Published in 2017

AIM: To assess the effect of elevated basal shear stress on angiogenesis in humans and the role of enhanced skeletal muscle capillarization on blood flow and O2 extraction.

METHODS: Limb haemodynamics and O2 extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24 W) in 10 healthy untrained young men before and after 4-week treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day-1 ). Corresponding biopsies were taken from the m. vastus lateralis.

RESULTS: Resting leg blood flow was increased by 57% 6 h following Terazosin treatment (P < 0.05), while basal capillary-to-fibre ratio was 1.69 ± 0.08 and increased to 1.90 ± 0.08 after treatment (P < 0.05). Leg O2 extraction during knee-extensor exercise was higher (4-5%; P < 0.05), leg blood flow and venous lactate levels lower (6-7%; P < 0.05), while leg VO2 was not different after Terazosin treatment.

CONCLUSIONS: These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarization resulted in an increased fractional O2 extraction, a lower blood flow and venous lactate levels in the exercising leg. The increase in capillarization, and concomitant functional readouts in the exercising leg, may provide a basis for novel angiotherapy.

Originalsprog Engelsk
Tidsskrift Acta physiologica (Oxford, England)
Vol/bind 221
Tidsskriftsnummer 1
Sider (fra-til) 32-43
Antal sider 12
ISSN 1748-1708
DOI
Status Udgivet - sep. 2017

An OMERACT Initiative Toward Consensus to Identify and Characterize Candidate Contextual Factors: Report from the Contextual Factors Working Group

Finger, M. E., Boonen, A., Woodworth, T. G., Escorpizo, R., Christensen, R., Nielsen, S. M., Leong, A. L., Scholte-Voshaar, M., Flurey, C. A., Milman, N., Verstappen, S. M. M., Alten, R., Guillemin, F., Kloppenburg, M., Beaton, D. E., Tugwell, P. S., March, L. M., Furst, D. E. & Pohl, C. 1 maj 2017 I : Journal of Rheumatology.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The importance of contextual factors (CF) for appropriate patient-specific care is widely acknowledged. However, evidence in clinical trials on how CF influence outcomes remains sparse. The 2014 Outcome Measures in Rheumatology (OMERACT) Handbook introduced the role of CF in outcome assessment and defined them as "potential confounders and/or effect modifiers of outcomes in randomized controlled trials." Subsequently, the CF Methods Group (CFMG) was formed to develop guidance on how to address CF in clinical trials.

METHODS: First, the CFMG conducted an e-mail survey of OMERACT working groups (WG) to analyze how they had addressed CF in outcome measurement so far. The results facilitated an informed discussion at the OMERACT 2016 CFMG Special Interest Group (SIG) session, with the aim of gaining preliminary consensus regarding an operational definition of CF and to make a first selection of potentially relevant CF.

RESULTS: The survey revealed that the WG had mostly used the OMERACT Handbook and/or the International Classification of Functioning, Disability and Health (ICF) definition. However, significant heterogeneity was found in the methods used to identify, refine, and categorize CF candidates. The SIG participants agreed on using the ICF as a framework along with the OMERACT Handbook definition. A list with 28 variables was collected including person-related factors and physical and social environments. Recommendations from the SIG guided the CFMG to formulate 3 preliminary projects on how to identify and analyze CF.

CONCLUSION: New methods are urgently needed to assist researchers to identify and characterize CF that significantly influence the interpretation of results in clinical trials. The CFMG defined first steps to develop further guidance.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
ISSN 0315-162X
DOI
Status Udgivet - 1 maj 2017

Ankylosing Spondylitis versus Nonradiographic Axial Spondyloarthritis: Comparison of Tumor Necrosis Factor Inhibitor Effectiveness and Effect of HLA-B27 Status. An Observational Cohort Study from the Nationwide DANBIO Registry

Glintborg, B., Sørensen, I. J., Østergaard, M., Dreyer, L., Mohamoud, A. A., Krogh, N. S., Hendricks, O., Andersen, L. S., Raun, J. L., Kowalski, M. R., Danielsen, L., Pelck, R., Nordin, H., Pedersen, J. K., Kraus, D. G., Christensen, S. R., Hansen, I. M., Esbesen, J., Schlemmer, A., Loft, A. G., Al Chaer, N., Salomonsen, L. & Hetland, M. L. jan. 2017 I : Journal of Rheumatology. 44, 1, s. 59-69 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status).

METHODS: Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e.g., Bath Ankylosing Spondylitis Activity Index (BASDAI) 50%/20 mm].

RESULTS: The study included 1250 TNFi-naive patients with axSpA (29% nr-axSpA, 50% AS, 21% lacked radiographs of sacroiliac joints). Patients with nr-axSpA were more frequently women (50%/27%) and HLA-B27-negative (85/338 = 25%), compared to AS (81/476 = 17%; p < 0.01). At TNFi start patients with nr-axSpA had higher visual analog scale scores [median (quartiles)] for pain: 72 mm (55-84)/65 mm (48-77); global: 76 mm (62-88)/68 mm (50-80); fatigue: 74 mm (55-85)/67 mm (50-80); and BASDAI: 64 (54-77)/59 (46-71); all p < 0.01. However, patients with nr-axSpA had lower C-reactive protein: 7 mg/l (3-17)/11 mg/l (5-22); and BAS Metrology Index: 20 (10-40)/40 (20-50); all p < 0.01. Median (95% CI) treatment adherence was poorer in nr-axSpA than in AS: 1.59 years (1.15-2.02) versus 3.67 years (2.86-4.49), p < 0.0001; but only in univariate and not confounder-adjusted analyses (p > 0.05). Response rates were similar in AS and nr-axSpA (p > 0.05). HLA-B27 negativity was associated with poorer treatment adherence [HLA-B27 negative/positive, nr-axSpA: HR 1.74 (1.29-2.36), AS: HR 2.04 (1.53-2.71), both p < 0.0001]; and lower response rates (nr-axSpA: 18/61 = 30% vs 93/168 = 55%; AS: 17/59 = 29% vs 157/291 = 54%, both p < 0.05).

CONCLUSION: In this nationwide cohort, patients with nr-axSpA had higher subjective disease activity at start of first TNFi treatment, but similar outcomes to patients with AS after confounder adjustment. HLA-B27 positivity was associated with better outcomes irrespective of axSpA subdiagnosis.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 44
Tidsskriftsnummer 1
Sider (fra-til) 59-69
Antal sider 11
ISSN 0315-162X
DOI
Status Udgivet - jan. 2017

OBJECTIVE: To examine the hypothesis that change in pain self-efficacy is associated with observed and self-reported activity, pain intensity, catastrophizing, and quality of life after multi-disciplinary rehabilitation of fibromyalgia patients.

DESIGN: In-depth analyses of secondary outcomes of a randomized-controlled trial.

SUBJECTS: Women (N = 187) with fibromyalgia.

METHODS: Outcomes were Pain Self-Efficacy, Assessment of Motor and Process Skills (AMPS), SF-36 Physical Function (SF-36-PF), pain intensity, and SF-36 Mental Composite Score (SF-36-MCS) to assess quality of life and pain catastrophizing. Individual and group associations between outcomes were examined.

RESULTS: Individual changes in pain self-efficacy were not associated with changes in observed activity: AMPS motor (rs = 0.08, p = 0.27) and process (rs = 0.12, p = 0.11), not even in those patients with a clinically relevant improvement in observed functioning (38.5%), and only weakly or moderatly with changes in SF-36-PF; (rs = 0.31, p < 0.0001), SF-36-MSC; (rs = 0.41, p < 0.0001), and pain catastrophizing (rs = -0.31, p < 0.0001). No differences in pain self-efficacy were observed between the rehabilitated group and controls (difference: 1.61; 95% CI: -0.84 to 4.06; p = 0.24). However, a subgroup (34%) had a clinically relevant improvement in pain self-efficacy. This group was younger (mean age 41.4 vs. 45.8, p = 0.01), more recently diagnosed (1.8 vs. 2.8 years, p = 0.003), but had an unresolved welfare situation (59% vs. 40%, p = 0.02).

CONCLUSION: The main hypothesis was falsified, as there was no association between pain self-efficacy and actual performance of activity. The relation to functioning may be limited to perceived, cognitive-emotional aspects, as indicated by the weak to moderate correlations to the self-reported measures. Implications for Rehabilitation Improvement in observed activity post multi-disciplinary rehabilitation was not associated with change in pain self-efficacy. Patients performed better after rehabilitation, but did not perceive to have improved their capacity. The relationship between pain self-efficacy and functioning may be limited to cognitive-emotional aspects rather than actual activity. Both observational and self-reported measures should be included in evaluating outcomes of rehabilitation for patients with fibromyalgia.

Originalsprog Engelsk
Tidsskrift Disability and rehabilitation
Vol/bind 39
Tidsskriftsnummer 17
Sider (fra-til) 1744-1752
Antal sider 9
ISSN 1464-5165
DOI
Status Udgivet - aug. 2017

BACKGROUND AND PURPOSE: Older adults acutely hospitalized for medical illness typically have comorbidity and disability, and inhospital physical inactivity greatly increases the likelihood of developing new disability. Thus, assessment of the patients' mobility status is crucial for planning and carrying out targeted interventions that ensure mobilization during hospital admission. The aim of this study was to determine convergent validity, known group validity, floor and ceiling effects, and anchor-based minimal clinically important difference (MCID) of the more time-consuming de Morton Mobility Index (DEMMI) and the less time-consuming Cumulated Ambulation Score (CAS) in older adults acutely hospitalized for medical illness.

METHODS: In this multicenter cohort study, 235 older hospitalized adults, with a mean (standard deviation) age of 84.8 (7.1) years, were consecutively included. Assessments of mobility using the DEMMI (score range 0-100), the CAS (score range 0-6), and the Barthel Index (BI, score range 0-100) were performed by physical or occupational therapists at hospital admission and discharge. In addition, at discharge patients and therapists were independently asked to assess the patients' current mobility status compared with their mobility status at hospital admission using the Global Rating of Change scale.

RESULTS AND DISCUSSION: Complete data sets were obtained for 155 patients. Baseline characteristics of those with complete data sets did not differ from those with incomplete data sets, except for the number of secondary diagnoses, which was lower in the latter. Significant and moderate relationships existed both at admission and at discharge between scores in the DEMMI and the BI (rs = 0.68, P < .0001, and rs = 0.71, P < .0001), and between scores in the CAS and the BI (rs = 0.60, P < .0001, and rs = 0.57, P < .0001). Use of a gait aid and discharge to inpatient rehabilitation or nursing home were associated with significantly lower DEMMI and CAS scores. No floor or ceiling effects were present in the DEMMI, while a ceiling effect was present in the CAS. The MCID scores based on patients' assessments were 10.7 points for the DEMMI and 0.67 for the CAS.

CONCLUSIONS: These data show that the DEMMI is valid and responsive to changes in mobility and can be considered to have the required properties for measuring mobility in older adults who are hospitalized in medical and geriatric wards. In contrast, the CAS appears to be appropriate to identify whether a patient is independently mobile or needs assistance, while the measure is less suitable for measuring improvements in mobility.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Originalsprog Engelsk
Tidsskrift Journal of geriatric physical therapy (2001)
ISSN 1539-8412
DOI
Status E-pub ahead of print - 15 dec. 2017

Association between baseline vitamin D metabolite levels and long-term cardiovascular events in patients with rheumatoid arthritis from the CIMESTRA trial: protocol for a cohort study with patient-record evaluated outcomes

Herly, M., Stengaard-Pedersen, K., Hørslev-Petersen, K., Hetland, M. L., Østergaard, M., Christensen, R., Løgstrup, B. B., Vestergaard, P., Pødenphant, J., Junker, P. & Ellingsen, T. 8 apr. 2017 I : B M J Open. 7, 4, s. e014816

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Cardiovascular morbidity and mortality is increased in patients with rheumatoid arthritis (RA), and among these patients, the prevalence of hypovitaminosis D is high. Moreover, low vitamin D levels have been associated with increased cardiovascular risk in healthy subjects.

OBJECTIVE: To evaluate the long-term risk of cardiovascular events in patients having low total 25-hydroxyvitamin D levels at baseline compared with patients with normal levels, in an efficiently treated, closed cohort of patients with an early diagnosis of RA.

METHODS AND ANALYSIS: This study is a prospective, closed, blinded endpoint cohort study, based on secondary analyses from a previous randomised trial (CIMESTRA study; NCT00209859, approved September 1999) including 160 patients with an early diagnosis of RA from Danish University clinics. Primary outcome will be the proportion of patients with any cardiovascular event in the follow-up period, evaluated using systematic journal audits. Logistic regression models will test the hypothesis that there are more cardiovascular events in enrolled patients with a low level of vitamin D (< 50 nmol/L). Secondarily, Cox regression models, based on survival analysis, will determine the extent to which independent variables (including different levels of vitamin D at baseline) predict whether a cardiovascular event will occur, and also when this will be.

ETHICS AND DISSEMINATION: All patients have received verbal and written information before enrolment, and have given written consent at baseline. To disseminate comprehension of factors of prognostic importance to cardiovascular outcome in RA, we will attempt to have a first draft ready no later than 1 year after the adjudication process has finished. If low vitamin D levels can predict cardiovascular events in RA, it is relevant to take into account in a prediction model, to be considered by patients, physicians and other decision-makers.

TRIAL REGISTRATION NUMBER: The parental controlled trial is registered as NCT00209859.

Originalsprog Engelsk
Tidsskrift B M J Open
Vol/bind 7
Tidsskriftsnummer 4
Sider (fra-til) e014816
ISSN 2044-6055
DOI
Status Udgivet - 8 apr. 2017

Association Between Use of Cannabis in Adolescence and Weight Change into Midlife

Jin, L. Z., Rangan, A., Mehlsen, J., Andersen, L. B., Larsen, S. C. & Heitmann, B. L. 2017 I : P L o S One. 12, 1, s. e0168897

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Cannabis use has been found to stimulate appetite and potentially promote weight gain via activation of the endocannabinoid system. Despite the fact that the onset of cannabis use is typically during adolescence, the association between adolescence cannabis use and long-term change in body weight is generally unknown. This study aims to examine the association between adolescence cannabis use and weight change to midlife, while accounting for the use of other substances. The study applied 20 to 22 years of follow-up data on 712 Danish adolescents aged between 15 and 19 years at baseline. Self-reported height and weight, cannabis, cigarette and alcohol use, socioeconomic status (SES) and physical activity levels were assessed in baseline surveys conducted in 1983 and 1985. The follow-up survey was conducted in 2005. In total 19.1% (n = 136) of adolescents reported having used/using cannabis. Weight gain between adolescence and midlife was not related to cannabis exposure during adolescence in either crude or adjusted models, and associations were not modified by baseline alcohol intake or smoking. However, cannabis use was significantly associated with cigarette smoking (p<0.001) and alcohol intake (p<0.001) and inversely associated with physical activity levels (p = 0.04). In conclusion, this study does not provide evidence of an association between adolescence cannabis use and weight change from adolescence to midlife.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 12
Tidsskriftsnummer 1
Sider (fra-til) e0168897
ISSN 1932-6203
DOI
Status Udgivet - 2017

Authors' reply: Refers to: Prognostic factors associated with mortality in patients with septic arthritis: a descriptive cohort study

Andreasen, R. A., Andersen, N. S., Just, S. A., Christensen, R. & Hansen, I. M. J. 31 maj 2017 I : Scandinavian Journal of Rheumatology. 46, 4, s. 332-333 2 s.

Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Rheumatology
Vol/bind 46
Tidsskriftsnummer 4
Sider (fra-til) 332-333
Antal sider 2
ISSN 0300-9742
DOI
Status Udgivet - 31 maj 2017

Bandager til Knælidelser

Henriksen, M. & Skou, S. T. 18 sep. 2017 I : Ugeskrift for laeger. 179, 38

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

The use of knee braces is common, and there is an abundance of different brace types available both "over the counter" and as "prescription devices". The braces are used for a range of knee problems ranging from minor knee discomfort to post-surgical rehabilitation. The available evidence is generally in favour of brace applications although the amount and quality of evidence is moderate to low with a positive benefit-harm balance. However, braces should generally not be used as a stand-alone or primary treatment strategy, but can be used as a potentially beneficial supplement to patients with knee disorders if needed.

Originalsprog Dansk
Tidsskrift Ugeskrift for laeger
Vol/bind 179
Tidsskriftsnummer 38
ISSN 0041-5782
Status Udgivet - 18 sep. 2017

Bursitis efter vaccination i skulderregionen

Bliddal, H., Torp-Pedersen, S., Falk-Riecke, B. & Bartels, E. 23 okt. 2017 I : Ugeskrift for laeger. 179, 43, s. V05170423

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Shoulder pain may develop after vaccination in the deltoid area due to inadvertent injection of the vaccine into the subdeltoid bursa, which may be located close to the skin. As far as we know, such vaccination reactions occur more frequently than officially registered, and doctors may not be aware of the problem. We present two of these cases of a suspected inflammatory reaction in the shoulder bursa after vaccination. Injection of cortisone in the bursa may relieve the reaction to some extent, but chronic shoulder pain may develop.

Originalsprog Dansk
Tidsskrift Ugeskrift for laeger
Vol/bind 179
Tidsskriftsnummer 43
Sider (fra-til) V05170423
ISSN 0041-5782
Status Udgivet - 23 okt. 2017

C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid

Hornum, L., Hansen, A. J., Tornehave, D., Fjording, M. S., Colmenero, P., Wätjen, I. F., Søe Nielsen, N. H., Bliddal, H. & Bartels, E. M. 2017 I : P L o S One. 12, 12, s. e0189017

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Complement activation correlates to rheumatoid arthritis disease activity, and increased amounts of the complement split product C5a is observed in synovial fluids from rheumatoid arthritis patients. Blockade of C5a or its receptor (C5aR) is efficacious in several arthritis models. The aim of this study was to investigate the role of C5a and C5aR in human rheumatoid arthritis and psoriatic arthritis-both with respect to expression and function. Synovial fluid, blood and synovial samples were obtained from rheumatoid arthritis, psoriatic arthritis and osteoarthritis patients as a less inflammatory arthritis type, and blood from healthy subjects. Cells infiltrating synovial tissue were analysed by immunohistochemistry and flow cytometry. SF and blood were analysed for biomarkers by flow cytometry or ELISA. The effect of a blocking anti-human C5aR mAb on leukocyte migration was determined using a Boyden chamber. Appropriate statistical tests were applied for comparisons. C5aR+ cells were detected in most rheumatoid arthritis, in all psoriatic arthritis, but not in non-inflammatory control synovia. C5aR+ cells were primarily neutrophils and macrophages. C5aR+ macrophages were mainly found in lymphoid aggregates in close contact with T cells. C5a levels were increased in both rheumatoid arthritis and psoriatic arthritis synovial fluid compared to osteoarthritis, and in blood from rheumatoid arthritis compared to healthy subjects. Neutrophil and monocyte migration to rheumatoid arthritis synovial fluid was significantly inhibited by anti-C5aR. The data support that the C5a-C5aR axis may be driving the infiltration of inflammatory cells into the synovial fluid and synovium in both rheumatoid and psoriatic arthritis, and suggest that C5a or C5aR may be a promising treatment target in both diseases.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 12
Tidsskriftsnummer 12
Sider (fra-til) e0189017
ISSN 1932-6203
DOI
Status Udgivet - 2017

Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers

Hellgren, K., Dreyer, L., Arkema, E. V., Glintborg, B., Jacobsson, L. T. H., Kristensen, L-E., Feltelius, N., Hetland, M. L., Askling, J. & ARTIS Study Group, For the DANBIO Study Group jan. 2017 I : Annals of the Rheumatic Diseases. 76, 1, s. 105-111 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Safety data on cancer risks following tumour necrosis factor α inhibitors (TNFi) in patients with spondyloarthritis (SpA) (here defined as ankylosing spondylitis (AS), undifferentiated spondarthropaties (SpA UNS), psoriatic arthritis (PsA)) are scarce. Our objective was to assess risks for cancer overall and for common subtypes in patients with SpA treated with TNFi compared with TNFi-naïve patients with SpA and to the general population.

METHODS: From the Swedish (Anti-Rheumatic Therapy in Sweden (ARTIS)) and Danish (DANBIO) biologics registers, we assembled 8703 (ARTIS=5448, DANBIO=3255) patients with SpA initiating a first TNFi 2001-2011. From the Swedish National Patient and Population Registers we assembled a TNFi-naïve SpA cohort (n=28,164) and a Swedish age-matched and sex-matched general population comparator cohort (n=131 687). We identified incident cancers by linkage with the nationwide Swedish and Danish Cancer Registers 2001-2011, and calculated age-standardised and sex-standardised incidence ratios as measures of relative risk (RR).

RESULTS: Based on 1188 cancers among the TNFi-naïve patients with SpA, RR of cancer overall was 1.1 (95% CI 1.0 to 1.2). Based on 147 cancers among TNFi initiators with SpA, RR versus TNFi-naïve was 0.8 (95% CI 0.7 to 1.0) and results were similar for AS and PsA when analysed separately. Site-specific cancer RRs: prostate 0.5 (95% CI 0.3 to 0.8), lung 0.6 (95% CI 0.3 to 1.3), colorectal 1.0 (95% CI 0.5 to 2.0), breast 1.3 (95% CI 0.9 to 2.0), lymphoma 0.8 (95% CI 0.4 to 1.8) and melanoma 1.4 (95% CI 0.7 to 2.6).

CONCLUSIONS: In patients with SpA, treatment with TNFi was not associated with increased risks of cancer, neither overall nor for the six most common cancer types.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer 1
Sider (fra-til) 105-111
Antal sider 7
ISSN 0003-4967
DOI
Status Udgivet - jan. 2017

Clinical characteristics of importance to outcome in patients with axial spondyloarthritis: protocol for a prospective descriptive and exploratory cohort study

Andreasen, R. A., Kristensen, L. E., Ellingsen, T., Christensen, R., Baraliakos, X., Wied, J., Aalykke, C., Ulstrup, T., Schiøttz-Christensen, B., Horn, H. C., Emamifar, A., Duerlund, B., Fischer, L. & Hansen, I. M. J. 10 jul. 2017 I : BMJ Paediatrics Open . 7, 7, s. e015536

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Spondyloarthritis (SpA) is a heterogeneous spectrum of rheumatic diseases with either predominantly axial inflammatory symptoms of the spine and sacroiliac joints or predominantly peripheral arthritis. The two main entities of axial SpA (axSpA) are ankylosing spondylitis or non-radiographic axSpA (nr-axSpA). Tumour necrosis factor-α inhibitors have revolutionised the treatment of patients with axSpA who failed to respond to non-steroidal anti-inflammatory drugs and physical therapy. Chronic pain is common in patients with SpA and may still persist despite the lack of signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in SpA. The painDETECT Questionnaire (PDQ) is a screening tool developed to detect neuropathic pain components. The primary objective is to explore the prognostic value of the PDQ regarding treatment response in patients with axSpA 3 months after initiating a biological agent. Secondary aim is to evaluate the impact of extra-articular manifestations, comorbidities and patient-reported outcomes and elucidate if these factors influence treatment response.

METHOD AND ANALYSIS: We will include 60 participants (≥18 years of age) diagnosed with axSpA independent of main entity, who initiate or switch treatment of a biologic. Data will be collected at baseline and at endpoint following Danish clinical practice (≥3 months) of treatment with biologics. We will explore whether the PDQ and other phenotypical patient characteristics are prognostically important for response to biological therapy according to established response criteria like 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (50%) and Ankylosing Spondylitis Disease Activity Score.

ETHICS AND DISSEMINATION: The study is approved by the Region of Southern Denmark's Ethics committee (S-20160094) and has been designed in cooperation with patient representatives. The study is registered at clinicaltrials.gov (NCT02948608, pre-results). Dissemination will occur through publication(s) in international peer-reviewed journal(s).

Originalsprog Engelsk
Tidsskrift BMJ Paediatrics Open
Vol/bind 7
Tidsskriftsnummer 7
Sider (fra-til) e015536
ISSN 2044-6055
DOI
Status Udgivet - 10 jul. 2017

Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study

Gunter, M. J., Murphy, N., Cross, A. J., Dossus, L., Dartois, L., Fagherazzi, G., Kaaks, R., Kühn, T., Boeing, H., Aleksandrova, K., Tjønneland, A., Olsen, A., Overvad, K., Larsen, S. C., Redondo Cornejo, M. L., Agudo, A., Sánchez Pérez, M. J., Altzibar, J. M., Navarro, C., Ardanaz, E., Khaw, K-T., Butterworth, A., Bradbury, K. E., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Palli, D., Grioni, S., Vineis, P., Panico, S., Tumino, R., Bueno-de-Mesquita, B., Siersema, P., Leenders, M., Beulens, J. W. J., Uiterwaal, C. U., Wallström, P., Nilsson, L. M., Landberg, R., Weiderpass, E., Skeie, G., Braaten, T., Brennan, P., Licaj, I., Muller, D. C., Sinha, R., Wareham, N. & Riboli, E. 15 aug. 2017 I : Annals of internal medicine. 167, 4, s. 236-247 12 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear.

Objective: To examine whether coffee consumption is associated with all-cause and cause-specific mortality.

Design: Prospective cohort study.

Setting: 10 European countries.

Participants: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition).

Measurements: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800).

Results: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels.

Limitations: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once.

Conclusion: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country.

Primary Funding Source: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.

Originalsprog Engelsk
Tidsskrift Annals of internal medicine
Vol/bind 167
Tidsskriftsnummer 4
Sider (fra-til) 236-247
Antal sider 12
ISSN 0003-4819
DOI
Status Udgivet - 15 aug. 2017
Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer Suppl 2
Sider (fra-til) 456-457
Antal sider 2
ISSN 0003-4967
Status Udgivet - 2017

Content and Construct Validity, Reliability, and Responsiveness of the Rheumatoid Arthritis Flare Questionnaire: OMERACT 2016 Workshop Report

Bartlett, S. J., Barbic, S. P., Bykerk, V. P., Choy, E. H., Alten, R., Christensen, R., den Broeder, A., Fautrel, B., Furst, D. E., Guillemin, F., Hewlett, S., Leong, A. L., Lyddiatt, A., March, L., Montie, P., Pohl, C., Scholte Voshaar, M., Woodworth, T. G. & Bingham, C. O. okt. 2017 I : Journal of Rheumatology. 44, 10, s. 1536-1543 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Flare Group was established to develop a reliable way to identify and measure RA flares in randomized controlled trials (RCT). Here, we summarized the development and field testing of the RA Flare Questionnaire (RA-FQ), and the voting results at OMERACT 2016.

METHODS: Classic and modern psychometric methods were used to assess reliability, validity, sensitivity, factor structure, scoring, and thresholds. Interviews with patients and clinicians also assessed content validity, utility, and meaningfulness of RA-FQ scores.

RESULTS: People with RA in observational trials in Canada (n = 896) and France (n = 138), and an RCT in the Netherlands (n = 178) completed 5 items (11-point numerical rating scale) representing RA Flare core domains. There was moderate to high evidence of reliability, content and construct validity, and responsiveness. Factor analysis supported unidimensionality. Rasch analysis showed acceptable fit to the Rasch model, with items and people covering a broad measurement continuum and evidence of appropriate targeting of items to people, ordered thresholds, minimal differential item functioning by language, sex, or age. A summative score across items is defensible, yielding an interval score (0-50) where higher scores reflect worsening flare. The RA-FQ received endorsement from 88% of attendees that it passed the OMERACT Filter 2.0 "Eyeball Test" for instrument selection.

CONCLUSION: The RA-FQ has been developed to identify and measure RA flares. Its review through OMERACT Filter 2.0 shows evidence of reliability, content and construct validity, and responsiveness. These properties merit its further validation as an outcome for clinical trials.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 44
Tidsskriftsnummer 10
Sider (fra-til) 1536-1543
Antal sider 8
ISSN 0315-162X
DOI
Status Udgivet - okt. 2017

STUDY DESIGN: Cross-sectional study.

OBJECTIVE: To investigate if adding a lumbar pillow in supine position during magnetic resonance imaging (MRI) is superior to standing positional MRI for diagnosing lumbar spinal stenosis (LSS).

SUMMARY OF BACKGROUND DATA: The upright standing position and especially extension of the lumbar spine seem to worsening symptoms of LSS. However, it is unclear whether a forced lumbar extension by a pillow in the lower back during conventional supine MRI may improve the diagnostics of LSS compared with standing MRI.

METHODS: Patients suspected for LSS and referred to conventional MRI were included to an additional positional MRI scan (0.25T G-Scan) performed in: (1) conventional supine, (2) standing, (3) supine with a lumbar pillow in the lower back. LSS was evaluated for each position in consensus on a 0 to 3 semi-quantitative grading scale. Independently, L2-S1 lordosis angle, spinal cross-sectional diameter (SCSD), dural cross-sectional diameter (DCSD), and dural cross-sectional diameter (DCSA) were measured. The smallest dural diameter was defined as stenosis level and the largest control level for comparison.

RESULTS: Twenty-seven patients (60.6 years; ±9.4) were included. The lordosis angle increased significantly from supine to standing (3.2° CI: 1.2-5.2) and with the lumbar pillow (12.8° CI: 10.3-15.3). One-way analysis of variance (ANOVA) showed significant differences between positions (P < 0.001). When compared with the supine position, pairwise comparisons showed decreased SCSD, DCSD, DCSA, and increasing semi-quantitative grading, during both standing and supine with the lumbar pillow. A difference in the semi-quantitative grades was only found between standing and supine with a lumbar pillow, and the scan with a lumbar pillow was significantly more painful.

CONCLUSION: Standing MRI and supine MRI with a lumbar pillow resulted in equal changes in the lumbar spine, although standing MRI may be more sensitive in the assessment of patients suspected for LSS.

LEVEL OF EVIDENCE: 2.

Originalsprog Engelsk
Tidsskrift Spine
Vol/bind 42
Tidsskriftsnummer 9
Sider (fra-til) 662-669
Antal sider 8
ISSN 0362-2436
DOI
Status Udgivet - 1 maj 2017

Correction to: Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment

Darzi, A., Harfouche, M., Arayssi, T., Alemadi, S., Alnaqbi, K. A., Badsha, H., Al Balushi, F., Elzorkany, B., Halabi, H., Hamoudeh, M., Hazer, W., Masri, B., Omair, M. A., Uthman, I., Ziade, N., Singh, J. A., Christensen, R. D. K., Tugwell, P., Schünemann, H. J. & Akl, E. A. 26 okt. 2017 I : Health and Quality of Life Outcomes. 15, 1, s. 214

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Tidsskrift Health and Quality of Life Outcomes
Vol/bind 15
Tidsskriftsnummer 1
Sider (fra-til) 214
ISSN 1477-7525
DOI
Status Udgivet - 26 okt. 2017

Critical Outcomes in Longitudinal Observational Studies and Registries in Patients with Rheumatoid Arthritis: An OMERACT Special Interest Group Report

Zamora, N. V., Christensen, R., Goel, N., Klokker, L., Lopez-Olivo, M. A., Kristensen, L. E., Carmona, L., Strand, V., Curtis, J. R. & Suarez-Almazor, M. E. 15 jun. 2017 I : Journal of Rheumatology.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Outcomes important to patients are those that are relevant to their well-being, including quality of life, morbid endpoints, and death. These outcomes often occur over the longterm and can be identified in prospective longitudinal observational studies (PLOS). There are no standards for which outcome domains should be considered. Our overarching goal is to identify critical longterm outcome domains for patients with rheumatic diseases, and to develop a conceptual framework to measure and classify them within the scope of OMERACT Filter 2.0.

METHODS: The steps of this initiative primarily concern rheumatoid arthritis (RA) and include (1) performing a systematic review of RA patient registries and cohorts to identify previously collected and reported outcome domains and measurement instruments; (2) developing a conceptual framework and taxonomy for identification and classification of outcome domains; (3) conducting focus groups to identify domains considered critical by patients with RA; and (4) surveying patients, providers, and researchers to identify critical outcomes that can be evaluated through the OMERACT filter.

RESULTS: In our initial evaluation of databases and registries across countries, we found both commonalities and differences, with no clear standardization. At the initial group meeting, participants agreed that additional work is needed to identify which critical outcomes should be collected in PLOS, and suggested several: death, independence, and participation, among others. An operational strategy for the next 2 years was proposed.

CONCLUSION: Participants endorsed the need for an initiative to identify and evaluate critical outcome domains and measurement instruments for data collection in PLOS.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
ISSN 0315-162X
DOI
Status Udgivet - 15 jun. 2017

Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review and meta-analysis of randomised trials

Tarp, S., Furst, D. E., Dossing, A., Østergaard, M., Lorenzen, T., Hansen, M. S., Singh, J. A., Choy, E. H., Boers, M., Suarez-Almazor, M. E., Kristensen, L. E., Bliddal, H. & Christensen, R. jun. 2017 I : Seminars in Arthritis and Rheumatism. 46, 6, s. 699-708 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy.

METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800.

RESULTS: The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included "DMARD-naïve", and 20 "DMARD-Inadequate responder" (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068).

CONCLUSIONS: Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 46
Tidsskriftsnummer 6
Sider (fra-til) 699-708
Antal sider 10
ISSN 0049-0172
DOI
Status Udgivet - jun. 2017

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