| 1. |
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| 2. |
- Milstead, David A., et al.
(författare)
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The active muon shield in the SHiP experiment
- 2017
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The SHiP experiment is designed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. An essential task for the experiment is to keep the Standard Model background level to less than 0.1 event after 2 x 10(20) protons on target. In the beam dump, around 10(11) muons will be produced per second. The muon rate in the spectrometer has to be reduced by at least four orders of magnitude to avoid muon-induced combinatorial background. A novel active muon shield is used to magnetically deflect the muons out of the acceptance of the spectrometer. This paper describes the basic principle of such a shield, its optimization and its performance.
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| 3. |
- Ahdida, C., et al.
(författare)
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Fast simulation of muons produced at the SHiP experiment using Generative Adversarial Networks
- 2019
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a fast approach to simulating muons produced in interactions of the SPS proton beams with the target of the SHiP experiment. The SHIP experiment will be able to search for new long-lived particles produced in a 400 GeV/c SPS proton beam dump and which travel distances between fifty metres and tens of kilometers. The SHiP detector needs to operate under ultra-low background conditions and requires large simulated samples of muon induced background processes. Through the use of Generative Adversarial Networks it is possible to emulate the simulation of the interaction of 400 GeV/c proton beams with the SHiP target, an otherwise computationally intensive process. For the simulation requirements of the SHiP experiment, generative networks are capable of approximating the full simulation of the dense fixed target, offering a speed increase by a factor of O(10(6)). To evaluate the performance of such an approach, comparisons of the distributions of reconstructed muon momenta in SHiP's spectrometer between samples using the full simulation and samples produced through generative models are presented. The methods discussed in this paper can be generalised and applied to modelling any non-discrete multi-dimensional distribution.
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| 4. |
- Ahdida, C., et al.
(författare)
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Sensitivity of the SHiP experiment to Heavy Neutral Leptons
- 2019
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Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- Heavy Neutral Leptons (HNLs) are hypothetical particles predicted by many extensions of the Standard Model. These particles can, among other things, explain the origin of neutrino masses, generate the observed matter-antimatter asymmetry in the Universe and provide a dark matter candidate. The SHiP experiment will be able to search for HNLs produced in decays of heavy mesons and travelling distances ranging between O(50 m) and tens of kilometers before decaying. We present the sensitivity of the SHiP experiment to a number of HNL's benchmark models and provide a way to calculate the SHiP's sensitivity to HNLs for arbitrary patterns of flavour mixings. The corresponding tools and data files are also made publicly available.
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| 5. |
- Ahdida, C., et al.
(författare)
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The experimental facility for the Search for Hidden Particles at the CERN SPS
- 2019
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The Search for Hidden Particles (SHiP) Collaboration has shown that the CERN SPS accelerator with its 400 GeV/c proton beam offers a unique opportunity to explore the Hidden Sector [1-3]. The proposed experiment is an intensity frontier experiment which is capable of searching for hidden particles through both visible decays and through scattering signatures from recoil of electrons or nuclei. The high-intensity experimental facility developed by the SHiP Collaboration is based on a number of key features and developments which provide the possibility of probing a large part of the parameter space for a wide range of models with light long-lived super-weakly interacting particles with masses up to O(10) GeV/c(2) in an environment of extremely clean background conditions. This paper describes the proposal for the experimental facility together with the most important feasibility studies. The paper focuses on the challenging new ideas behind the beam extraction and beam delivery, the proton beam dump, and the suppression of beam-induced background.
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| 6. |
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| 7. |
- Bursill, D., et al.
(författare)
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Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout
- 2019
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 78:11, s. 1592-1600
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Tidskriftsartikel (refereegranskat)abstract
- Objective There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. Methods A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. Results The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). Conclusion Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.
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| 8. |
- Bursill, D., et al.
(författare)
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Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout
- 2019
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Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X. ; 71:3, s. 427-434
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Tidskriftsartikel (refereegranskat)abstract
- Objective The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. Methods Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. Results There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (>= 80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. Conclusion Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.
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| 9. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 10. |
- Glintborg, B., et al.
(författare)
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Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries
- 2018
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:6, s. 465-474
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. Method: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. Results: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). Conclusion: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.
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| 11. |
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| 12. |
- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 13. |
- Warrington, N M, et al.
(författare)
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Maternal and fetal genetic contribution to gestational weight gain.
- 2018
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Ingår i: International journal of obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 42:4, s. 775-84
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Tidskriftsartikel (refereegranskat)abstract
- Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10543 mothers and 16317 offspring of European origin, with replication in 10660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.International Journal of Obesity advance online publication, 21 November 2017; doi:10.1038/ijo.2017.248.
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| 14. |
- Agca, R., et al.
(författare)
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EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update
- 2017
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Ingår i: Ann Rheum Dis. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:1, s. 17-28
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Tidskriftsartikel (refereegranskat)abstract
- Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.
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| 15. |
- Brantsaeter, A. L., et al.
(författare)
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Maternal intake of seafood and supplementary long chain n-3 poly-unsaturated fatty acids and preterm delivery
- 2017
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery. Methods: The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations. Results: Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (> 5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0. 85) for >= 3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery. Conclusions: Any intake of seafood above no/rare consumption was associated with lower prevalence of preterm delivery. The association was stronger for lean than for fatty fish. Intake of supplementary LCn-3PUFA was associated only with early preterm delivery. The findings corroborate the current advice to include fish and seafood as part of a balanced diet during pregnancy.
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| 16. |
- Dehlin, Mats, 1968, et al.
(författare)
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Factors associated with initiation and persistence of urate-lowering therapy
- 2017
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Ingår i: Arthritis Resarch and Therapy. - 1478-6354. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gout is the most common inflammatory arthritic disease and is caused by crystal deposition secondary to persistent hyperuricemia. Etiological treatment with urate-lowering therapy (ULT) has been available since the 1950s but previous studies have demonstrated suboptimal degree of treatment. In recent years we have seen recommendations for ULT earlier in the course of the disease, but there are few contemporary reports reflecting the current situation. Therefore we set out to investigate proportion receiving and persisting with ULT after gout diagnosis and predictors thereof. Method: A population-based cohort study using regional and national population-based registers. Cohort of patients (n = 7709) from western Sweden with incident gout aged 18 years and above from 2011 to 2013. An incident case of gout was defined as having been given a diagnosis of gout (ICD-10 M10, M14.0-14.1) not preceded by a gout diagnosis or a dispensation of ULT during the previous 5 years. Main outcome measures were cumulative incidence and predictors for start of, and persistence with, ULT in gout. Results: Within the first year after first gout diagnosis, 32% received ULT. Male sex, presence of diabetes or cardiovascular comorbidity, reduced kidney function but not diagnosed "end-stage kidney failure"increased the likelihood of receiving ULT. Of those starting ULT a majority (75%) did not persist with ULT treatment within the first 2 years. Age < 50 years, lack of comorbidities, and "normal kidney function"or "end-stage kidney failure"were associated with non-persistence with ULT. Conclusions: Only a minority of patients received ULT and a majority of these did not persist with treatment over the next 2 years. However, the older patients with renal impairment and comorbidities, possibly suffering from a more severe gout disease, were more likely to receive and persist with treatment. There is thus still room for considerable improvement with regards to management of ULT in gout.
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| 17. |
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| 18. |
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| 19. |
- Felix, Janine F, et al.
(författare)
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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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| 20. |
- Gislason, S.R., et al.
(författare)
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Environmental pressure from the 2014–15 eruption of Bárðarbunga volcano, Iceland
- 2015
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Ingår i: Geochemical Perspectives Letters. - : European Association of Geochemistry. - 2410-3403 .- 2410-339X. ; 1:2015, s. 84 - 93
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Tidskriftsartikel (refereegranskat)abstract
- The effusive six months long 2014-2015 Bárðarbunga eruption (31 August-27 February) was the largest in Iceland for more than 200 years, producing 1.6 ± 0.3 km3 of lava. The total SO2 emission was 11 ± 5 Mt, more than the amount emitted from Europe in 2011. The ground level concentration of SO2 exceeded the 350 μg m−3 hourly average health limit over much of Iceland for days to weeks. Anomalously high SO2 concentrations were also measured at several locations in Europe in September. The lowest pH of fresh snowmelt at the eruption site was 3.3, and 3.2 in precipitation 105 km away from the source. Elevated dissolved H2SO4, HCl, HF, and metal concentrations were measured in snow and precipitation. Environmental pressures from the eruption and impacts on populated areas were reduced by its remoteness, timing, and the weather. The anticipated primary environmental pressure is on the surfacewaters, soils, and vegetation of Iceland.
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| 21. |
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| 22. |
- KARLSSON WALLMAN, JOHAN, et al.
(författare)
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Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy: a population-based regional cohort study from southern Sweden
- 2017
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 56:5, s. 716-724
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Methods. Bionaive nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-TNF initiation. Matched population references were included for comparison and to adjust for secular trends. Results. The nr-axSpA patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-TNF initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axSpA group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Conclusion. Anti-TNF therapy in nr-axSpA was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up.
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| 23. |
- Kristensen, L. E., et al.
(författare)
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Societal costs and patients' experience of health inequities before and after diagnosis of psoriatic arthritis: a Danish cohort study
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:9, s. 1495-1501
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To comprehensively study the comorbidities, healthcare and public transfer (allowance) costs in patients with psoriatic arthritis (PsA) before and after diagnosis. Methods Nationwide cohort study, using data from Danish registries from January 1998 through December 2014. A total of 10 525 patients with PsA and 20 777 matched general population comparator (GPC) subjects were included. Societal costs, employment status and occurrence of comorbidities in patients with PsA both before and after diagnosis were compared with GPC subjects. Results At baseline, patients with PsA had significantly more comorbidities, including cardiovascular disease (OR 1.70 95% CI 1.55 to 1.86), respiratory diseases (OR 1.73 95% CI 1.54 to 1.96) and infectious diseases (OR 2.03 95% CI 1.69 to 2.42) compared with GPC subjects. At all time points, patients with PsA had higher total healthcare and public transfer costs; they also had lower income (p<0.001) and incurred a net average increased societal cost of (sic)10 641 per patient-year compared with GPC subjects following diagnosis. The relative risk (RR) for being on disability pension 5 years prior to PsA diagnosis was 1.36 (95% CI 1.24 to 1.49) compared with GPC subjects. The RR increased to 1.60 (95% CI 1.49 to 1.72) at the time of diagnosis and was 2.69 (95% CI 2.40 to 3.02) 10 years after diagnosis, where 21.8% of the patients with PsA received disability pension. Conclusions Our findings are suggestive of health inequity for patients with PsA and call for individual preventive measures and societal action.
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| 24. |
- Lee, James J, et al.
(författare)
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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
- 2018
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 50:8, s. 1112-1121
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Tidskriftsartikel (refereegranskat)abstract
- Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1million individuals and identify 1,271independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
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| 25. |
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| 26. |
- Middeldorp, C. M., et al.
(författare)
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A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts
- 2016
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 55:10
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46× 10−6 and 2.66× 10−6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants. © 2016 American Academy of Child and Adolescent Psychiatry
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| 27. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 28. |
- Mulay, A. L., et al.
(författare)
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Borderline personality disorder diagnosis in a new key
- 2019
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Ingår i: Borderline Personality Disorder and Emotion Dysregulation. - : Springer Science and Business Media LLC. - 2051-6673. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Conceptualizations of personality disorders (PD) are increasingly moving towards dimensional approaches. The definition and assessment of borderline personality disorder (BPD) in regard to changes in nosology are of great importance to theory and practice as well as consumers. We studied empirical connections between the traditional DSM-5 diagnostic criteria for BPD and Criteria A and B of the Alternative Model for Personality Disorders (AMPD). Method Raters of varied professional backgrounds possessing substantial knowledge of PDs (N = 20) characterized BPD criteria with the four domains of the Level of Personality Functioning Scale (LPFS) and 25 pathological personality trait facets. Mean AMPD values of each BPD criterion were used to support a nosological cross-walk of the individual BPD criteria and study various combinations of BPD criteria in their AMPD translation. The grand mean AMPD profile generated from the experts was compared to published BPD prototypes that used AMPD trait ratings and the DSM-5-III hybrid categorical-dimensional algorithm for BPD. Divergent comparisons with DSM-5-III algorithms for other PDs and other published PD prototypes were also examined. Results Inter-rater reliability analyses showed generally robust agreement. The AMPD profile for BPD criteria rated by individual BPD criteria was not isomorphic with whole-person ratings of BPD, although they were highly correlated. Various AMPD profiles for BPD were generated from theoretically relevant but differing configurations of BPD criteria. These AMPD profiles were highly correlated and showed meaningful divergence from non-BPD DSM-5-III algorithms and other PD prototypes. Conclusions Results show that traditional DSM BPD diagnosis reflects a common core of PD severity, largely composed of LPFS and the pathological traits of anxiousness, depressively, emotional lability, and impulsivity. Results confirm the traditional DSM criterion-based BPD diagnosis can be reliably cross-walked with the full AMPD scheme, and both approaches share substantial construct overlap. This relative equivalence suggests the vast clinical and research literatures associated with BPD may be brought forward with DSM-5-III diagnosis of BPD.
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| 29. |
- Ortolan, A., et al.
(författare)
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Are gender-specific approaches needed in diagnosing early axial spondyloarthritis? Data from the SPondyloArthritis Caught Early cohort
- 2018
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Ingår i: Arthritis Res Ther. - : Springer Science and Business Media LLC. - 1478-6354. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although gender differences have been observed in the severity of axial spondyloarthritis (axSpA), gender differences in disease presentation of early axSpA have not been thoroughly investigated. In particular, their impact on the diagnostic process is unknown. Methods: Baseline data from the SPondyloArthritis Caught Early cohort, which includes patients with chronic back pain (CBP; duration >= 3 months and <= 2 years, age of onset <45 years), were analysed. Patients underwent a full diagnostic work-up, including MRI and radiograph of the sacroiliac joints (MRI-SIJ and X-SIJ), to establish a diagnosis of axSpA. Characteristics of male and female patients with a certain diagnosis of axSpA (confidence level by the physician >= 7 on a 0-10 rating scale) were compared. Regression models were built for: the whole CBP cohort stratified by gender, to study which SpA features were associated most with diagnosis in each gender; and for axSpA patients, to test whether gender was associated with imaging positivity (MRI-SU+ and/or X-SU+). Results: Of the 719 CBP patients, 275 were male. With 146/275 males and 155/444 females diagnosed as axSpA, males were more likely to be diagnosed with axSpA (OR 2.1, 95% CI 1.5-2.9). Despite similar symptom duration, male axSpA patients were younger at diagnosis (27.4 +/- 7.5 vs 29.5 +/- 7.8 years; p = 0.02). Presence of SpA features was similar in male and female axSpA patients, except for HLA-B27 and imaging positivity that were more common in male axSpA patients (80% vs 60%; p < 0.01 and 78% vs 64%; p = 0.01). Nevertheless, these SpA features were still more prevalent in female axSpA patients than in no-axSpA patients, both females (HLA-B27(+) 23%, positive imaging 7%) and males (HLAB27(+) 34%, positive imaging 11%) (all p < 0.01). Moreover, in multivariable models with diagnosis of axSpA as outcome, HLA-B27 and imaging positivity were associated with the diagnosis in both sexes. In models with imaging positivity as outcome, male gender and HLA-B27 were both independently associated with MRI+ and/or X-SI+. Conclusions: While our data show clear gender differences in early axSpA, they highlight that HLA-B27 and imaging are still key elements for diagnosis in both genders. Our study does not suggest that separate diagnostic strategies for men and women are required.
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| 30. |
- Ostergaard, M., et al.
(författare)
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MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:6, s. 1156-1163
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). Methods Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400mg every 2weeksat weeks 0-4; CZP 200mg every 2weeksat weeks 6-16) or placeboCZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200mg every 2weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures. Results Forty patients were treated (27 CZP, 13 placeboCZP), and 36 (24 CZP, 12 placeboCZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group. Conclusions CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.
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| 31. |
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| 32. |
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| 33. |
- van Lunteren, M., et al.
(författare)
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In Early Axial Spondyloarthritis, Increasing Disease Activity Is Associated with Worsening of Health-related Quality of Life over Time
- 2018
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 45:6, s. 779-784
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Tidskriftsartikel (refereegranskat)abstract
- Objective. In early axial spondyloarthritis (axSpA), data are lacking about the relationship between disease activity and health-related quality of life (HRQOL). We assessed and quantified the association between change in Ankylosing Spondylitis Disease Activity Score (ASDAS) and HRQOL over time in early axSpA. Methods. Baseline and 1-year data of patients with axSpA fulfilling the Assessment of Spondyloarthritis international Society (ASAS) classification criteria from the SPondyloArthritis Caught Early (SPACE) cohort were analyzed. Associations between change in ASDAS and in physical (PCS) or mental component summary (MCS) of the Medical Outcomes Study Short Form-36 were tested by linear regression models. Age. sex. ASAS criteria arm, and blue- versus white-collar work were tested for effect modification. Subsequently, these factors and medication were tested for confounding. Results. There were 161 patients with axSpA [53% male, mean (+/- SD) age 29.7 (+/- 7.5) yrs, symptom duration 13.6 (+/- 7.2) months, HLA-B27-positive 91%, radiographic sacroiliitis 22%] who had ASDAS of 2.5 (+/- 1.0) and 2.0 (+/- 0.8), PCS of 28.4 (+/- 14.3) and 36.9 (+/- 13.1), and MCS of 48.2 (+/- 13.8) and 493 (+/- 12.0) at baseline and 1 year, respectively. Per unit increase in ASDAS between baseline and 1 year, PCS worsened by 93 points. The same level of disease activity had fewer adverse effects on physical HRQOL in women and white-collar workers. Conclusion. To our knowledge, our data are the first to show that in a broad group of patients with early axSpA, increasing ASDAS is associated with worsening of physical HRQOL, but not mental HRQOL, over time.
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| 34. |
- Alanko Blomé, M., et al.
(författare)
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Vaccination against hepatitis B virus among people who inject drugs – A 20 year experience from a Swedish needle exchange program
- 2017
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 35:1, s. 84-90
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Tidskriftsartikel (refereegranskat)abstract
- Background People who inject drugs (PWID) are at particular risk of hepatitis B virus (HBV) acquisition, but often have poor access or adherence to HBV vaccination. Vaccination against HBV has been offered at a major Swedish needle exchange program (NEP) since 1994. The aim of this study was to evaluate vaccine completion and response rates, and the effect of sequential booster doses to non-responders to the standard vaccination schedule. Methods PWID enrolled in the NEP 1994–2013, without serological markers for HBV at baseline (negative for HBsAg/anti-HBc/anti-HBs), were offered a three-dose standard intramuscular vaccination schedule (Engerix®-B, GSK, 20 μg/mL, intended to be received at months 0, 1 and 6). Vaccination response was defined as protective levels of anti-HBs (⩾10 mIU/mL). Up to three booster doses were then offered for non-responders, each followed by anti-HBs testing. Results HBV data was available for 2352 identifiable individuals at NEP enrolment, of whom 1516 (64.5%) had no markers for previous HBV exposure or vaccination. Vaccination was initiated for 1142 (75.3%) individuals and 898 (59.2%) completed the standard vaccination schedule. Post-vaccination anti-HBs levels were available from 800 individuals, with 598 (74.8%) responding to the basic vaccination schedule. After up to three booster doses a total of 676 (84.5%) individuals achieved protective anti-HBs levels. Non-response to vaccination was associated with higher age and anti-HCV positivity (p < 0.001). Eighteen incident cases of HBV infection were observed among vaccine non-responders, as well as 30 cases among those who had not completed vaccination. Conclusion We demonstrate the feasibility of including HBV vaccination in the services offered by a NEP, with completion of vaccination in a majority of HBV-susceptible PWID. The response to HBV vaccination among PWID was relatively low; however, the addition of up to three booster doses improved the response rate from 74.8 to 84.5%.
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| 35. |
- Andersson, Joel, 1981-, et al.
(författare)
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Improved understanding of Varestraint Testing : Nickel-based superalloys
- 2016
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Ingår i: Cracking Phenomena in Welds IV. - : Springer Publishing Company. - 9783319284323 - 3319284320
-
Konferensbidrag (refereegranskat)abstract
- Information about the book:This is the fourth volume in the well-established series of compendiums devoted to the subject of weld hot cracking. It contains the papers presented at the 4th International Cracking Workshop held in Berlin in April 2014. In the context of this workshop, the term “cracking” refers to hot cracking in the classical and previous sense, but also to cold cracking, stress-corrosion cracking and elevated temp. solid-state cracking. A variety of different cracking subjects are discussed, including test standards, crack prediction, weldability determination, crack mitigation, stress states, numerical modelling, and cracking mechanisms. Likewise, many different alloys were investigated such as aluminum alloys, copper-aluminum dissimilar metal, austenitic stainless steel, nickel base alloys, duplex stainless steel, creep resistant steel, and high strength steel.
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| 36. |
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| 37. |
- Asplund, Annika, 1979-, et al.
(författare)
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One Standardized Differentiation Procedure Robustly Generates Homogenous Hepatocyte Cultures Displaying Metabolic Diversity from a Large Panel of Human Pluripotent Stem Cells
- 2016
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Ingår i: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 1550-8943 .- 1558-6804. ; 12:1, s. 90-104
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Tidskriftsartikel (refereegranskat)abstract
- Human hepatocytes display substantial functional inter-individual variation regarding drug metabolizing functions. In order to investigate if this diversity is mirrored in hepatocytes derived from different human pluripotent stem cell (hPSC) lines, we evaluated 25 hPSC lines originating from 24 different donors for hepatic differentiation and functionality. Homogenous hepatocyte cultures could be derived from all hPSC lines using one standardized differentiation procedure. To the best of our knowledge this is the first report of a standardized hepatic differentiation procedure that is generally applicable across a large panel of hPSC lines without any adaptations to individual lines. Importantly, with regard to functional aspects, such as Cytochrome P450 activities, we observed that hepatocytes derived from different hPSC lines displayed inter-individual variation characteristic for primary hepatocytes obtained from different donors, while these activities were highly reproducible between repeated experiments using the same line. Taken together, these data demonstrate the emerging possibility to compile panels of hPSC-derived hepatocytes of particular phenotypes/genotypes relevant for drug metabolism and toxicity studies. Moreover, these findings are of significance for applications within the regenerative medicine field, since our stringent differentiation procedure allows the derivation of homogenous hepatocyte cultures from multiple donors which is a prerequisite for the realization of future personalized stem cell based therapies.
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| 38. |
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| 39. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study
- 2017
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP). Methods: This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001-2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively. Results: Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31-1.82)), PsA (1.76 (1.59-1.95)) and uSpA (1.36 (1.05-1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37-0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06-1.48)) and PsA (1.34 (1.22-1.48)), and nonsignificantly increased in uSpA (1.16 (0.91-1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP. Conclusions: Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.
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| 40. |
- Bengtsson, Karin, et al.
(författare)
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Cardiac conduction disturbances in patients with ankylosing spondylitis : results from a 5-year follow-up cohort study
- 2019
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Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe electrocardiographic (ECG) development in patients with ankylosing spondylitis (AS) and identify associations between baseline characteristics and cardiac conduction disturbances (CCD) at 5-year follow-up.Methods: In a longitudinal cohort study, 172 patients (54% men, mean age (SD) of 50 (13) years at baseline) with AS underwent ECG, physical examination, questionnaires and laboratory testing at baseline and at 5-year follow-up. Descriptive statistics and univariate and age- and sex-adjusted logistic regression analyses were used. CCD included both atrioventricular and intraventricular blocks.Results: Twenty-three of the 172 patients (13.4%) had a CCD at follow-up. Eight patients had developed a new CCD and eight had normalised their ECG. In the age- and sex-adjusted analyses, CCD at baseline (OR 24.8, 95% CI 7.3 to 84.5), male sex (OR 6.4, 95% CI 2.0 to 20.8), history of anterior uveitis (OR 4.4, 95% CI 1.3 to 14.5), higher ASDAS-CRP (OR 2.3, 95% CI 1.3 to 4.0), greater waist circumference (OR 1.3, 95% CI 1.1 to 1.6, per 5 cm), and medication with antiplatelets (OR 7.0, 95% CI 1.5 to 31.8) and beta-blockers (OR 3.4, 95% CI 1.0 to 11.5) were associated with a CCD at follow-up. Higher age and longer symptom duration were highly correlated and were both associated with a CCD at follow-up.Conclusions: The presence of CCD in AS is in part dynamic and associated with both AS and non-AS characteristics. Our results suggest that patients especially prone to present with CCDs are older men with a previous CCD, longer symptom duration, higher AS disease activity, a history of anterior uveitis and medication reflecting cardiovascular disease.
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| 41. |
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| 42. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Comparisons between comorbid conditions and health care consumption in rheumatoid arthritis patients with or without biological disease-modifying antirheumatic drugs : a register-based study
- 2016
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Symptoms and prognosis of patients with rheumatoid arthritis (RA) have improved with more intensive therapy, including the biological disease-modifying anti-rheumatic drugs (bDMARDs). Real life data concerning how comorbidities are distributed among patients treated or not treated with bDMARDs are scarce. Our objective was to investigate differences in comorbidity and health care consumption in RA patients, with and without bDMARDs.METHODS: This cross-sectional study was performed in the Southwestern part of Sweden. Patients, aged ≥ 18 years and diagnosed with RA in secondary health care during 2009-2010, were identified in the regional health care database. Aggregated data of comorbidity and health care consumption were retrieved between 2006 and 2010. RA patients treated with bDMARDs on 31st December 2010 were identified in the Swedish Rheumatology Quality Register (SRQ), which includes the biologics register Anti-Rheumatic Therapy in Sweden (ARTIS). Descriptive, comparative, univariate and multiple logistic regression analyses were used to identify factors associated with bDMARDs.RESULTS: Seven thousand seven hundred and twelve (7712) RA patients were identified (age 64.8 ± 14.9 years, women 74.3%), of whom 1137 (14.7%) were treated with bDMARDs. Overall, the most common comorbidities were infections (69.2%), hypertension (41.1%), chronic respiratory disease (15.3%), ischemic heart disease (14.0%) and malignancy (13.7%). Patients without bDMARDs were older and had more comorbidity. In the multiple logistic regression analysis, older age, cerebrovascular and chronic respiratory disease, heart failure, depression and malignancy were all associated with no present bDMARDs. Infections were associated with bDMARDs. Patients treated with bDMARDs consumed more secondary outpatient care but less visits in primary health care compared to patients without bDMARDs.CONCLUSIONS: Patients treated with bDMARDs versus no bDMARDs were younger and had significantly lower period prevalence for most common comorbidities, with the exception of infections. Differences in comorbidities between RA patients with or without bDMARDs should be taken into consideration when evaluating effectiveness and safety of bDMARDs in ordinary care.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population : A register-based study from Sweden
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 541-548
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To describe the incidence of atrioventricular (AV) block II-III, atrial fibrillation (AF), pacemaker implantation (PM) and aortic regurgitation in patients with ankylosing spondylitis (AS), undifferentiated spondyloarthritis (uSpA) and psoriatic arthritis (PsA) compared with the general population (GP) and with each other. Methods A prospective nationwide study with cohorts of patients with AS (n=6448), PsA (n=16 063) and uSpA (n=5190) and a GP (n=2 66 435) cohort, identified in 2001-2009 in the Swedish National Patient and Population registers. Follow-up began on 1 January 2006 and ended at event, death, emigration or 31 December 2012. Age-standardised and sex-standardised incidence rates and hazard ratios (HRs) were calculated. Results The highest incidence rates were noted for AF (5.5-7.4 events per 1000 person-years), followed by PM (1.0-2.0 events per 1000 person-years). HRs for AV block, AF, PM and aortic regurgitation were significantly increased in AS (HRs 2.3, 1.3, 2.1 and 1.9), uSpA (HRs 2.9, 1.3, 1.9 and 2.0) and PsA (HRs 1.5, 1.5, 1.6 and 1.8) compared with the GP cohort. The highest HRs were seen for AV block in male uSpA (HR 4.2) and AS (HR 2.5) compared with GP. Compared with PsA, significantly increased HRs were noted for PM (HR 1.5) in AS and for AV block (HR 1.8) in uSpA. Conclusions Patients with SpA are at increased risk of aortic regurgitation, cardiac rhythm disturbances and, as a probable consequence, also PM. Particularly for AF, the most common arrhythmia, increased caution is warranted, whereas AV block should be looked for especially in men with AS or uSpA.
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| 47. |
- Bergenfelz, A., et al.
(författare)
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Risk of recurrent laryngeal nerve palsy in patients undergoing thyroidectomy with and without intraoperative nerve monitoring
- 2016
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 103:13, s. 1828-1838
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vocal cord palsy occurs in 3-5 per cent of patients after thyroidectomy. To reduce this complication, intraoperative nerve monitoring (IONM) has been introduced, although its use remains controversial. This study investigated the risk of postoperative vocal cord palsy with and without the use of intermittent IONM. Methods: Patients registered in the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery, 2009-2013, were included. Early palsy of the recurrent laryngeal nerve was diagnosed within 6weeks after surgery. Permanent palsy was defined as that persisting after 6months. Univariable and multivariable logistic regression analyses were used to examine risk factors for vocal cord palsy. Results: The cohort consisted of 5252 patients undergoing thyroidectomy. IONM was used in 3277 operations (62·4 per cent); routine postoperative laryngoscopy was performed in 1757 patients (33·5 per cent). Early vocal cord palsy occurred in 217 patients (4·1 per cent), of which three were bilateral, all in the group without IONM. Permanent vocal cord palsy occurred in 62 patients (1·2 per cent). In the multivariable analysis of 1757 patients who had postoperative laryngoscopy, the use of IONM was not associated with a decreased risk of early vocal cord palsy (odds ratio (OR) 0·67, 95 per cent c.i. 0·44 to 1·01), but decreased the risk of permanent vocal cord palsy (OR 0·43, 0·19 to 0·93). Conclusion: IONM reduced the risk of permanent vocal cord palsy. No bilateral recurrent laryngeal nerve injury occurred following IONM.
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| 48. |
- Bergsten, U., et al.
(författare)
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A randomized study comparing regular care with a nurse-led clinic based on tight disease activity control and person-centred care in patients with rheumatoid arthritis with moderate/high disease activity: A 6-month evaluation
- 2019
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Ingår i: Musculoskeletal Care. - : Wiley. - 1478-2189 .- 1557-0681. ; 17:3, s. 215-225
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A recent survey showed that 27% of rheumatoid arthritis (RA) patients had inadequately controlled disease activity. Hence, there is a need for new strategies aiming at improving patient outcomes. The aim of the present study was to evaluate the effect of a nurse-led clinic with frequent visits, treat-to-target and person-centred care of patients with established RA and moderate-to-high disease activity compared with patients receiving regular care. Methods: The study was a randomized, controlled trial over 26weeks, with a nonrandomized extension to week 50. Patients were randomized to an intervention group (IG; nurse-led clinic) based on person-centred care, frequent visits and “treat to target”, or to a control group (CG) which visited the clinic according to care as usual. The primary outcome was the difference in the DAS28 change between the IG and the CG groups. Results: A total of 332 patients were screened for eligibility, of which 70 were randomly assigned to either the IG (n=36) or the CG (n=34) group. The primary outcome was not met, although patients in the IG group tended to improve more than those in the CG group (difference: 0.43 (95% confidence interval [CI] –0.27, 1.13). In both the IG and CG groups, delta-DAS28 improved significantly. The European League Against Rheumatology moderate or good response was achieved by 76% (95% CI 58, 89) in the IG and 49% (95% CI 32, 65) in the CG group. Conclusions: Disease activity tended to improve more with the nurse-led intervention compared with regular care, although the difference was not significant, probably partly due to the lack of statistical power. © 2019 The Authors Musculoskeletal Care published by John Wiley & Sons Ltd
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| 49. |
- Bergström, Ulf, et al.
(författare)
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Effects of Treatment with Adalimumab on Blood Lipid Levels and Atherosclerosis in Patients with Rheumatoid Arthritis
- 2018
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Ingår i: Current Therapeutic Research - Clinical and Experimental. - : Elsevier BV. - 0011-393X. ; 89, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment with tumor necrosis factor inhibitors for rheumatoid arthritis has been associated with a decreased risk of cardiovascular disease in observational studies. There are conflicting data on the influence of tumor necrosis factor inhibitors on lipid levels. Objectives: To evaluate the effect of treatment with adalimumab on blood lipid levels, lipoproteins, and atherosclerosis of the carotid artery. Methods: Fourteen patients with active rheumatoid arthritis (11 women and 3 men; mean age 63.7 years; median disease duration 9.0 years; and 78% rheumatoid factor positive) were treated with adalimumab 40 mg subcutaneously every 2 weeks and followed for 3 months. The patients had not been treated with adalimumab previously and had not received other tumor necrosis factor inhibitors within the past 3 months or moderate/high dose corticosteroids within the past 2 weeks. The intima-media thickness of the common carotid artery was assessed using B mode ultrasonography. Triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol levels were analyzed in fresh fasting blood samples, whereas apolipoprotein B and apolipoprotein A1 (apoA1) levels were determined in thawed plasma samples using standard turbidimetric immunoassays. Results: Total cholesterol (mean = 5.36 vs 5.96 mmol/L; P = 0.005), LDL cholesterol (mean = 3.33 vs 3.77 mmol/L; P =.005), HDL cholesterol (mean = 1.43 vs 1.55 mmol/L; P = 0.048), apolipoprotein B (mean = 1.04 vs 1.13 g/L; P =.012), and apoA1 (mean = 1.42 vs 1.58 g/L; P = 0.005) all increased, but there were no major changes in the LDL to HDL cholesterol ratio (median = 2.56 vs 2.35; P = 0.27) or the apolipoprotein B to apoA1 ratio (mean = 0.76 vs 0.74; P = 0.46). There was no change in triglyceride levels (P = 0.55). Disease activity decreased significantly from baseline to the 3-month evaluation (disease activity score based on 28 joints mean = 5.6 vs 4.1; P = 0.007). An increase in apoA1 correlated with decreases in the patient global assessment of disease severity (r = 0.79; P = 0.001) and C-reactive protein level (r = 0.74; P = 0.003). Changes in the apoliprotein B to apoA1 ratio correlated with changes in erythrocyte sedimentation rate (r = 0.54; P = 0.046). There was no major change in the common carotid artery intima-media thickness (mean = 0.78 vs 0.80 mm; P = 0.48). Conclusions: Although these results suggest that control of inflammation could have a beneficial effect on the lipid profile through an increase in HDL cholesterol levels, the observed protective effect on cardiovascular disease events by tumor necrosis factor blockers is likely to be explained by other mechanisms than changes in lipid levels or short-term effects on atherosclerosis of the carotid artery. © 2018 The Authors
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- Bremander, Ann, et al.
(författare)
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Smoking is associated with a worse self-reported health status in patients with psoriatic arthritis: data from a Swedish population-based cohort
- 2015
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Ingår i: Clinical Rheumatology. - London : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 34:3, s. 579-583
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to study possible associations between smoking habits and self-reported clinical features in a large population-based cohort of patients with psoriatic arthritis (PsA). All subjects with PsA who had sought health care in the period 2003-2007 were identified using a regional health-care register. In 2009, all those identified who were 18 years of age or more (n = 2,003) were sent a questionnaire with questions on smoking, health-related quality of life [EuroQol five-dimension (EQ-5D)questionnaire], function [Health Assessment Questionnaire (HAQ)], pain, fatigue, and global health. We performed age- and sex-adjusted regression analysis to compare health status outcomes in never and ever smokers. Altogether, 1,185 subjects (59 %) returned the questionnaire. Mean age was 57 years (SD 13.5), and 58 % were women; 38 % were never smokers and 62 % were ever smokers. Mean age at disease onset was 38.2 years (SD 13.2) and 41.2 years (SD 13.6), respectively (p = 0.001). In age- and sex-adjusted data, ever smokers reported worse EQ-5D (p = 0.009); worse reports of global health (p = 0.01), pain (p = 0.01), and fatigue (p = 0.04); and a higher number of painful body regions (p = 0.04) compared to never smokers. In this population-based PsA cohort, patients who were ever smokers reported worse health status than never smokers. Besides being a possible result of a worse PsA in ever smokers, impaired health status could also be an effect of unstudied comorbidities. Further longitudinal studies are needed to gain a better understanding of cause and effect. However, smoking cessation should be recommended because of general health considerations as well as disease-specific issues.
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