Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

Background Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. Methods In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. Results In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. Conclusions Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.

Use of amorphous silicon for the design of a photonic crystal based MZ modulator at 1.55μm

The design of an amorphous silicon based Mach-Zehnder electro-optic modulator integrated into a two-dimensional (2D) photonic crystal (PhC) has been designed for wavelengths of ~1.55 μ m. The numerical analysis has been performed by using a finite-difference time domain (FDTD) based simulation tool. The design of the PhC-based MZ Modulator relies on the exploitation of the refractive index tunability of the hydrogenated amorphous silicon (a-Si:H) for the fabrication of PhC waveguides requiring minimum critical technological processes

A comparative study of root canal shaping using protaper universal and protaper next rotary files in preclinical dental education

Background. Dentistry has undergone an evolution in endodontics practice caused by the advancement of rotary techniques for root canal preparation and their subsequent incorporation into the teaching of dentistry undergraduates. This research aimed to evaluate the shaping ability of third-year dental students as their first experience in rotary instrumentation using ProTaper Universal (PTU) and ProTaper Next (PTN) (Dentsply Maillefer) rotary instruments in simulated curved canals. Methods. Forty students instrumented 200 simulated canals with a 40° curvature in resin blocks according to the manufacturer's instructions with PTU and 39 students and 195 canals with PTN files. The canals were prepared at a speed of 300 rpm using a 16:1 reduction hand-piece powered by an electric motor (Xsmart; Dentsply Maillefer). The final apical preparation was set to F2 for the PTU and X2 for the PTN group. The change in canal curvature was evaluated based on Schneider technique using the AutoCAD 2007 software on post-digital photographs. The incidence of instrument fracture and deformation, the incidence of ledge, the change in working length (WL), and the working time were noted. The data were analyzed with Student's t -test and Chi-Square test at a significance level of 0.05 using SPSS. Results. PTN maintained the original canal curvature better, resulting in fewer fractures and ledges, and shaped the canals faster than the PTU (P 0:05). The change in WL after instrumentation was 0.97 mm ± 0.95 mm in PTU and 0.96 mm ± 0.80 mm in PTN (p<0:05). The mean times were 627 s ± 18 s for PTU and 379 s ± 18 s for PTN (p<0:000). Discussion. PTN can be recommended in severely curved root canals in terms of maintenance of the original canal curvature, superior instrument fracture and fewer ledges. Even if training before preparation provides an acceptable level of canal shaping for preclinical students, the use of NiTi rotary instruments should be included in the undergraduate dental curriculum, contributing to an increase in the quality of root canal shaping and, consequently, to an improvement of the clinical experience of students. © 2019 Celik et al

Characteristics predicting tuberculosis risk under tumor necrosis factor-? inhibitors: Report from a large multicenter cohort with high background prevalence

PubMedID: 26773107Objective. Screening strategies for latent tuberculosis (TB) before starting tumor necrosis factor (TNF)- inhibitors have decreased the prevalence of TB among patients who are treated with these agents. However, despite vigilant screening, TB continues to be an important problem, especially in parts of the world with a high background TB prevalence. The aim of this study was to determine the factors related to TB among a large multicenter cohort of patients who were treated with anti-TNF. Methods. Fifteen rheumatology centers participated in this study. Among the 10,434 patients who were treated with anti-TNF between September 2002 and September 2012, 73 (0.69%) had developed TB. We described the demographic features and disease characteristics of these 73 patients and compared them to 7695 patients who were treated with anti-TNF, did not develop TB, and had complete data available. Results. Among the 73 patients diagnosed with TB (39 men, 34 women, mean age 43.6 ± 13 yrs), the most frequent diagnoses were ankylosing spondylitis (n = 38) and rheumatoid arthritis (n = 25). More than half of the patients had extrapulmonary TB (39/73, 53%). Six patients died (8.2%). In the logistic regression model, types of anti-TNF drugs [infliximab (IFX), OR 3.4, 95% CI 1.88-6.10, p = 0.001] and insufficient and irregular isoniazid use (< 9 mos; OR 3.15, 95% CI 1.43-6.9, p = 0.004) were independent predictors of TB development. Conclusion. Our results suggest that TB is an important complication of anti-TNF therapies in Turkey. TB chemoprophylaxis less than 9 months and the use of IFX therapy were independent risk factors for TB development. Copyright © 2016 The Journal of Rheumatology. All rights reserved

Design of amorphous silicon photonic crystal-based M-Z modulator operating at 1.55 μm

The design of an amorphous silicon-based Mach-Zehnder electro-optic modulator including two guiding pi-n structures integrated inside a two-dimensional (2-D) photonic crystal (PhC) working at 1.55 μm, is reported. Electrically induced free carrier dispersion effect in this photonic material with a very cost-effective technology, is investigated for modulation. Our numerical analysis, performed by a time-domain (FDTD)-based software, proves that the voltage-length product can be remarkably reduced by taking advantage of both the strong PhC confinement and the wide refractive index tunability of amorphous silicon

Hydrodynamic conditions in front of a vertical wall with an overhanging horizontal cantilever slab

Transforming wave heights from offshore to the shoreline is the first step of any coastal engineering work. Wave breaking is analyzed to understand hydrodynamic conditions. For vertical breakwaters and sea walls, wave reflection is an important process that affects the determination of the wave height. Many of the design formulas presented in the literature depend on empirical studies based on the structures tested. In this study, the hydrodynamic conditions in front of a vertical wall with an overhanging horizontal cantilever slab with a foreshore slope of 1/20 are determined experimentally under regular wave conditions to assess the applicability of the formulas of Goda (2000) for predicting the nearshore wave height and breaker index equation (Goda, 2010). The selection of wave measurements used to determine the design wave height, the reflection coefficients, and wave breaking is also analyzed, and the reflection equations are derived from the dataset covering different breaker types. Small-scale tests show that the incident wave height is a good representative of the design wave height and that the values predicted by Goda are in good agreement with actual measurements. However, the predicted H-max values are overestimated. In addition, the inception of the wave breaking point is postponed because of the reflection and/or turbulence left over from preceding waves, which is an effect of the vertical wall. At higher water levels, the effect of the vertical wall on the inception point becomes more significant

Lipid profile of patients with aortic stenosis might be predictive of rate of progression

Background Aortic stenosis is one of the most commonly encountered valvular pathology requiring surgery in developed countries. There are similarities between risk factors for coronary atherosclerosis and the development of aortic stenosis. We designed a retrospective study, evaluated the lipid profile and previous echocardiographic recordings of patients with aortic stenosis, and searched the association of rate of progression and lipid profile