| 1. |
- Kalincik, Tomas, et al.
(författare)
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Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis
- 2023
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 80:7, s. 702-713
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Tidskriftsartikel (refereegranskat)abstract
- Importance Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).Objective To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.Design, Setting, and Participants This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics.Exposure AHSCT vs fingolimod, natalizumab, or ocrelizumab.Main outcomes Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement.Results Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%).Conclusion In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.
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| 2. |
- Chlouba, Tomas, et al.
(författare)
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Diamond-based dielectric laser acceleration
- 2022
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Ingår i: Optics Express. - 1094-4087. ; 30:1, s. 505-510
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Tidskriftsartikel (refereegranskat)abstract
- The field of dielectric laser accelerators (DLA) garnered a considerable interest in the past six years as it offers novel opportunities in accelerator science and potentially transformative applications. Currently, the most widespread approach considers silicon-based structures due to their low absorption and high refractive index in the infrared spectral region and the well-developed silicon processing technology. In this paper we investigate a diamond as an alternative to silicon, mainly due to its considerably higher damage threshold. In particular, we find that our diamond grating allows a three times higher acceleration gradient (60 MeV/m) compared to silicon gratings designed for a similar electron energy. Using more complex geometries, GeV/m acceleration gradients are within reach for subrelativistic electrons.
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| 3. |
- Minea, T., et al.
(författare)
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Modeling the high power impulse magnetron sputtering discharge
- 2019
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Ingår i: High Power Impulse Magnetron Sputtering. - : Elsevier. - 9780128124543 - 9780128124550 ; , s. 159-221
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Modeling has the possibility to capture the main interacting mechanisms in a plasma discharge, which are typically very difficult to identify (isolate) in experiments. A large variety of computer models describing the plasma behavior in HiPIMS discharges have been developed and used to gain insight into various physical and chemical mechanisms operating in these discharges. In this chapter we give an extended overview and, when possible, a comparison of the theoretical and numerical methods used to tackle the different challenges encountered in HiPIMS discharges, from the cathode through the ionization region, the diffusion region, and, finally, to the substrate and chamber walls. We also highlight some important modeling results, which have been selected to emphasize the added understanding brought by computational modeling, but also to validate certain model approaches, or highlight model-specific results.
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| 4. |
- Snowden, John A., et al.
(författare)
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Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases
- 2017
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Ingår i: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 1:27, s. 2742-2755
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [<1-62]) in 247 centers in 40 countries from 1994 to 2015. Predominant countries of activity were Italy, Germany, Sweden, the United Kingdom, The Netherlands, Spain, France, and Australia. National activity correlated with the Human Development Index (P = .006). For autologous HSCT, outcomes varied significantly between diseases. There was chronological improvement in progression-free survival (PFS, P < 10(-5)), relapse/ progression (P < 10(-5)), and nonrelapse mortality (P = .01). Health care expenditure was associated with improved outcomes in systemic sclerosis and multiple sclerosis (MS). On multivariate analysis selecting adults for MS, systemic sclerosis, and Crohn disease, better PFSwas associated with experience (>= 23 transplants for AD, P = .001), learning (time from first HSCT for AD >= 6 years, P = .01), and Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation accreditation status (P = .02). Despite improved survival over time (P = .02), allogeneic HSCT use remained low and largely restricted to pediatric practice. Autologous HSCT has evolved into a treatment modality to be considered alongside other modern therapies in severe AD. Center experience, accreditation, interspecialty networking, and national socioeconomic factors are relevant for health service delivery of HSCT in AD.
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