| 1. |
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| 2. |
- Kankare, E., et al.
(author)
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Search for transient optical counterparts to high-energy IceCube neutrinos with Pan-STARRS1
- 2019
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 626
-
Journal article (peer-reviewed)abstract
- In order to identify the sources of the observed diffuse high-energy neutrino flux, it is crucial to discover their electromagnetic counterparts. To increase the sensitivity of detecting counterparts of transient or variable sources by telescopes with a limited field of view, IceCube began releasing alerts for single high-energy (E-v > 60 TeV) neutrino detections with sky localisation regions of order 1 degrees radius in 2016. We used Pan-STARRS1 to follow-up five of these alerts during 2016-2017 to search for any optical transients that may be related to the neutrinos. Typically 10-20 faint m(ip1) less than or similar to 22.5 mag) extragalactic transients are found within the Pan-STARRS1 footprints and are generally consistent with being unrelated field supernovae (SNe) and AGN. We looked for unusual properties of the detected transients, such as temporal coincidence of explosion epoch with the IceCube timestamp, or other peculiar light curve and physical properties. We found only one transient that had properties worthy of a specific follow-up. In the Pan-STARRS1 imaging for IceCube-160427A (probability to be of astrophysical origin of similar to 50%), we found a SN PS16cgx, located at 10.0' from the nominal IceCube direction. Spectroscopic observations of PS16cgx showed that it was an H-poor SN at redshift z = 0.2895 +/- 0.0001. The spectra and light curve resemble some high-energy Type Ic SNe, raising the possibility of a jet driven SN with an explosion epoch temporally coincident with the neutrino detection. However, distinguishing Type Ia and Type Ic SNe at this redshift is notoriously difficult. Based on all available data we conclude that the transient is more likely to be a Type Ia with relatively weak Sin absorption and a fairly normal rest-frame r-band light curve. If, as predicted, there is no high-energy neutrino emission from Type Ia SNe, then PS16cgx must be a random coincidence, and unrelated to the IceCube-160427A. We find no other plausible optical transient for any of the five IceCube events observed down to a 5 sigma limiting magnitude of mip1 approximate to 22 mag, between 1 day and 25 days after detection.
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| 3. |
- Aartsen, M. G., et al.
(author)
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A Search for Neutrino Emission from Fast Radio Bursts with Six Years of IceCube Data
- 2018
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 857:2
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Journal article (peer-reviewed)abstract
- We present a search for coincidence between IceCube TeV neutrinos and fast radio bursts (FRBs). During the search period from 2010 May 31 to 2016 May 12, a total of 29 FRBs with 13 unique locations have been detected in the whole sky. An unbinned maximum likelihood method was used to search for spatial and temporal coincidence between neutrinos and FRBs in expanding time windows, in both the northern and southern hemispheres. No significant correlation was found in six years of IceCube data. Therefore, we set upper limits on neutrino fluence emitted by FRBs as a function of time window duration. We set the most stringent limit obtained to date on neutrino fluence from FRBs with an E-2 energy spectrum assumed, which is 0.0021 GeV cm(-2) per burst for emission timescales up to similar to 10(2) s from the northern hemisphere stacking search.
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| 4. |
- Aartsen, M. G., et al.
(author)
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Constraints on Minute-Scale Transient Astrophysical Neutrino Sources
- 2019
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In: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 122:5
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Journal article (peer-reviewed)abstract
- High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E-2.5 neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to < 5% of the detected astrophysical flux and the energy released in neutrinos (100 GeV to 10 PeV) by a median bright GRB-like source is < 10(52.5) erg. For a harder E-2.13 neutrino spectrum up to 30% of the flux could be produced by GRBs and the allowed median source energy is < 10(52) erg. A hypothetical population of transient sources has to be more common than 10(-5) Mpc(-3) yr(-1) (5 x 10(-8) Mpc(-3) yr(-1) for the E-2.13 spectrum) to account for the complete astrophysical neutrino flux.
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| 5. |
- Aartsen, M. G., et al.
(author)
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Detection of the Temporal Variation of the Sun's Cosmic Ray Shadow with the IceCube Detector
- 2019
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In: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 872:2
-
Journal article (peer-reviewed)abstract
- We report on the observation of a deficit in the cosmic ray flux from the directions of the Moon and Sun with five years of data taken by the IceCube Neutrino Observatory. Between 2010 May and 2011 May the IceCube detector operated with 79 strings deployed in the glacial ice at the South Pole, and with 86 strings between 2011 May and 2015 May. A binned analysis is used to measure the relative deficit and significance of the cosmic ray shadows. Both the cosmic ray Moon and Sun shadows are detected with high statistical significance (>10σ) for each year. The results for the Moon shadow are consistent with previous analyses and verify the stability of the IceCube detector over time. This work represents the first observation of the Sun shadow with the IceCube detector. We show that the cosmic ray shadow of the Sun varies with time. These results make it possible to study cosmic ray transport near the Sun with future data from IceCube.
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| 6. |
- Aartsen, M. G., et al.
(author)
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Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
- 2018
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In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 98:6
-
Journal article (peer-reviewed)abstract
- We report a quasidifferential upper limit on the extremely-high-energy (EHE) neutrino flux above 5 x 10(6) GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above 10(6) GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between 5 x 10(6) and 2 x 10(10) GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of E-nu(2)phi(nu e+nu mu+nu tau) similar or equal to 2 x 10(-8) GeV/cm(2) sec sr at 10(9) GeV. A significant part of the parameter space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is disfavored independently of uncertain models of the extragalactic background light which previous IceCube constraints partially relied on.
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| 7. |
- Aartsen, M. G., et al.
(author)
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Measurement of atmospheric tau neutrino appearance with IceCube DeepCore
- 2019
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In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 99:3
-
Journal article (peer-reviewed)abstract
- We present a measurement of atmospheric tau neutrino appearance from oscillations with three years of data from the DeepCore subarray of the IceCube Neutrino Observatory. This analysis uses atmospheric neutrinos from the full sky with reconstructed energies between 5.6 and 56 GeV to search for a statistical excess of cascadelike neutrino events which are the signature of nu(tau) interactions. For CC thorn NC (CC-only) interactions, we measure the tau neutrino normalization to be 0.73(-0.24)(+0.30) (0.57(-0.30)(+0.36)) and exclude the absence of tau neutrino oscillations at a significance of 3.2 sigma (2.0 sigma) These results are consistent with, and of similar precision to, a confirmatory IceCube analysis also presented, as well as measurements performed by other experiments.
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| 8. |
- Aartsen, M. G., et al.
(author)
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Measurements using the inelasticity distribution of multi-TeV neutrino interactions in IceCube
- 2019
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In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 99:3
-
Journal article (peer-reviewed)abstract
- Inelasticity, the fraction of a neutrino's energy transferred to hadrons, is a quantity of interest in the study of astrophysical and atmospheric neutrino interactions at multi-TeV energies with IceCube. In this work, a sample of contained neutrino interactions in IceCube is obtained from five years of data and classified as 2650 tracks and 965 cascades. Tracks arise predominantly from charged-current nu(mu) interactions, and we demonstrate that we can reconstruct their energy and inelasticity. The inelasticity distribution is found to be consistent with the calculation of Cooper-Sarkar et al. across the energy range from similar to 1 to similar to 100 TeV. Along with cascades from neutrinos of all flavors, we also perform a fit over the energy, zenith angle, and inelasticity distribution to characterize the flux of astrophysical and atmospheric neutrinos. The energy spectrum of diffuse astrophysical neutrinos is described well by a power law in both track and cascade samples, and a best-fit index gamma = 2.62 +/- 0.07 is found in the energy range from 3.5 TeV to 2.6 PeV. Limits are set on the astrophysical flavor composition and are compatible with a ratio of (1/3 : 1/3 : 1/3)(circle plus). Exploiting the distinct inelasticity distribution of nu(mu) and (nu) over bar (mu) interactions, the atmospheric nu(mu) to (nu) over bar (mu) flux ratio in the energy range from 770 GeV to 21 TeV is found to be 0.77(-0.25)(+0.44) times the calculation by Honda et al. Lastly, the inelasticity distribution is also sensitive to neutrino charged-current charm production. The data are consistent with a leading-order calculation, with zero charm production excluded at 91% confidence level. Future analyses of inelasticity distributions may probe new physics that affects neutrino interactions both in and beyond the Standard Model.
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| 9. |
- Aartsen, M. G., et al.
(author)
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Neutrino emission from the direction of the blazar TXS 0506+056 prior to the IceCube-170922A alert
- 2018
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 361:6398, s. 147-151
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Journal article (peer-reviewed)abstract
- A high-energy neutrino event detected by IceCube on 22 September 2017 was coincident in direction and time with a gamma-ray flare from the blazar TXS 0506+056. Prompted by this association, we investigated 9.5 years of IceCube neutrino observations to search for excess emission at the position of the blazar. We found an excess of high-energy neutrino events, with respect to atmospheric backgrounds, at that position between September 2014 and March 2015. Allowing for time-variable flux, this constitutes 3.5 sigma evidence for neutrino emission from the direction of TXS 0506+056, independent of and prior to the 2017 flaring episode. This suggests that blazars are identifiable sources of the high-energy astrophysical neutrino flux.
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| 10. |
- Aartsen, M. G., et al.
(author)
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Search for steady point-like sources in the astrophysical muon neutrino flux with 8 years of IceCube data
- 2019
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 79:3
-
Journal article (peer-reviewed)abstract
- The IceCube Collaboration has observed a high-energy astrophysical neutrino flux and recently found evidence for neutrino emission from the blazar TXS 0506+056. These results open a new window into the high-energy universe. However, the source or sources of most of the observed flux of astrophysical neutrinos remains uncertain. Here, a search for steady point-like neutrino sources is performed using an unbinned likelihood analysis. The method searches for a spatial accumulation of muon-neutrino events using the very high-statistics sample of about 497,000 neutrinos recorded by IceCube between 2009 and 2017. The median angular resolution is approximate to 1 degrees at 1 TeV and improves to approximate to 0.3 degrees for neutrinos with an energy of 1 PeV. Compared to previous analyses, this search is optimized for point-like neutrino emission with the same flux-characteristics as the observed astrophysical muon-neutrino flux and introduces an improved event-reconstruction and parametrization of the background. The result is an improvement in sensitivity to the muon-neutrino flux compared to the previous analysis of approximate to 35% assuming an E-2 spectrum. The sensitivity on the muon-neutrino flux is at a level of E2dN/dE=310-13s-1. No new evidence for neutrino sources is found in a full sky scan and in an a priori candidate source list that is motivated by gamma-ray observations. Furthermore, no significant excesses above background are found from populations of sub-threshold sources. The implications of the non-observation for potential source classes are discussed.
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| 11. |
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| 12. |
- Aartsen, M. G., et al.
(author)
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Cosmic ray spectrum and composition from PeV to EeV using 3 years of data from IceTop and IceCube
- 2019
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In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 100:8
-
Journal article (peer-reviewed)abstract
- We report on measurements of the all-particle cosmic ray energy spectrum and composition in the PeV to EeV energy range using 3 years of data from the IceCube Neutrino Observatory. The IceTop detector measures cosmic ray induced air showers on the surface of the ice, from which the energy spectrum of cosmic rays is determined by making additional assumptions about the mass composition. A separate measurement is performed when IceTop data are analyzed in coincidence with the high-energy muon energy loss information from the deep in-ice IceCube detector. In this measurement, both the spectrum and the mass composition of the primary cosmic rays are simultaneously reconstructed using a neural network trained on observables from both detectors. The performance and relative advantages of these two distinct analyses are discussed, including the systematic uncertainties and the dependence on the hadronic interaction models, and both all-particle spectra as well as individual spectra for elemental groups are presented.
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| 13. |
- Garrappa, S., et al.
(author)
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Investigation of Two Fermi-LAT Gamma-Ray Blazars Coincident with High-energy Neutrinos Detected by IceCube
- 2019
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 880:2
-
Journal article (peer-reviewed)abstract
- After the identification of the gamma-ray blazar TXS 0506+056 as the first compelling IceCube neutrino source candidate, we perform a systematic analysis of all high-energy neutrino events satisfying the IceCube realtime trigger criteria. We find one additional known gamma-ray source, the blazar GB6 J1040+0617, in spatial coincidence with a neutrino in this sample. The chance probability of this coincidence is 30% after trial correction. For the first time, we present a systematic study of the gamma-ray flux, spectral and optical variability, and multiwavelength behavior of GB6 J1040+0617 and compare it to TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the Fermi-Large Area Telescope gamma-ray band, being in an active state around the arrival of IceCube-170922A, but in a low state during the archival IceCube neutrino flare in 2014/15. In both cases the spectral shape is statistically compatible (<= 2 sigma) with the average spectrum showing no indication of a significant relative increase of a high-energy component. While the association of GB6 J1040+0617 with the neutrino is consistent with background expectations, the source appears to be a plausible neutrino source candidate based on its energetics and multiwavelength features, namely a bright optical flare and modestly increased gamma-ray activity. Finding one or two neutrinos originating from gamma-ray blazars in the given sample of high-energy neutrinos is consistent with previously derived limits of neutrino emission from gamma-ray blazars, indicating the sources of the majority of cosmic high-energy neutrinos remain unknown.
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| 14. |
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| 15. |
- Clark, DW, et al.
(author)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Journal article (peer-reviewed)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 16. |
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| 17. |
- Nicolas, Aude, et al.
(author)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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In: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Journal article (peer-reviewed)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 18. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 19. |
- Satizabal, Claudia L., et al.
(author)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Journal article (peer-reviewed)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 20. |
- van der Lee, S. J., et al.
(author)
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A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
- 2019
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 237-250
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Journal article (peer-reviewed)abstract
- The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
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| 21. |
- van Rheenen, Wouter, et al.
(author)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Journal article (peer-reviewed)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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| 22. |
- Kenna, Kevin P., et al.
(author)
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NEK1 variants confer susceptibility to amyotrophic lateral sclerosis
- 2016
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1037-1042
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Journal article (peer-reviewed)abstract
- To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.
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| 23. |
- Van Der Spek, Rick A., et al.
(author)
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Reconsidering the causality of TIA1 mutations in ALS
- 2018
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In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : TAYLOR & FRANCIS LTD. - 2167-8421 .- 2167-9223. ; 19:1-2, s. 1-3
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Journal article (other academic/artistic)
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| 24. |
- Smolen, JS, et al.
(author)
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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:6, s. 960-977
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Journal article (peer-reviewed)abstract
- Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
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| 25. |
- Radner, H, et al.
(author)
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2017 EULAR recommendations for a core data set to support observational research and clinical care in rheumatoid arthritis
- 2018
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 77:4, s. 476-479
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Journal article (peer-reviewed)abstract
- Personalised medicine, new discoveries and studies on rare exposures or outcomes require large samples that are increasingly difficult for any single investigator to obtain. Collaborative work is limited by heterogeneities, both what is being collected and how it is defined. To develop a core set for data collection in rheumatoid arthritis (RA) research which (1) allows harmonisation of data collection in future observational studies, (2) acts as a common data model against which existing databases can be mapped and (3) serves as a template for standardised data collection in routine clinical practice to support generation of research-quality data. A multistep, international multistakeholder consensus process was carried out involving voting via online surveys and two face-to-face meetings. A core set of 21 items (‘what to collect’) and their instruments (‘how to collect’) was agreed: age, gender, disease duration, diagnosis of RA, body mass index, smoking, swollen/tender joints, patient/evaluator global, pain, quality of life, function, composite scores, acute phase reactants, serology, structural damage, treatment and comorbidities. The core set should facilitate collaborative research, allow for comparisons across studies and harmonise future data from clinical practice via electronic medical record systems.
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