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- Delcoigne, B, et al.
(författare)
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EXPOSURE TO SPECIFIC TUMOR NECROSIS FACTOR INHIBITORS AND RISK OF DEMYELINATING AND INFLAMMATORY NEUROPATHY IN PATIENTS WITH INFLAMMATORY ARTHRITIS. A COLLABORATIVE OBSERVATIONAL STUDY ACROSS FIVE NORDIC RHEUMATOLOGY REGISTERS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 41-41
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Though rare, studies have reported increased risk of neurological events including demyelinating disease of CNS (DML), multiple sclerosis (MS), and inflammatory neuropathy (INP) in patients with inflammatory joint disease treated with tumor necrosis factor inhibitors (TNFi).1,2 More in-depth investigations are required to elucidate the association between TNFi and neurological events in these patients, especially whether rates differ across type of TNFi mode of action.ObjectivesTo estimate the incidence of neurological events in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA, including axial spondyloarthritis and psoriatic arthritis) starting treatment with TNFi across five Nordic countries. To compare the incidence of neurological events in etanercept (ETN)-treated patients to patients treated with other TNFi (oTNFi).MethodsWe defined treatment cohorts of patients initiating TNFi between 2001 through 2018 from clinical rheumatology registers in Denmark (DK), Finland (FI), Iceland (IS), Norway (NO), and Sweden (SE). One patient could contribute to more than one treatment episode. Demographic data (sex, age), co-medication (methotrexate) and clinical variables (CRP, disease duration (<1 year, 1 to 5 years, >5 years) were extracted and used as covariates. We estimated crude incidence rates (IR) for neurological events and subtypes (ICD-10 codes: MS: G35, DML: G35, G36.0, G36.8-9, G37.1, G37.3, G37.5, G37.8-9, H46, H48.1, G04.8-9, INP: G61.0, G61.8-9), all countries pooled. We compared risk of neurological events between patients treated with ETN and oTNFi using Cox regression with time since treatment start, adjusted for the above covariates, robust standard errors, and stratified by country.ResultsWe included 52,682 treatment starts, in 33,885 RA patients (DK 8,259, FI 3,765, IS 723, NO 1353, SE 19,785; 75% women, mean age 56 years) and 46,549 treatment starts in 28,772 SpA patients (DK 7,000, FI 2,885, IS 962, NO 2,684, SE 15,241; 47% women, mean age 45 years).Numbers of DML, MS, INP and all neurological events, person-years (pyrs), and IRs in RA and SpA patients, for the two treatment groups are displayed in Figure 1. IRs for these neurological events showed some variation by diagnosis (RA vs. SpA), with rates of DML (and MS) in SpA patients around two (and three, respectively) times higher than the corresponding rates in RA (p<0.01), but similar rates for INP in RA and SpA patients. Comparing oTNFi to ETN, all Cox regression hazard ratios (HR) were statistically non-significant and close to one, whatever the outcome and the group of patients (Figure 1), with the adjusted HR (95%CI) for developing any neurological event in oTNFi compared to ETN being 1.08 (0.91-1.28) in RA patients and 0.96 (0.78-1.19) in SpA patients.Figure 1.Number of events, pyrs and IRs of DML, MS, INP and all neurological events (NE) in RA and SpA patients, treated with ETN or oTNFi. HRs (95%CI) comparing oTNFi to ETN.ConclusionThe incidences of DML and MS were lower in RA compared to SpA patients, while rates of INP were similar in both patients’ groups. There was no evidence of differences in these rates between ETN and oTNFi. The findings are of importance from a safety perspective for patients starting TNFi.References[1]Kopp T ARD 2020;79(5):566[2]Kunchok A JAMA Neurol 2020;77(8):937AcknowledgementsNordForsk and Foreum partially funded this research project.Disclosure of InterestsBénédicte Delcoigne: None declared, Tine Iskov Kopp Paid instructor for: T. I. Kopp has served on scientific advisory board from Novartis, Consultant of: T. I. Kopp has received support to congress participation from Biogen, Grant/research support from: T. I. Kopp has received support to congress participation from Biogen, Elizabeth Arkema: None declared, Karin Hellgren: None declared, Sella Aarrestad Provan: None declared, Heikki Relas Paid instructor for: Abbvie, Pfizer, Kalle Aaltonen: None declared, Nina Trokovic: None declared, Björn Gudbjornsson Speakers bureau: Novartis _ not related to this work, Consultant of: Novartis _ not related to this work, Gerdur Gröndal: None declared, Eirik kristianslund: None declared, Lene Dreyer Speakers bureau: Speakers bureau: Eli Lilly, Galderma and Janssen, Grant/research support from: Grant from BMS outside the present work, Johan Askling Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB.
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- Ericsson, J., et al.
(författare)
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The lamprey provides a vertebrate blueprint of the mammalian basal ganglia
- 2010
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Konferensbidrag (refereegranskat)abstract
- The basal ganglia are a group of subcortical nuclei that play a prominent role in motor function in mammals as well as in lamprey. The aim of the present study was to characterize the different components of the lamprey basal ganglia, and determine to what extent they correspond to those found in the mammalian basal ganglia. Anatomical tract tracing, immunohistochemistry and acute brain slice patch clamp recordings were employed to address this question.Two pallidal regions were identified in the lamprey; one region, considered homologous to the mammalian globus pallidus, was located ventral to the ementia thalami on the telencephalic/diencephalic border. It receives striatal input from inwardly rectifying neurons (IRNs) and contains GABAergic projection neurons, of which those projecting to the tectum were shown to be tonically active. It also contains neurons immunoreactive for parvalbumin. Separate subpopulations of pallidal neurons project to the optic tectum, the diencephalic and mesencephalic locomotor regions (MLR).Another region, in the midbrain, considered homologous to the substantia nigra pars reticulata receives input from a different subset of IRNs and sends GABAergic projections to the tectum and the diencephalic locomotor region. This midbrain region also contains parvalbumin immunoreactive neurons. The main population of striatal neurons, IRNs, displays the anatomical and electrophysiological hallmarks of mammalian medium spiny neurons, including inward rectification and ramping responses to first spike. It also contains neurons with properties similar to fast-spiking neurons. The striatum receives pallial and thalamic input as well as ascending dopaminergic, serotonergic and histaminergic inputs, similar to that in mammals.Our results suggest that the basic features of the basal ganglia with regard to both structure and function are conserved throughout the vertebrate phylogeny, including striatal/pallidal subdivisions.
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- Ghandriz, Toheed, 1982, et al.
(författare)
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Optimization Based Design of Heterogeneous Truck Fleet and Electric Propulsion
- 2016
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Ingår i: Proceedings, ITSC. IEEE 19th International Conference on Intelligent Transportation Systems (ITSC), November 1-4, 2016, Rio de Janeiro, Brazil. - 9781509018895 ; , s. Art no 7795575, Pages 328-335
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Konferensbidrag (refereegranskat)abstract
- Many researches have been focused on vehicle routing problem during past decades where subject vehicles are previously fully designed and ready to start operation. Further, extensive studies have been done on powertrain design irrespective of the routes where the vehicle is going to be employed. In the present paper, we try to define a new branch of problems where the vehicle design, in particular its propulsion system and loading capacity, is treated simultaneously with the routing problem. The focus is on optimization based design of heterogeneous electric truck fleet to perform a prescribed task with a lowest cost on an available set of routes. The approach is illustrated in a simple case study problem. It is shown that long heavy combination vehicles are energy-efficient but not cost-optimal on short routes.
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- Ghandriz, Toheed, 1982, et al.
(författare)
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Sensitivity Analysis of Optimal Energy Management in Plug-in Hybrid Heavy Vehicles
- 2017
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Ingår i: 2017 2nd IEEE International Conference on Intelligent Transportation Engineering (ICITE). - 9781509062737 ; , s. 320-327
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Konferensbidrag (refereegranskat)abstract
- Optimal energy management strategies of hybrid vehicles are computationally expensive when considering the entire trip ahead rather than a short upcoming horizon. Considering the entire representative trip is already needed in concept design stages of the vehicle. In order to come up with an appropriate design while minimizing the total ownership cost the energy management strategies must already be used together with early concept evaluations. To investigate the possibility of replacing the optimal energy management with simpler approaches, here, the sensitivity of optimal solution to some of vehicle parameters and traffic flow is studied. It is seen that a simpler approach, i.e. an instantaneous optimization, can be used, in case of smooth traffic flow, since the gain of optimal strategy in reduction of operational cost is less than 4% for different vehicle hardware setup and for selected representative driving cycle. Dynamic programming is used as a solution method for finding the optimal strategy.
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- Hellgren, Jonas, 1974, et al.
(författare)
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A Systematic Way of Choosing Driveline Confriguration and Sizing Components in Hybrid Vehicles
- 2000
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Ingår i: 2000 Future Transportation Technology Conference, August 21-23, 2000, in Costa Mesa, California, USA, 2000.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Energy saving in general and less polluting vehicles in specific, become more and more urgent topics. One reason is that, in a world where the demand for fast transportation is increasing, the risk of global warming is a fact. Hybrid Vehicles (HV:s) are proposed as a more environmentally friendly candidate than conventional vehicles. Nowadays, there are numerous different types of HV:s and the components can, in theory, be sized in infinite ways. There is no simple answer to how to choose driveline configuration and size components in a HV. This paper describes one method, Driveline Synthesis (DS), that systematically presents a suitable driveline, on the basis of demands and conditions. Examples of demands are driving cycle and emission free zones. Some conditions are fuel price, tax on pollution and discount rate. The most suitable driveline is defined as the most cost effective. Total cost is defined as the sum of: cost of components, fuel cost, cost of external energy and cost of pollution. Genetic algorithms are used as an optimization method.Two major types of drivelines are compared in a case study, a conventional bus with a diesel engine and automatic transmission versus a series hybrid bus with different types of primary power units (diesel engine or fuel cell) and storage devices (super capacitor or NiMH battery). DS gives reasonable answers but needs further validation and development. One conclusion from the work is that the most suitable driveline configuration depends very much on demands, conditions and present technology, i.e. HV:s are only preferable to conventional vehicles under special circumstances.
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