Optimal antithrombotic treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention:triple therapy is too much!

Patients with atrial fibrillation who undergo a coronary intervention are eligible for both anticoagulation and (dual) antiplatelet therapy ((D) APT). An optimal balance has to be found to reduce the thromboembolic risk (i.e. stroke, systemic embolism and myocardial infarction) and to minimise the increased risk of bleeding with concomitant use of an anticoagulant and (D) APT. Owing to a lack of evidence, the guideline recommendations are predominantly based on expert opinion. Current evidence indicates that the combination of a non-vitamin K oral anticoagulant (NOAC) and clopidogrel is safer than vitamin-K oral antagonists plus DAPT, which increases the risk of bleeding, without clear advantages in regard to efficacy. Concerning whether (N) OACs should be combined with single APT rather than DAPT, the findings of the WOEST, PIONEER AF-PCI and RE-DUAL PCI trials seem to favour a combination with clopidogrel only, thus omitting aspirin. Choosing the optimal treatment strategies for individual patients on NOACs and (D) APT will remain a challenge for clinicians, though triple therapy seems to be the less favourable option owing to the increased risk of bleeding

Electrostatics of ions inside the nanopores and trans-membrane channels

A model of a finite cylindrical ion channel through a phospholipid membrane of width $L$ separating two electrolyte reservoirs is studied. Analytical solution of the Poisson equation is obtained for an arbitrary distribution of ions inside the trans-membrane pore. The solution is asymptotically exact in the limit of large ionic strength of electrolyte on the two sides of membrane. However, even for physiological concentrations of electrolyte, the electrostatic barrier sizes found using the theory are in excellent agreement with the numerical solution of the Poisson equation. The analytical solution is used to calculate the electrostatic potential energy profiles for pores containing charged protein residues. Availability of a semi-exact interionic potential should greatly facilitate the study of ionic transport through nanopores and ion channels

Screening for Atrial Fibrillation in Sub-Saharan Africa:A Health Economic Evaluation to Assess the Feasibility in Nigeria

Background: Cardiovascular disease reflects a major burden of non-communicable disease in Sub-Saharan Africa (SSA). Early detection and treatment of atrial fibrillation (AF), as a preventive measure against stroke, is currently not in the scope of the World Health Organization recommendation to reduce cardiovascular disease. Objective: We hypothesized that screening for AF would be an important approach to determine the true AF prevalence in the general population in African countries and to identify asymptomatic AF patients at risk for stroke to optimize prevention. Methods: A decision analytic model was developed to study the health-economic impact of AF screening in Nigeria over a life-time horizon. The patient population explored in the model was a population of newly detected AF cases that would be diagnosed with a one-time systematic screening for AF with a single lead ECG device in community health centres across Nigeria. Conclusions: The health gain per newly detected AF patient (N = 31,687) was 0.41 QALY at a cost of $5,205 per patient with 100$12,587 per QALY gained. The intervention was cost-effective with a 99.9% warfarin use with an ICER of $1,363 per QALY gained. The total cost of a single screening session was$7.3 million for the total screened population in Nigeria or $1.60 per patient screened. Screening for AF to detect AF patients in need for stroke prevention can be a cost-effective intervention in the Sub-Saharan region, depending on type of anticoagulant used and drug costs

Effects of manipulated food availability and seasonality on innate immune function in a passerine

The innate immune system is essential for survival, yet many immune traits are highly variable between and within individuals. In recent years, attention has shifted to the role of environmental factors in modulating this variation. A key environmental factor is food availability, which plays a major role in shaping life histories, and may affect resource allocation to immune function through its effect on nutritional state. We developed a technique to permanently increase foraging costs in seed-eating birds, and leveraged this technique to study the effects of food availability on the innate immune system over a 3-year period in 230 zebra finches housed in outdoor aviaries. The immune components we studied were haptoglobin, ovotransferrin, nitric oxide, natural antibodies through agglutination, complement-mediated lysis, and killing capacity of Escherichia coli and Candida albicans, covering a broad spectrum of the innate immune system. We explored the effects of food availability in conjunction with other potentially important variables: season, age, sex and manipulated natal brood size. Increased foraging costs affected multiple components of the immune system, albeit in a variable way. Nitric oxide and agglutination levels were lower under harsh foraging conditions, while Escherichia coli killing capacity was increased. Agglutination levels also varied seasonally, but only at low foraging costs. C. albicans killing capacity was lower in winter, and even more so for animals in harsh foraging conditions that were raised in large broods. Effects of food availability on ovotransferrin were also seasonal, and only apparent in males. Haptoglobin levels were independent of foraging costs and season. Males had higher levels of immune function than females for three of the measured immune traits. Innate immune function was independent of age and manipulated natal brood size. Our finding that food availability affects innate immune function suggests that fitness effects of food availability may at least partially be mediated by effects on the immune system. However, food availability effects on innate immunity varied in direction between traits, illustrating the complexity of the immune system and precluding conclusions on the level of disease resistance

Multi-ion conduction bands in a simple model of calcium ion channels

We report self-consistent Brownian dynamics simulations of a simple electrostatic model of the selectivity filters (SF) of calcium ion channels. They reveal regular structure in the conductance and selectivity as functions of the fixed negative charge Qf at the SF. This structure consists of distinct regions of high conductance (conduction bands) M0, M1, M2 separated by regions of zero-conductance (stop-bands). Two of these conduction bands, M1 and M2, demonstrate high calcium selectivity and prominent anomalous mole fraction effects and can be identified with the L-type and RyR calcium channels.Comment: 14 pages, 9 figures, 38 reference

Heart rate increase and inappropriate sinus tachycardia after cryoballoon pulmonary vein isolation for atrial fibrillation

Background: Cryoballoon pulmonary vein isolation (PVI) is a common therapy for atrial fibrillation (AF). While moderately increased sinus rhythm heart rate (HR) after PVI has been observed, inappropriate sinus tachycardia (IST) is a rare phenomenon. We aimed to investigate the prevalence and natural history of an abnormal sinus HR response after cryoballoon PVI. Methods: We included 169/646 (26.2%) patients with AF undergoing PVI with available Holter recordings before and 3, 6 and 12 months after the procedure. Patients with AF on Holter monitoring were excluded. Mean HR increase >= 20 bpm or an IST-like pattern (mean HR > 90 bpm or > 80 bpm when beta-blocking agents were used) following PVI was categorised as abnormal sinus HR response. Results: Following PVI, mean HR +/- standard deviation increased in the entire group from 63.5 +/- 8.4 to 69.1 +/- 9.9 bpm at 3 months (p < 0.001), and to 71.9 +/- 9.4 bpm at 6 months (p < 0.001). At 12 months, mean HR was 71.2 +/- 10.1 bpm (p < 0.001). Only 7/169 patients (4.1%) met criteria for abnormal sinus HR response: mean HR was 61.9 +/- 10.6 bpm (pre-ablation), 84.6 +/- 9.8 bpm (3 months), 80.1 +/- 6.5 bpm (6 months) and 76.3 +/- 10.1 bpm (12 months). Even at 12 months, mean HR was significantly different from that pre-ablation in this group (p = 0.033). However, in patients meeting IST-like pattern criteria, mean HR at 12 months was no longer significantly different from that pre-ablation. Conclusion: Few patients had an abnormal sinus HR response after PVI. Peak HR was observed 3 months after PVI, but HR was still significantly increased 12 months post-ablation compared with pre-ablation. An IST-like pattern was rarely observed. In these patients, HR decreased to pre-ablation values within a year