Impact of early vs. delayed initiation of dutasteride/tamsulosin combination therapy on the risk of acute urinary retention or BPH-related surgery in LUTS/BPH patients with moderate-to-severe symptoms at risk of disease progression

Purpose: To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression. Methods: Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1–24 months). AUR/S incidence was described by Kaplan–Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment. Results: Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively. Conclusions: Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression

Skyrmions and edge spin excitations in quantum Hall droplets

We present an analysis of spin-textures in Quantum Hall droplets, for filling factors $\nu \simeq 1$. Analytical wavefunctions with well defined quantum numbers are given for the low-lying states of the system which result to be either bulk skyrmions or edge spin excitations. We compute dispersion relations and study how skyrmions become ground states of the Quantum Hall droplet at $\nu \gtrsim 1$. A Hartree-Fock approximation is recovered and discussed for those spin textures.Comment: RevTeX, four postscript figures appende

Quantum dots with two electrons: Singlet-triplet transitions

The magnetic character of the ground-state of two electrons on a double quantum dot, connected in series to left and right single-channel leads, is considered. By solving exactly for the spectrum of the two interacting electrons, it is found that the coupling to the continuum of propagating states on the leads, in conjunction with the electron-electron interactions, may result in a delocalization of the bound state of the two electrons. This, in turn, reduces significantly the range of the Coulomb interaction parameters over which singlet-triplet transitions can be realized. It is also found that the coupling to the leads favors the singlet ground-state.Comment: 8 pages, submitted to Phys. Rev.

Impact of disease progression on individual IPSS trajectories and consequences of immediate versus delayed start of treatment in patients with moderate or severe LUTS associated with BPH

PURPOSE: Despite superiority of tamsulosin-dutasteride combination therapy versus monotherapy for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH), patients at risk of disease progression are often initiated on α-blockers. This study evaluated the impact of initiating tamsulosin monotherapy prior to switching to tamsulosin-dutasteride combination therapy versus immediate combination therapy using a longitudinal model describing International Prostate Symptom Score (IPSS) trajectories in moderate/severe LUTS/BPH patients at risk of disease progression. METHODS: Clinical trial simulations (CTS) were performed using data from 10,238 patients from Phase III/IV dutasteride trials. The effect of varying disease progression rates was explored by comparing profiles on- and off-treatment. CTS scenarios were investigated, including a reference (immediate combination therapy) and six alternative virtual treatment arms (delayed combination therapy of 1-24 months). Clinical response (≥ 25% IPSS reduction relative to baseline) was analysed using log-rank test. Differences in IPSS relative to baseline at various on-treatment time points were assessed by t tests. RESULTS: Delayed combination therapy initiation led to significant (p < 0.01) decreases in clinical response. At month 48, clinical response rate was 79.7% versus 74.1%, 70.3% and 71.0% and IPSS was 6.3 versus 7.6, 8.1 and 8.0 (switchers from tamsulosin monotherapy after 6, 12 and 24 months, respectively) with immediate combination therapy. More patients transitioned from severe/moderate to mild severity scores by month 48. CONCLUSIONS: CTS allows systematic evaluation of immediate versus delayed combination therapy. Immediate response to α-blockers is not predictive of long-term symptom improvement. Observed IPSS differences between immediate and delayed combination therapy (6-24 months) are statistically significant

Anticoagulation in Patients With COVID-19: JACC Review Topic of the Week.

Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).Dr Farkouh has received research grants from Amgen, Novo Nordisk, and Novartis. Dr Stone has received speaker honoraria from Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Miracor, Neovasc, Abiomed, Ancora, Vectorious, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, and Amgen; and has equity/ options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Godoy is supported by the Frederick Banting and Charles Best Canada Graduate Scholarship (Doctoral Research Award) from the Canadian Institutes of Health Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

A vertical diatomic artificial molecule in the intermediate coupling regime in a parallel and perpendicular magnetic field

We present experimental results for the ground state electrochemical potentials of a few electron semiconductor artificial molecule made by vertically coupling two quantum dots, in the intermediate coupling regime, in perpendicular and parallel magnetic fields up to 5 T. We perform a quantitative analysis based on local-spin density functional theory. The agreement between theoretical and experimental results is good, and the phase transitions are well reproduced.Comment: Typeset using Revtex, 13 pages and 8 Postscript figure

Study of Inclusive J/psi Production in Two-Photon Collisions at LEP II with the DELPHI Detector

Inclusive J/psi production in photon-photon collisions has been observed at LEP II beam energies. A clear signal from the reaction gamma gamma -> J/psi+X is seen. The number of observed N(J/psi -> mu+mu-) events is 36 +/- 7 for an integrated luminosity of 617 pb^{-1}, yielding a cross-section of sigma(J/psi+X) = 45 +/- 9 (stat) +/- 17 (syst) pb. Based on a study of the event shapes of different types of gamma gamma processes in the PYTHIA program, we conclude that (74 +/- 22)% of the observed J/psi events are due to `resolved' photons, the dominant contribution of which is most probably due to the gluon content of the photon.Comment: 13 pages, 8 figures, Accepted by Phys. Lett.

Study of Leading Hadrons in Gluon and Quark Fragmentation

The study of quark jets in e+e- reactions at LEP has demonstrated that the hadronisation process is reproduced well by the Lund string model. However, our understanding of gluon fragmentation is less complete. In this study enriched quark and gluon jet samples of different purities are selected in three-jet events from hadronic decays of the Z collected by the DELPHI experiment in the LEP runs during 1994 and 1995. The leading systems of the two kinds of jets are defined by requiring a rapidity gap and their sum of charges is studied. An excess of leading systems with total charge zero is found for gluon jets in all cases, when compared to Monte Carlo Simulations with JETSET (with and without Bose-Einstein correlations included) and ARIADNE. The corresponding leading systems of quark jets do not exhibit such an excess. The influence of the gap size and of the gluon purity on the effect is studied and a concentration of the excess of neutral leading systems at low invariant masses (<~ 2 GeV/c^2) is observed, indicating that gluon jets might have an additional hitherto undetected fragmentation mode via a two-gluon system. This could be an indication of a possible production of gluonic states as predicted by QCD.Comment: 19 pages, 6 figures, Accepted by Phys. Lett.

Evidence for an Excess of Soft Photons in Hadronic Decays of Z^0

Soft photons inside hadronic jets converted in front of the DELPHI main tracker (TPC) in events of qqbar disintegrations of the Z^0 were studied in the kinematic range 0.2 < E_gamma < 1 GeV and transverse momentum with respect to the closest jet direction p_T < 80 MeV/c. A clear excess of photons in the experimental data as compared to the Monte Carlo predictions is observed. This excess (uncorrected for the photon detection efficiency) is (1.17 +/- 0.06 +/- 0.27) x 10^{-3} gamma/jet in the specified kinematic region, while the expected level of the inner hadronic bremsstrahlung (which is not included in the Monte Carlo) is (0.340 +/- 0.001 +/- 0.038) x 10^{-3} gamma/jet. The ratio of the excess to the predicted bremsstrahlung rate is then (3.4 +/- 0.2 +/- 0.8), which is similar in strength to the anomalous soft photon signal observed in fixed target experiments with hadronic beams.Comment: 37 pages, 9 figures, Accepted by Eur. Phys. J.