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- Roseman, C., et al.
(author)
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Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis : what is the role of inflammation control?
- 2024
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In: Scandinavian Journal of Rheumatology. - 0300-9742 .- 1502-7732. ; 53:2, s. 94-103
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Journal article (peer-reviewed)abstract
- Objective: While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. Method: Bionaïve PsA patients starting a first anti-TNF therapy 2004–2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. Results: Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator’s global assessment were associated with a lower risk of 12-month refractory pain. Conclusions: A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.
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| 3. |
- Ahlström, Aisling, 1976, et al.
(author)
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A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer
- 2022
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:4, s. 708-717
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Journal article (peer-reviewed)abstract
- STUDY QUESTION Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone? SUMMARY ANSWER The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone. WHAT IS KNOWN ALREADY Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection. STUDY DESIGN, SIZE, DURATION A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics. LIMITATIONS, REASONS FOR CAUTION During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks. WIDER IMPLICATIONS OF THE FINDINGS The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose. DATE OF FIRST PATIENT'S ENROLMENT 11 June 2018.
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- Geirsson, H., et al.
(author)
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Overview of results from continuous GPS observations in Iceland from 1995 to 2010
- 2010
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In: Jökull. - 0449-0576. ; 60:1, s. 1-21
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Journal article (peer-reviewed)abstract
- Iceland is a natural laboratory for a variety of processes associated with crustal deformation, such as earthquakes, magmatic events, tectonic plate motions, and glacial load changes. Continuous GPS (CGPS) measurements started in Iceland in 1995, and since then data from the network have helped to shed light on many different active deformation processes. The number of CGPS sites in Iceland tripled during 2006–2008, as a result of an international collaborative effort coordinated by Icelandic scientists. By early 2010 the number of CGPS stations in Iceland had reached 64, located primarily around and within the North- American–Eurasian plate boundary zone. Since its initiation, the CGPS network has played an important role in monitoring volcanoes and seismogenic areas, most notably during the 2009–2010 Eyjafjallajökull volcano unrest. Plate spreading of up to 2 cm per year usually dominates the horizontal motion observed at the CGPS sites, while uplift is observed at many of the stations due to recent retreat of the Icelandic ice caps. Co-seismic and post-seismic deformation of the largest earthquakes in 2000 and 2008 in the South Iceland Seismic Zone were captured by the network, and high-rate (1 Hz) CGPS observations helped to identify two magnitude 6 mainshocks in 2008 that were separated in time by only 2–3 seconds. The CGPS network has thus enabled us to monitor deformation occurring over days to months caused by migration of magma or fluids, post-seismic transients, rapid deformation caused by earthquakes and eruptions, as well as the long term plate spreading signal.
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- Mueller, M., et al.
(author)
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Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity
- 2015
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In: Journal of Hepatology. - 0168-8278. ; 62:6, s. 1398-1404
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Journal article (peer-reviewed)abstract
- Background & Aims: Bile acids (BAs) are major regulators of hepatic BA and lipid metabolism but their mechanisms of action in non-alcoholic fatty liver disease (NAFLD) are still poorly understood. Here we aimed to explore the molecular and biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross-talk between liver and visceral white adipose tissue (vWAT) regarding BA and cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD patients. Methods: In this randomized controlled pharmacodynamic study, we analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese patients receiving UDCA (20 mg/ kg/day) or no treatment three weeks prior to bariatric surgery. Results: Short term UDCA administration stimulated BA synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X receptor (FXR) activation, resulting in cholesterol 7 alpha-hydroxylase induction mirrored by elevated C4 and 7 alpha-hydroxycholesterol. Enhanced BA formation depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the liver, thereby increasing hepatic triglyceride content. In addition, induced SCD activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic and more lipogenic monounsaturated fatty acids such as oleic acid. Conclusion: These data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces neutral lipid accumulation in both liver and vWAT. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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- Sigmundsson, F., et al.
(author)
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Segmented lateral dyke growth in a rifting event at Bardarbunga volcanic system, Iceland
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 517:7533
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Journal article (peer-reviewed)abstract
- Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long(1). Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens(2-4), or magma flowing vertically into dykes from an underlying source(5,6), with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bardarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System(GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bardarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bardarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.
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| 21. |
- Skuladottir, AT, et al.
(author)
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A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1598-
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Journal article (peer-reviewed)abstract
- Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10−24, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.
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| 22. |
- von Horn, H, et al.
(author)
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GH is a regulator of IGF2 promoter-specific transcription in human liver
- 2002
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In: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 172:3, s. 457-465
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Journal article (peer-reviewed)abstract
- The regulation of the insulin-like growth factor-II gene (IGF2) is complex and involves the usage of four promoters resulting in different 5' untranslated regions, but with a common translated product. The IGF2 gene product is a mitogenic and survival factor that has been suggested to be important for a normal fetal development and cancer. In this paper we present evidence suggesting that the human IGF2 gene is regulated by GH, and that this regulation occurs in a promoter-specific way. Three lines of evidence support this finding. First, in vivo data from patients treated with GH (one injection or daily injections for 5 consecutive days) showed an increase in the IGF2 P2 promoter derived transcript after acute treatment, and of the P4 promoter transcript after short-term treatment while the P1 promoter derived transcript did not show any significant change. Secondly, isolated human liver cells treated with GH for 2 h displayed an upregulation of the P2 promoter derived transcript. Thirdly, employing transfection experiments in GH-receptor positive CHO cells with P2 and P4 promoter-luciferase constructs, an upregulation by GH was evident, while a P1 promoter construct was unresponsive. We suggest that GH may be a physiological regulator of IGF2 in humans.
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| 29. |
- Andersson, L-O, et al.
(author)
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A new neutron beam facility
- 2004
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In: Proc. of the 9th European Particle Accelerator Conference.
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Conference paper (peer-reviewed)
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| 34. |
- Bargholtz, C, et al.
(author)
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Using a CdTe detector for Te-125 Mossbauer Spectroscopy: Application to the f-factor in Mg3TeO6
- 2000
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In: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS. - : ELSEVIER SCIENCE BV. - 0168-583X. ; 170:1-2, s. 239-244
-
Journal article (peer-reviewed)abstract
- An apparatus for Mossbauer spectroscopy has been developed with a cadmium telluride (CdTe) gamma-ray detector. Complete data regarding gamma-ray energy, source velocity, temperature and real time are stored for off-line analysis. The apparatus has been us
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| 35. |
- Bjorkhem, I, et al.
(author)
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Differences in the regulation of the classical and the alternative pathway for bile acid synthesis in human liver : no coordinate regulation of CYP7A1 and CYP27A1.
- 2002
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:30, s. 26804-26807
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Journal article (peer-reviewed)abstract
- It has been reported that there is a coordinate regulation of sterol 27-hydroxylase (CYP27A1) and cholesterol 7_-hydroxylase (CYP7A1) in rats. Thus, the levels of the mRNA corresponding to these two enzymes were found to change in the same direction in rat liver and in isolated rat hepatocytes. In contrast, other groups have not seen such regulation of CYP27A1 in rabbit liver or in rat liver when using an activity assay. In the present work, the effect of bile acid treatment on human CYP27A1/luciferase reporter activity was studied in a transient transfection assay in human liver-derived HepG2 cells. Neither the endogenous 27-hydroxylase activity nor the CYP27A1/luciferase reporter activity were down-regulated by treatment of HepG2 cells with chenodeoxycholic acid or taurochenodeoxycholic acid. We also measured CYP27A1 mRNA and CYP7A1 mRNA in liver of humans subjected to treatment with chenodeoxycholic acid, ursodeoxycholic acid, hydroxymethylglutaryl (HMG)-CoA reductase inhibitor and a combination of HMG-CoA reductase inhibitor and cholestyramine. There was a 60-fold variation in the levels of CYP7A1 mRNA but only a 5-fold variation in the levels of CYP27A1 mRNA. There was no correlation between the two mRNA species. It is concluded that, in humans, there is little or no coordinate regulation of CYP7A1 and CYP27A1 at the transcriptional level, and that CYP27A1 is not subject to a negative feedback control by bile acids. The results underline that marked species differences may exist in mechanisms for control of synthesis of bile acids and cholesterol homeostasis.
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| 45. |
- Einarsson, Jon Thorkell, et al.
(author)
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Prevalence of sustained remission in rheumatoid arthritis: impact of criteria sets and disease duration, a Nationwide Study in Sweden
- 2019
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In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 58:2, s. 227-236
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Journal article (peer-reviewed)abstract
- Objectives The aims of this national study in Sweden of patients with RA were to: examine the prevalence of sustained remission (SR), that is, remission lasting for at least 6 months; compare the prevalence of SR in patients with early RA and established RA; study the timing of onset of and time spent in SR; and study possible predictors of SR. Methods Adult patients with RA included in the Swedish Rheumatology Quality registry were studied. The registry was searched for patients fulfilling remission criteria: DAS28-ESR, Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and ACR/EULAR remission for at least 6 months. Early RA was defined as symptom duration ⩽6 months at inclusion in the Swedish Rheumatology Quality. Results Of 29 084 patients, 12 193 (41.9%) reached DAS28 SR at some time point during follow-up compared with 6445 (22.2%), 6199 (21.3%) and 5087 (17.5%) for CDAI, SDAI and ACR/EULAR SR, respectively. SR was more common in early RA (P < 0.001). The median time from symptom onset to SR was 1.9, 2.4, 2.4 and 2.5 years according to DAS28, CDAI, SDAI and ACR/EULAR criteria, respectively. Lower age, male sex and milder disease characteristics were associated with SR. Conclusion The majority of patients in this nationwide study never reached SR. Patients with early RA are more likely to reach SR than patients with established RA.
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| 46. |
- Einarsson, Jon Thorkell, et al.
(author)
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Rituximab in clinical practice : dosage, drug adherence, Ig levels, infections, and drug antibodies
- 2017
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In: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 36:12, s. 2743-2750
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Journal article (peer-reviewed)abstract
- The objective of this study is to explore the following: (1) the impact of two different initial doses and cumulative 2-year dose of rituximab (RTX) on drug adherence and predictors of adherence to treatment in rheumatoid arthritis (RA) patients in an observational clinical setting, (2) immunoglobulin levels (IgG/IgM/IgA) during repeated treatment and their relation to infections, and (3) development of anti-rituximab antibodies (ADA). All RA patients receiving RTX from January 2003 to April 2012 at the department were included. The initiating doses were 500 or 1000 mg intravenously days 1 and 15. Drug adherence was estimated using life-table. Baseline predictors of adherence to treatment were analyzed using Cox regression model. Levels of immunoglobulins were measured at treatment initiation and before retreatment. Serum levels of RTX and ADA were measured in 96 patients at 6 months using ELISA. One hundred fifty-three patients were included. Seventy-four (48%) started treatment with 500 and 79 (52%) with 1000 mg. No difference in drug adherence was seen between the different initial or cumulative RTX doses. Methotrexate (MTX) use and low DAS28 at baseline predicted better drug adherence. Ig levels decreased with repeated treatments but low levels were not associated with infections. 11/96 patients had developed ADA at 6 months. Long-term adherence to RTX in RA patient was not influenced by starting- or cumulative 2-year doses. MTX use and low DAS28 at baseline was positively associated with drug adherence. Decreasing Ig levels during treatment were not associated with risk of infections. Development of ADA may influence treatment efficacy and tolerability.
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| 47. |
- Einarsson, Jon T., et al.
(author)
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Secular trends of sustained remission in rheumatoid arthritis, a nationwide study in Sweden
- 2020
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In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 59:1, s. 205-212
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The aim of this study of patients with RA in Sweden was to investigate secular trends in achieving sustained remission (SR), i.e. DAS28 <2.6 on at least two consecutive occasions and lasting for at least 6 months. METHODS: All adult RA patients registered in the Swedish Rheumatology Quality register through 2012, with at least three registered visits were eligible, a total of 29 084 patients. Year of symptom onset ranged from 1955, but for parts of the analysis only patients with symptom onset between 1994 and 2009 were studied. In total, 95% of patients fulfilled the ACR 1987 classification criteria for RA. Odds of reaching SR for each decade compared with the one before were calculated with logistic regression and individual years of symptom onset were compared with life table analysis. RESULTS: Of patients with symptom onset in the 1980s, 1990s and 2000s, 35.0, 43.0 and 45.6% reached SR, respectively (P < 0.001 for each increment), and the odds of SR were higher in every decade compared with the one before. The hazard ratio for reaching SR was 1.15 (95% CI 1.14, 1.15) for each year from 1994 to 2009 compared with the year before. Five years after symptom onset in 2009, 45.3% of patients had reached SR compared with 15.9% in 1999. CONCLUSION: There is a clear secular trend towards increased incidence of SR in patients with RA in Sweden. This trend most likely reflects earlier diagnosis and treatment start, and adherence to national and international guidelines recommending the treat to target approach.
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| 48. |
- Einarsson, Jon Thorkell, et al.
(author)
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Sustained Remission Improves Physical Function in Patients with Established Rheumatoid Arthritis, and Should Be a Treatment Goal : A Prospective Observational Cohort Study from Southern Sweden
- 2016
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 43:6, s. 1017-1023
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Journal article (peer-reviewed)abstract
- OBJECTIVE: It has been proposed that remission should be maintained throughout the course of rheumatoid arthritis (RA); however, the evidence supporting this is limited. Physical function measured by the Health Assessment Questionnaire (HAQ) is a major outcome in RA, and HAQ is shown to be one of the strongest predictors of longterm outcomes. The purpose of this study was to investigate the physical function over a long time in patients with RA who achieved sustained remission (SR) compared with that of patients occasionally achieving remission [non-sustained remission (NSR)].METHODS: Patients with RA treated with antitumor necrosis factor and included in the South Swedish Arthritis Treatment Group register were eligible for this study. We identified patients with a Disease Activity Score at 28 joints (DAS28) < 2.6 or Simplified Disease Activity Index (SDAI) ≤ 3.3 at some point and those who achieved SR, i.e., remission during consecutive visits for at least 6 months. The course of functional status was assessed using the HAQ at each visit.RESULTS: Of the 2416 patients, 1177 (48.7%) reached DAS28 remission at some point. SR was achieved by 382 (15.8%) for the DAS28 and 186 (7.7%) for the SDAI criteria. Comparing the SR and NSR groups, HAQ improved during the first 12 months in the DAS28 remission. HAQ continued to improve relatively as long as SR was maintained. A higher proportion of patients in SR reached full physical function.CONCLUSION: In patients with established RA, physical function measured by the HAQ improves in patients reaching SR compared with patients who only occasionally reach remission. The improvement continues while in remission, which supports that maintaining remission should be a treatment goal.
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| 49. |
- Einarsson, Jon Thorkell, et al.
(author)
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Sustained Remission in Tumor Necrosis Factor Inhibitor-treated Patients with Rheumatoid Arthritis: A Population-based Cohort Study.
- 2015
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 42:5, s. 741-748
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Journal article (peer-reviewed)abstract
- To study frequency, possible baseline predictors, timing, and duration of sustained remission [SR; defined as 28-joint Disease Activity Score (DAS28) < 2.6 for at least 6 mos] in patients with established rheumatoid arthritis (RA) treated with different tumor necrosis factor (TNF) inhibitors [etanercept (ETN), infliximab (IFX), adalimumab (ADA)]. In addition, the aim was to compare (head-to-head) the effectiveness of individual drugs in patients receiving their first anti-TNF treatment.
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