Published in 2018

2018 update of the EULAR recommendations for the management of Behçet's syndrome

Hatemi, G., Christensen, R., Bang, D., Bodaghi, B., Celik, A. F., Fortune, F., Gaudric, J., Gul, A., Kötter, I., Leccese, P., Mahr, A., Moots, R., Ozguler, Y., Richter, J., Saadoun, D., Salvarani, C., Scuderi, F., Sfikakis, P. P., Siva, A., Stanford, M., Tugal-Tutkun, I., West, R., Yurdakul, S., Olivieri, I. & Yazici, H. jun. 2018 I : Annals of the Rheumatic Diseases. 77, 6, s. 808-818 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Tidsskriftsnummer 6
Sider (fra-til) 808-818
Antal sider 11
ISSN 0003-4967
DOI
Status Udgivet - jun. 2018

A systematic review of measurement properties of patient reported outcome measures in psoriatic arthritis: A GRAPPA-OMERACT initiative

Højgaard, P., Klokker, L., Orbai, A-M., Holmsted, K., Bartels, E. M., Leung, Y. Y., Goel, N., de Wit, M., Gladman, D. D., Mease, P., Dreyer, L., Kristensen, L. E., FitzGerald, O., Tillett, W., Gossec, L., Helliwell, P., Strand, V., Ogdie, A., Terwee, C. B. & Christensen, R. 2018 I : Seminars in Arthritis and Rheumatism.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

BACKGROUND: An updated psoriatic arthritis (PsA) core outcome set (COS) for randomized controlled trials (RCTs) was endorsed at the Outcome Measures in Rheumatology (OMERACT) meeting in 2016.

OBJECTIVES: To synthesize the evidence on measurement properties of patient reported outcome measures (PROMs) for PsA and thereby contribute to development of a PsA core outcome measurement set (COMS) as described by the OMERACT Filter 2.0.

METHODS: A systematic literature search was performed in EMBASE, MEDLINE and PsycINFO on Jan 1, 2017 to identify full-text articles with an aim of assessing the measurement properties of PROMs in PsA. Two independent reviewers rated the quality of studies using the COnsensus based standards for the Selection of health Measurement INstruments (COSMIN) checklist, and performed a qualitative evidence synthesis.

RESULTS: Fifty-five studies were included in the systematic review. Forty-four instruments and a total of 89 scales were analyzed. PROMs measuring COS domains with at least fair quality evidence for good validity and reliability (and no evidence for poor properties) included the Stockerau Activity Score for PsA (German), Psoriasis Symptom Inventory, visual analogue scale for Patient Global, 36 Item Short Form Health Survey Physical Function subscale, Health Assessment Questionnaire Disability Index, Bath Ankylosing Spondylitis Functional Index, PsA Impact of Disease questionnaire, PsA Quality of Life questionnaire, VITACORA-19, Functional Assessment of Chronic Illness Therapy Fatigue scale and Social Role Participation Questionnaire.

CONCLUSIONS: At least one PROM with some evidence for aspects of validity and reliability was available for six of the eight mandatory domains of the PsA COS.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
ISSN 0049-0172
DOI
Status E-pub ahead of print - 2018

Bibliografisk note

COPECARE

Acute sensory and motor response to 45-s heavy isometric holds for the plantar flexors in patients with Achilles tendinopathy

O'Neill, S., Radia, J., Bird, K., Rathleff, M. S., Bandholm, T., Jorgensen, M. & Thorborg, K. 1 aug. 2018 I : Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: The purpose of this study was to explore the immediate effects of heavy isometric plantar flexor exercise on sensory output (pain during a functional task and mechanical pain sensitivity) and motor output (plantar flexor torque) in individuals with Achilles tendinopathy.

METHODS: Sixteen subjects with Achilles tendinopathy participated in the study, mean (SD) age 48.6 (8.9) years and Victorian institute assessment-Achilles (VISA-A) score 61.3 (23.0). Sensory testing assessing pain during a functional task, mechanical pain sensitivity and motor output, and plantar flexor peak torque was completed prior to the intervention. All subjects completed a 45-s heavy isometric plantar flexor contraction and were then re-tested using the same sensory and motor tests. Motor output was assessed using isokinetic dynamometry at speeds previously identified as of interest in subjects with Achilles tendinopathy.

RESULTS: Only 9 of the 16 subjects experienced pain during a functional task, self-reported pain was 4.2 (1.9) numerical rating scale (NRS) pre-intervention and 4.9 (3.2) NRS postintervention (n.s.). Mechanical pressure sensitivity was 446.5 (± 248.5) g/mm2 pre-intervention and 411.8 (± 211.8) g/mm2 post-intervention (n.s.). Mean concentric plantar flexor torque at 90 and 225°/s was 47.1 (14.5) and 33.6 (11.6) Nm, respectively, pre-intervention and 53.0 (18.5) and 33.4 (6.6) Nm post-intervention (p = 0.039 and n.s.). Eccentric torque at 90°/s was 98.5 (34.2) Nm preintervention versus 106.0 (41.4) Nm post-intervention (n.s.).

CONCLUSION: In this exploratory study, patients with Achilles tendinopathy had a varied sensory and motor output response to heavy isometric contractions. Using the recommended approach of heavy 45-s isometric contractions did not offer a meaningful acute benefit for sensory or motor output for subjects with Achilles tendinopathy. Based on this study, heavy 45-s isometric contractions cannot be recommended for immediate pain relief or improved motor output for patients with Achilles tendinopathy.

LEVEL OF EVIDENCE: IV, prospective cohort study.

Originalsprog Engelsk
Tidsskrift Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
ISSN 0942-2056
DOI
Status E-pub ahead of print - 1 aug. 2018

Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

Almholt, K., Hebsgaard, J. B., Nansen, A., Andersson, C., Pass, J., Rønø, B., Thygesen, P., Pelzer, H., Loftager, M., Lund, I. K., Høyer-Hansen, G., Frisch, T., Jensen, C. H., Otte, K. S., Søe, N. H., Bartels, E. M., Andersen, M., Bliddal, H. & Usher, P. A. 1 feb. 2018 I : Journal of immunology (Baltimore, Md. : 1950). 200, 3, s. 957-965

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target-mediated drug disposition consistent with a high turnover of endogenous uPA. The cellular expression patterns of uPA and uPAR were characterized by double immunofluorescence in the inflamed synovium from patients with rheumatoid arthritis and compared with synovium from healthy donors. The arthritic synovium showed expression of uPA and uPAR in neutrophils, macrophages, and a fraction of endothelial cells, whereas there was little or no expression in synovium from healthy donors. The data from animal models and human material provide preclinical proof-of-principle that validates uPA as a novel therapeutic target in rheumatic diseases.

Originalsprog Engelsk
Tidsskrift Journal of immunology (Baltimore, Md. : 1950)
Vol/bind 200
Tidsskriftsnummer 3
Sider (fra-til) 957-965
ISSN 0022-1767
DOI
Status Udgivet - 1 feb. 2018

Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study

Andersen, M., Boesen, M., Ellegaard, K., Söderström, K., Søe, N. H., Spee, P., Mørch, U. G. W., Torp-Pedersen, S., Bartels, E. M., Danneskiold-Samsøe, B., Karlsson, L. & Bliddal, H. 2018 I : PLoS One. 13, 5, s. e0197001

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline.

METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant.

RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.

CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 13
Tidsskriftsnummer 5
Sider (fra-til) e0197001
ISSN 1932-6203
DOI
Status Udgivet - 2018

Association between NICE guidance on biologic therapies with rates of hip and knee replacement among rheumatoid arthritis patients in England and Wales: An interrupted time-series analysis

Hawley, S., Cordtz, R., Dreyer, L., Edwards, C. J., Arden, N. K., Delmestri, A., Silman, A., Cooper, C., Judge, A. & Prieto-Alhambra, D. 2018 I : Seminars in Arthritis and Rheumatism. 47, 5, s. 605-610

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To estimate the impact of NICE approval of tumor necrosis factor inhibitor (TNFi) therapies on the incidence of total hip replacement (THR) and total knee replacement (TKR) among rheumatoid arthritis (RA) patients in England and Wales.

METHODS: Primary care data [Clinical Practice Research Datalink (CPRD)] for the study period (1995-2014) were used to identify incident adult RA patients. The age and sex-standardised 5-year incidence of THR and TKR was calculated separately for RA patients diagnosed in each six-months between 1995-2009. We took a natural experimental approach, using segmented linear regression to estimate changes in level and trend following the publication of NICE TA 36 in March 2002, incorporating a 1-year lag. Regression coefficients were used to calculate average change in rates, adjusted for prior level and trend.

RESULTS: We identified 17,505 incident RA patients of whom 465 and 650 underwent THR and TKR surgery, respectively. The modeled average incidence of THR and TKR over the biologic-era was 6.57/1000 person years (PYs) and 8.51/1000 PYs, respectively, with projected (had pre-NICE TA 36 level and trend continued uninterrupted) figures of 5.63/1000 PYs and 12.92 PYs, respectively. NICE guidance was associated with a significant average decrease in TKR incidence of -4.41/1000 PYs (95% C.I. -6.88 to -1.94), equating to a relative 34% reduction. Overall, no effect was seen on THR rates.

CONCLUSIONS: Among incident RA patients in England and Wales, NICE guidance on TNFi therapies for RA management was temporally associated with reduced rates of TKR but not THR.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 47
Tidsskriftsnummer 5
Sider (fra-til) 605-610
ISSN 0049-0172
DOI
Status Udgivet - 2018

Bibliografisk note

COPECARE

Better outcome from arthroscopic partial meniscectomy than skin incisions only? A sham-controlled randomised trial in patients aged 35-55 years with knee pain and an MRI-verified meniscal tear

Roos, E. M., Hare, K. B., Nielsen, S. M., Christensen, R. & Lohmander, L. S. 2 feb. 2018 I : BMJ Open. 8, 2, s. e019461

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Compare arthroscopic partial meniscectomy to a true sham intervention.

METHODS: Sham-controlled superiority trial performed in three county hospitals in Denmark comparing arthroscopic partial meniscectomy to skin incisions only in patients aged 35-55 years with persistent knee pain and an MRI-confirmed medial meniscus lesion. A computer-generated table of random numbers generated two comparison groups. Participants and outcome assessors were blinded to group allocation. Exclusions were locking knees, high-energy trauma or severe osteoarthritis. Outcomes were collected at baseline, 3 and 24 months. We hypothesised no difference between groups. The primary outcome was the between-group difference in change from baseline to 2 years in the mean score across all five normalised Knee injury and Osteoarthritis Outcome Score (KOOS) subscales (KOOS5).

RESULTS: Forty-four patients (of the estimated 72) underwent randomisation; 22 in each group. Sixteen participants (36%) were non-blinded and eight participants (36%) from the sham group crossed over to the surgery group prior to the 2-year follow-up. At 2 years, both groups reported clinically relevant improvements (surgery 21.8, skin incisions only 13.6), the mean difference between groups was 8.2 in favour of surgery, which is slightly less than the cut-off of 10 prespecified to represent a clinically relevant difference; judged by the 95% CI (-3.4 to 19.8), a possibility of clinically relevant difference could not be excluded. In total, nine participants experienced 11 adverse events; six in the surgery group and three in the skin-incisions-only group.

CONCLUSION: We found greater improvement from arthroscopic partial meniscectomy compared with skin incisions only at 2 years, with the statistical uncertainty of the between-group difference including what could be considered clinically relevant. Because of the study being underpowered, nearly half in the sham group being non-blinded and one-third crossing over to surgery, the results cannot be generalised to the greater patient population.

TRIAL REGISTRATION NUMBER: NCT01264991.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 8
Tidsskriftsnummer 2
Sider (fra-til) e019461
ISSN 2044-6055
DOI
Status Udgivet - 2 feb. 2018

Burden of rheumatoid arthritis in the Nordic region, 1990-2015: a comparative analysis using the Global Burden of Disease Study 2015

Kiadaliri, A. A., Kristensen, L-E. & Englund, M. mar. 2018 I : Scandinavian Journal of Rheumatology. 47, 2, s. 1-101 101 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To report mortality and disability due to rheumatoid arthritis (RA) in the Nordic region (Denmark, Finland, Greenland, Iceland, Norway, and Sweden) using data from the Global Burden of Disease Study (GBD) 2015.

METHOD: Using the results of GBD 2015, we present rates and trends in prevalence, mortality, years of life lost, years lived with disability (YLD), and disability-adjusted life-years (DALYs) of RA in the Nordic region during 1990-2015.

RESULTS: In 2015, the age-standardized prevalence of RA was higher in the Nordic region than the global level (0.44%, 95% uncertainty interval 0.40-0.48%, vs 0.35%, 0.32-0.38%). For women (men), DALYs increased by 2.4% (12.9%), from 29 263 (10 909) in 1990 to 29 966 (12 311) in 2015. The burden of RA as a proportion of total DALYs in women (men) increased from 0.90% (0.29%) in 1990 to 0.94% (0.36%) in 2015. Age-standardized DALY rates declined in all countries except Denmark and Greenland between 1990 and 2015. Of 315 conditions studied, RA was ranked as the 16th (37th) leading cause of YLD in women (men) in the region. Of 195 countries studied, Greenland, Finland, Denmark, Norway, Sweden, and Iceland had the 7th, 11th, 28th, 38th, 48th, and 78th highest age-standardized YLD rates for RA, respectively.

CONCLUSIONS: The prevalence of RA in the Nordic region is higher than the global average. Current trends in population growth and ageing suggest a potential increase in RA burden in the coming decades in the region that should be considered in healthcare resources allocation.

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Rheumatology
Vol/bind 47
Tidsskriftsnummer 2
Sider (fra-til) 1-101
Antal sider 101
ISSN 0300-9742
DOI
Status Udgivet - mar. 2018

Carotid intima-media thickness (IMT) and ankle brachial index (ABI) are non-invasive indicators of generalised atherosclerosis. The aim was to determine the association between carotid IMT and ABI in subjects with and without diabetes mellitus (DM), and to analyse specific age change-points. We included 2744 subjects from the Copenhagen City Heart Study (mean age (SD) 56.6 (17.2) years, 56.8% women and body mass index (BMI) 25.4 (4.1) kg/m2). Carotid IMT and ABI measurements were performed during the fifth examination. Of the 2744 subjects, 125 subjects (4.6%) had DM. Average carotid IMT was 0.667 (0.145) mm and ABI was 1.06 (0.14). Subjects with DM were older, had higher BMI and systolic blood pressure (SBP) (all p < .001). Carotid IMT was higher in subjects with DM (0.754 (0.150) mm) compared to subjects without DM (0.662 (0.144) mm) (p < .001), whereas there was no difference in ABI between the two groups. ABI was inversely associated with carotid IMT (slope = -0.17 [-0.207; -0.137] (p < .001). The association remained significant after adjustment for risk factors both in subjects with DM (slope = -0.168 [-0.328; -0.007], p = .040), and in subjects without DM (slope = -0.100 [-0.148; -0.052], p < .001), with a stronger effect of carotid IMT on ABI among subjects with DM. Carotid IMT and ABI were inversely associated in subjects with DM and without DM, but with a stronger effect in subjects with DM. Age and ABI revealed a change-point with a stronger inverse association among subjects aged >60 years.

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Clinical and Laboratory Investigation
Sider (fra-til) 1-6
Antal sider 6
ISSN 0036-5513
DOI
Status E-pub ahead of print - 3 aug. 2018

Changes in job strain and subsequent weight gain: a longitudinal study, based on the Danish Nurse Cohort

Vesterlund, G. K., Keller, A. C. & Heitmann, B. L. apr. 2018 I : Public Health Nutrition. 21, 6, s. 1131-1138 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Obesity as well as job strain is increasing, and job strain might contribute to weight gain. The objective of the current study was to examine associations between longitudinal alterations in the components of job strain and subsequent weight gain.

DESIGN: The study was designed as a prospective cohort study with three questionnaire surveys enabling measurement of job-strain alterations over 6 years and subsequent measurements of weight gain after further 10 years of follow-up. ANCOVA and trend analyses were conducted. Job demands were measured as job busyness and speed, and control as amount of influence.

SETTING: Employed nurses in Denmark.

SUBJECTS: We included a sub-sample of 6188 female nurses from the Danish Nurse Cohort, which consisted of the nurses who participated in surveys in 1993, 1999 and 2009.

RESULTS: A linear trend in weight gain was seen in nurses who were often busy in 1999 between those who were rarely v. sometimes v. often busy in 1993 (P=0·03), with the largest weight gain in individuals with sustained high busyness in both years. Loss of influence between 1993 and 1999 was associated with larger subsequent weight gain than sustained high influence (P=0·003) or sustained low influence (P=0·02). For speed, no associations were found.

CONCLUSIONS: Busyness, speed and influence differed in their relationship to subsequent weight gain. A decrease in job influence and a sustained burden of busyness were most strongly related to subsequent weight gain. Focus on job strain reduction and healthy diet is essential for public health.

Originalsprog Engelsk
Tidsskrift Public Health Nutrition
Vol/bind 21
Tidsskriftsnummer 6
Sider (fra-til) 1131-1138
Antal sider 8
ISSN 1368-9800
DOI
Status Udgivet - apr. 2018

Concentration of 25-hydroxyvitamin D from neonatal dried blood spots and the relation to gestational age, birth weight and Ponderal Index: the D-tect study

Keller, A., Händel, M. N., Frederiksen, P., Jacobsen, R., Cohen, A. S., McGrath, J. J. & Heitmann, B. L. jun. 2018 I : The British journal of nutrition. 119, 12, s. 1416-1423 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Studies have suggested that vitamin D status at birth may be associated with a range of neonatal outcomes. The aim of this study was to assess the association between neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration and gestational age, birth weight, Ponderal Index and size for gestational age. Neonatal capillary blood stored as dried blood spots was used to assess 25(OH)D3 concentrations among 2686 subjects selected from a random population sub-sample of individuals, born in Denmark from 1 May 1981 to 31 December 2002. There was an inverse association between 25(OH)D3 concentration and gestational age at birth of -0·006 (95 % CI -0·009, -0·003, P<0·001) weeks of gestation per 1 nmol/l increase in 25(OH)D3 concentration. An inverted U-shaped association between 25(OH)D3 and birth weight and Ponderal Index (P=0·04) was found, but no association with size for gestational age was shown. This study suggests that neonatal 25(OH)D3 concentration is associated with anthropometric measures at birth known to be correlated with many subsequent health outcomes such as obesity and type 2 diabetes.

Originalsprog Engelsk
Tidsskrift The British journal of nutrition
Vol/bind 119
Tidsskriftsnummer 12
Sider (fra-til) 1416-1423
Antal sider 8
ISSN 0007-1145
DOI
Status Udgivet - jun. 2018

Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF treatment in rheumatoid arthritis

Sode, J., Vogel, U., Bank, S., Andersen, P. S., Hetland, M. L., Locht, H., Heegaard, N. H. H. & Andersen, V. 2018 I : The pharmacogenomics journal.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Several genetic variants in Toll-like receptor (TLR) and nuclear factor (NF)-κB signalling pathways have been reported associated with responsiveness to tumour necrosis factor inhibitor (anti-TNF) treatment in rheumatoid arthritis (RA). The present study was undertaken to replicate these findings. In a retrospective case-case study including 1007 Danish anti-TNF-treated RA patients, we genotyped 7 previously reported associated single-nucleotide polymorphisms (SNPs) in these pathways. Furthermore, 5 SNPs previously reported by our group were genotyped in a subcohort (N=469). Primary analyses validated the IRAK3 rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR (European League Against Rheumatism) good/moderate vs none response at 4±2 months), and found the NLRP3 rs461266 variant associated (OR=0.75, 95% CI: 0.60-0.94, P=0.014) with a negative treatment response. Meta-analyses combining data from previous studies suggested smaller effect sizes of associations between variant alleles of CHUK rs11591741, NFKBIB rs3136645 and rs9403 and a negative treatment response. In conclusion, this study validates rs11541076 in IRAK3, a negative regulator of TLR signalling, as a predictor of anti-TNF treatment response, and suggests true positive associations of previously reported SNPs within genes encoding activators/inhibitors of NF-κB (CHUK, MYD88, NFKBIB, and NLRP3).The Pharmacogenomics Journal advance online publication, 4 October 2016; doi:10.1038/tpj.2016.66.

Originalsprog Engelsk
Tidsskrift The pharmacogenomics journal
ISSN 1470-269X
DOI
Status E-pub ahead of print - 2018

Cross-sectional associations between maternal self-efficacy and dietary intake and physical activity in four-year-old children of first-time Swedish mothers

Rohde, J. F., Bohman, B., Berglind, D., Hansson, L. M., Frederiksen, P., Mortensen, E. L., Heitmann, B. L. & Rasmussen, F. 1 jun. 2018 I : Appetite. 125, s. 131-138 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Healthy dietary and physical activity behaviours are established early in life where children learn by observing their parents. Therefore, parents can act as role models and influence their children toward a healthier lifestyle. Besides a strong association between parental and child health behaviours, parents also influence their children's health behaviours through socio-cognitive processes, where perceived self-efficacy is the central component. The objective was to examine if parental self-efficacy among Swedish mothers was associated with their four-year-old children's dietary and physical activity behaviours.

METHODS: This cross-sectional study was based on information from control participants that took part in the Swedish primary prevention trial of childhood obesity (PRIMROSE) (n = 420 mother-child pairs). Linear regression models were used to examine the associations between parental self-efficacy (Parental Self-Efficacy for Promoting Healthy Physical Activity and Dietary Behaviours in Children Scale) and children's dietary intake (parent reported) and levels of physical activity (accelerometer) with adjustments for potential confounders.

RESULTS: Mothers' efficacy beliefs in promoting healthy dietary or physical activity behaviours in their children were associated with a slightly higher consumption of fruit and vegetables among their children (β: 0.03 [95%CI: 0.01; 0.04] P < 0.001) and slightly higher levels of moderate-to-vigorous activity (β: 0.43 [95%CI: 0.05; 0.81] P = 0.03). Mothers' belief in their ability to limit unhealthy dietary and physical activity behaviours was inversely associated with children's intake of unhealthy snacks (β: -0.06 [95%CI: -0.10; -0.02] P < 0.01).

CONCLUSION: Our cross-sectional study suggests weak positive correlations between maternal self-efficacy and healthy dietary and physical activity behaviours, and weak inverse associations between maternal self-efficacy and unhealthy dietary and physical activity behaviours among their children.

Originalsprog Engelsk
Tidsskrift Appetite
Vol/bind 125
Sider (fra-til) 131-138
Antal sider 8
ISSN 0195-6663
DOI
Status Udgivet - 1 jun. 2018

Diverse hepatic microbial DNA fingerprints in healthy lean and obese steatotic humans

Bagger, J. I., Suppli, M. P., Nielsen, T., Lelouvier, B., Broha, A., Demant, M. G., Kønig, M. J., Strandberg, C., Lund, A., Vilsbøll, T. & Knop, F. K. 2 okt. 2018 (Accepteret/In press)

Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

Originalsprog Engelsk
Publikationsdato 2 okt. 2018
Status Accepteret/In press - 2 okt. 2018
Begivenhed 54th EASD Annual Meeting: EASD 2018 - Berlin, Tyskland
Varighed: 1 okt. 20185 okt. 2018
https://www.easd.org/programme-2018.html

Konference

Konference 54th EASD Annual Meeting
Land Tyskland
By Berlin
Periode 01/10/201805/10/2018
Internetadresse

Objectives: A cohort of routine care RA patients in sustained remission had biological DMARD (bDMARDs) tapered according to a treatment guideline. We studied: the proportion of patients whose bDMARD could be successfully tapered or discontinued; unwanted consequences of tapering/discontinuation; and potential baseline predictors of successful tapering and discontinuation.

Methods: One-hundred-and-forty-three patients (91% receiving TNF inhibitor and 9% a non-TNF inhibitor) with sustained disease activity score (DAS28-CRP)⩽2.6 and no radiographic progression the previous year were included. bDMARD was reduced to two-thirds of standard dose at baseline, half after 16 weeks, and discontinued after 32 weeks. Patients who flared (defined as either DAS28-CRP ⩾ 2.6 and ΔDAS28-CRP ⩾ 1.2 from baseline, or erosive progression on X-ray and/or MRI) stopped tapering and were escalated to the previous dose level.

Results: One-hundred-and-forty-one patients completed 2-year follow-up. At 2 years, 87 patients (62%) had successfully tapered bDMARDs, with 26 (18%) receiving two-thirds of standard dose, 39 (28%) half dose and 22 (16%) having discontinued; and 54 patients (38%) were receiving full dose. ΔDAS28-CRP0-2yrs was 0.1((-0.2)-0.4) (median (interquartile range)) and mean ΔTotal-Sharp-Score0-2yrs was 0.01(1.15)(mean(s.d.)). Radiographic progression was observed in nine patients (7%). Successful tapering was independently predicted by: ⩽1 previous bDMARD, male gender, low baseline MRI combined inflammation score or combined damage score. Negative IgM-RF predicted successful discontinuation.

Conclusion: By implementing a clinical guideline, 62% of RA patients in sustained remission in routine care were successfully tapered, including 16% successfully discontinued at 2 years. Radiographic progression was rare. Maximum one bDMARDs, male gender, and low baseline MRI combined inflammation and combined damage scores were independent predictors for successful tapering.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
ISSN 1462-0324
DOI
Status E-pub ahead of print - 28 aug. 2018

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Effects of Lifestyle on Muscle Strength in a Healthy Danish Population

Bartels, E. M., Robertson, S., Danneskiold-Samsøe, B., Appleyard, M. & Stockmarr, A. jan. 2018 I : Journal of lifestyle medicine. 8, 1, s. 16-22 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: Lifestyle is expected to influence muscle strength. This study aimed at assessing a possible relationship between smoking, alcohol intake and physical activity, and muscle strength in a healthy Danish population aged 20-79 years. Population study based on data collected from The Copenhagen City Heart Study (CCHS) and measurements of Isokinetic muscle strength from a sub-study of randomly selected healthy participants from CCHS.

Methods: 126 women and 63 men were studied. All participants completed a questionnaire regarding their lifestyle, including physical activity, alcohol intake and smoking habits. Isokinetic muscle strength was measured over the upper extremities (UE), trunk, and lower extremities (LE). Multivariate analyses including all of the variables were carried out.

Results: The level of daily physical activity during leisure was positively correlated to muscle strength in the lower extremities (p = 0.03) for women, and lower extremities (p = 0.03) and trunk (p = 0.007) for men. Alcohol Intake was in general not correlated to muscle strength. No clear effect of smoking was seen on muscle strength.

Conclusion: Our results show that physical activity during leisure is associated with a positive effect on muscle strength in both sexes. When keeping alcohol intake within the recommended limits, alcohol does not seem to affect muscle strength negatively. No effect of smoking on muscle strength was found in our group of healthy subjects. The findings are of importance when considering recommendation on life style when wishing to keeping fit with age to be able to carry out daily activities.

Originalsprog Engelsk
Tidsskrift Journal of lifestyle medicine
Vol/bind 8
Tidsskriftsnummer 1
Sider (fra-til) 16-22
Antal sider 7
ISSN 2234-8549
DOI
Status Udgivet - jan. 2018

Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial

Kragsnaes, M. S., Kjeldsen, J., Horn, H. C., Munk, H. L., Pedersen, F. M., Holt, H. M., Pedersen, J. K., Holm, D. K., Glerup, H., Andersen, V., Fredberg, U., Kristiansen, K., Christensen, R. & Ellingsen, T. 27 apr. 2018 I : BMJ Open. 8, 4, s. e019231

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA.

METHODS AND ANALYSIS: This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study.

ETHICS AND DISSEMINATION: This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s).

TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 8
Tidsskriftsnummer 4
Sider (fra-til) e019231
ISSN 2044-6055
DOI
Status Udgivet - 27 apr. 2018

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

Skaaby, T., Taylor, A. E., Thuesen, B. H., Jacobsen, R. K., Friedrich, N., Møllehave, L. T., Hansen, S., Larsen, S. C., Völker, U., Nauck, M., Völzke, H., Hansen, T., Pedersen, O., Jørgensen, T., Paternoster, L., Munafò, M., Grarup, N. & Linneberg, A. 2018 I : Allergy. 73, 1, s. 153-64

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC).

METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI).

RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m(2) higher BMI.

CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Originalsprog Engelsk
Tidsskrift Allergy
Vol/bind 73
Tidsskriftsnummer 1
Sider (fra-til) 153-64
ISSN 0105-4538
DOI
Status Udgivet - 2018

EULAR recommendations for the health professional's approach to pain management in inflammatory arthritis and osteoarthritis

Geenen, R., Overman, C. L., Christensen, R., Åsenlöf, P., Capela, S., Huisinga, K. L., Husebø, M. E. P., Köke, A. J. A., Paskins, Z., Pitsillidou, I. A., Savel, C., Austin, J., Hassett, A. L., Severijns, G., Stoffer-Marx, M., Vlaeyen, J. W. S., Fernández-de-Las-Peñas, C., Ryan, S. J. & Bergman, S. jun. 2018 I : Annals of the Rheumatic Diseases. 77, 6, s. 797-807 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional's approach to pain management. A multidisciplinary task force including professionals and patient representatives conducted a systematic literature review of systematic reviews to evaluate evidence regarding effects on pain of multiple treatment modalities. Overarching principles and recommendations regarding assessment and pain treatment were specified on the basis of reviewed evidence and expert opinion. From 2914 review studies initially identified, 186 met inclusion criteria. The task force emphasised the importance for the health professional to adopt a patient-centred framework within a biopsychosocial perspective, to have sufficient knowledge of IA and OA pathogenesis, and to be able to differentiate localised and generalised pain. Treatment is guided by scientific evidence and the assessment of patient needs, preferences and priorities; pain characteristics; previous and ongoing pain treatments; inflammation and joint damage; and psychological and other pain-related factors. Pain treatment options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta-analyses, these recommendations enable health professionals to provide knowledgeable pain-management support for people with IA and OA.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Tidsskriftsnummer 6
Sider (fra-til) 797-807
Antal sider 11
ISSN 0003-4967
DOI
Status Udgivet - jun. 2018

Exposure to vitamin D from fortified margarine during fetal life and later risk of pre-eclampsia: the D-tect Study

Stougaard, M., Damm, P., Frederiksen, P., Jacobsen, R. & Heitmann, B. L. 24 mar. 2018 I : Public Health Nutrition. 21, 4, s. 721-731 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To examine if fetal exposure to a small dosage of extra vitamin D from food fortification was associated with a decrease in the risk of pre-eclampsia later in life.

DESIGN: Cancellation of the mandatory vitamin D fortification of margarine in 1985 created a societal experiment, with entire adjacent birth cohorts exposed or unexposed to extra vitamin D during fetal development. The Danish national medical health registries allowed the identification of pre-eclampsia cases later in life among all exposed and unexposed female individuals.

SETTING: Denmark.

SUBJECTS: Women born between June 1983 and August 1988, who gave birth to their first child at age 14·5-27·5 years (n 32 621).

RESULTS: OR (95 % CI) for pre-eclampsia among women exposed v. unexposed to extra vitamin D from fortification during fetal development was 0·86 (0·76, 0·97). Exposure to extra vitamin D was associated with further reduced odds of pre-eclampsia (0·49 (0·34, 0·72)) among current smokers, but not among former smokers and non-smokers.

CONCLUSIONS: Additional vitamin D in fetal life from food fortification seems to reduce the risk of pre-eclampsia later in life. The risk reduction may be particularly strong among women who smoke during pregnancy.

Originalsprog Engelsk
Tidsskrift Public Health Nutrition
Vol/bind 21
Tidsskriftsnummer 4
Sider (fra-til) 721-731
Antal sider 11
ISSN 1368-9800
DOI
Status Udgivet - 24 mar. 2018

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