Published in 2017

Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis

Tarp, S., Eric Furst, D., Boers, M., Luta, G., Bliddal, H., Tarp, U., Heller Asmussen, K., Brock, B., Dossing, A., Schjødt Jørgensen, T., Thirstrup, S. & Christensen, R. 1 mar. 2017 I : Rheumatology (Oxford, England). 56, 3, s. 417-425 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Objectives.: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.

Methods.: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).

Results.: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.

Conclusion.: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs.

Systematic review registration number.: PROSPERO CRD42014014842.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 56
Tidsskriftsnummer 3
Sider (fra-til) 417-425
Antal sider 9
ISSN 1462-0324
DOI
Status Udgivet - 1 mar. 2017

Slow down to strengthen sport and exercise medicine research

Bandholm, T., Henriksen, M. & Thorborg, K. okt. 2017 I : British Journal of Sports Medicine. 51, 20, s. 1453

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Tidsskrift British Journal of Sports Medicine
Vol/bind 51
Tidsskriftsnummer 20
Sider (fra-til) 1453
ISSN 0306-3674
DOI
Status Udgivet - okt. 2017

Societal costs and patients' experience of health inequities before and after diagnosis of psoriatic arthritis: a Danish cohort study

Kristensen, L. E., Jørgensen, T. S., Christensen, R., Gudbergsen, H., Dreyer, L., Ballegaard, C., Jacobsson, L. T. H., Strand, V., Mease, P. J. & Kjellberg, J. 30 jan. 2017 I : Annals of the Rheumatic Diseases. 76, 9, s. 1495-1501

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To comprehensively study the comorbidities, healthcare and public transfer (allowance) costs in patients with psoriatic arthritis (PsA) before and after diagnosis.

METHODS: Nationwide cohort study, using data from Danish registries from January 1998 through December 2014. A total of 10 525 patients with PsA and 20 777 matched general population comparator (GPC) subjects were included. Societal costs, employment status and occurrence of comorbidities in patients with PsA both before and after diagnosis were compared with GPC subjects.

RESULTS: At baseline, patients with PsA had significantly more comorbidities, including cardiovascular disease (OR 1(.)70 95% CI 1(.)55 to 1(.)86), respiratory diseases (OR 1(.)73 95% CI 1(.)54 to 1(.)96) and infectious diseases (OR 2(.)03 95% CI 1(.)69 to 2(.)42) compared with GPC subjects. At all time points, patients with PsA had higher total healthcare and public transfer costs; they also had lower income (p<0.001) and incurred a net average increased societal cost of €10 641 per patient-year compared with GPC subjects following diagnosis. The relative risk (RR) for being on disability pension 5 years prior to PsA diagnosis was 1(.)36 (95% CI 1(.)24 to 1(.)49) compared with GPC subjects. The RR increased to 1(.)60 (95% CI 1(.)49 to 1(.)72) at the time of diagnosis and was 2(.)69 (95% CI 2(.)40 to 3(.)02) 10 years after diagnosis, where 21(.)8% of the patients with PsA received disability pension.

CONCLUSIONS: Our findings are suggestive of health inequity for patients with PsA and call for individual preventive measures and societal action.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer 9
Sider (fra-til) 1495-1501
ISSN 0003-4967
DOI
Status Udgivet - 30 jan. 2017

Some Cochrane risk of bias items are not important in osteoarthritis trials: A meta-epidemiological study based on Cochrane reviews

Bolvig, J., Juhl, C. B., Boutron, I., Tugwell, P., Ghogomu, E. A. T., Pardo, J. P., Rader, T., Wells, G. A., Mayhew, A., Maxwell, L., Lund, H., Bliddal, H., Christensen, R. & Editorial Board of the Cochrane Musculoskeletal Group 5 dec. 2017 I : Journal of Clinical Epidemiology.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

OBJECTIVE: To evaluate the impact of bias-related study characteristics on treatment effects in osteoarthritis (OA) trials.

STUDY DESIGN: Based on OA trials included in Cochrane reviews the impact of study characteristics on treatment effect estimates were evaluated. Characteristics included items of the risk of bias tool (RoB), trial size, single vs multi-site, and source of funding. Effect sizes were calculated as standardized mean differences (SMDs). Meta-regression was performed to identify "relevant study-level covariates" that decreases the between-study variance (τˆ2).

RESULTS: Twenty reviews including 126 OA trials with a high degree of heterogeneity was included (τˆ2=0.1247). Among RoB domains only patient blinding had an impact on the results (reducing heterogeneity according to τˆ2 <7%). Inadequate blinding of patients yielded larger effects (SMDDifference = 0.15; 95% CI: 0.11 to 0.29, P=0.035). The most important study characteristic was trial size (heterogeneity reduced by 25%), with small trials reporting larger effects (SMDDifference = 0.29; 95% CI: 0.16 to 0.42, P<0.001).

CONCLUSION: In musculoskeletal reviews addressing pain, all the items included in the Cochrane risk of bias tool might not be equally important. OA trial results may be affected by bias constructs that are not yet fully elucidated.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
ISSN 0895-4356
DOI
Status Udgivet - 5 dec. 2017

Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project

Mercer, L. K., Regierer, A. C., Mariette, X., Dixon, W. G., Baecklund, E., Hellgren, K., Dreyer, L., Hetland, M. L., Cordtz, R., Hyrich, K., Strangfeld, A., Zink, A., Canhao, H., Hernandez, M. V., Tubach, F., Gottenberg, J-E., Morel, J., Zavada, J., Iannone, F., Askling, J. & Listing, J. dec. 2017 I : Annals of the Rheumatic Diseases. 76, 12, s. 2025-2030 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Lymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes.

METHODS: Patients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD.

RESULTS: Among 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population.

CONCLUSION: This large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer 12
Sider (fra-til) 2025-2030
Antal sider 6
ISSN 0003-4967
DOI
Status Udgivet - dec. 2017

Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA): a systematic review update and individual participant data meta-analysis protocol

Holden, M. A., Burke, D. L., Runhaar, J., van Der Windt, D., Riley, R. D., Dziedzic, K., Legha, A., Evans, A. L., Abbott, J. H., Baker, K., Brown, J., Bennell, K. L., Bossen, D., Brosseau, L., Chaipinyo, K., Christensen, R., Cochrane, T., de Rooij, M., Doherty, M., French, H. P., Hickson, S., Hinman, R. S., Hopman-Rock, M., Hurley, M. V., Ingram, C., Knoop, J., Krauss, I., McCarthy, C., Messier, S. P., Patrick, D. L., Sahin, N., Talbot, L. A., Taylor, R., Teirlinck, C. H., van Middelkoop, M., Walker, C., Foster, N. E. & OA Trial Bank 22 dec. 2017 I : BMJ Paediatrics Open . 7, 12, s. e018971

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Knee and hip osteoarthritis (OA) is a leading cause of disability worldwide. Therapeutic exercise is a recommended core treatment for people with knee and hip OA, however, the observed effect sizes for reducing pain and improving physical function are small to moderate. This may be due to insufficient targeting of exercise to subgroups of people who are most likely to respond and/or suboptimal content of exercise programmes. This study aims to identify: (1) subgroups of people with knee and hip OA that do/do not respond to therapeutic exercise and to different types of exercise and (2) mediators of the effect of therapeutic exercise for reducing pain and improving physical function. This will enable optimal targeting and refining the content of future exercise interventions.

METHODS AND ANALYSIS: Systematic review and individual participant data meta-analyses. A previous comprehensive systematic review will be updated to identify randomised controlled trials that compare the effects of therapeutic exercise for people with knee and hip OA on pain and physical function to a non-exercise control. Lead authors of eligible trials will be invited to share individual participant data. Trial-level and participant-level characteristics (for baseline variables and outcomes) of included studies will be summarised. Meta-analyses will use a two-stage approach, where effect estimates are obtained for each trial and then synthesised using a random effects model (to account for heterogeneity). All analyses will be on an intention-to-treat principle and all summary meta-analysis estimates will be reported as standardised mean differences with 95% CI.

ETHICS AND DISSEMINATION: Research ethical or governance approval is exempt as no new data are being collected and no identifiable participant information will be shared. Findings will be disseminated via national and international conferences, publication in peer-reviewed journals and summaries posted on websites accessed by the public and clinicians.

PROSPERO REGISTRATION NUMBER: CRD42017054049.

Originalsprog Engelsk
Tidsskrift BMJ Paediatrics Open
Vol/bind 7
Tidsskriftsnummer 12
Sider (fra-til) e018971
ISSN 2044-6055
DOI
Status Udgivet - 22 dec. 2017

Systematic review of measurement properties of patient reported outcome measures in psoriatic arthritis: a grappa-omeract initiative

Højgaard, P., Klokker, L., Orbai, A-M., Holmsted, K., Bartels, E. M., Leung, YY., N, G., de Wit, M., Gladman, D., Mease, P., Dreyer, L., Kristensen, L. E., FitzGerald, O., Tillett, W., Gossec, L., Helliwell, P., Strand, V., Ogdie, A., Terwee, C. & Christensen, R. D. K. 2017 I : Annals of the Rheumatic Diseases. 76, 2, s. 1132 1 s., AB0786

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer AB0786
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer 2
Sider (fra-til) 1132
Antal sider 1
ISSN 0003-4967
Status Udgivet - 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

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