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- Kloprogge, F., et al.
(författare)
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Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis
- 2018
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Background The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. A search in PubMed, Embase, ClinicalTrials. gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing < 15 kg and 15-25 kg, respectively, and 20.2% lower in pregnant women compared with non-pregnant adults. Lumefantrine exposure decreased with increasing pre-treatment parasitaemia, and the dose limitation on absorption of lumefantrine was substantial. Simulations using the lumefantrine pharmacokinetic model suggest that, in young children and pregnant women beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (twice daily for 3 days). The model was developed using venous plasma data from patients receiving intact tablets with fat, and evaluations of alternative dosing regimens were consequently only representative for venous plasma after administration of intact tablets with fat. The absence of artemether-dihydroartemisinin data limited the prediction of parasite killing rates and recrudescent infections. Thus, the suggested optimised dosing schedule was based on the pharmacokinetic endpoint of lumefantrine plasma exposure at day 7. Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment.
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- Eriksson, Elin, et al.
(författare)
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Strong current sheet at a magnetosheath jet : Kinetic structure and electron acceleration
- 2016
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 121:10, s. 9608-9618
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Tidskriftsartikel (refereegranskat)abstract
- Localized kinetic-scale regions of strong current are believed to play an important role in plasma thermalization and particle acceleration in turbulent plasmas. We present a detailed study of a strong localized current, 4900 nA m(-2), located at a fast plasma jet observed in the magnetosheath downstream of a quasi-parallel shock. The thickness of the current region is similar to 3 ion inertial lengths and forms at a boundary separating magnetosheath-like and solar wind-like plasmas. On ion scales the current region has the shape of a sheet with a significant average normal magnetic field component but shows strong variations on smaller scales. The dynamic pressure within the magnetosheath jet is over 3 times the solar wind dynamic pressure. We suggest that the current sheet is forming due to high velocity shears associated with the jet. Inside the current sheet we observe local electron acceleration, producing electron beams, along the magnetic field. However, there is no clear sign of ongoing reconnection. At higher energies, above the beam energy, we observe a loss cone consistent with part of the hot magnetosheath-like electrons escaping into the colder solar wind-like plasma. This suggests that the acceleration process within the current sheet is similar to the one that occurs at shocks, where electron beams and loss cones are also observed. Therefore, electron beams observed in the magnetosheath do not have to originate from the bow shock but can also be generated locally inside the magnetosheath.
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- Hietala, M., et al.
(författare)
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Moisture stability and mechanical durability of peat biocomposites
- 2017
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Ingår i: ICCM21 Proceedings. - : ICCM, International Committee on Composite Materials.
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Konferensbidrag (refereegranskat)abstract
- Peat, the organic matter formed from incomplete degradation of vegetation in peatlands, was studied as lignocellulosic raw material in manufacture of biocomposites. Peat mosses with varying degree of decomposition, namely slightly decomposed peat (H2) and moderately decomposed peat (H6), were ground into different particle size fractions which were used to prepare peat-polypropylene (PP) composites with 50 wt% peat content using extrusion compounding. The moisture absorption and dimensional stability as well as the mechanical properties and microstructure before and after cyclic freeze-thaw conditioning of the peat-PP composites were analysed and compared to reference wood-plastic composite (WPC). The mechanical properties of peat-PP composites were better than the properties of reference WPC before the freeze-thaw conditioning, and the mechanical permanence of peat-PP composites was better after the cyclic conditioning. Especially when peat with higher decomposition degree was used (H6), the mechanical permanence of peat-PP composites was improved. Likewise, the moisture absorption and the dimensional stability properties were improved the more decomposed the used peat was. The particle size did not affect the composite properties as much as the decomposition degree of peat, though the dimensional stability of peat-PP composite with moderately decomposed peat was better with smaller particle size peat.
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- Kurko, TAT, et al.
(författare)
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Long-term use of benzodiazepines: Definitions, prevalence and usage patterns - a systematic review of register-based studies
- 2015
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Cambridge University Press (CUP). - 1778-3585. ; 30:8, s. 1037-1047
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNumerous treatment guidelines recommend that long-term use of benzodiazepines (BZD) should be avoided primarily due to development of tolerance and a risk for BZD dependence. Despite this, long-term BZD use remains a controversial subject in clinical patient care with “for and against” debates. However, there is no explicit understanding of what is meant by long-term BZD use in real world. The aim of this study was to assess different definitions, usage patterns, prevalence and other characteristics of long-term BZD use based on published register-based studies. Synthesis of these characteristics is essential to derive a meaningful definition of long-term BZD.MethodsSystematic review of register-based studies on long-term BZD use published in 1994–2014.ResultsFourty-one studies met our predetermined inclusion criteria. The length of BZD use defined as “long-term” varied in these studies ranging from one month to several years. The most common definition was six months or longer during a year. The prevalence of long-term BZD use in the general population was estimated to be about 3%. The relative proportion of long-term BZD users (all definitions) in adult BZD users ranged from 6% to 76% (mean 24%; 95% CL 13–36%). The estimates were higher in studies only on the elderly (47%; 95% CL 31–64%). Long-term use involved typically steady treatment with low BZD doses. However, in elderly patients long-term BZD use and exceeding recommended doses was relatively common. Several characteristics associated with long-term use were found.ConclusionsLong-term BZD use is common and a clinical reality. Uniform definitions for “long-term”, which is in line with population-based evidence, is needed to have more comparable results between studies. Our systematic review suggests that duration of BZD treatment over six months, the most common definition for long-term BZD use in the included studies. As also recommended previously, it is a useful starting point for further analyses on disadvantages but also potential advantages associated with long-term BZD use.
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