No abstract

This phase III study assessed the efficacy and safety of sacubitril/valsartan compared with those of olmesartan in Japanese patients with essential hypertension. Patients (n = 1161, aged ≥20 years) with mild to moderate hypertension (mean sitting systolic blood pressure [msSBP] ≥150 to <180 mmHg) were randomized to receive sacubitril/valsartan 200 mg (n = 387), sacubitril/valsartan 400 mg (n = 385), or olmesartan 20 mg (n = 389) once daily for 8 weeks. The primary assessment was a reduction in msSBP from baseline with sacubitril/valsartan 200 mg vs. olmesartan 20 mg at Week 8. Secondary assessments included msSBP reduction with sacubitril/valsartan 400 mg vs. olmesartan at Week 8 and reductions in mean sitting diastolic blood pressure (msDBP), mean sitting pulse pressure (msPP), and overall blood pressure (BP) control rate for all treatment groups at Week 8. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP from baseline than olmesartan at Week 8 (between-treatment difference: −5.01 mmHg [95% confidence interval: −6.95 to −3.06 mmHg, P < 0.001 for noninferiority and superiority]). Greater reductions in msSBP with sacubitril/valsartan 400 mg vs. olmesartan, as well as in msDBP and msPP with both doses of sacubitril/valsartan vs. olmesartan (P < 0.05 for all), were also observed. Patients treated with sacubitril/valsartan achieved an overall higher BP control rate. The safety and tolerability profiles of sacubitril/valsartan were generally comparable to those of olmesartan. The adverse event rate with sacubitril/valsartan was not dose-dependent. Treatment with sacubitril/valsartan was effective and provided superior BP reduction, with a higher proportion of patients achieving target BP goals than treatment with olmesartan in Japanese patients with mild to moderate essential hypertension.

This paper addresses a detailed experimental study of collective instability bands generated near every half-integer tune per lattice period by coherent dipole and quadrupole resonances. Both instabilities appear side by side or overlap each other but are mostly separable because the dipole resonance often creates a narrower stop band accompanied by more severe particle losses. The separation of these low-order resonance bands becomes greater as the beam intensity increases. In principle, the double stop-band structure can be formed even without machine imperfections when the beam's initial phase-space profile is deviated from the ideal stationary distribution. The tabletop ion-trap system called "S-POD" is employed to experimentally demonstrate the parameter dependence of the double stop-band structure. Numerical simulations are also performed for comparison with experimental observations.

This is a description of the role of Streptococcus sanguis in the oral flora of patients with Behcet's disease (BD) in contrast to the flora of healthy controls. The proportion of S. sanguis in the flora of patients with BD was always higher than that of healthy and disease controls. The types of S. sanguis in the oral flora of the BD patients were uncommon ones. Agglutinating antibody titers against isolated strains of S. sanguis were higher in BD patients than in controls. When S. sanguis antigens were used in skin reaction, the erythema of skin in BD patients was greater than that in healthy controls. It is proposed that uncommon serotypes of S. sanguis may play a role in the pathogenesis of BD.

There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate‐to‐severe psoriasis. In this multicenter, open‐label, phase IV study, 34 patients with moderate‐to‐severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end‐point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end‐point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy.