Published in 2015

EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice

Mandl, P., Navarro-Compán, V., Terslev, L., Aegerter, P., van der Heijde, D., D'Agostino, M. A., Baraliakos, X., Pedersen, S. J., Jurik, A. G., Naredo, E., Schueller-Weidekamm, C., Weber, U., Wick, M. C., Bakker, P. A. C., Filippucci, E., Conaghan, P. G., Rudwaleit, M., Schett, G., Sieper, J., Tarp, S., Marzo-Ortega, H. & Østergaard, M. jul. 2015 I : Annals of the Rheumatic Diseases. 74, 7, s. 1327-1339 13 s.

Publikation: Forskning - peer reviewTidsskriftartikel

A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 74
Tidsskriftsnummer 7
Sider (fra-til) 1327-1339
Antal sider 13
ISSN 0003-4967
DOI
Status Udgivet - jul. 2015

IMPORTANCE: Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and disability. Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach, but no evidence supports the recommendation.

OBJECTIVE: To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee.

DESIGN, SETTING, AND PARTICIPANTS: We performed a randomized, blinded, placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1, 2012, through April 2, 2014. The participants had radiographic confirmation of clinical OA of the knee, clinical signs of localized inflammation in the knee, and knee pain during walking (score >4 on a scale of 0 to 10).

INTERVENTIONS: Participants were randomly allocated (1:1) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate (Depo-Medrol), 40 mg/mL, dissolved in 4 mL of lidocaine hydrochloride (10 mg/mL) (corticosteroid group) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride (10 mg/mL) (placebo group). Two weeks after the injections, all participants started a 12-week supervised exercise program.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire (range, 0-100; higher scores indicate greater improvement) at week 14. Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation. Outcomes were measured at baseline, week 2 (exercise start), week 14 (exercise stop), and week 26 (follow-up).

RESULTS: One hundred patients were randomized to the corticosteroid group (n = 50) or the placebo group (n = 50); 45 and 44 patients, respectively, completed the trial. The mean (SE) changes in the KOOS Pain subscale score at week 14 were 13.6 (1.8) and 14.8 (1.8) points in the corticosteroid and placebo groups, respectively, corresponding to a statistically insignificant mean difference of 1.2 points (95% CI, -3.8 to 6.2; P = .64). We found no statistically significant group differences in any of the secondary outcomes at any time point.

CONCLUSIONS AND RELEVANCE: No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee. Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments.

TRIAL REGISTRATION: clinicaltrialsregister.eu Identifier: 2012-002607-18; clinicaltrials.gov Identifier: NCT01945749.

Originalsprog Engelsk
Tidsskrift JAMA Internal Medicine
Vol/bind 175
Tidsskriftsnummer 6
Sider (fra-til) 923-30
Antal sider 8
DOI
Status Udgivet - 1 jun. 2015
Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 74
Tidsskriftsnummer Suppl. 2
Sider (fra-til) 306
Antal sider 1
ISSN 0003-4967
Status Udgivet - 2015

Feasibility and Domain Validation of Rheumatoid Arthritis (RA) Flare Core Domain Set: Report of the OMERACT 2014 RA Flare Group Plenary

Bartlett, S. J., Bykerk, V. P., Cooksey, R., Choy, E. H., Alten, R., Christensen, R., Furst, D. E., Guillemin, F., Halls, S., Hewlett, S., Leong, A. L., Lyddiatt, A., March, L., Montie, P., Orbai, A. M., Pohl, C., Voshaar, M. S., Woodworth, T. G. & Bingham, C. O. nov. 2015 I : Journal of Rheumatology. 42, 11, s. 2185-9 5 s.

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Flare Group was established to develop an approach to identify and measure RA flares. An overview of our OMERACT 2014 plenary is provided.

METHODS: Feasibility and validity of flare domains endorsed at OMERACT 11 (2012) were described based on initial data from 3 international studies collected using a common set of questions specific to RA flare. Mean flare frequency, severity, and duration data were presented, and domain scores were compared by flare status to examine known-groups validity. Breakout groups provided input for stiffness, self-management, contextual factors, and measurement considerations.

RESULTS: Flare data from 501 patients in an observational study indicated 39% were in flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation, and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were obtained: r = 0.46 to 0.93. A combined definition (patient report of flare and 28-joint Disease Activity Score increase) was evaluated in 2 other trials, with similar results. Breakout groups debated specific measurement issues.

CONCLUSION: These data contribute initial evidence of feasibility and content validation of the OMERACT RA Flare Core Domain Set. Our research agenda for OMERACT 2016 includes establishing duration/intensity criteria and developing criteria to identify RA flares using existing disease activity measures. Ongoing work will also address discordance between patient and physician ratings, facilitate application of flare criteria to clinical care, elucidate the role of self-management, and finalize recommendations for RA flare measurement.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 42
Tidsskriftsnummer 11
Sider (fra-til) 2185-9
Antal sider 5
ISSN 0315-162X
DOI
Status Udgivet - nov. 2015

Forebyggelse af skeletrelaterede hændelser hos patienter med knoglemetastaser ved solide tumorer

Kamby, C., Tarp, S., Mellemgaard, A., Christensen, R., Cold, S., Eiken, P., Jakobsen, E. H., Langkilde, N. C., Langkjer, S. T., Laursen, T., Ottesen, S. S., Pedersen, A. G., Stenbygaard, L. E. & Vestlev, P. M. 2015 I : Ugeskrift for læger [online]. 177, 7, s. 645-48

Publikation: Forskning - peer reviewTidsskriftartikel

This article is based on a systematic literature search and meta-analyses of clinical data regarding effects of bisphosphonates (BP) and denosumab (DS) on preventing skeletal related events (SRE) in patients with bone metastases from solid tumours. Although there are pharmacological differences between the different types of BP no major differences were observed between BP in preventing SRE or in adverse events. Treatment with DS has in three randomised trials showed a greater effect than BP in preventing SRE. The optimal choice of bone-anti-resorptive agent should depend on the patient's general condition, renal function and treatment logistics.

Originalsprog Dansk
Tidsskrift Ugeskrift for læger [online]
Vol/bind 177
Tidsskriftsnummer 7
Sider (fra-til) 645-48
ISSN 1603-6824
Status Udgivet - 2015

Gait variability and motor control in people with knee osteoarthritis

Alkjaer, T., Raffalt, P. C., Dalsgaard, H., Simonsen, E. B., Petersen, N. C., Bliddal, H. & Henriksen, M. okt. 2015 I : Gait & posture. 42, 4, s. 479-84 6 s.

Publikation: Forskning - peer reviewTidsskriftartikel

Knee osteoarthritis (OA) is a common disease that impairs walking ability and function. We compared the temporal gait variability and motor control in people with knee OA with healthy controls. The purpose was to test the hypothesis that the temporal gait variability would reflect a more stereotypic pattern in people with knee OA compared with healthy age-matched subjects. To assess the gait variability the temporal structure of the ankle and knee joint kinematics was quantified by the largest Lyapunov exponent and the stride time fluctuations were quantified by sample entropy and detrended fluctuation analysis. The motor control was assessed by the soleus (SO) Hoffmann (H)-reflex modulation and muscle co-activation during walking. The results showed no statistically significant mean group differences in any of the gait variability measures or muscle co-activation levels. The SO H-reflex amplitude was significantly higher in the knee OA group around heel strike when compared with the controls. The mean group difference in the H-reflex in the initial part of the stance phase (control-knee OA) was -6.6% Mmax (95% CI: -10.4 to -2.7, p=0.041). The present OA group reported relatively small impact of their disease. These results suggest that the OA group in general sustained a normal gait pattern with natural variability but with suggestions of facilitated SO H-reflex in the swing to stance phase transition. We speculate that the difference in SO H-reflex modulation reflects that the OA group increased the excitability of the soleus stretch reflex as a preparatory mechanism to avoid sudden collapse of the knee joint which is not uncommon in knee OA.

Originalsprog Engelsk
Tidsskrift Gait & posture
Vol/bind 42
Tidsskriftsnummer 4
Sider (fra-til) 479-84
Antal sider 6
ISSN 0966-6362
DOI
Status Udgivet - okt. 2015

Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis

Sode, J., Vogel, U., Bank, S., Andersen, P. S., Hetland, M. L., Locht, H., Heegaard, N. H. H. & Andersen, V. 2015 I : P L o S One. 10, 10, s. e0139781

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVES: To determine whether genetic variation within genes related to the Toll-like receptor, inflammasome and interferon-γ pathways contributes to the differences in treatment response to tumour necrosis factor inhibitors (anti-TNF) in patients with rheumatoid arthritis (RA).

METHODS: In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs) in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value<0.05) between genotypes and European League Against Rheumatism (EULAR) treatment responses. False Discovery Rate corrections for multiple testing (q-value) and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF) status.

RESULTS: Six of twenty successfully genotyped polymorphisms were nominally associated with EULAR treatment response. Three of these were in weak to moderate linkage disequilibrium with polymorphisms previously reported associated with anti-TNF treatment response. TLR5(rs5744174) variant allele carriers (odds ratio(OR) = 1.7(1.1-2.5),p = 0.010,q = 0.46) and TLR1(rs4833095) homozygous variant carriers (OR = 2.8(1.1-7.4),p = 0.037,q = 0.46) had higher odds for a positive treatment response. NLRP3(rs10754558) variant allele carriers (odds ratio(OR) = 0.6(0.4-1.0),p = 0.045,q = 0.46) were more likely to have a negative treatment response. The association in TLR5(rs5744174) remained significant after correction for multiple comparisons among patients negative for RF (OR = 6.2(2.4-16.3),p = 0.0002,q = 0.024). No other association withstood correction for multiple testing. Post hoc analyses showed that change in Patient Global score on a visual analogue scale (VAS) and change in pain VAS were the main factors responsible for the association.

CONCLUSIONS: We reproduced previously reported associations between genetic variation in the TLR10/1/6 gene cluster, TLR5, and NLRP3 loci and response to anti-TNF treatment in RA. Changes in VAS pain and patient global scores were the main contributors to the association found for TLR5. Furthermore, we identified other candidate genes that require replication in independent cohorts.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 10
Tidsskriftsnummer 10
Sider (fra-til) e0139781
ISSN 1932-6203
DOI
Status Udgivet - 2015

The objective of the study was to assess whether gestational and early infancy exposure to low dose vitamin D from a mandatory margarine fortification programme in Denmark influenced the risk of developing type 1 diabetes (T1D) before age of 15 years. The study population included all individuals born in Denmark from 1983 to 1988 and consisted of 331,623 individuals. The 1st of June 1985, which was the date of issue of the new ministerial order cancelling mandatory fortification of margarine with vitamin D in Denmark, served as a reference point separating the studied population into various exposure groups. We further modelled birth cohort effects in children developing T1D as a linear spline, and compared the slopes between the birth cohorts with various prenatal and infancy exposures to vitamin D fortification. In total, 886 (0.26%) individuals developed T1D before the age of 15 years. The beta coefficients (95% CI), or slopes, for linear birth cohort effect in log Hazard Ratio (HR) per one month of birth in individuals born during the periods of gestational exposure, wash-out, and non-exposure were: 0.010 (-0.002/0.021), -0.010 (-0.035/0.018), and 0.008 (- 0.017/0.032), respectively. The beta coefficients (95% CI) for individuals born during the periods of first postnatal year exposure, wash-out, and non-exposure were: 0.007 (-0.016/0.030), 0.006 (-0.004/0.016), and 0.007 (-0.002/0.016), respectively. In conclusion, we found no evidence to support that exposure to low dose vitamin D from the Danish mandatory margarine fortification regimen during gestational and first postnatal year of life changed the risk of developing T1D before the age of 15 years.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 10
Tidsskriftsnummer 6
Sider (fra-til) e0128631
ISSN 1932-6203
DOI
Status Udgivet - 2015

INTRODUCTION: Current pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the corner stone in the management of T2D. However, there is a lack of knowledge regarding the optimal intervention programmes in T2D ensuring both compliance as well as long-term health outcomes. Our objective is to assess the effects of an intensive lifestyle intervention (the U-TURN intervention) on glycaemic control in patients with T2D. Our hypothesis is that intensive lifestyle changes are equally effective as standard diabetes care, including pharmacological treatment in maintaining glycaemic control (ie, glycated haemoglobin (HbA1c)) in patients with T2D. Furthermore, we expect that intensive lifestyle changes will decrease the need for antidiabetic medications.

METHODS AND ANALYSIS: The study is an assessor-blinded, parallel group and a 1-year randomised trial. The primary outcome is change in glycaemic control (HbA1c), with the key secondary outcome being reductions in antidiabetic medication. Participants will be patients with T2D (T2D duration <10 years) without complications who are randomised into an intensive lifestyle intervention (U-TURN) or a standard care intervention in a 2:1 fashion. Both groups will be exposed to the same standardised, blinded, target-driven pharmacological treatment and can thus maintain, increase, reduce or discontinue the pharmacological treatment. The decision is based on the standardised algorithm. The U-TURN intervention consists of increased training and basal physical activity level, and an antidiabetic diet including an intended weight loss. The standard care group as well as the U-TURN group is offered individual diabetes management counselling on top of the pharmacological treatment.

ETHICS AND DISSEMINATION: This study has been approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-1-2014-114). Positive, negative or inconclusive findings will be disseminated in peer-reviewed journals, at national and international conferences.

TRIAL REGISTRATION NUMBER: NCT02417012.

Originalsprog Engelsk
Tidsskrift B M J Open
Vol/bind 5
Tidsskriftsnummer 12
Sider (fra-til) e009764
ISSN 2044-6055
DOI
Status Udgivet - 2015

OBJECTIVES: By whole-body MRI (WBMRI), we aimed to examine the frequency and distribution of inflammatory and structural lesions in PsA patients, SpA patients and healthy subjects (HSs), to introduce global WBMRI inflammation/damage scores, and to assess WBMRI's reproducibility and correlation with conventional MRI (convMRI).

METHODS: WBMRI (3.0-T) of patients with peripheral PsA (n = 18) or axial SpA (n = 18) and of HS (n = 12) was examined for proportion of evaluable features (readability) and the presence and pattern of lesions in axial and peripheral joints. Furthermore, global WBMRI scores of inflammation and structural damage were constructed, and WBMRI findings were compared with clinical measures and convMRI (SpA/HS: spine and SI joints; PsA/HS: hand).

RESULTS: The readability (92-100%) and reproducibility (intrareader intraclass correlation coefficient: 0.62-1.0) were high in spine/SI joint, but lower in the distal peripheral joints. Wrists, shoulders, knees, ankles and MTP joints were most commonly involved, with frequency of synovitis > bone marrow oedema (BMO) > erosion. WBMRI global BMO scores of peripheral and axial joints were higher in PsA {median 7 [interquartile range (IQR) 3-15]} and SpA [8 (IQR 2-14)] than in HSs [2.5 (IQR 1-4.5)], both P < 0.05. WBMRI global structural damage scores (erosion, fat infiltration and ankylosis) were higher in SpA [7 (IQR 3-12)] than HSs [1.5 (IQR 0-4.5)], P = 0.012. Correlations between WBMRI and convMRI spine and SI joint scores were ρ = 0.20-0.78.

CONCLUSION: WBMRI allows simultaneous assessment of peripheral and axial joints in PsA and SpA, and the distribution of inflammatory and structural lesions and global scores can be determined. The study strongly encourages further development and longitudinal testing of WBMRI techniques and assessment methods in PsA and SpA.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Udgivelsesdato 2015
ISSN 1462-0324
DOI
Status E-pub ahead of print

IKs Gain- and Loss-of-Function in Early-Onset Lone Atrial Fibrillation

Steffensen, A. B., Refsgaard, L., Andersen, M. N., Vallet, C., Mujezinovic, A., Haunsø, S., Svendsen, J. H., Olesen, S-P., Olesen, M. S. & Schmitt, N. jul 2015 I : Journal of cardiovascular electrophysiology. 26, 7, s. 715-23 9 s.

Publikation: Forskning - peer reviewTidsskriftartikel

INTRODUCTION: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.1), was the first ion channel dysfunction to be associated with familial AF. We hypothesized that early-onset lone AF is associated with a high prevalence of mutations in KCNQ1.

METHODS AND RESULTS: We bidirectionally sequenced the entire coding sequence of KCNQ1 in 209 unrelated patients with early-onset lone AF (<40 years) and investigated the identified mutations functionally in a heterologous expression system. We found 4 nonsynonymous KCNQ1 mutations (A46T, R195W, A302V, and R670K) in 4 unrelated patients (38, 31, 39, and 36 years, respectively). None of the mutations were present in the control group (n = 416 alleles). No other mutations were found in genes previously associated with AF. The mutations A46T, R195W, and A302V have previously been associated with long-QT syndrome. In line with previous reports, we found A302V to display a pronounced loss-of-function of the IKs current, while the other mutants exhibited a gain-of-function phenotype.

CONCLUSIONS: Mutations in the IKs channel leading to gain-of-function have previously been described in familial AF, yet this is the first time a loss-of-function mutation in KCNQ1 is associated with early-onset lone AF. These findings suggest that both gain-of-function and loss-of-function of cardiac potassium currents enhance the susceptibility to AF.

Originalsprog Engelsk
Tidsskrift Journal of cardiovascular electrophysiology
Udgivelsesdato jul 2015
Vol/bind 26
Tidsskriftsnummer 7
Sider 715-23
Antal sider 9
ISSN 1045-3873
DOI
Status Udgivet

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, progressive joint disease, which frequently leads to irreversible joint deformity and severe functional impairment. Although patients are treated according to existing guidelines and reach clinical remission, erosive progression still occurs. This demonstrates that additional methods for prognostication and monitoring of the disease activity are needed. Bone marrow edema (BME) detected by magnetic resonance imaging (MRI) has proved to be an independent predictor of subsequent radiographic progression. Guiding the treatment based on the presence/absence of BME may therefore be clinically beneficial. We present the design of a randomized controlled trial (RCT) aiming to evaluate whether an MRI-guided treatment strategy compared to a conventional treatment strategy in anti-CCP-positive erosive RA is better to prevent progression of erosive joint damage and increase the remission rate in patients with low disease activity or clinical remission.

METHODS/DESIGN: The study is a non-blinded, multicenter, 2-year RCT with a parallel group design. Two hundred anti-CCP-positive, erosive RA patients characterized by low disease activity or remission, no clinically swollen joints and treatment with synthetic disease-modifying antirheumatic drugs (DMARDs) will be included. Patients will be randomized to either a treatment strategy based on conventional laboratory and clinical examinations (control group) or a treatment strategy based on conventional laboratory and clinical examinations as well as MRI (intervention group). Treatment is intensified according to a predefined treatment algorithm in case of inflammation defined as a disease activity score (DAS28) >3.2 and at least one clinically swollen joint (control and intervention groups) and/or MRI-detected BME (intervention group only). The primary outcome measures are DAS28 remission (DAS28 < 2.6) and radiographic progression (Sharp/vdHeijde score).

DISCUSSION: The perspectives, strengths and weaknesses of this study are discussed. This study has been approved by The Regional Scientific Ethical Committees for Southern Denmark, S-20110109. Dissemination will occur through presentations and publication in international peer-reviewed journals.

TRIAL REGISTRATION: The study is registered in http://www.ClinicalTrials.gov identifier: NCT01656278 (5 July 2012).

Originalsprog Engelsk
Tidsskrift Trials
Vol/bind 16
Tidsskriftsnummer 1
Sider (fra-til) 178
ISSN 1745-6215
DOI
Status Udgivet - 2015

PURPOSE: To evaluate the efficacy of a specialized rosehip powder nutraceutical on the biomechanical function of the knee joint during walking in individuals with knee-related walking limitations.

METHODS: Randomized, participant and outcome assessor blinded trial. Participants with self-reported knee-related walking limitations were randomized (1:1) to receive three capsules/day of either rosehip powder or identically appearing placebo capsules for 12 weeks. At baseline and the 12 weeks follow-up, 3-dimensional gait analyses were performed from which the peak resultant knee moment was selected as primary outcome. Secondary outcomes included sagittal and frontal plane knee joint moments, knee joint kinematics, peaks in the vertical ground reaction forces, and self-selected walking speeds. Analyses were based on ANCOVA with the 'Intention-To-Treat' (ITT) population, defined as all randomized participants using last observation carried forward imputation for missing data.

RESULTS: 100 participants were randomized to rosehip (n=50) or placebo (n=50) and defined the ITT population. Of these 94 completed the study (47 in each group). There were statistically significant group differences in the change from baseline in the primary outcome: the resultant knee moment (0.06 nm/kg, 95%CI: 0.00-0.12; P=0.039) and in the peaks in the sagittal plane moments and kinematics during the stance phase of walking with the rosehip group exhibiting greater joint moments and more knee joint flexion during walking than the placebo group.

CONCLUSION: A daily intake of rosehip powder for 12 weeks improved important indices of knee joint function and dynamics during walking compared to placebo in persons with knee-related walking limitations.

Originalsprog Engelsk
Tidsskrift Gait & posture
Vol/bind 42
Tidsskriftsnummer 3
Sider (fra-til) 340-7
Antal sider 8
ISSN 0966-6362
DOI
Status Udgivet - sep. 2015

Increase in waist circumference over 6 years predicts subsequent cardiovascular disease and total mortality in nordic women

Klingberg, S., Mehlig, K., Lanfer, A., Björkelund, C., Heitmann, B. L. & Lissner, L. okt. 2015 I : Obesity (Silver Spring, Md.). 23, 10, s. 2123-30 8 s.

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVE: Despite solid evidence of an association between centralized body fatness and subsequent disease risk, little is known about the consequences of changes in body fat distribution. Recently it was shown that large hip circumference (HC), measured once, was protective against total and cardiovascular disease (CVD) mortality in women but that gain or loss in HC was unrelated to these outcomes. This study examines whether a 6-year change in waist circumference (WC) predicts mortality and CVD in the same study sample.

METHODS: Baseline WC and 6-year change in WC as predictors of mortality and CVD were analyzed in 2,492 women from the Danish MONICA study and the Prospective Population Study of Women in Gothenburg, Sweden.

RESULTS: Increase in WC was significantly associated with increased subsequent mortality and CVD adjusting for BMI and other covariates, with some evidence of a J-shaped association. Associations between increase in WC and outcomes were restricted to women with normal weight at baseline and to ever-smokers.

CONCLUSIONS: In contrast to changes in HC which did not predict mortality and CVD, a 6-year increase in WC is strongly predictive, particularly among initially lean women and ever-smokers. This implies the importance of developing strategies to prevent central fat deposition.

Originalsprog Engelsk
Tidsskrift Obesity (Silver Spring, Md.)
Vol/bind 23
Tidsskriftsnummer 10
Sider (fra-til) 2123-30
Antal sider 8
ISSN 1930-7381
DOI
Status Udgivet - okt. 2015

International Consensus for ultrasound lesions in gout: results of Delphi process and web-reliability exercise

Gutierrez, M., Schmidt, W. A., Thiele, R. G., Keen, H. I., Kaeley, G. S., Naredo, E., Iagnocco, A., Bruyn, G. A., Balint, P. V., Filippucci, E., Mandl, P., Kane, D., Pineda, C., Delle Sedie, A., Hammer, H. B., Christensen, R., D'Agostino, M. A., Terslev, L. & OMERACT Ultrasound Gout Task Force group okt. 2015 I : Rheumatology (Oxford, England). 54, 10, s. 1797-805 9 s.

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVE: To produce consensus-based definitions of the US elementary lesions in gout and to test their reliability in a web-based exercise.

METHODS: The process consisted of two steps. In the first step a written Delphi questionnaire was developed from a systematic literature review and expert international consensus. This collated information resulted in four statements defining US elementary lesions: double contour (DC), tophus, aggregates and erosion. The Delphi questionnaire was sent to 35 rheumatology experts in US, asking them to rate their level of agreement or disagreement with each statement. The second step tested the reliability by a web-exercise. US images of both normal and gouty elementary lesions were collected by the participants. A facilitator then constructed an electronic database of 110 images. The database was sent to the participants, who evaluated the presence/absence of US elementary lesions. A group of 20 images was displayed twice to evaluate intra-reader reliability.

RESULTS: A total of 32 participants responded to the questionnaires. Good agreement (>80%) was obtained for US definitions on DC, tophus, aggregates and erosion in the Delphi exercise after three rounds. The reliability on images showed inter-reader κ values for DC, tophus, aggregates, erosion findings of 0.98, 0.71, 0.54 and 0.85, respectively. The mean intra-reader κ values were also acceptable: 0.93, 0.78, 0.65 and 0.78, respectively.

CONCLUSION: This, the first consensus-based US definition of elementary lesions in gout, demonstrated good reliability overall. It constitutes an essential step in developing a core outcome measurement that permits a higher degree of homogeneity and comparability between multicentre studies.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 54
Tidsskriftsnummer 10
Sider (fra-til) 1797-805
Antal sider 9
ISSN 1462-0324
DOI
Status Udgivet - okt. 2015

Magnetic resonance imaging in rheumatoid arthritis

Østergaard, M., Axelsen, M. B. & Boesen, M. 2015 Atlas of Rheumatoid Arthritis. Springer Healthcare

Publikation: Forskning - peer reviewBidrag til bog/antologi

Originalsprog Engelsk
Titel Atlas of Rheumatoid Arthritis
Udgiver Springer Healthcare
Publikationsdato 2015
Status Udgivet - 2015

Managing chronic pain in survivors of torture

Amris, K. & Williams, A. C. D. C. jan. 2015 I : Pain Management. 5, 1, s. 5-12 8 s.

Publikation: Forskning - peer reviewTidsskriftartikel

All generalist and specialist clinicians are likely to encounter torture survivors among refugees and asylum seekers. A minority of people survive torture and a smaller minority reach a developed country; those who do tend to be the more resilient and resourceful. They have many health, social and welfare problems; persistent pain in the musculoskeletal system is one of the most common. There is little specific evidence on pain in survivors of torture; the guidelines on interdisciplinary specialist management are applicable. Most of the literature on refugee survivors of torture has an exclusive focus on psychological disorders, with particularly poor understanding of pain problems. This article summarizes the current status of assessment and treatment of pain problems in the torture survivor.

Originalsprog Engelsk
Tidsskrift Pain Management
Vol/bind 5
Tidsskriftsnummer 1
Sider (fra-til) 5-12
Antal sider 8
ISSN 1758-1869
DOI
Status Udgivet - jan. 2015

OBJECTIVE: To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs)) for rheumatoid arthritis (RA).

METHODS: We conducted a meta-epidemiological study of all trials evaluating a targeted therapy approved by regulatory authorities for treating RA. The database search was completed on December 11th 2013. Eligible trials reported ACR20 data at months 3-6 and used an add-on design. Odds ratios (ORs) were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR).

RESULTS: Sixty-two trials (19,923 RA patients) were included in the primary analyses using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI) 3.41 to 4.60). The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower in trials including "DMARD-naïve" patients compared with trials including "DMARD inadequate responders" (ROR = 0.45, 95%CI 0.31 to 0.66) and trials including "targeted therapy inadequate responders" (0.50, 95%CI 0.29 to 0.87), test for interaction: p = 0.0002. Longer mean disease duration was associated with a higher likelihood of responding to treatment (β = 1.05, 95%CI 1.00 to 1.11 OR's per year; p = 0.03). Analyses conducted using DAS28-remission as the outcome supported the above-mentioned findings.

CONCLUSION: Our results suggest that a highly selective inclusion is not associated with greater treatment effect, as might otherwise be expected. The added benefit of a targeted therapy was lower in trials including patients who were DMARD-naïve and trials including patients with shorter disease durations.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 10
Tidsskriftsnummer 9
Sider (fra-til) e0136982
ISSN 1932-6203
DOI
Status Udgivet - 2015

MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16

Østergaard, M., Jacobsson, L. T. H., Schaufelberger, C., Hansen, M. S., Bijlsma, J. W. J., Dudek, A., Rell-Bakalarska, M., Staelens, F., Haake, R., Sundman-Engberg, B. & Bliddal, H. 2015 I : Annals of the Rheumatic Diseases. 74, s. 1156-1163 8 s.

Publikation: Forskning - peer reviewTidsskriftartikel

OBJECTIVES: To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA).

METHODS: Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0-4; CZP 200 mg every 2 weeks at weeks 6-16) or placebo→CZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200 mg every 2 weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures.

RESULTS: Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group.

CONCLUSIONS: CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01235598.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Tidsskriftsnummer 74
Sider (fra-til) 1156-1163
Antal sider 8
ISSN 0003-4967
DOI
Status Udgivet - 2015

BACKGROUND: Soccer players are commonly affected by long-standing adductor-related groin pain (ARGP), but the clinical significance of MRI findings in these athletes is largely unknown. Our aims were (1) to evaluate whether MRI findings are associated with long-standing ARGP in soccer players, (2) to assess MRI findings in asymptomatic soccer players and non-soccer playing controls.

METHODS: This cross-sectional study included 28 male soccer players with long-standing ARGP, 17 male asymptomatic soccer players and 20 male asymptomatic non-soccer playing athletes of matching age and athletic exposure. Participants underwent identical standardised and reliable clinical examination, and MRI scans (3 T) of the pelvis performed by a blinded observer. Images were consensus rated by three blinded radiologists according to a standardised MRI evaluation protocol. The associations between clinical adductor-related findings and pathological MRI findings were investigated with χ(2) statistics and OR.

RESULTS: Central disc protrusion (p=0.027) and higher grades of pubic bone marrow oedema (BMO; p=0.027) were significantly more present in symptomatic players than asymptomatic players. However, up to 71% of asymptomatic soccer players displayed different positive MRI findings, and asymptomatic soccer players had significantly higher odds (OR ranging from 6.3 to 13.3) for BMO, adductor tendinopathy and degenerative changes than non-soccer players.

CONCLUSIONS: ARGP in soccer players was associated with central disc protrusion and higher grades of pubic BMO. Moreover, positive MRI findings were significantly more frequent in soccer players compared with non-soccer players irrespective of symptoms, suggesting that these MRI changes may be associated with soccer play itself rather than clinical symptoms.

Originalsprog Engelsk
Tidsskrift British Journal of Sports Medicine
Vol/bind 49
Sider (fra-til) 681-91
ISSN 0306-3674
DOI
Status Udgivet - 2015

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