Published in 2017

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study

Riis, R. G. C., Gudbergsen, H., Simonsen, O., Henriksen, M., Al-Mashkur, N., Eld, M., Petersen, K. K., Kubassova, O., Bay-Jensen, A. C., Damm, J., Bliddal, H., Arendt-Nielsen, L. & Boesen, M. feb. 2017 I : Osteoarthritis and Cartilage. 25, 2, s. 272-280 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA).

METHODS: Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R(2)). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3).

RESULTS: 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R(2)-value obtained in Model 1 was R(2) = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R(2) = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R(2) = 0.71.

CONCLUSION: DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA.

Originalsprog Engelsk
Tidsskrift Osteoarthritis and Cartilage
Vol/bind 25
Tidsskriftsnummer 2
Sider (fra-til) 272-280
Antal sider 9
ISSN 1063-4584
DOI
Status Udgivet - feb. 2017

The dynamics of the pain system is intact in patients with knee osteoarthritis: An exploratory experimental study

Jørgensen, T. S., Henriksen, M., Rosager, S., Klokker, L., Ellegaard, K., Danneskiold-Samsøe, B., Bliddal, H. & Graven-Nielsen, T. 29 dec. 2017 I : Scandinavian Journal of Pain. 6, 1, s. 43-49 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background and aims Despite the high prevalence of knee osteoarthritis (OA) it remains one of the most frequent knee disorders without a cure. Pain and disability are prominent clinical features of knee OA. Knee OA pain is typically localized but can also be referred to the thigh or lower leg. Widespread hyperalgesia has been found in knee OA patients. In addition, patients with hyperalgesia in the OA knee joint show increased pain summation scores upon repetitive stimulation of the OA knee suggesting the involvement of facilitated central mechanisms in knee OA. The dynamics of the pain system (i.e., the adaptive responses to pain) has been widely studied, but mainly from experiments on healthy subjects, whereas less is known about the dynamics of the pain system in chronic pain patients, where the pain system has been activated for a long time. The aim of this study was to assess the dynamics of the nociceptive system quantitatively in knee osteoarthritis (OA) patients before and after induction of experimental knee pain. Methods Ten knee osteoarthritis (OA) patients participated in this randomized crossover trial. Each subject was tested on two days separated by 1 week. The most affected knee was exposed to experimental pain or control, in a randomized sequence, by injection of hypertonic saline into the infrapatellar fat pad and a control injection of isotonic saline. Pain areas were assessed by drawings on anatomical maps. Pressure pain thresholds (PPT) at the knee, thigh, lower leg, and arm were assessed before, during, and after the experimental pain and control conditions. Likewise, temporal summation of pressure pain on the knee, thigh and lower leg muscles was assessed. Results Experimental knee pain decreased the PPTs at the knee (P <0.01) and facilitated the temporal summation on the knee and adjacent muscles (P < 0.05). No significant difference was found at the control site (the contralateral arm) (P =0.77). Further, the experimental knee pain revealed overall higher VAS scores (facilitated temporal summation of pain) at the knee (P < 0.003) and adjacent muscles (P < 0.0001) compared with the control condition. The experimental knee pain areas were larger compared with the OA knee pain areas before the injection. Conclusions Acute experimental knee pain induced in patients with knee OA caused hyperalgesia and facilitated temporal summation of pain at the knee and surrounding muscles, illustrating that the pain system in individuals with knee OA can be affected even after many years of nociceptive input. This study indicates that the adaptability in the pain system is intact in patients with knee OA, which opens for opportunities to prevent development of centralized pain syndromes.

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Pain
Vol/bind 6
Tidsskriftsnummer 1
Sider (fra-til) 43-49
Antal sider 7
ISSN 1877-8860
DOI
Status Udgivet - 29 dec. 2017

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory rheumatic disease with the potential to induce significant disability. Patients with RA are at increased risk of cardiovascular diseases (CVD). Smokers with RA tend to experience more pain and fatigue, higher disease activity, more erosive joint destruction and a lower health-related quality of life (HR-QoL) than non-smokers. It remains to be determined whether these effects can be reduced by smoking cessation. This randomised controlled trial (RCT) in patients with RA aims to examine the effect of intensive smoking cessation intervention (motivational counselling combined with tailored nicotine replacement therapy) versus standard care on smoking cessation, and consequently on disease activity. Secondary objectives are to explore the effect on flare, risk factors for CVD, lung function, physical function, HR-QoL, pain and fatigue in patients with RA.

METHODS: This will be a multicentre, open label, two arm, parallel group, RCT, including 150 daily smokers with RA, being in remission or having low-moderate disease activity (DAS28 ≤ 5.1). The intervention group (n = 75) will receive five counselling sessions with a trained smoking cessation counsellor based on the principles of motivational counselling. Furthermore, intervention patients will be offered nicotine replacement therapy tailored to individual needs. Participants randomised to the control group will receive standard care. The co-primary outcome is a hierarchical endpoint, which will be evaluated at 3 months follow-up and will include (1) self-reported smoking cessation biochemically validated by exhaled carbon monoxide and (2) achievement of EULAR clinical response (an improvement in DAS28 of > 0.6). Follow-up visits will be performed at 3, 6 and 12 months post-intervention.

DISCUSSION: This trial will reveal whether intensive smoking cessation counselling helps smokers with RA to achieve continuous smoking cessation and whether, as a concomitant benefit, it will reduce their RA disease activity. The trial aims to generate high quality evidence for the feasibility of a health promotion intervention for smokers with RA.

TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02901886 . Registered on 10 September 2016. Recruitment status updated on 10th October 2016.

Originalsprog Engelsk
Tidsskrift Trials
Vol/bind 18
Tidsskriftsnummer 1
Sider (fra-til) 570-580
Antal sider 11
ISSN 1745-6215
DOI
Status Udgivet - 28 nov. 2017

Bibliografisk note

COPECARE

The effect of instruction in analgesic use compared with neuromuscular exercise on knee-joint load in patients with knee osteoarthritis: a randomized, single-blind, controlled trial

Holsgaard-Larsen, A., Clausen, B., Søndergaard, J., Christensen, R., Andriacchi, T. P. & Roos, E. M. apr. 2017 I : Osteoarthritis and Cartilage. 25, 4, s. 470-480 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To investigate the effect of a neuro-muscular exercise (NEMEX) therapy program compared with instructions in optimized analgesics and anti-inflammatory drug use (PHARMA), on measures of knee-joint load in people with mild to moderate knee osteoarthritis (OA). We hypothesized that knee joint loading during walking would be reduced by NEMEX and potentially increased by PHARMA.

DESIGN: Single-blind, randomized controlled trial (RCT) comparing NEMEX therapy twice a week with PHARMA. Participants with mild-to-moderate medial tibiofemoral knee OA were randomly allocated (1:1) to one of two 8-week treatments. Primary outcome was change in knee load during walking (Knee Index, a composite score from all three planes based on 3D movement analysis) after 8 weeks of intervention. Secondary outcomes were frontal plane peak knee adduction moment (KAM), Knee Injury and Osteoarthritis Outcome Scores (KOOS) and functional performance tests.

RESULTS: Ninety three participants (57% women, 58 ± 8 years with a body mass index [BMI] of 27 ± 4 kg/m(2) (mean ± standard deviation [SD])) were randomized to NEMEX group (n = 47) or PHARMA (n = 46); data from 44 (94%) and 41 (89%) participants respectively, were available at follow-up. 49% of the participants in NEMEX and only 7% in PHARMA demonstrated good compliance. We found no difference in the primary outcome as evaluated by the Knee Index -0.07 [-0.17; 0.04] Nm/%BW HT. Secondary outcomes largely supported this finding.

CONCLUSIONS: We found no difference in the primary outcome; knee joint load change during walking from a NEMEX program vs information on the recommended use of analgesics and anti-inflammatory drugs. ClinicalTrials.gov Identifier: NCT01638962 (July 3, 2012). Ethical Committee: S-20110153.

Originalsprog Engelsk
Tidsskrift Osteoarthritis and Cartilage
Vol/bind 25
Tidsskriftsnummer 4
Sider (fra-til) 470-480
Antal sider 11
ISSN 1063-4584
DOI
Status Udgivet - apr. 2017

OBJECTIVE: The aims of the present knee osteoarthritis (KOA)-study were to: (1) describe and compare the changes in magnetic resonance imaging (MRI)-measures of synovitis following an exercise program preceded by an intra-articular injection of either corticosteroid or isotonic saline and (2) investigate if any of the changes in patient reported outcome measures (PROMs) were associated with changes in MRI-measures of synovitis.

DESIGN: We performed a randomized, double-blinded, placebo-controlled clinical trial evaluating the effects of intra-articular corticosteroid vs placebo injections given before exercise therapy in KOA-patients. PROMs were assessed using the KOOS (knee injury and osteoarthritis outcome score). Synovitis was assessed on conventional non-contrast-enhanced, conventional contrast-enhanced (CE) and dynamic contrast-enhanced (DCE) MRI. PROMs and MRIs were obtained prior to the intra-articular injection, after termination of the exercise program (week 14-primary time point) and week 26.

RESULTS: Of 100 randomized participants (50 in each allocation group), 91 had complete MRI-data at baseline (63% female, mean age: 62 years, median Kellgren-Lawrence-grade: 3). There were no statistically significant differences between the two interventions in regards of changes in MRI-measures of synovitis at any time-point. At week 14, we found no statistical significant MRI-explanatory variables of either of the PROMs.

CONCLUSIONS: The present study does not justify the use of intra-articular corticosteroids over intra-articular saline when combined with an exercise program for reduction of synovitis in KOA. The improvement in pain and function following the intervention with intra-articular corticosteroids/saline and exercise could not be explained by a decrease in synovitis on MRI indicating other pain causing/relieving mechanisms in KOA.

Originalsprog Engelsk
Tidsskrift Osteoarthritis and Cartilage
Vol/bind 25
Tidsskriftsnummer 4
Sider (fra-til) 481-491
Antal sider 11
ISSN 1063-4584
DOI
Status Udgivet - apr. 2017

OBJECTIVES: The aim of this report is to investigate the efficacy of an individually tailored, theory-based behavioural intervention for reducing daily sitting time, pain and fatigue, as well as improving health-related quality of life, general self-efficacy, physical function and cardiometabolic biomarkers in patients with rheumatoid arthritis (RA).

METHODS: In this randomised controlled trial 150 patients with RA were randomised to an intervention or a no-intervention control group. The intervention group received three individual motivational counselling sessions and short message service or text messages aimed at reduction of sedentary behaviour during the 16-week intervention period. Primary outcome was change in daily sitting time measured objectively by ActivPAL. Secondary outcomes included change in pain, fatigue, physical function, general self-efficacy, quality of life, blood pressure, blood lipids, haemoglobin A1c, body weight, body mass index, waist circumference and waist-hip ratio.

RESULTS: 75 patients were allocated to each group. Mean reduction in daily sitting time was -1.61 hours/day in the intervention versus 0.59 hours/day increase in the control group between-group difference -2.20 (95% CI -2.72 to -1.69; p<0.0001) hours/day in favour of the intervention group. Most of the secondary outcomes were also in favour of the intervention.

CONCLUSION: An individually tailored, behavioural intervention reduced daily sitting time in patients with RA and improved patient-reported outcomes and cholesterol levels.

TRIAL REGISTRATION NUMBER: NCT01969604; Results.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer 9
Sider (fra-til) 1603-1606
ISSN 0003-4967
DOI
Status Udgivet - 2017

The GRADE Working Group clarifies the construct of certainty of evidence

Hultcrantz, M., Rind, D., Akl, E. A., Treweek, S., Mustafa, R. A., Iorio, A., Alper, B. S., Meerpohl, J., Murad, M. H., Ansari, M. T., Katikireddi, S. V., Östlund, P., Tranæus, S., Christensen, R., Gartlehner, G., Brozek, J., Izcovich, A., Schunemann, H. J. & Guyatt, G. 18 maj 2017 I : Journal of Clinical Epidemiology.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To clarify the GRADE (grading of recommendations assessment, development and evaluation) definition of certainty of evidence and suggest possible approaches to rating certainty of the evidence for systematic reviews, health technology assessments and guidelines.

STUDY DESIGN AND SETTING: This work was carried out by a project group within the GRADE Working Group, through brainstorming and iterative refinement of ideas, using input from workshops, presentations, and discussions at GRADE Working Group meetings to produce this document, which constitutes official GRADE guidance.

RESULTS: Certainty of evidence is best considered as the certainty that a true effect lies on one side of a specified threshold, or within a chosen range. We define possible approaches for choosing threshold or range. For guidelines, what we call a fully contextualized approach requires simultaneously considering all critical outcomes and their relative value. Less contextualized approaches, more appropriate for systematic reviews and health technology assessments, include using specified ranges of magnitude of effect, e.g. ranges of what we might consider no effect, trivial, small, moderate, or large effects.

CONCLUSION: It is desirable for systematic review authors, guideline panelists, and health technology assessors to specify the threshold or ranges they are using when rating the certainty in evidence.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
ISSN 0895-4356
DOI
Status Udgivet - 18 maj 2017
Originalsprog Engelsk
Artikelnummer OP0106
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer Suppl 2
Sider (fra-til) 96
Antal sider 1
ISSN 0003-4967
Status Udgivet - 2017

Bibliografisk note

COPECARE

The influence of unilateral oophorectomy on the age of menopause

Rosendahl, M., Simonsen, M. K. & Kjer, J. J. dec. 2017 I : Climacteric : the journal of the International Menopause Society. 20, 6, s. 540-544

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To determine the age of menopause after premenopausal unilateral oophorectomy (UO) and to establish whether UO at a young age leads to menopause at a younger age than if UO occurs at an older age.

METHODS: A cohort of 28 731 women, of whom 17 781 (62%) were menopausal, was investigated. Information on menopause was obtained from self-reported questionnaires. Surgical data were obtained from the National Patient Register to avoid recollection bias. Age of menopause after UO/not UO was determined using Kaplan-Meier curves. Cox regression was used to identify factors of importance for early menopause.

RESULTS: UO was performed in 1148 women. Women with UO after the age of 45 years, premenopausal hysterectomy, bilateral oophorectomy and cancer were excluded, leaving 236 in the analysis. Menopause occurred 1.8 years earlier after UO compared to women with two intact ovaries (mean 49.5 vs. 51.3 years), and younger age at UO was significantly linearly correlated to younger age at menopause. UO (hazard ratio 1.23) and smoking (hazard ratio 1.12) significantly decreased the age of menopause.

CONCLUSIONS: Premenopausal unilateral oophorectomy significantly reduces the age of menopause by 1.8 years. Younger age at UO leads to significantly younger age at menopause.

Originalsprog Engelsk
Tidsskrift Climacteric : the journal of the International Menopause Society
Vol/bind 20
Tidsskriftsnummer 6
Sider (fra-til) 540-544
ISSN 1369-7137
DOI
Status Udgivet - dec. 2017

The risk associated with spinal manipulation: an overview of reviews

Nielsen, S. M., Tarp, S., Christensen, R., Bliddal, H., Klokker, L. & Henriksen, M. 24 mar. 2017 I : Systematic Reviews. 6, 1, s. 64

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Spinal manipulative therapy (SMT) is a widely used manual treatment, but many reviews exist with conflicting conclusions about the safety of SMT. We performed an overview of reviews to elucidate and quantify the risk of serious adverse events (SAEs) associated with SMT.

METHODS: We searched five electronic databases from inception to December 8, 2015. We included reviews on any type of studies, patients, and SMT technique. Our primary outcome was SAEs. Quality of the included reviews was assessed using a measurement tool to assess systematic reviews (AMSTAR). Since there were insufficient data for calculating incidence rates of SAEs, we used an alternative approach; the conclusions regarding safety of SMT were extracted for each review, and the communicated opinion were judged by two reviewers independently as safe, harmful, or neutral/unclear. Risk ratios (RRs) of a review communicating that SMT is safe and meeting the requirements for each AMSTAR item, were calculated.

RESULTS: We identified 283 eligible reviews, but only 118 provided data for synthesis. The most frequently described adverse events (AEs) were stroke, headache, and vertebral artery dissection. Fifty-four reviews (46%) expressed that SMT is safe, 15 (13%) expressed that SMT is harmful, and 49 reviews (42%) were neutral or unclear. Thirteen reviews reported incidence estimates for SAEs, roughly ranging from 1 in 20,000 to 1 in 250,000,000 manipulations. Low methodological quality was present, with a median of 4 of 11 AMSTAR items met (interquartile range, 3 to 6). Reviews meeting the requirements for each of the AMSTAR items (i.e. good internal validity) had a higher chance of expressing that SMT is safe.

CONCLUSIONS: It is currently not possible to provide an overall conclusion about the safety of SMT; however, the types of SAEs reported can indeed be significant, sustaining that some risk is present. High quality research and consistent reporting of AEs and SAEs are needed.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015030068 .

Originalsprog Engelsk
Tidsskrift Systematic Reviews
Vol/bind 6
Tidsskriftsnummer 1
Sider (fra-til) 64
ISSN 2046-4053
DOI
Status Udgivet - 24 mar. 2017

OBJECTIVES: To analyze if exercise interventions for patients with knee osteoarthritis (OA) following the American College of Sports Medicine (ACSM) definition of muscle strength training differs from other types of exercise, and to analyze associations between changes in muscle strength, pain, and disability.

METHODS: A systematic search in 5 electronic databases was performed to identify randomized controlled trials comparing exercise interventions with no intervention in knee OA, and reporting changes in muscle strength and in pain or disability assessed as standardized mean differences (SMD) with 95% confidence intervals (95% CI). Interventions were categorized as ACSM interventions or not-ACSM interventions and compared using stratified random effects meta-analysis models. Associations between knee extensor strength gain and changes in pain/disability were assessed using meta-regression analyses.

RESULTS: The 45 eligible trials with 4699 participants and 56 comparisons (22 ACSM interventions) were included in this analysis. A statistically significant difference favoring the ACSM interventions with respect to knee extensor strength was found [SMD difference: 0.448 (95% CI: 0.091-0.805)]. No differences were observed regarding effects on pain and disability. The meta-regressions indicated that increases in knee extensor strength of 30-40% would be necessary for a likely concomitant beneficial effect on pain and disability, respectively.

CONCLUSION: Exercise interventions following the ACSM criteria for strength training provide superior outcomes in knee extensor strength but not in pain or disability. An increase of less than 30% in knee extensor strength is not likely to be clinically beneficial in terms of changes in pain and disability (PROSPERO: CRD42014015344).

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 47
Tidsskriftsnummer 1
Sider (fra-til) 9-21
ISSN 0049-0172
DOI
Status Udgivet - aug. 2017

The Use of Acoustic MyoGraphy as a Measure of Training Effects in Athletes: A 10 Month Case Study of a BMX Rider

Bartels, E. M., Harder, A., Salomons Heide, K., Pingel, J., Torp Andersen, I. & Harrison, A. P. 2017 I : Annals of Sports Medicine and Research. 4, 1, 1101

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Artikelnummer 1101
Tidsskrift Annals of Sports Medicine and Research
Vol/bind 4
Tidsskriftsnummer 1
Status Udgivet - 2017

Three Months of Progressive High-Load Versus Traditional Low-Load Strength Training Among Patients With Rotator Cuff Tendinopathy: Primary Results From the Double-Blind Randomized Controlled RoCTEx Trial

Ingwersen, K. G., Jensen, S. L., Sørensen, L., Jørgensen, H. R., Christensen, R., Søgaard, K. & Juul-Kristensen, B. aug. 2017 I : Orthopaedic Journal of Sports Medicine. 5, 8, s. 2325967117723292

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Progressive high-load exercise (PHLE) has led to positive clinical results in patients with patellar and Achilles tendinopathy. However, its effects on rotator cuff tendinopathy still need to be investigated.

PURPOSE: To assess the clinical effects of PHLE versus low-load exercise (LLE) among patients with rotator cuff tendinopathy.

STUDY DESIGN: Randomized controlled trial; Level of evidence, 1.

METHODS: Patients with rotator cuff tendinopathy were recruited and randomized to 12 weeks of PHLE or LLE, stratified for concomitant administration of corticosteroid injection. The primary outcome measure was change from baseline to 12 weeks in the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, assessed in the intention-to-treat population.

RESULTS: A total of 100 patients were randomized to PHLE (n = 49) or LLE (n = 51). Mean changes in the DASH questionnaire were 7.11 points (95% CI, 3.07-11.16) and 8.39 points (95% CI, 4.35-12.44) in the PHLE and LLE groups, respectively; this corresponded to a statistically nonsignificant adjusted mean group difference of -1.37 points (95% CI, -6.72 to 3.99; P = .61). Similar nonsignificant results were seen for pain, range of motion, and strength. However, a significant interaction effect was found between the 2 groups and concomitant corticosteroid use (P = .028), with the largest positive change in DASH in favor of PHLE for the group receiving concomitant corticosteroid.

CONCLUSION: The study results showed no superior benefit from PHLE over traditional LLE among patients with rotator cuff tendinopathy. Further investigation of the possible interaction between exercise type and corticosteroid injection is needed to establish optimal and potentially synergistic combinations of these 2 factors.

REGISTRATION: NCT01984203 (ClinicalTrials.gov identifier): Rotator Cuff Tendinopathy Exercise Trial (RoCTEx).

Originalsprog Engelsk
Tidsskrift Orthopaedic Journal of Sports Medicine
Vol/bind 5
Tidsskriftsnummer 8
Sider (fra-til) 2325967117723292
ISSN 2325-9671
DOI
Status Udgivet - aug. 2017

Toward the Development of a Core Set of Outcome Domains to Assess Shared Decision-making Interventions in Rheumatology: Results from an OMERACT Delphi Survey and Consensus Meeting

Toupin-April, K., Barton, J., Fraenkel, L., Li, L. C., Brooks, P., De Wit, M., Stacey, D., Légaré, F., Meara, A., Shea, B., Lyddiatt, A., Hofstetter, C., Gossec, L., Christensen, R., Scholte-Voshaar, M., Suarez-Almazor, M. E., Boonen, A., Meade, T., March, L., Pohl, C., Jull, J. E., Sivarajah, S., Campbell, W., Alten, R., Karuranga, S., Morgan, E., Kaufman, J., Hill, S., Maxwell, L. J., Welch, V., Beaton, D., El-Miedany, Y. & Tugwell, P. S. okt. 2017 I : Journal of Rheumatology. 44, 10, s. 1544-1550 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The aim of this Outcome Measures in Rheumatology (OMERACT) Working Group was to determine the core set of outcome domains and subdomains for measuring the effectiveness of shared decision-making (SDM) interventions in rheumatology clinical trials.

METHODS: Following the OMERACT Filter 2.0, and based on a previous literature review of SDM outcome domains and a nominal group process at OMERACT 2014, (1) an online Delphi survey was conducted to gather feedback on the draft core set and refine its domains and subdomains, and (2) a workshop was held at the OMERACT 2016 meeting to gain consensus on the draft core set.

RESULTS: A total of 170 participants completed Round 1 of the Delphi survey, and 116 completed Round 2. Respondents came from 29 countries, with 49% being patients/caregivers. Results showed that 14 out of the 17 subdomains within the 7 domains exceeded the 70% criterion (endorsement ranged from 83% to 100% of respondents). At OMERACT 2016, only 8% of the 96 attendees were patients/caregivers. Despite initial votes of support in breakout groups, there was insufficient comfort about the conceptualization of these 7 domains and 17 subdomains for these to be endorsed at OMERACT 2016 (endorsement ranged from 17% to 68% of participants).

CONCLUSION: Differences between the Delphi survey and consensus meeting may be explained by the manner in which the outcomes were presented, variations in participant characteristics, and the context of voting. Further efforts are needed to address the limited understanding of SDM and its outcomes among OMERACT participants.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 44
Tidsskriftsnummer 10
Sider (fra-til) 1544-1550
Antal sider 7
ISSN 0315-162X
DOI
Status Udgivet - okt. 2017

Tumour necrosis factor inhibitor treatment and occurrence of anterior uveitis in ankylosing spondylitis: results from the Swedish biologics register

Lie, E., Lindström, U., Zverkova-Sandström, T., Olsen, I. C., Forsblad-d'Elia, H., Askling, J., Kapetanovic, M. C., Kristensen, L. E. & Jacobsson, L. T. H. sep. 2017 I : Annals of the Rheumatic Diseases. 76, 9, s. 1515-1521 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: Tumour necrosis factor-α inhibitor (TNFi) treatment has been shown to reduce the rates of anterior uveitis (AU) in patients with ankylosing spondylitis (AS). Our objective was to compare the effect of adalimumab (ADA), etanercept (ETN) and infliximab (IFX) on AU occurrence in AS, using real-world data.

METHODS: Patients with AS starting ADA, ETN or IFX as their first TNFi from January 2003 to December 2010 were extracted from the Swedish Rheumatology Quality Register. AU rates, based on visits to an ophthalmologist with International Classification of Diseases 10 codes for AU, were obtained by linkage to the Swedish National Patient Register. For each TNFi, AU rates 2 years before TNFi start and for the first 2 years on TNFi treatment were compared. In the subgroup of patients who were AU-free during the 2 years before TNFi start, we also compared the risk of a first AU event.

RESULTS: 1365 patients with AS were included (406 ADA, 354 ETN, 605 IFX). Compared with pretreatment rates, we noted a reduction in overall AU rates for ADA and IFX, and an increase for ETN. The adjusted HRs for AU in 1127 patients who were free of AU in the last 2 years before TNFi start were significantly higher for ETN versus ADA (HR: 3.86 95% CI 1.85 to 8.06) and ETN versus IFX (HR: 1.99, 95% CI 1.23 to 3.22), while the HR for IFX versus ADA was not statistically significant.

CONCLUSIONS: The results suggest differences in effect on AU risk between ADA, ETN and IFX, with a clear advantage for ADA/IFX over ETN.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer 9
Sider (fra-til) 1515-1521
Antal sider 7
ISSN 0003-4967
DOI
Status Udgivet - sep. 2017

Ultrasound detected pathology in the enthesis of the lower limb in an age stratified cohort of asymptomatic subjects -a prospectively designed descriptive cross-sectional study

Guldberg-Møller , J., Nielsen, S. M., Koenig, M. J., Torp-Pedersen, S., Terslev, L., Torp-Pedersen, A., Christensen, R., Bliddal, H. & Ellegaard, K. 2017 I : Annals of the Rheumatic Diseases. 76, Suppl 2, s. 737-738 2 s., FRI0654

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Background Ultrasound (US) examination of the entheses is increasingly used to document pathological changes in e.g. psoriasis arthritis and spondyloarthritis. Grey-scale (GS) US is used to assess morphological changes and Doppler US to assess increased blood flow.

The OMERACT expert group has agreed on the following elementary components when assessing the entheses on US examination; hypoechogenicity, increased thickness, enthesophytes/ calcifications, erosions, and Doppler activity (1).

Little is known about US assessment of the entheses in asymptomatic persons, thus the frequency and distribution of the above components between genders and age groups is uncertain.

Objectives To investigate the frequency of enthesitis components in the entheses of the lower limb in a group of healthy subjects.

Methods We recruited 64 subjects (32 women and 32 men), eight women and eight men in four decades, from 20 to 59 years. None of the subjects had previous or present signs of tendon or joint disease in the lower extremities. None of the participants took any kind of medication.

All subjects were examined by a rheumatologist and blood samples were collected to rule out any clinical signs of tendon or joint disease e.g. swollen and tender entheses or increased inflammatory markers in the blood. The dominant leg was examined with US using a Logiq 9 (GE Medical, Milwaukee, WI, USA) with a ML 6–15 MHz transducer and a fixed pre-set with Doppler settings optimised for inflammatory flow. Both GS and Doppler examination were made.

The entheses were examined for hypoechogenicity, increased thickness, enthesophytes/ calcifications, erosions, and Doppler activity.

Results No subjects had clinical signs of tendon or joint disease. Seven displayed various degrees of hypermobility and seven had various degrees of flatfoot; some in combination. None of the blood tests indicated any pathology.

On US erosions were only seen in one Achilles insertion (not shown in table). The Doppler activity was not measured in plantar fascia due to attenuation of the heel fad pad. All other US pathology present is seen in the table below.

Originalsprog Engelsk
Artikelnummer FRI0654
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer Suppl 2
Sider (fra-til) 737-738
Antal sider 2
ISSN 0003-4967
Status Udgivet - 2017

Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016

Orbai, A-M., de Wit, M., Mease, P. J., Callis Duffin, K., Elmamoun, M., Tillett, W., Campbell, W., FitzGerald, O., Gladman, D. D., Goel, N., Gossec, L., Hoejgaard, P., Leung, Y. Y., Lindsay, C., Strand, V., van der Heijde, D. M., Shea, B., Christensen, R., Coates, L., Eder, L., McHugh, N., Kalyoncu, U., Steinkoenig, I. & Ogdie, A. okt. 2017 I : Journal of Rheumatology. 44, 10, s. 1522-1528 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS).

METHODS: At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants.

RESULTS: We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda.

CONCLUSION: The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 44
Tidsskriftsnummer 10
Sider (fra-til) 1522-1528
Antal sider 7
ISSN 0315-162X
DOI
Status Udgivet - okt. 2017

Validity and completeness of rheumatoid arthritis diagnoses in the nationwide DANBIO clinical register and the Danish National Patient Registry

Ibfelt, E. H., Sørensen, J., Jensen, D. V., Dreyer, L., Schiøttz-Christensen, B., Thygesen, P. H., Colic, A., Raun, J. L., Manilo, N., Rødgaard, A., Poulsen, U. E., Rasmussen, C., Hansen, T., Unger, B., Pelck, R., Kincses, A., Nordin, H., Lorenzen, T., Theibich, A., Jensen Hansen, I. M., Espesen, J., Grydehøj, J., Holland-Fischer, M., Loft, A. G. & Hetland, M. L. 2017 I : Clinical Epidemiology. 9, s. 627-632 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Objectives: In Denmark, patients with rheumatoid arthritis (RA) are registered in the nationwide clinical DANBIO quality register and the Danish National Patient Registry (DNPR). The aim was to study the validity of the RA diagnosis and to estimate the completeness of relevant RA cases in each registry.

Study design and setting: Patients registered for the first time in 2011 with a diagnosis of RA were identified in DANBIO and DNPR in January 2013. For DNPR, filters were applied to reduce false-positive cases. The diagnosis was verified by a review of patient records. We calculated the positive predictive values (PPVs) of the RA diagnosis registrations in DANBIO and DNPR, and estimated the registry completeness of relevant RA cases for both DANBIO and DNPR. Updated data from 2011 to 2015 from DANBIO were retrieved to identify patients with delayed registration, and the registry completeness and PPV was recalculated.

Results: We identified 1,678 unique patients in DANBIO or in DNPR. The PPV (2013 dataset) was 92% in DANBIO and 79% in DNPR. PPV for DANBIO on the 2015 update was 96%. The registry completeness of relevant RA cases was 43% in DANBIO, increasing to 91% in the 2015 update and 90% in DNPR.

Conclusion: DANBIO held a high proportion of true RA cases (96%) and was found to be superior to the DNPR (79%) with regard to the validity of the diagnosis. Both registries were estimated to have a high completeness of RA cases treated in hospital care (~90%).

Originalsprog Engelsk
Tidsskrift Clinical Epidemiology
Vol/bind 9
Sider (fra-til) 627-632
Antal sider 6
ISSN 1179-1349
DOI
Status Udgivet - 2017

OBJECTIVES: Weight loss is commonly recommended for gout, but the magnitude of the effect has not been evaluated in a systematic review. The aim of this systematic review was to determine benefits and harms associated with weight loss in overweight and obese patients with gout.

METHODS: We searched six databases for longitudinal studies, reporting the effect of weight loss in overweight/obese gout patients. Risk of bias was assessed using the tool Risk of Bias in Non-Randomised Studies of Interventions. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation.

RESULTS: From 3991 potentially eligible studies, 10 were included (including one randomised trial). Interventions included diet with/without physical activity, bariatric surgery, diuretics, metformin or no intervention. Mean weight losses ranged from 3 kg to 34 kg. Clinical heterogeneity in study characteristics precluded meta-analysis. The effect on serum uric acid (sUA) ranged from -168 to 30 μmol/L, and 0%-60% patients achieving sUA target (<360 μmol/L). Six out of eight studies (75%) showed beneficial effects on gout attacks. Two studies indicated dose-response relationship for sUA, achieving sUA target and gout attacks. At short term, temporary increased sUA and gout attacks tended to occur after bariatric surgery.

CONCLUSIONS: The available evidence is in favour of weight loss for overweight/obese gout patients, with low, moderate and low quality of evidence for effects on sUA, achieving sUA target and gout attacks, respectively. At short term, unfavourable effects may occur. Since the current evidence consists of a few studies (mostly observational) of low methodological quality, there is an urgent need to initiate rigorous prospective studies (preferably randomised controlled trials).

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016037937.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer 11
ISSN 0003-4967
DOI
Status Udgivet - 2 sep. 2017

Work Disability in Newly Diagnosed Patients with Primary Sjögren Syndrome

Mandl, T., Jørgensen, T. S., Skougaard, M., Olsson, P. & Kristensen, L-E. feb. 2017 I : Journal of Rheumatology. 44, 2, s. 209-215 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To study longterm work disability and possible predictors in newly diagnosed patients with primary Sjögren syndrome (pSS).

METHODS: Because we wanted to include only patients with full work availability potential, eligible patients were aged 18-62 years. Fifty-one patients (mean age 46 yrs, range 18-61 yrs, 50 women) diagnosed with pSS between January 2001 and December 2012 were included in the study. For each patient we randomly selected 4 reference subjects from the general population and matched for age, sex, and area of residence. We linked data to the Swedish Social Insurance Agency and calculated the proportion as well as net days of work disability in 30-day intervals from 12 months before pSS diagnosis until 24 months after .

RESULTS: Work disability was increased in patients with pSS in comparison to general population comparators. At diagnosis, 26% of patients were work-disabled, while 37% and 41% were disabled at 12 and 24 months after diagnosis, respectively (p < 0.05 and p < 0.05 vs baseline). Prior work disability status at diagnosis (OR 15.4, 95% CI 2.9-81.9; p = 0.001), concomitant fibromyalgia (OR 10.5, 95% CI 2.0-56.0; p = 0.006), and each additional year of age (OR 1.1, 95% CI 1.0-1.2; p = 0.009) were found to be associated with work disability 24 months after diagnosis.

CONCLUSION: Patients with pSS showed an increased work disability, in comparison with the general population, which increased significantly during the first 2 years after diagnosis. Work disability at diagnosis, concomitant fibromyalgia, and increasing age, but not anti-SSA/anti-SSB antibodies or disease activity, were associated with longterm work disability.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 44
Tidsskriftsnummer 2
Sider (fra-til) 209-215
Antal sider 7
ISSN 0315-162X
DOI
Status Udgivet - feb. 2017

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