF diagnosis over time, by cause, and by patient features. METHODS: Individuals aged ≥16 years with a first diagnosis of AF were identified from the UK Clinical Practice Research Datalink-GOLD dataset from Jan 1, 2001 to Dec 31, 2017. The primary outcomes were all-cause and cause-specific mortality and hospitalisation at 1 year following diagnosis. Poisson regression was used to calculate rate ratios (RRs) for mortality and incidence rate ratios (IRRs) for hospitalisation and 95% confidence intervals (CIs) comparing 2001/02 and 2016/17, adjusted for age, sex, region, socioeconomic status and 18 major comorbidities. RESULTS: Of 72 412 participants, mean (SD) age was 75.6 (12.4) years and 44 762 (61.8%) had ≥3 comorbidities. All-cause mortality declined (RR 2016/17 vs 2001/02 0.72; 95% CI 0.65-0.80), with large declines for cardiovascular (RR 0.46; 95% CI 0.37-0.58) and cerebrovascular mortality (RR 0.41; 95% CI 0.29-0.60) but not for non-cardio/cerebrovascular causes of death (RR 0.91; 95% CI 0.80-1.04). By 2016/17 deaths from dementia (67, 8.0%), outstripped deaths from acute myocardial infarction, heart failure and acute stroke combined (56, 6.7%, p < 0.001). Overall hospitalisation rates increased (IRR 2016/17 vs 2001/02 1.17; 95% CI, 1.13-1.22), especially for non-cardio/cerebrovascular causes (IRR 1.42; 95% CI 1.39-1.45). Older, more deprived, and hospital-diagnosed AF patients experienced higher event rates. CONCLUSIONS: After AF diagnosis, cardio/cerebrovascular mortality and hospitalisation has declined, whilst hospitalisation for non-cardio/cerebrovascular disease has increased

Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation: data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated. METHODS AND RESULTS: The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data. CONCLUSION: Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy

Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial.

AIMS: Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested. METHODS AND RESULTS: The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02-1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62). CONCLUSION: Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation

Starcounts Redivivus. IV. Density Laws Through Photometric Parallaxes

In an effort to more precisely define the spatial distribution of Galactic field stars, we present an analysis of the photometric parallaxes of 70,000 stars covering nearly 15 square degrees in seven Kapteyn Selected Areas. We address the affects of Malmquist Bias, subgiant/giant contamination, metallicity and binary stars upon the derived density laws. The affect of binary stars is the most significant. We find that while the disk-like populations of the Milky Way are easily constrained in a simultaneous analysis of all seven fields, no good simultaneous solution for the halo is found. We have applied halo density laws taken from other studies and find that the Besancon flattened power law halo model (c/a=0.6, r^-2.75) produces the best fit to our data. With this halo, the thick disk has a scale height of 750 pc with an 8.5% normalization to the old disk. The old disk scale height is 280-300 pc. Corrected for a binary fraction of 50%, these scale heights are 940 pc and 350-375 pc, respectively. Even with this model, there are systematic discrepancies between the observed and predicted density distributions. Our model produces density overpredictions in the inner Galaxy and density underpredictions in the outer Galaxy. A possible solution is modeling the stellar halo as a two-component system in which the halo has a flattened inner distribution and a roughly spherical, but substructured outer distribution. Further reconciliation could be provided by a flared thick disk, a structure consistent with a merger origin for that population. (Abridged)Comment: 66 pages, accepted to Astrophysical journal, some figures compresse

Critical dynamics of self-gravitating Langevin particles and bacterial populations

We study the critical dynamics of the generalized Smoluchowski-Poisson system (for self-gravitating Langevin particles) or generalized Keller-Segel model (for the chemotaxis of bacterial populations). These models [Chavanis & Sire, PRE, 69, 016116 (2004)] are based on generalized stochastic processes leading to the Tsallis statistics. The equilibrium states correspond to polytropic configurations with index $n$ similar to polytropic stars in astrophysics. At the critical index $n_{3}=d/(d-2)$ (where $d\ge 2$ is the dimension of space), there exists a critical temperature $\Theta_{c}$ (for a given mass) or a critical mass $M_{c}$ (for a given temperature). For $\Theta>\Theta_{c}$ or $M<M_{c}$ the system tends to an incomplete polytrope confined by the box (in a bounded domain) or evaporates (in an unbounded domain). For $\Theta<\Theta_{c}$ or $M>M_{c}$ the system collapses and forms, in a finite time, a Dirac peak containing a finite fraction $M_c$ of the total mass surrounded by a halo. This study extends the critical dynamics of the ordinary Smoluchowski-Poisson system and Keller-Segel model in $d=2$ corresponding to isothermal configurations with $n_{3}\to +\infty$. We also stress the analogy between the limiting mass of white dwarf stars (Chandrasekhar's limit) and the critical mass of bacterial populations in the generalized Keller-Segel model of chemotaxis

Thermodynamics and collapse of self-gravitating Brownian particles in D dimensions

We address the thermodynamics (equilibrium density profiles, phase diagram, instability analysis...) and the collapse of a self-gravitating gas of Brownian particles in D dimensions, in both canonical and microcanonical ensembles. In the canonical ensemble, we derive the analytic form of the density scaling profile which decays as f(x)=x^{-\alpha}, with alpha=2. In the microcanonical ensemble, we show that f decays as f(x)=x^{-\alpha_{max}}, where \alpha_{max} is a non-trivial exponent. We derive exact expansions for alpha_{max} and f in the limit of large D. Finally, we solve the problem in D=2, which displays rather rich and peculiar features

Synthesis of Fluorine-18 Functionalized Nanoparticles for use as in vivo Molecular Imaging Agents

Nanoparticles containing fluorine-18 were prepared from block copolymers made by ring opening metathesis polymerization (ROMP). Using the fast initiating ruthenium metathesis catalyst (H_2IMes)(pyr)_2(Cl)_2Ru=CHPh, low polydispersity amphiphilic block copolymers were prepared from a cinnamoyl-containing hydrophobic norbornene monomer and a mesyl-terminated PEG-containing hydrophilic norbornene monomer. Self-assembly into micelles and subsequent cross-linking of the micelle cores by light-activated dimerization of the cinnamoyl groups yielded stable nanoparticles. Incorporation of fluorine-18 was achieved by nucleophilic displacement of the mesylates by the radioactive fluoride ion with 31% incorporation of radioactivity. The resulting positron-emitting nanoparticles are to be used as in vivo molecular imaging agents for use in tumor imaging

Human factors and missed solutions to Enigma design weaknesses

The German World War II Enigma suffered from design weaknesses that facilitated its large-scale decryption by the British throughout the war. The author shows that the main technical weaknesses (self-coding and reciprocal coding) could have been avoided using simple contemporary technology, and therefore the true cause of the weaknesses is not technological but must be sought elsewhere. Specifically, human factors issues resulted in the persistent failure to seek out more effective designs. Similar limitations seem to beset the literature on the period, which misunderstands the Enigma weaknesses and therefore inhibits broader thinking about design or realising the critical role of human factors engineering in cryptography

Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options