Long-term safety and efficacy of Eculizumab in Aquaporin-4 IgG-positive NMOSD

Objective During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy. Methods Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. Results Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1–276.9 weeks), for a combined total of 362.3 patient-years (PY). Treatment-related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab-treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6–97.3) of patients remained adjudicated relapse-free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013–0.048) in all eculizumab-treated patients versus 0.350 (95% CI = 0.199–0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use. Interpretation This analysis demonstrates that eculizumab's long-term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long-term eculizumab treatment to reduce relapse risk in patients with AQP4-IgG+ NMOSD. ANN NEUROL 2021;89:1088–109

A multilayered approach for the analysis of perinatal mortality using different classification systems

Many classification systems for perinatal mortality are available, all with their own strengths and weaknesses: none of them has been universally accepted. We present a systematic multilayered approach for the analysis of perinatal mortality based on information related to the moment of death, the conditions associated with death and the underlying cause of death, using a combination of representatives of existing classification systems. We compared the existing classification systems regarding their definition of the perinatal period, level of complexity, inclusion of maternal, foetal and/or placental factors and whether they focus at a clinical or pathological viewpoint. Furthermore. we allocated the classification systems to one of three categories: 'when', 'what' or 'why', dependent on whether the allocation of the individual cases of perinatal mortality is based on the moment of death ('when'), the clinical conditions associated with death ('what'), or the underlying cause of death ('why'). A multilayered approach for the analysis and classification of perinatal mortality is possible by using combinations of existing systems; for example the Wigglesworth or Nordic Baltic ('when'), ReCoDe ('what') and Tulip ('why') classification systems. This approach is useful not only for in depth analysis of perinatal mortality in the developed world but also for analysis of perinatal mortality in the developing countries, where resources to investigate death are often limited. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Clustering by kernel density

Clustering, Kernel,

Rates of bone loss among women initiating antidepressant medication use in midlife

10.1210/jc.2013-1971Journal of Clinical Endocrinology and Metabolism98114355-436

Fast wave direct electron heating in advanced inductive and ITER baseline scenario discharges in DIII-D

Fast Wave (FW) heating and electron cyclotron heating (ECH) are used in the DIII-D tokamak to study plasmas with low applied torque and dominant electron heating characteristic of burning plasmas. FW heating via direct electron damping has reached the 2.5 MW level in high performance ELMy H-mode plasmas. In Advanced Inductive (AI) plasmas, core FW heating was found to be comparable to that of ECH, consistent with the excellent first-pass absorption of FWs predicted by ray-tracing models at high electron beta. FW heating at the ∼2 MW level to ELMy H-mode discharges in the ITER Baseline Scenario (IBS) showed unexpectedly strong absorption of FW power by injected neutral beam (NB) ions, indicated by significant enhancement of the D-D neutron rate, while the intended absorption on core electrons appeared rather weak. The AI and IBS discharges are compared in an effort to identify the causes of the different response to FW