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1.
  • Bursill, D., et al. (författare)
  • Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout
  • 2019
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 78:11, s. 1592-1600
  • 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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2.
  • Ahdida, C., et al. (författare)
  • Fast simulation of muons produced at the SHiP experiment using Generative Adversarial Networks
  • 2019
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 14
  • 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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3.
  • Ahdida, C., et al. (författare)
  • Sensitivity of the SHiP experiment to Heavy Neutral Leptons
  • 2019
  • Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :4
  • 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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4.
  • Ahdida, C., et al. (författare)
  • The experimental facility for the Search for Hidden Particles at the CERN SPS
  • 2019
  • Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 14
  • 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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5.
  • Bursill, D., et al. (författare)
  • Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout
  • 2019
  • Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X. ; 71:3, s. 427-434
  • 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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6.
  • Milstead, David A., et al. (författare)
  • The active muon shield in the SHiP experiment
  • 2017
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 12
  • 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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7.
  • Warrington, N M, et al. (författare)
  • Maternal and fetal genetic contribution to gestational weight gain.
  • 2018
  • Ingår i: International journal of obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 42:4, s. 775-84
  • 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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10.
  • Agca, R., et al. (författare)
  • EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update
  • 2017
  • Ingår i: Ann Rheum Dis. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:1, s. 17-28
  • 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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11.
  • Glintborg, B., et al. (författare)
  • Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries
  • 2018
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:6, s. 465-474
  • 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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14.
  • Felix, Janine F, et al. (författare)
  • Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
  • 2016
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
  • 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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15.
  • Gislason, S.R., et al. (författare)
  • Environmental pressure from the 2014–15 eruption of Bárðarbunga volcano, Iceland
  • 2015
  • Ingår i: Geochemical Perspectives Letters. - : European Association of Geochemistry. - 2410-3403 .- 2410-339X. ; 1:2015, s. 84 - 93
  • 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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16.
  • Kapetanovic, Meliha C., et al. (författare)
  • Prevalence and incidence of gout in southern Sweden from the socioeconomic perspective
  • 2016
  • Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 2:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To estimate the prevalence and cumulative incidence of gout in southern Sweden with respect to socioeconomic status. Methods Among residents of Skåne region in the year 2013 (total population 1.3 million), adult persons (age 18 years +) who between 1998 and 2013 received a diagnosis of gout (International Classification of Disease 10th Edition (ICD-10) code M10) by any physician were identified using the Skåne Healthcare Register. We calculated the point prevalence by end of 2013 and annual cumulative incidence in 2013 standardised to the whole Skåne population according to sex, individual information on occupation (white collar/blue collar), income (low/middle/high) and level of education (primary school/high school/university). Results The crude 2013 point prevalence of gout and 2013 cumulative incidence (95% CI) were 1.69% (1.66% to 1.71%) and 24 cases per 10 000 persons (23-25), respectively. Compared to women, men had higher point prevalence (2.44% (2.40% to 2.49%) vs 0.96% (0.93% to 0.98%)) and higher annual cumulative incidence (33 cases per 10 000 (32-35)) versus 15 (14-16)). These figures increased with higher age but decreased with higher level of education, being the lowest in individuals with a university degree. Persons with middle income had highest point prevalence and cumulative incidence of gout, while those with white collar occupations had the lowest. Conclusions Gout is the most common inflammatory arthritis in southern Sweden with a prevalence of 1/41.7% in the adult population. There is a socioeconomic gradient with more gout present in the lower level of education and with more manual labour. © 2016 Published by the BMJ Publishing Group Limited.
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17.
  • Krag Jakobsen, Ane, et al. (författare)
  • Surgical interventions for nephrolithiasis in ankylosing spondylitis and the general population
  • 2015
  • Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 49:6, s. 486-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The aim of this study was to estimate rates and type of definitive surgical interventions for nephrolithiasis in Swedish patients with ankylosing spondylitis (AS) compared to the general population. Materials and methods. This national prospective cohort study linked data from Swedish population and healthcare registries. Incidence rates and interventions for nephrolithiasis during follow-up in patients with AS were compared to general population comparator (GPC) subjects. Results. In total, 8572 AS patients were followed for 49,959 person-years and 39,639 matched GPCs were followed for 225,221 person-years. Mean age at study entry was 46 years [interquartile range (IQR) 36-56 years] and 65% were male. In AS patients with a diagnosis of nephrolithiasis during the study period, 29% (72/250) underwent similar intervention for nephrolithiasis compared to 24% (114/466) GPCs (p = 0.21). The incidence rate ratio (RR) in overall AS patients was 2.9 [95% confidence interval (CI) 2.1-3.8] during a median follow-up of 6.2 years (IQR 3.2-8.6 years). With prior diagnosis of nephrolithiasis, the RR for AS patients compared to GPCs was 3.7 (95% CI 1.8-7.7); without prior nephrolithiasis the RR was 2.1 (95% CI 1.5-3.0). Increasing age [odds ratio (OR) 1.02, 95% CI 1.01-1.03], prior nephrolithiasis diagnosis (OR 3.3, 95% CI 1.97-5.62) and atherosclerotic cardiac disease (OR 2.0, 95% CI 1.03-3.91) were identified as predictors of intervention for nephrolithiasis. Conclusions. Patients with AS have an almost three-fold increased risk of surgical intervention for kidney stones, with similar management, compared to the general population.
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18.
  • Kristensen, L. E., et al. (författare)
  • Societal costs and patients' experience of health inequities before and after diagnosis of psoriatic arthritis: a Danish cohort study
  • 2017
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:9, s. 1495-1501
  • 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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19.
  • Liu, Xueping, et al. (författare)
  • Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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20.
  • Middeldorp, Christel M., et al. (författare)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • 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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21.
  • Musilova, I., et al. (författare)
  • Vaginal fluid interleukin-6 concentrations as a point-of-care test is of value in women with pretermprelabor rupture of membranes
  • 2016
  • Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 215:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Preterm prelabor rupture of membranes is frequently complicated/accompanied by infection and inflammation in the amniotic cavity. A point-of-care determination of amniotic fluid interleukin-6 has been shown to be a potentially clinically useful approach to assess inflammatory status of the amniotic cavity. Amniocentesis in preterm prelabor rupture of membranes is not broadly used in clinical practice, and therefore, a shift toward a noninvasive amniotic fluid sampling method is needed. Objective The first aim of this study was to evaluate the association between the point-of-care vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously. The second goal was to determine the diagnostic indices and predictive value of the point-of-care assessment of vaginal fluid interleukin-6 concentration in the identification of microbial invasion of the amniotic cavity, intraamniotic inflammation, and microbial-associated intraamniotic inflammation in patients with preterm prelabor rupture of membranes. Study Design A prospective cohort study was conducted in women with singleton gestation complicated by preterm prelabor rupture of membranes at between 24+0 and 36+6 weeks. A total of 153 women with singleton pregnancies were included in this study. Vaginal fluid was obtained from the posterior vaginal fornix by aspiration with a sterile urine sample tube with a suction tip. Amniotic fluid was obtained by transabdominal amniocentesis. Interleukin-6 concentrations were assessed with a lateral flow immunoassay in both fluids immediately after sampling. Microbial invasion of the amniotic cavity was determined based on a positive polymerase chain reaction analysis. Intraamniotic inflammation was defined as an amniotic fluid point-of-care interleukin-6 concentration ≥745 pg/mL. Results Several results were obtained in this study. First, it was possible to perform the point-of-care assessment of interleukin-6 in vaginal fluid in 92% of the women (141 of 153), and only those women were included in the analyses. Second, the rate of microbial invasion of the amniotic cavity and intraamniotic inflammation was 26% (36 of 141) and 19% (27 of 141), respectively. Microbial-associated intraamniotic inflammation was identified in 12% of the women (17 of 141). Third, a strong positive correlation was found between the interleukin-6 concentrations in vaginal and amniotic fluids (Spearman rho 0.68; P <.0001). Fourth, the presence of microbial invasion of the amniotic cavity, intraamniotic inflammation, or microbial-associated intraamniotic inflammation was associated with higher vaginal fluid interleukin-6 concentrations in both crude and adjusted analyses. Fifth, a vaginal fluid interleukin-6 concentration of 2500 pg/mL was determined to be the best cutoff value for the identification of microbial invasion of the amniotic cavity (sensitivity of 53% [19 of 36], specificity of 89% [93 of 104], positive predictive value of 63% [19 of 30], negative predictive value of 85% [93 of 110], positive likelihood ratio of 5.0 [95% confidence interval, 2.5–9.5], and negative likelihood ratio of 0.5 [95% confidence interval, 0.4–0.8]); intraamniotic inflammation (sensitivity of 74% [20/27], specificity of 91% [104/114], positive predictive value of 67% [20 of 30], negative predictive value of 94% [104 of 111], positive likelihood ratio of 8.4 [95% confidence interval, 4.5–15.9], and negative likelihood ratio of 0.3 [95% confidence interval, 0.2–0.5]); and microbial-associated intraamniotic inflammation (sensitivity of 100% [17 of 17], specificity of 90% [111 of 124), positive predictive value of 57% [17 of 30], negative predictive value of 100% [111 of 111], positive likelihood ratio of 9.5 [95% confidence interval, 5.7–16.0], and negative likelihood ratio of 0). Conclusion The point-of-care assessment of interleukin-6 in vaginal fluid is an easy, rapid, noninvasive, and inexpensive method for the identification of intraamniotic inflammation and microbial-associated intraamniotic inflammati n in preterm prelabor rupture of membranes pregnancies, showing good specificity and negative predictive value. © 2016 Elsevier Inc.
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22.
  • Petrache, C. M., et al. (författare)
  • Search for the terminating 27(-) state in Nd-140
  • 2015
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 92:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In the search for the fully aligned 27(-) state in Nd-140 predicted by cranked Nilsson-Strutinsky calculations, new close-to-spherical high-spin states have been discovered. Both the close-to-spherical and the triaxial calculated states are in good agreement with the experimental results, supporting the existence of shape coexistence up to very high spins. Shell-model calculations using a newly developed effective interaction for the 50 <= N, Z <= 82 mass region are in good agreement with the observed spherical states. The comparison between the experimental and calculated level energies allowed the relative energy to be established between several proton and neutron orbitals at high energy and spins.
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23.
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24.
  • van der Valk, Ralf J P, et al. (författare)
  • A novel common variant in DCST2 is associated with length in early life and height in adulthood.
  • 2015
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
  • 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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25.
  • Beaumont, Robin N, et al. (författare)
  • Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
  • 2018
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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26.
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27.
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28.
  • Bengtsson, Karin, 1980, et al. (författare)
  • Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study
  • 2017
  • 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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29.
  • Bengtsson, Karin, et al. (författare)
  • Cardiac conduction disturbances in patients with ankylosing spondylitis : results from a 5-year follow-up cohort study
  • 2019
  • Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 5:2
  • 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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30.
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31.
  • Bengtsson, Karin, 1980, et al. (författare)
  • 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
  • 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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32.
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33.
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34.
  • Bengtsson, Karin, 1980, et al. (författare)
  • Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population : A register-based study from Sweden
  • 2018
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 541-548
  • 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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35.
  • Bergsten, U., et al. (författare)
  • 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
  • Ingår i: Musculoskeletal Care. - : Wiley. - 1478-2189 .- 1557-0681. ; 17:3, s. 215-225
  • 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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36.
  • Bergström, Ulf, et al. (författare)
  • Effects of Treatment with Adalimumab on Blood Lipid Levels and Atherosclerosis in Patients with Rheumatoid Arthritis
  • 2018
  • Ingår i: Current Therapeutic Research - Clinical and Experimental. - : Elsevier BV. - 0011-393X. ; 89, s. 1-6
  • 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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37.
  • Bremander, Ann, et al. (författare)
  • Smoking is associated with a worse self-reported health status in patients with psoriatic arthritis: data from a Swedish population-based cohort
  • 2015
  • Ingår i: Clinical Rheumatology. - London : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 34:3, s. 579-583
  • 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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38.
  • Bustamante, Mariona, et al. (författare)
  • A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways.
  • 2016
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:18, s. 4127-4142
  • Tidskriftsartikel (refereegranskat)abstract
    • More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study, we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms. The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around 1 year of age and around 2 years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistical tests were applied to the 1000 Genomes imputed genotypic data. The meta-analysis (N=5758) followed by replication (N=3784) identified a genome-wide significant association between rs8111874 and diarrhoea at age 1 year. Conditional analysis suggested that the causal variant could be rs601338 (W154X) in the FUT2 gene. Children with the A allele, which results in a truncated FUT2 protein, had lower risk of diarrhoea. FUT2 participates in the production of histo-blood group antigens and has previously been implicated in the susceptibility to infections, including Rotavirus and Norovirus Gene-set enrichment analysis suggested pathways related to the histo-blood group antigen production, and the regulation of ion transport and blood pressure. Among others, the gastrointestinal tract, and the immune and neuro-secretory systems were detected as relevant organs. In summary, this genome-wide association meta-analysis suggests the implication of the FUT2 gene in diarrhoeal disease in young children from the general population.
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39.
  • Castaneda, Oscar, et al. (författare)
  • 1-bit Massive MU-MIMO Precoding in VLSI
  • 2017
  • Ingår i: IEEE Journal on Emerging and Selected Topics in Circuits and Systems. - : Institute of Electrical and Electronics Engineers (IEEE). - 2156-3365 .- 2156-3357. ; 7:4, s. 508-522
  • Tidskriftsartikel (refereegranskat)abstract
    • Massive multi-user (MU) multiple-input multiple-output (MIMO) will be a core technology in fifth-generation (5G) wireless systems as it offers significant improvements in spectral efficiency compared to existing multi-antenna technologies. The presence of hundreds of antenna elements at the base station (BS), however, results in excessively high hardware costs and power consumption, and requires high interconnect throughput between the baseband-processing unit and the radio unit. Massive MU-MIMO that uses low-resolution analog-to-digital and digital-toanalog converters (DACs) has the potential to address all these issues. In this paper, we focus on downlink precoding for massive MU-MIMO systems with 1-bit DACs at the BS. The objective is to design precoders that simultaneously mitigate MU interference and quantization artifacts. We propose two nonlinear 1-bit precoding algorithms and corresponding very large-scale integration (VLSI) designs. Our algorithms rely on biconvex relaxation, which enables the design of efficient 1-bit precoding algorithms that achieve superior error-rate performance compared with that of linear precoding algorithms followed by quantization. To showcase the efficacy of our algorithms, we design VLSI architectures that enable efficient 1-bit precoding for massive MU-MIMO systems, in which hundreds of antennas serve tens of user equipments. We present corresponding field-programmable gate array (FPGA) reference implementations to demonstrate that 1-bit precoding enables reliable and high-rate downlink data transmission in practical systems.
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40.
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41.
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42.
  • de Vries, Mirjam K, et al. (författare)
  • Tuberculosis risk in ankylosing spondylitis, other spondyloarthritis and psoriatic arthritis in Sweden: a population-based cohort study.
  • 2018
  • Ingår i: Arthritis care & research. - : Wiley. - 2151-4658 .- 2151-464X. ; 70:10, s. 1563-1567
  • Tidskriftsartikel (refereegranskat)abstract
    • Rheumatoid arthritis (RA) is a risk factor for tuberculosis (TB), particularly following treatment with biologicals. Since these therapies are increasingly used in ankylosing spondylitis (AS), other types of spondyloarthritis (SpA) and psoriatic arthritis (PsA), we investigated the corresponding TB risks in these patients.We identified individuals with AS/SpA/PsA, and non-AS/SpA/PsA comparators by linking Swedish national Patient, Population, TB and Rheumatology registers, and followed them for TB occurrence. Incidence rates were estimated for biological-naïve and biological-exposed patients, and the comparators. We calculated hazard ratios (HR) adjusted for age, sex and country of birth.38,702 patients with AS/SpA/PsA, and 200,417 general population persons were included. Among patients, 11 active TB cases were identified, with an incidence rate (per 105 ) of 22 (95%CI 8.3 to 59.2) for biological-exposed patients, 2.7 (95%CI 1.3 to 5.6) for biological-naïve patients and 2.4 (95%CI 1.8 to 3.3) for non-AS/SpA/PsA comparators. The adjusted HR comparing biological-naïve patients to the general population was 1.2 (95%CI 0.5 to 2.7), and 7.5 (95%CI 1.9 to 29) comparing biological-exposed to biological-naïve patients.Biological-naïve AS/PsA /SpA are not at an increased TB risk in Sweden. Following treatment with biologicals, risks increased but the absolute TB risk was low. This article is protected by copyright. All rights reserved.
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43.
  • Dehlin, Mats, et al. (författare)
  • Dr. Dehlin, et al reply.
  • 2019
  • Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 46:11
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • It was with great interest that we read the letter from Watson and colleagues1 describing their investigation of how a primary care diagnosis of gout compares to a primary care diagnostic rule for gout and the 1977 American Rheumatism Association (ARA) classification criteria of acute arthritis of primary gout. They present positive predictive values (PPV) of 74% for the diagnostic rule and 80% for the ARA criteria.
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44.
  • Dehlin, Mats, 1968, et al. (författare)
  • Factors associated with initiation and persistence of urate-lowering therapy
  • 2017
  • Ingår i: Arthritis Resarch and Therapy. - 1478-6354. ; 19
  • 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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45.
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46.
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47.
  • Dehlin, Mats, 1968, et al. (författare)
  • Incidence and prevalence of gout in Western Sweden
  • 2016
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of the present study was to describe prevalence and trends in the incidence of gout and patterns of urate-lowering treatment (ULT) in the Western Swedish Health Care Region (WSHCR) from 2002 to 2012. Methods: We used regional and national healthcare registers to estimate the prevalence and incidence of gout in 2012, and trends in incidence for each calendar year from 2005 to 2012. We also investigated the pattern of ULT for gout using the Swedish Prescribed Drug Register. Results: In 2012, in the population aged 20 years and above, the prevalence of gout was 1.8 % (95 % confidence interval (CI) 1.77 to 1.82) and the incidence was 190 cases (95 % CI 180 to 200) per 100,000 person-years. Applying more strict definitions for a gout case rendered a prevalence of 1.36 % (95 % CI 1.34 to 1.38) and 0.5 (95 % CI 0.49 to 0.51) per 100,000 person-years, respectively. The incidence of gout increased steadily and significantly from 2005 to 2012, with an almost 50 % increase in the total population. There was no significant difference in the prevalence of gout in rural compared to urban areas. ULT was dispensed to only 42 % of patients with gout in 2012 who had ever been diagnosed with gout during the preceding 10-year period. Conclusions: Gout is the most common arthritic disease in WSHCR, Sweden, and has increased substantially over the last decade, with only a minority of prevalent cases in 2012 receiving ULT.
  •  
48.
  • Dehlin, Mats, 1968, et al. (författare)
  • The Validity of Gout Diagnosis in Primary Care: Results from a Patient Survey.
  • 2019
  • Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 46:11, s. 1531-1534
  • Tidskriftsartikel (refereegranskat)abstract
    • Validate primary care diagnosis of gout by the Mexico and the Netherlands classification criteria.Questionnaires on gout characteristics were sent to all individuals aged ≥ 18 with ≥ 1 International Classification of Diseases, 10th ed. diagnosis of gout at 12 primary care centers.Positive predictive values for gout diagnosis ranged from 71% for the Netherlands criteria to 80% for the Mexico criteria. Maximum inflammation within 24 h was the most common reported symptom (86%).The vast majority of gout cases in primary care fulfill classification criteria and are valid for research purposes.
  •  
49.
  • Dehlin, Mats, 1968, et al. (författare)
  • Trends in Gout Hospitalization in Sweden.
  • 2018
  • Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 45:1, s. 145-146
  • Tidskriftsartikel (refereegranskat)
  •  
50.
  • Dehlin, Mats, 1968, et al. (författare)
  • Validity of gout diagnosis in Swedish primary and secondary care - a validation study
  • 2015
  • Ingår i: Bmc Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 16:149
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The diagnostic golden standard for gout is to detect monosodium urate (MSU) crystals in synovial fluid. While some gout classification criteria include this variable, most gout diagnoses are based on clinical features. This discrepancy between clinical practice and classification criteria can hinder gout epidemiological studies. Here, the objective was to validate gout diagnoses (International Classification of Diseases (ICD)-10 gout codes) in primary and secondary care relative to five classification criteria (Rome, New York, ARA, Mexico, and Netherlands). The frequency with which MSU crystal identification was used to establish gout diagnosis was also determined. Methods: In total, 394 patients with >= 1 ICD-10 gout diagnosis between 2009 and 2013 were identified from the medical records of two primary care centers (n = 262) and one secondary care center (n = 132) in Gothenburg, Sweden. Medical records were assessed for all classification criteria. Results: Primary care patients met criteria cutoffs more frequently when >= 2 gout diagnoses were made. Even then, few primary care patients met the Rome and New York cutoffs (19 % and 8 %, respectively). The ARA, Mexico, and Netherlands cutoffs were met more frequently by primary care patients with >= 2 gout diagnoses (54 %, 81 %, and 80 %, respectively). Mexico and Netherlands cutoffs were met more frequently by the rheumatology department patients (80 % and 71 %, respectively), even when patients with only 1 gout diagnosis were included. Analysis of MSU crystals served to establish gout diagnoses in only 27 % of rheumatology department and 2 % of primary care cases. Conclusions: If a patient was deemed to have gout at >= 2 primary care center or >= 1 rheumatology-center visits according to an ICD-10 gout code, the positive predictive value of this variable in relation with the Mexico and Netherlands classification criteria was >= 80 % for both primary care and rheumatology care settings in Sweden. MSU crystal identification was rarely used to establish gout diagnosis.
  •  
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