A National Spinal Muscular Atrophy Registry for Real-World Evidence.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population. METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials. RESULTS: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner. CONCLUSION: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients

2D non-linear seismic response of the Dinar basin,TURKEY

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Local geological conditions generate significant amplification of ground motion and concentrated damage during earthquakes. The highly concentrated damages at the edges of the Dinar basin during occurred earthquakes at regions close to rock outcrop bring up the effect of the inclined bedrock effect on the dynamic behavior of the basin with 2D geometry. In this study, first the idealized 2D model of the basin based on the results of the underground explorations and geologic investigations is proposed. Results show that Dinar basin has an asymmetric 2D geometry with two different bedrock angles at edges. Then, a numerical study using finite difference based nonlinear code which utilizes appropriate static and dynamic boundary conditions, and includes hysteresis damping formulation based on the user defined degradation curves is conducted using real earthquake motions of different strength and frequency content. The constructed model is subjected to the collection of 16 earthquakes with different PGA's of 0.1, 0.2, 0.3 and 0.4 g, four motions for each PGA. It was seen that the dynamic behavior of the basin is broadly affected by the two dimensional bedrock. The results indicates the higher effect of the 6° bedrock inclination at east part on the amplification with respect to the steeper 20° bedrock slope at the west. Also, the results show the insignificant effect of the bedrock at the depth more than 150 m on the amplification of the east edge. While the effect of the 6° bedrock angle at the east part continues until 1500 m from the outcrop, it affects the amplification until 700 m from the outcrop at the west part with 20° bedrock angle

Omalizumab versus cyclosporin-A for the treatment of chronic spontaneous urticaria: can we define better-responding endotypes?

Background: Chronic Spontaneous Urticaria (CSU) is characterized by recurrent wheals and/or angioedema for longer than 6-weeks. Guidelines recommend Omalizumab (Oma) as first-line and Cyclosporine-A (Cs-A) as second-line treatment in antihistamine resistant CSU. This step-wise algorithm might be time-consuming and costly