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1.
  • Aad, G., et al. (författare)
  • Commissioning of the ATLAS Muon Spectrometer with cosmic rays
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
  • Tidskriftsartikel (refereegranskat)abstract
    • The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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3.
  • Aad, G, et al. (författare)
  • Determination of spin and parity of the Higgs boson in the [Formula: see text] decay channel with the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of the spin and parity quantum numbers of the Higgs boson in the [Formula: see text] final state are presented, based on proton-proton collision data collected by the ATLAS detector at the Large Hadron Collider, corresponding to an integrated luminosity of 20.3 fb[Formula: see text] at a centre-of-mass energy of [Formula: see text] TeV. The Standard Model spin-parity [Formula: see text] hypothesis is compared with alternative hypotheses for both spin and CP. The case where the observed resonance is a mixture of the Standard-Model-like Higgs boson and CP-even ([Formula: see text]) or CP-odd ([Formula: see text]) Higgs boson in scenarios beyond the Standard Model is also studied. The data are found to be consistent with the Standard Model prediction and limits are placed on alternative spin and CP hypotheses, including CP mixing in different scenarios.
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6.
  • Aad, G, et al. (författare)
  • Measurements of fiducial cross-sections for [Formula: see text] production with one or two additional b-jets in pp collisions at [Formula: see text]=8 TeV using the ATLAS detector.
  • 2016
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
  • Tidskriftsartikel (refereegranskat)abstract
    • Fiducial cross-sections for [Formula: see text] production with one or two additional b-jets are reported, using an integrated luminosity of 20.3 fb[Formula: see text] of proton-proton collisions at a centre-of-mass energy of 8 TeV at the Large Hadron Collider, collected with the ATLAS detector. The cross-section times branching ratio for [Formula: see text] events with at least one additional b-jet is measured to be 950 [Formula: see text] 70 (stat.) [Formula: see text] (syst.) fb in the lepton-plus-jets channel and 50 [Formula: see text] 10 (stat.) [Formula: see text] (syst.) fb in the [Formula: see text] channel. The cross-section times branching ratio for events with at least two additional b-jets is measured to be 19.3 [Formula: see text] 3.5 (stat.) [Formula: see text] 5.7 (syst.) fb in the dilepton channel ([Formula: see text], [Formula: see text], and ee) using a method based on tight selection criteria, and 13.5 [Formula: see text] 3.3 (stat.) [Formula: see text] 3.6 (syst.) fb using a looser selection that allows the background normalisation to be extracted from data. The latter method also measures a value of 1.30 [Formula: see text] 0.33 (stat.) [Formula: see text] 0.28 (syst.)% for the ratio of [Formula: see text] production with two additional b-jets to [Formula: see text] production with any two additional jets. All measurements are in good agreement with recent theory predictions.
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7.
  • Aad, G, et al. (författare)
  • Measurements of the Higgs boson production and decay rates and coupling strengths using pp collision data at [Formula: see text] and 8 TeV in the ATLAS experiment.
  • 2016
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
  • Tidskriftsartikel (refereegranskat)abstract
    • Combined analyses of the Higgs boson production and decay rates as well as its coupling strengths to vector bosons and fermions are presented. The combinations include the results of the analyses of the [Formula: see text] and [Formula: see text] decay modes, and the constraints on the associated production with a pair of top quarks and on the off-shell coupling strengths of the Higgs boson. The results are based on the LHC proton-proton collision datasets, with integrated luminosities of up to 4.7 [Formula: see text] at [Formula: see text] TeV and 20.3 [Formula: see text] at [Formula: see text] TeV, recorded by the ATLAS detector in 2011 and 2012. Combining all production modes and decay channels, the measured signal yield, normalised to the Standard Model expectation, is [Formula: see text]. The observed Higgs boson production and decay rates are interpreted in a leading-order coupling framework, exploring a wide range of benchmark coupling models both with and without assumptions on the Higgs boson width and on the Standard Model particle content in loop processes. The data are found to be compatible with the Standard Model expectations for a Higgs boson at a mass of 125.36 GeV for all models considered.
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8.
  • Aad, G, et al. (författare)
  • Observation and measurements of the production of prompt and non-prompt [Formula: see text] mesons in association with a [Formula: see text] boson in [Formula: see text] collisions at [Formula: see text] with the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The production of a [Formula: see text] boson in association with a [Formula: see text] meson in proton-proton collisions probes the production mechanisms of quarkonium and heavy flavour in association with vector bosons, and allows studies of multiple parton scattering. Using [Formula: see text] of data collected with the ATLAS experiment at the LHC in [Formula: see text] collisions at [Formula: see text], the first measurement of associated [Formula: see text] production is presented for both prompt and non-prompt [Formula: see text] production, with both signatures having a significance in excess of [Formula: see text]. The inclusive production cross-sections for [Formula: see text] boson production (analysed in [Formula: see text] or [Formula: see text] decay modes) in association with prompt and non-prompt [Formula: see text] are measured relative to the inclusive production rate of [Formula: see text] bosons in the same fiducial volume to be [Formula: see text] and [Formula: see text] respectively. Normalised differential production cross-section ratios are also determined as a function of the [Formula: see text] transverse momentum. The fraction of signal events arising from single and double parton scattering is estimated, and a lower limit of [Formula: see text] at [Formula: see text] confidence level is placed on the effective cross-section regulating double parton interactions.
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9.
  • Aad, G, et al. (författare)
  • Search for a new resonance decaying to a W or Z boson and a Higgs boson in the [Formula: see text] final states with the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:6
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for a new resonance decaying to a W or Z boson and a Higgs boson in the [Formula: see text] final states is performed using 20.3 fb[Formula: see text] of pp collision data recorded at [Formula: see text] 8 TeV with the ATLAS detector at the Large Hadron Collider. The search is conducted by examining the WH / ZH invariant mass distribution for a localized excess. No significant deviation from the Standard Model background prediction is observed. The results are interpreted in terms of constraints on the Minimal Walking Technicolor model and on a simplified approach based on a phenomenological Lagrangian of Heavy Vector Triplets.
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11.
  • Aad, G, et al. (författare)
  • Search for direct pair production of a chargino and a neutralino decaying to the 125 GeV Higgs boson in [Formula: see text] TeV [Formula: see text] collisions with the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A search is presented for the direct pair production of a chargino and a neutralino [Formula: see text], where the chargino decays to the lightest neutralino and the [Formula: see text] boson, [Formula: see text], while the neutralino decays to the lightest neutralino and the 125 GeV Higgs boson, [Formula: see text]. The final states considered for the search have large missing transverse momentum, an isolated electron or muon, and one of the following: either two jets identified as originating from bottom quarks, or two photons, or a second electron or muon with the same electric charge. The analysis is based on 20.3 [Formula: see text] of [Formula: see text] proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with the Standard Model expectations, and limits are set in the context of a simplified supersymmetric model.
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13.
  • Aad, G, et al. (författare)
  • Search for heavy long-lived multi-charged particles in pp collisions at [Formula: see text] TeV using the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:8
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for heavy long-lived multi-charged particles is performed using the ATLAS detector at the LHC. Data collected in 2012 at [Formula: see text] TeV from pp collisions corresponding to an integrated luminosity of 20.3 fb[Formula: see text]are examined. Particles producing anomalously high ionisation, consistent with long-lived massive particles with electric charges from [Formula: see text] to [Formula: see text] are searched for. No signal candidate events are observed, and 95 % confidence level cross-section upper limits are interpreted as lower mass limits for a Drell-Yan production model. The mass limits range between 660 and 785 GeV.
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14.
  • Aad, G, et al. (författare)
  • Search for Higgs boson pair production in the [Formula: see text] final state from pp collisions at [Formula: see text] TeVwith the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:9
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for Higgs boson pair production [Formula: see text] is performed with 19.5 fb[Formula: see text] of proton-proton collision data at [Formula: see text] TeV, which were recorded by the ATLAS detector at the Large Hadron Collider in 2012. The decay products of each Higgs boson are reconstructed as a high-momentum [Formula: see text] system with either a pair of small-radius jets or a single large-radius jet, the latter exploiting jet substructure techniques and associated b-tagged track-jets. No evidence for resonant or non-resonant Higgs boson pair production is observed. The data are interpreted in the context of the Randall-Sundrum model with a warped extra dimension as well as the two-Higgs-doublet model. An upper limit on the cross-section for [Formula: see text] of 3.2 (2.3) fb is set for a Kaluza-Klein graviton [Formula: see text] mass of 1.0 (1.5) TeV, at the 95 % confidence level. The search for non-resonant Standard Model hh production sets an observed 95 % confidence level upper limit on the production cross-section [Formula: see text] of 202 fb, compared to a Standard Model prediction of [Formula: see text] fb.
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15.
  • Aad, G, et al. (författare)
  • Search for Higgs Boson Pair Production in the γγbb[over ¯] Final State Using pp Collision Data at sqrt[s]=8 TeV from the ATLAS Detector.
  • 2015
  • Ingår i: Physical Review Letters. - 1079-7114. ; 114:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Searches are performed for resonant and nonresonant Higgs boson pair production in the γγbb[over ¯] final state using 20 fb^{-1} of proton-proton collisions at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the CERN Large Hadron Collider. A 95% confidence level upper limit on the cross section times branching ratio of nonresonant production is set at 2.2 pb, while the expected limit is 1.0 pb. The difference derives from a modest excess of events, corresponding to 2.4 standard deviations from the background-only hypothesis. The limit observed in the search for a narrow X→hh resonance ranges between 0.7 and 3.5 pb as a function of the resonance mass.
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17.
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18.
  • Aad, G, et al. (författare)
  • Search for production of [Formula: see text] resonances decaying to a lepton, neutrino and jets in [Formula: see text] collisions at [Formula: see text] TeV with the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A search is presented for narrow diboson resonances decaying to [Formula: see text] or [Formula: see text] in the final state where one [Formula: see text] boson decays leptonically (to an electron or a muon plus a neutrino) and the other [Formula: see text] boson decays hadronically. The analysis is performed using an integrated luminosity of 20.3 fb[Formula: see text] of [Formula: see text] collisions at [Formula: see text] TeV collected by the ATLAS detector at the large hadron collider. No evidence for resonant diboson production is observed, and resonance masses below 700 and 1490 GeV are excluded at 95 % confidence level for the spin-2 Randall-Sundrum bulk graviton [Formula: see text] with coupling constant of 1.0 and the extended gauge model [Formula: see text] boson respectively.
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19.
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20.
  • Aad, G, et al. (författare)
  • Searches for scalar leptoquarks in pp collisions at [Formula: see text] = 8 TeV with the ATLAS detector.
  • 2016
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
  • Tidskriftsartikel (refereegranskat)abstract
    • Searches for pair-produced scalar leptoquarks are performed using 20 fb[Formula: see text] of proton-proton collision data provided by the LHC and recorded by the ATLAS detector at [Formula: see text] TeV. Events with two electrons (muons) and two or more jets in the final state are used to search for first (second)-generation leptoquarks. The results from two previously published ATLAS analyses are interpreted in terms of third-generation leptoquarks decaying to [Formula: see text] and [Formula: see text] final states. No statistically significant excess above the Standard Model expectation is observed in any channel and scalar leptoquarks are excluded at 95 % CL with masses up to [Formula: see text] 1050 GeV for first-generation leptoquarks, [Formula: see text] 1000 GeV for second-generation leptoquarks, [Formula: see text] 625 GeV for third-generation leptoquarks in the [Formula: see text] channel, and 200 [Formula: see text] 640 GeV in the [Formula: see text] channel.
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21.
  • Aad, G., et al. (författare)
  • Studies of the performance of the ATLAS detector using cosmic-ray muons
  • 2011
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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22.
  • Aad, G, et al. (författare)
  • Study of the [Formula: see text] and [Formula: see text] decays with the ATLAS detector.
  • 2016
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
  • Tidskriftsartikel (refereegranskat)abstract
    • The decays [Formula: see text] and [Formula: see text] are studied with the ATLAS detector at the LHC using a dataset corresponding to integrated luminosities of 4.9 and 20.6 fb[Formula: see text] of pp collisions collected at centre-of-mass energies [Formula: see text] TeV and 8 TeV, respectively. Signal candidates are identified through [Formula: see text] and [Formula: see text] decays. With a two-dimensional likelihood fit involving the [Formula: see text] reconstructed invariant mass and an angle between the [Formula: see text] and [Formula: see text] candidate momenta in the muon pair rest frame, the yields of [Formula: see text] and [Formula: see text], and the transverse polarisation fraction in [Formula: see text] decay are measured. The transverse polarisation fraction is determined to be [Formula: see text], and the derived ratio of the branching fractions of the two modes is [Formula: see text], where the first error is statistical and the second is systematic. Finally, a sample of [Formula: see text] decays is used to derive the ratios of branching fractions [Formula: see text] and [Formula: see text], where the third error corresponds to the uncertainty of the branching fraction of [Formula: see text] decay. The available theoretical predictions are generally consistent with the measurement.
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23.
  • Aad, G., et al. (författare)
  • The ATLAS Inner Detector commissioning and calibration
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
  • Tidskriftsartikel (refereegranskat)abstract
    • The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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24.
  • Aad, G., et al. (författare)
  • The ATLAS Simulation Infrastructure
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
  • Tidskriftsartikel (refereegranskat)abstract
    • The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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27.
  • Bagge, August, et al. (författare)
  • High-dose omega-3 fatty acids have no effect on platelet aggregation or coagulation measured with static and flow-based aggregation instruments and Sonoclot; an observational study in healthy volunteers
  • 2018
  • Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 78:7-8, s. 539-545
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of omega-3 fatty acids on platelet aggregation and coagulation is highly unclear. Studies both support and refute the impacts of omega-3 fatty acids on prolonged bleeding time and platelet inhibition as well as its purported positive effects on cardiovascular disease. In a previous pilot study we suggested an inhibition of platelet aggregation measured with multiple electrode aggregometry. Following on that, the aim of the present study was to investigate the effects of supplementary high doses of omega-3 fatty acids on platelet aggregation and coagulation in a sample-size calculated number of healthy volunteers using Sonoclot, multiple electrode aggregometry, and flow-based Cellix instruments after 10 days of omega-3 fatty acid intake. Twelve healthy human volunteers ingested 2520 mg of supplementary omega-3 fatty acids per day for 10 days. Venous blood was sampled and platelet aggregation and coagulation were measured before and after the treatment period. The viscoelastic test instrument Sonoclot, multiple electrode aggregometry, and flow-based Cellix instruments with collagen-coated channels were used to evaluate platelet aggregation and coagulation. There were no differences in any of the measured variables after the treatment period as compared to before. In this well-powered study on healthy volunteers, no effects of high doses of omega-3 fatty acids after 10 days of intake could be demonstrated, either on coagulation or platelet function. Further studies are needed to clarify whether omega-3 fatty acids have a role in the regulation of the putative complex processes in vivo.
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28.
  • Bagger, Harald, et al. (författare)
  • Synergistic platelet inhibition between Omega-3 and acetylsalicylic acid dose titration; an observational study
  • 2020
  • Ingår i: BMC Complementary Medicine and Therapies. - : Springer Science and Business Media LLC. - 2662-7671. ; 20, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Omega-3 and acetylsalicylic acid (ASA) are two widely used “over-the-counter” drugs. Previous researchhas shown multiple electrode aggregometry (MEA) can detect ASA and varying Omega-3 platelet inhibiting effects.Synergistic platelet inhibiting effects of ASA and Omega-3 have been found using other methods than MEA. The aimof this study was to investigate the antiplatelet effects of Omega-3, and ASA synergism with MEA.Methods: Ten healthy male volunteers ingested Omega-3 (1260mg/day) for 5 days. MEA was used to analyse plateletfunction before and after Omega-3 intake. Aggregation was initiated using three different agonists and measured asarea under the curve (AUC): adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) andarachidonic acid (ASPI). Two concentrations of ASA were dose titrated ex vivo to 2 out of 3 ASPI test cells in order tomeasure synergism between Omega-3 and ASA.Results: Following 5 days Omega-3 intake, ADP, TRAP and ASPI AUC did not change significantly. In vitro ASA beforeOmega-3 intake, reduced ASPI AUC < 30 U, indicating a strong platelet inhibiting effect. Below this AUC level, the 5 daysOmega-3 intake increased ASPI-AUC with the ex vivo added low dose ASA (P = 0.02) and high dose ASA (P = 0.04).Conclusions: No synergism between ASA and Omega-3 was found using the MEA ASPI test. The surprising increase inASPI-AUC following Omega-3 intake and ex vivo ASA suggest that there are methodological issuses with the MEA ASPI test.
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29.
  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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30.
  • Chen, H.Y., et al. (författare)
  • Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
  • 2023
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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32.
  • Dahlberg, Sofia, et al. (författare)
  • Intravenous Vitamin K1 for the Correction of Prolonged Prothrombin Times in Non-Bleeding Critically Ill Patients: A Prospective Observational Study
  • 2021
  • Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:8, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate the effects of vitamin K1 on various vitamin K-dependent proteins in critically ill patients with prolonged Owren PT. We included critically ill non-bleeding adult patients without liver failure or anticoagulation treatment, with Owren PT > 1.2, who were prescribed intravenous vitamin K1. Blood was drawn at baseline and at 20–28 h after vitamin K1 administration. At both time points, we measured various vitamin K-dependent proteins and coagulation assays. ClinicalTrials.gov; Identifier: NTC3782025. In total, 52 patients were included. Intravenous vitamin K1 reduced Owren PT, Quick PT, protein induced by vitamin K absence/antagonist-II and desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), but not to normal levels. Concomitantly, there were increases in thrombin generation and the activity of coagulation factors II, VII, IX and X that was only counteracted with a small increase in Protein C activity. In conclusion, the results suggest that vitamin K1 strengthens coagulation as measured by PT decrease and increases in the activity of vitamin K-dependent clotting factors and thrombin generation. The decreased dp-ucMGP, and its potential positive short- and long-term non-coagulative effects, merits further research.
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33.
  • Dahlberg, Sofia, et al. (författare)
  • Vitamin K2 (Menaquinone-7) Supplementation and its Effect on Glucose Tolerance Test in Healthy Volunteers
  • 2019
  • Ingår i: Journal of Diabetes Management and Metabolism. - 2652-4430. ; 2:JDMM-10002, s. 1-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 2 diabetes can often be managed by healthier diet and exercise in early stages of the disease, but as it progresses oral medication is needed and later on the patients will require insulin to survive. Vitamin K is a fat soluble vitamin that is a cofactor in gamma-carboxylation and activation of coagulation proteins produced in the liver. There are also extrahepatic proteins named Gla proteins that require vitamin K to be activated. Previous studies suggest that some of these proteins have a connection to calcification of vessels, bone mineralization, metabolic syndrome and diabetes, but results are conflicting.
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34.
  • KANDER, THOMAS, et al. (författare)
  • Effect of hypothermia on haemostasis and bleeding risk : a narrative review
  • 2019
  • Ingår i: Journal of International Medical Research. - : SAGE Publications. - 0300-0605 .- 1473-2300. ; 47:8, s. 3559-3568
  • Forskningsöversikt (refereegranskat)abstract
    • It must be remembered that clinically important haemostasis occurs in vivo and not in a tube, and that variables such as the number of bleeding events and bleeding volume are more robust measures of bleeding risk than the results of analyses. In this narrative review, we highlight trauma, surgery, and mild induced hypothermia as three clinically important situations in which the effects of hypothermia on haemostasis are important. In observational studies of trauma, hypothermia (body temperature <35°C) has demonstrated an association with mortality and morbidity, perhaps owing to its effect on haemostatic functions. Randomised trials have shown that hypothermia causes increased bleeding during surgery. Although causality between hypothermia and bleeding risk has not been well established, there is a clear association between hypothermia and negative outcomes in connection with trauma, surgery, and accidental hypothermia; thus, it is crucial to rewarm patients in these clinical situations without delay. Mild induced hypothermia to ≥33°C for 24 hours does not seem to be associated with either decreased total haemostasis or increased bleeding risk.
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35.
  • Kornhall, Ludvig, et al. (författare)
  • ROTEM and vitro reversal of warfarin with APCC
  • 2019
  • Ingår i: Journal of Cardiovascular Medicine and Cardiology. - : Peertechz Publications Private Limited. - 2455-2976. ; 6:1, s. 6-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Warfarin-treated patients with a prolonged Prothrombin Time (PT) can have a normal rotational thromboelastometry (ROTEM) clotting time (CT). A previous in vitro study found that activated prothrombin complex concentrates (APCC) could reverse an albumin-induced coagulopathy monitored with ROTEM, but that prothrombin complex concentrates (PCC) could not. The aim of this study was to investigate the ability of ROTEM to monitor the in vitro reversal of warfarin-induced coagulopathy using APCC and to define an APCC dose response. Method: During the routine control of PT in 27 patients treated with warfarin, one extra 4.5 ml test tube of citrated whole blood was retrieved. Two concentrations of tissue factor ROTEM tissue factor (TF) activating reagents were used: a standard ROTEM ExTEM and a diluted 1:19000 concentration. The effects of two separate doses of APCC added in vitro corresponding to in vivo doses of 50 IE or 100 IE/kg were then studied on the ROTEM. Results: The ROTEM EXTEM CT was prolonged beyond the upper normal range of 68 s in patients with PT >3.0, with a correlation coefficient of 0.88 to PT. ROTEM with the ExTEM reagent alongside high and low doses of APCC resulted in a significant shortening of median CT, both compared to baseline (100 s) and after low (65 s) and high doses (57 s). This was most evident in patients with PT >2.0. ROTEM signals of clot propagation to clot formation time (CFT) and α angle had the reverse pattern. There was no effect on maximal clot strength with APCC. With the diluted TF no CT shortening was found with APCC. Conclusion: A clear dose response of APCC added in vitro to correct the effects of warfarin on ROTEM EXTEM CT was verified. ROTEM CT should be tested with non-activated PCC for in vivo reversal of warfarin in patients along with verification of a normalised PT. Further studies are needed to verify if a ROTEM CT in the lower normal range of <57-65 s, as found in our in vitro APCC-spiked warfarin blood, is safe for invasive procedures.
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36.
  • Obrocki, Pawel, et al. (författare)
  • Perspectives in fluid biomarkers in neurodegeneration from the 2019 biomarkers in neurodegenerative diseases course - A joint PhD student course at University College London and University of Gothenburg
  • 2020
  • Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
  • Forskningsöversikt (refereegranskat)abstract
    • Until relatively recently, a diagnosis of probable Alzheimer's disease (AD) and other neurodegenerative disorders was principally based on clinical presentation, with post-mortem examination remaining a gold standard for disease confirmation. This is in sharp contrast to other areas of medicine, where fluid biomarkers, such as troponin levels in myocardial infarction, form an integral part of the diagnostic and treatment criteria. There is a pressing need for such quantifiable and easily accessible tools in neurodegenerative diseases. In this paper, based on lectures given at the 2019 Biomarkers in Neurodegenerative Diseases Course, we provide an overview of a range of cerebrospinal fluid (CSF) and blood biomarkers in neurodegenerative disorders, including the 'core' AD biomarkers amyloid β (Aβ) and tau, as well as other disease-specific and general markers of neuroaxonal injury. We then highlight the main challenges in the field, and how those could be overcome with the aid of new methodological advances, such as assay automation, mass spectrometry and ultrasensitive immunoassays. As we hopefully move towards an era of disease-modifying treatments, reliable biomarkers will be essential to increase diagnostic accuracy, allow for earlier diagnosis, better participant selection and disease activity and treatment effect monitoring.
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37.
  • Pannee, Josef, 1979, et al. (författare)
  • The global Alzheimer's Association round robin study on plasma amyloid beta methods
  • 2021
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Blood-based assays to measure brain amyloid beta (A beta) deposition are an attractive alternative to the cerebrospinal fluid (CSF)-based assays currently used in clinical settings. In this study, we examined different blood-based assays to measure A beta and how they compare among centers and assays. Methods Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass-spectrometric methods were used to measure plasma A beta concentrations. Results Correlations were weak for A beta 42 while A beta 40 correlations were stronger. The ratio A beta 42/A beta 40 did not improve the correlations and showed weak correlations. Discussion The poor correlations for A beta 42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre-analytical sample handling and specificity, and cross-reactivity of different antibodies. Different methods might also measure different pools of plasma A beta 42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study.
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38.
  •  
39.
  • Paterson, R W, et al. (författare)
  • A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology.
  • 2016
  • Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility.
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40.
  • Paterson, Ross W, et al. (författare)
  • Dissecting IWG-2 typical and atypical Alzheimer's disease: insights from cerebrospinal fluid analysis.
  • 2015
  • Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 262, s. 2722-2730
  • Tidskriftsartikel (refereegranskat)abstract
    • Pathobiological factors underlying phenotypic diversity in Alzheimer's disease (AD) are incompletely understood. We used an extended cerebrospinal fluid (CSF) panel to explore differences between "typical" with "atypical" AD and between amnestic, posterior cortical atrophy, logopenic aphasia and frontal variants. We included 97 subjects fulfilling International Working Group-2 research criteria for AD of whom 61 had "typical" AD and 36 "atypical" syndromes, and 30 controls. CSF biomarkers included total tau (T-tau), phosphorylated tau (P-tau), amyloid β1-42, amyloid βX-38/40/42, YKL-40, neurofilament light (NFL), and amyloid precursor proteins α and β. The typical and atypical groups were matched for age, sex, severity and rate of cognitive decline and had similar biomarker profiles, with the exception of NFL which was higher in the atypical group (p=0.03). Sub-classifying the atypical group into its constituent clinical syndromes, posterior cortical atrophy was associated with the lowest T-tau [604.4 (436.8-675.8) pg/mL], P-tau (79.8±21.8pg/L), T-tau/Aβ1-42 ratio [2.3 (1.4-2.6)], AβX-40/X-42 ratio (22.1±5.8) and rate of cognitive decline [1.9 (0.75-4.25) MMSE points/year]. Conversely, the frontal variant group had the highest levels of T-tau [1185.4 (591.7-1329.3) pg/mL], P-tau (116.4±45.4pg/L), T-tau/Aβ1-42 ratio [5.2 (3.3-6.9)] and AβX-40/X-42 ratio (27.9±7.5), and rate of cognitive decline. Whilst on a group level IWG-2 "typical" and "atypical" AD share similar CSF profiles, which are very different from controls, atypical AD is a heterogeneous entity with evidence for subtle differences in amyloid processing and neurodegeneration between different clinical syndromes. These findings also have practical implications for the interpretation of clinical CSF biomarker results.
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41.
  •  
42.
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43.
  • Schott, Ulf, et al. (författare)
  • NOMI after cardiac arrest. Could refined diagnostics improve outcome?
  • 2020
  • Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572.
  • Tidskriftsartikel (refereegranskat)abstract
    • Intestinal ischaemia is usually classified into acute mesenteric ischaemia (AMI), chronic mesenteric ischaemia and colonic ischaemia. Coeliac, inferior and superior mesenteric arterial/venous emboli/thrombi and non-occlusive mesenteric ischaemia (NOMI) can cause AMI. NOMI pathophysiology involves hypoperfusion, aggravated by bacterial translocation, reperfusion injury, apoptosis and decreased proliferation of enterocytes. NOMI was first reported in 1958 by Ende in three heart failure patients. 1 NOMI is the most lethal form of AMI due to initial mild and nonspecific symptoms that delay diagnosis and treatment. 2 , 3 NOMI is a rare complication. Suspicion of NOMI is vital for early diagnosis, initially depending on the clinical signs of sudden abdominal pain, abdominal distention, peritonitis/muscular guarding, gastrointestinal bleeding and laboratory signs of intestinal ischaemia/multiple organ failure (MOF). Since patients are often ventilated and sedated and/or neurologically compromised after successful cardiopulmonary resuscitation, NOMI is underdiagnosed and potentially life-saving treatment is delayed, 4 which is also true for intensive care patients in general. 5
  •  
44.
  • Schott, Ulf, et al. (författare)
  • Prophylaxis Against Venous Thromboembolism (VTE) in Patients with Traumatic Brain Injury (TBI)
  • 2020. - 2
  • Ingår i: Management of Severe Traumatic Brain Injury. - 9783030393823 ; , s. 509-514
  • Bokkapitel (refereegranskat)abstract
    • Several recent national guidelines and reviews conclude that pharmacologic, in addition to mechanical thromboprophylaxis, appears to be safe among TBI patients with stabilized hemorrhagic patterns. Despite this, there are many issues concerning efficiency and safety in severe TBI, especially in patients with coagulopathies.
  •  
45.
  • Schott, Ulf, et al. (författare)
  • Time to peak effect of aspirin-induced platelet inhibition and ex vivo effects of desmopressin: An observational study
  • 2021
  • Ingår i: Journal of Integrative Cardiology. - 2058-3702. ; 7, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate time to maximal platelet inhibition after an oral loading dose of ASA. The effect of ex vivo reversal platelet inhibition by desmopressin (DDAVP) was also studied. Methods: Ten healthy volunteers were given a 300 mg ASA-tablet. Blood was sampled at 0, 15, 30, 60, 120 and 180 minutes. DDAVP was added to the samples taken at 120 minutes. Samples were analysed with a Multiplate® platelet aggregometer (MEA) using arachidonic acid (AA), collagen and thrombin aggregation agonists. Results: Platelet inhibition was observed in the sample activated by AA at 15 minutes but not until 120 minutes in the samples activated by collagen. No platelet inhibition was seen in the samples activated by thrombin. The median time to maximal AA-induced platelet inhibition of <30 U was 30 (interquartile range 15-90) minutes. Ex vivo DDAVP did not reverse platelet inhibition. Subgroup analysis did not show any gender differences. Conclusions: ASA induces a strong platelet inhibition within 30 minutes of oral ingestion, with no gender differences. Ex vivo DDAVP did not reverse ASA’s platelet inhibition.
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46.
  • Schott, Ulf, et al. (författare)
  • Vitamin K Effects on Gas6 and Soluble Axl Receptors in Intensive Care Patients : An Observational Screening Study
  • 2021
  • Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth arrest-specific gene 6 protein (Gas6) is avitamin K-dependent tissue bound protein. Gas6 has been shown to promote growth and therapy resistance among different types of cancer as well as thromboembolism. The aim of this prospective screening study: ClinicalTrials.gov; Identifier: NTC3782025, was to evaluate the effects of intravenously administered vitamin K1 on Gas6 and its soluble (s)Axl receptor plasma levels in intensive care patients. Vitamin K1 was intravenously injected in non-warfarin treated patients with prolonged Owren prothrombin time international normalized ratio (PT-INR) > 1.2 and blood samples were retrieved before and 20-28 h after injection. Citrate plasma samples from 52 intensive care patients were analysed for different vitamin K dependent proteins. There was a significant, but small increase in median Gas6. Only one patient had a large increase in sAxl, but overall, no significant changes in sAxl Gas6 did not correlate to PT-INR, thrombin generation assay, coagulation factors II, VII, IX and X, but to protein S and decarboxylated matrix Gla protein (dp-ucMGP). In conclusion, there was a small increase in Gas6 over 20-28 h. The pathophysiology and clinical importance of this remains to be investigated. To verify a true vitamin K effect, improvement of Gas6 carboxylation defects needs to be studied.
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47.
  • Svensson Mjöbo, Helena, et al. (författare)
  • Massiv blödning
  • 2021. - Fjärde Utgåva
  • Ingår i: Förebygg och hantera kriser inom anestesiologi. - 9789151995960 ; , s. 93-100
  • Bokkapitel (refereegranskat)
  •  
48.
  • Svensson Mjöbo, Helena, et al. (författare)
  • Massive haemorrhage
  • 2021. - 4
  • Ingår i: TAASK Prevent and Manage crisis in Anaesthesiology. - 9789151995953 ; , s. 93-100
  • Bokkapitel (refereegranskat)
  •  
49.
  • Thomas, Owain, et al. (författare)
  • A Narrative Review on Central Neuraxial Blocks and Direct Oral Anticoagulants
  • 2024
  • Ingår i: Journal of Anesthesia & Pain Medicine. ; 9:1, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective In numerous studies aspiring to clarify when to discontinue direct oral anticoagulants (DOAC) before central nerve blocks (CNB), information about the technique: spinal, epidural, indwelling catheter, multiple attempts, ‘bloody tap’: is incomplete. This creates difficulty making evidence-based recommendations regarding the safest time frame between the last dose of DOAC and CNB to avoid spinal haematoma. Current guidelines and recommendations are based mainly on pharmacokinetic predictions of the time taken to reach low residual plasma levels of DOAC. Empirical research is almost impossible since the risk of haemorrhagic complication is very low.Design A structured search of publications on DOAC and CNB was performed on Pubmed.Results Accurate plasma level measurements by mass spectrometry are usually not available. Indirect calibrated anti-Xa and IIa methods are unreliable at DOAC levels <30 ng/ml. DOAC plasma levels that are safe for CNB are presently unknown.Conclusion We recommend at least 5 half-lives (T1/2) after the last dose of DOAC before performing CNB, as there is wide interindividual variation in T1/2 and thereby residual plasma concentrations. The maximal residual DOAC plasma level should then be below 3% of therapeutic levels. Such long interruption times prior to surgery are problematic in patients at high risk of arterial and venous thromboembolism, it may be safer to withhold DOAC for 4 half-lives and conduct surgery without CNB. Bridging with low molecular weight heparin (LMWH) may increase the risk of spinal haematoma with CNB.
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50.
  • Thomas, Owain, et al. (författare)
  • Direct oral anticoagulants should often be suspended for longer before neuraxial blockade.
  • 2023
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 67:5, s. 682-683
  • Tidskriftsartikel (refereegranskat)abstract
    • Direct oral anticoagulants (DOACs) require perioperative vigilance to reduce the risk of spinal haematoma. There is a little of information concerning which plasma concentrations of DOACs are safe when administering central neuraxial blocks (CNBs) and there is a wide variability in the rate of elimination, both between individuals and DOACs.
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