Published in 2017

Relationship between pickiness and subsequent development in body mass index and diet intake in obesity prone normal weight preschool children

Rohde, J. F., Händel, M. N., Stougaard, M., Olsen, N. J., Trærup, M., Mortensen, E. L. & Heitmann, B. L. 2017 I : P L o S One. 12, 3, s. e0172772

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Most children have periods in their life where they reject familiar as well as non-familiar food items and this is often referred to as pickiness. The consequences of pickiness may be malnutrition and, if prolonged, potentially lower body weight. However, studies investigating the consequence of pickiness on subsequent changes in diet intake and weight are limited.

OBJECTIVES: To examine whether pickiness influences body mass index as well as diet intake over subsequent 15 months among obesity prone normal weight children aged 2-6 years.

METHODS: Data was obtained from the "Healthy Start" intervention study which included 271 children aged 2-6 years susceptible to overweight later in life. Information on pickiness was obtained from a parental questionnaire. Dietary habits were collected by 4-day dietary records filled in by the parents and height and weight were measured by trained health professionals and both measured twice over a 15 month period. Linear regression models were performed to assess the influence of pickiness on body mass index and diet with adjustments for possible confounders.

RESULTS: No differences in mean BMI Z-score were seen between picky/non-picky (P = 0.68) and little picky/non-picky (P = 0.68) children at 15 month follow-up. Picky children had a lower intake of protein (P = 0.01) than non-picky children despite no differences in total energy intake (P = 0.74), or in the other macronutrients, or the intake of fruit and vegetables, though children being a little picky had a lower intake of starch compared to non-picky children (P = 0.05). Results were essentially similar before and after adjustment for key covariates.

CONCLUSION: Our study showed that BMI Z-score after 15 months follow-up was similar for picky and non-picky children. Picky children seemed to develop a lower protein intake despite similar total energy intake and diet composition.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 12
Tidsskriftsnummer 3
Sider (fra-til) e0172772
ISSN 1932-6203
DOI
Status Udgivet - 2017

OBJECTIVE: To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population.

DESIGN: 192 obese KOA patients followed a 16 week weight loss intervention and 52 weeks weight maintenance (ClinicalTrials.gov identifier: NCT00655941). Assessments were at 0, 8, 16 and 68 weeks. Serum Coll2-1 and Fib3-2 were determined with ELISA, and symptoms by the Knee Osteoarthritis Outcome Score (KOOS) questionnaire. Changes from week 0 and association between changes from baseline in body weight and Coll2-1, Fib3-2, and the 5 KOOS domains were assessed at all time points.

RESULTS: Coll2-1 changes from baseline showed a decrease at week 8 (P = 0.0002), no change at week 16 (P = 0.49), and an increase at week 68 (P = 0.036). Fib3-2 showed an increase from baseline at week 8 (P = 0.0015) and 16 (P < 0.0001), but none at week 68 (P = 0.23). No statistically significant correlations were found between changes in body weight and Coll2-1 and Fib3-2 at any time point (r < 0.05; P > 0.49). At all time-points there were significant positive correlations between changes from baseline in Coll2-1 and in KOOSSports/Recreation (week 8, 16, 68: r = 0.17; P = 0.03; r = 0.16; P = 0.04; and r = 0.17; P = 0.04, respectively).

CONCLUSION: The clinical improvement after a substantial weight loss and weight maintenance in KOA patients was not associated with decrease in markers of cartilage breakdown Coll2-1 or Fib3-2, even with indications of a slightly negative effect.

Originalsprog Engelsk
Tidsskrift Osteoarthritis and Cartilage
ISSN 1063-4584
DOI
Status Udgivet - 6 jul. 2017

Reliability of an Omeract Semiquantitative Scoring System and Imaging Atlas for the Assessment of Cartilage in Hand Osteoarthritis

Mathiessen, A., Hammer, H. B., Terslev, L., Bruyn, G. A. W., D'Agostino, M. A., Filippucci, E., Haugen, I. K., Kortekaas, . M., Mandl, P., Moller, I., Naredo, E., Wittoek, . R., Iagnocco, A. & Ellegaard, K. 2017 I : Arthritis & Rheumatology. 69, S10, 265

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer 265
Tidsskrift Arthritis & Rheumatology
Vol/bind 69
Tidsskriftsnummer S10
ISSN 1537-2960
Status Udgivet - 2017

INTRODUCTION: Computerized pneumatic cuff pressure algometry (CPA) using the DoloCuff is a new method for pain assessment. Intra- and inter-rater reliabilities have not yet been established. Our aim was to examine the inter- and intrarater reliabilities of DoloCuff measures in healthy subjects.

METHODS: Twenty healthy subjects (ages 20 to 29 years) were assessed three times at 24-hour intervals by two trained raters. Inter-rater reliability was established based on the first and second assessments, whereas intrarater reliability was based on the second and third assessments. Subjects were randomized 1:1 to first assessment at either rater 1 or rater 2. The variables of interest were pressure pain threshold (PT), pressure pain tolerance (PTol), and temporal summation index (TSI). Reliability was estimated by a two-way mixed intraclass correlation coefficient (ICC) absolute agreement analysis. Reliability was considered excellent if ICC > 0.75, fair to good if 0.4 < ICC < 0.75, and poor if ICC < 0.4. Bias and random errors between raters and assessments were evaluated using 95% confidence interval (CI) and Bland-Altman plots.

RESULTS: Inter-rater reliability for PT, PTol, and TSI was 0.88 (95% CI: 0.69 to 0.95), 0.86 (95% CI: 0.65 to 0.95), and 0.81 (95% CI: 0.42 to 0.94), respectively. The intrarater reliability for PT, PTol, and TSI was 0.81 (95% CI: 0.53 to 0.92), 0.89 (95% CI: 0.74 to 0.96), and 0.75 (95% CI: 0.28 to 0.91), respectively.

CONCLUSION: Inter-rater reliability was excellent for PT, PTol, and TSI. Similarly, the intrarater reliability for PT and PTol was excellent, while borderline excellent/good for TSI. Therefore, the DoloCuff can be used to obtain reliable measures of pressure pain parameters in healthy subjects.

Originalsprog Engelsk
Tidsskrift Pain practice : the official journal of World Institute of Pain
Vol/bind 17
Tidsskriftsnummer 6
Sider (fra-til) 708-717
Antal sider 10
ISSN 1530-7085
DOI
Status Udgivet - jul. 2017

Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers

Mercer, L. K., Askling, J., Raaschou, P., Dixon, W. G., Dreyer, L., Hetland, M. L., Strangfeld, A., Zink, A., Mariette, X., Finckh, A., Canhao, H., Iannone, F., Zavada, J., Morel, J., Gottenberg, J-E., Hyrich, K. L. & Listing, J. feb. 2017 I : Annals of the Rheumatic Diseases. 76, 2, s. 386-391 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: Some studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy.

METHODS: Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were calculated across countries by taking the size of the register into account.

RESULTS: Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naïve patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9).

CONCLUSIONS: This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer 2
Sider (fra-til) 386-391
Antal sider 6
ISSN 0003-4967
DOI
Status Udgivet - feb. 2017

Risk of revision, prosthetic joint infection and death following total hip or knee arthroplasty in patients with rheumatoid arthritis – a nationwide cohort study from denmark

Cordtz, R. L., Kristensen, L. E., Overgaard, S., Odgaard, A., Lindegaard, H. & Dreyer, L. 2017 I : Annals of the Rheumatic Diseases. 76, Suppl 2, s. 226 1 s., THU0072

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer THU0072
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer Suppl 2
Sider (fra-til) 226
Antal sider 1
ISSN 0003-4967
Status Udgivet - 2017

Bibliografisk note

COPECARE

Risk of Second Malignant Neoplasm and Mortality in Rheumatoid Arthritis Patients Treated with Biological Dmards: A Danish Population-Based Cohort Study

Dreyer, L., Cordtz, R. L., Hansen, I. M. J., Kristensen, L. E., Hetland, M. L. & Mellemkjær, L. 2017 I : Arthritis & Rheumatology. 69, S10, 11L

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer 11L
Tidsskrift Arthritis & Rheumatology
Vol/bind 69
Tidsskriftsnummer S10
ISSN 1537-2960
Status Udgivet - 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

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