Safety of continuing mineralocorticoid receptor antagonist treatment in patients with heart failure with reduced ejection fraction and severe kidney disease: Data from Swedish Heart Failure Registry

AIMS Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD. METHODS AND RESULTS We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or ≥60 ml/min/1.73 m$^{2}$ , respectively. An eGFR ≥60 ml/min/1.73 m$^{2}$ and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD. CONCLUSIONS The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum

Hyponatraemia and changes in natraemia during hospitalization for acute heart failure and associations with in-hospital and long-term outcomes - from the ESC-HFA EORP Heart Failure Long-Term Registry

AIMS: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes. METHODS AND RESULTS: Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively. CONCLUSION: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk

Study of Spin and Decay-Plane Correlations of W Bosons in the e+e- -> W+W- Process at LEP

Data collected at LEP at centre-of-mass energies \sqrt(s) = 189 - 209 GeV are used to study correlations of the spin of W bosons using e+e- -> W+W- -> lnqq~ events. Spin correlations are favoured by data, and found to agree with the Standard Model predictions. In addition, correlations between the W-boson decay planes are studied in e+e- -> W+W- -> lnqq~ and e+e- -> W+W- -> qq~qq~ events. Decay-plane correlations, consistent with zero and with the Standard Model predictions, are measured

Ultrarelativistic sources in nonlinear electrodynamics

The fields of rapidly moving sources are studied within nonlinear electrodynamics by boosting the fields of sources at rest. As a consequence of the ultrarelativistic limit the delta-like electromagnetic shock waves are found. The character of the field within the shock depends on the theory of nonlinear electrodynamics considered. In particular, we obtain the field of an ultrarelativistic charge in the Born-Infeld theory.Comment: 10 pages, 3 figure

Measurement of the Cross Section for Open-Beauty Production in Photon-Photon Collisions at LEP

The cross section for open-beauty production in photon-photon collisions is measured using the whole high-energy and high-luminosity data sample collected by the L3 detector at LEP. This corresponds to 627/pb of integrated luminosity for electron-positron centre-of-mass energies from 189GeV to 209GeV. Events containing b quarks are identified through their semi-leptonic decay into electrons or muons. The e+e- -> e+e-b b~X cross section is measured within our fiducial volume and then extrapolated to the full phase space. These results are found to be in significant excess with respect to Monte Carlo predictions and next-to-leading order QCD calculations

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Different perceptions of the burden of upper GI endoscopy: an empirical study in three patient groups

Background: Few studies have evaluated patients' perceived burden of cancer surveillance tests. Cancer screening and surveillance, however, require a large number of patients to undergo potentially burdensome tests with only some experiencing health gains from it. We investigated the determinants of patients' reported burden of upper gastrointestinal (GI) endoscopy by comparing data from three patient groups. Patients and methods: A total of 476 patients were included: 180 patients under regular surveillance for Barrett esophagus (BE), a premalignant disorder; 214 patients with non-specific upper GI symptoms (NS), and 82 patients recently diagnosed with upper GI cancer (CA). We assessed pain, discomfort and overall burden experienced during endoscopy, symptoms in the week afterwards and psychological distress over time (Hospital Anxiety and Depression scale and Impact of Event Scale). Results: Two-thirds (66%) of patients reported discomfort and overall burden of upper GI endoscopy. Only 23% reported any pain. BE patients reported significantly less discomfort, pain and overall burden than the other patients: those with NS reported more discomfort, CA patients more pain, and both more overall burden. These differences could be statistically explained by the number of previous endoscopies and whether sedation was provided or not, but not by patient characteristics. Conclusion: The perception of upper GI endoscopy varies by patient group, due to potential adaptation after multiple endoscopies and aspects of th

Sex Differences in Neoplastic Progression in Barrett's Esophagus:A Multicenter Prospective Cohort Study

Recommendations in Barrett’s esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as highgrade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11–4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33–10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29–0.95) and HGD (AR 0.40, 95% CI 0.19–0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models