Published in 2018

The influence of prenatal exposure to trans-fatty acids for development of childhood haematopoietic neoplasms (EnTrance): a natural societal experiment and a case-control study

Specht, I. O., Huybrechts, I., Frederiksen, P., Steliarova-Foucher, E., Chajes, V. & Heitmann, B. L., 24 jan. 2018, I : Nutrition Journal. 17, 1, s. 13

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Little is known about the causes of childhood cancer, partly as not many children develop cancer, although childhood cancer is a leading cause of death by disease in the young. The young age of the children suggests that risk factors for childhood cancer may be present during pregnancy. Previous studies have shown that exposure to trans-fat, a type of unsaturated fat common in industrially produced foods (iTFA), has adverse health effects in adults, including the risk of developing cancer. Haematopoietic neoplasms are the most common cancer types among European children under the age of 15 years. This study will bring new knowledge as to whether trans-fat and other fatty acids may also increase the risk of developing haematopoietic neoplasms during childhood.

METHODS: We will investigate if the Danish iTFA legislation ban, which radically reduced the use of iTFA in foodstuffs, influenced the risk of childhood haematopoietic neoplasms in children born either before or after the change in legislation, adjusting for relevant secular trends. Further, in a case-control study, we will examine if levels of fatty acids in dried blood spots from newborns can predict the risk of developing childhood haematopoietic neoplasms. Permission from the Danish Data Protection Agency and the Ethical Committee has been granted.

DISCUSSION: The results from this study will provide important information about fatty acids in the mother's diet as a contributor to development of haematopoietic neoplasms during childhood, which may result in relevant preventive action.

TRIAL REGISTRATION: Not relevant.

Originalsprog Engelsk
Tidsskrift Nutrition Journal
Vol/bind 17
Udgave nummer 1
Sider (fra-til) 13
ISSN 1475-2891
DOI
Status Udgivet - 24 jan. 2018

The Parker Model: Applying a Qualitative Three-Step Approach to Optimally Utilize Input from Stakeholders When Introducing New Device Technologies in the Management of Chronic Rheumatic Diseases

Jørgensen, T. S., Skougaard, M., Taylor, P. C., Asmussen, H. C., Lee, A., Klokker, L., Svejstrup, L., Mountian, I., Gudbergsen, H. & Kristensen, L. E., okt. 2018, I : The Patient. 11, 5, s. 515-526 12 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND AND OBJECTIVE: Qualitative methods such as semi-structured interviews and focus-groups are used to evaluate the applicability and relevance of device technologies in clinical practice, but when used alone, often lack generalizability. This study aimed to assess the face validity and feasibility of using a composite, three-step qualitative method (the Parker Model), to inform the development and implementation of ava®, an electromechanical device (e-Device) for subcutaneous self-administration of the biologic, certolizumab pegol (CZP), used to treat rheumatic diseases.

METHODS: The Parker Model combines concept mapping (CM), participatory design (PD), and stakeholder evaluation (SE). CM, a structured group process, was used to identify patients' opinions and concerns regarding the e-Device. Patients used this information in iterative PD sessions to create personal e-Device prototypes in cooperation with a designer and a healthcare professional. SE was performed based on semi-structured group and individual interviews with patients and disease-management stakeholders.

RESULTS: The study recruited 14 patients, two doctors, two nurses, one medical secretary, and four other public servants. Three CM workshops revealed four key considerations: technical usability, physical design, concerns, and enthusiasm. Four personalized prototypes were developed during PD sessions. SE confirmed that the identified considerations were pivotal for the implementation and adaptation of the e-Device.

CONCLUSIONS: This study is the first to apply a composite, qualitative research model when introducing an e-Device for the treatment and management of rheumatic disease. Results show that input from patients and other stakeholders using the Parker Model can add value to the development and implementation of an e-Device.

Originalsprog Engelsk
Tidsskrift The Patient
Vol/bind 11
Udgave nummer 5
Sider (fra-til) 515-526
Antal sider 12
ISSN 1178-1653
DOI
Status Udgivet - okt. 2018

The relation between maximal voluntary force in m. palmaris longus and the temporal and spatial summation of muscle fiber recruitment in human subjects

Claudel, C. G., Ahmed, W., Elbrønd, V. S., Harrison, A. P. & Bartels, E. M., jan. 2018, I : Physiological Reports. 6, 1

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

This study aimed at looking at the frequency (T-score) and the amplitude (S-score) of fiber use during contraction of a forearm muscle, m. palmaris longus, as measured by acoustic myography (AMG). An additional aim was to relate the T- and S-scores to the recorded force obtained from a hand dynamometer. The hypothesis being that temporal and spatial summation of muscle fiber contraction in a given muscle during a given movement, can together describe a given obtained force. Force measurements were carried out on 12 healthy human subjects aged 19-68 years (6 men & 6 women), while their m. palmaris longus contractile function was measured using an acoustic myography CURO device. Force production was varied from 90 to 10% of assessed maximal voluntary force (MVF), and also monitored over a 1 min period of 50% MVF. Linear regression analysis was applied to relate force to spatial and temporal summation. Muscle strength was sustained by changing the frequency and/or the number of active fibere at any given point in time. Force production, whilst stronger for men than women, was regulated in a similar fashion for both sexes and was closely correlated with the AMG T- and S-scores. It is concluded that AMG is a noninvasive method which can be readily applied to accurately describe how a subject uses a given muscle during any given movement. These findings have relevance when considering training strategies in subjects with muscle trauma or disease, in the elderly, or for both amateur and top professional athletes.

Originalsprog Engelsk
Tidsskrift Physiological Reports
Vol/bind 6
Udgave nummer 1
ISSN 2051-817X
DOI
Status Udgivet - jan. 2018

BACKGROUND: Exercise reduces the amount of visceral adipose tissue (VAT) and the risk of cardiometabolic diseases. The underlying mechanisms responsible for these exercise-induced adaptations are unclear, but they may involve lipolytic actions of interleukin-6 (IL-6). Contracting skeletal muscles secrete IL-6, leading to increased circulating IL-6 levels in response to exercise. The aim of this study is to investigate whether IL-6 is involved in mediating the effects of exercise on visceral and epicardial adipose tissue volume and glycaemic control.

METHODS/DESIGN: Seventy-five physically inactive males and females aged > 18 years with a waist-to-height ratio > 0.5 and/or waist circumference ≥ 88 cm (females) or ≥ 102 cm (males) are being recruited to participate in a 12-week intervention study. Participants are randomly allocated to one of five groups (1:1:1:1:1). Two groups consist of supervised endurance exercise training combined with the IL-6 blocker tocilizumab (ET) or saline used as placebo (EP), two groups consist of no exercise combined with tocilizumab (NT) or placebo (NP), and one group consists of resistance exercise and placebo (RP). Although the study is an exploratory trial, the primary outcome is change in VAT volume from before to after intervention, with secondary outcomes being changes in (1) epicardial adipose tissue, (2) pericardial adipose tissue and (3) gastric emptying. Depots of adipose tissue are quantitated by magnetic resonance imaging Gastric emptying and glucose metabolism are assessed using mixed-meal tolerance tests.

DISCUSSION: Understanding the role of IL-6 in mediating the effects of exercise on visceral and epicardial adipose tissue and glycaemic control may lead to novel therapeutic approaches in the prevention of cardiometabolic diseases.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02901496 . Registered on 1 August 2016 and posted retrospectively on 15 September 2016.

Originalsprog Engelsk
Tidsskrift Trials
Vol/bind 19
Udgave nummer 1
Sider (fra-til) 266
ISSN 1745-6215
DOI
Status Udgivet - 2 maj 2018

The value of adding MRI to a clinical treat-to-target strategy in rheumatoid arthritis patients in clinical remission: Clinical and radiographic outcomes from the IMAGINE-RA randomised controlled trial

Møller-Bisgaard, S. K., Hørslev-Petersen, K., Ejbjerg, B., Hetland, M. L., Ørnbjerg, L. M., Glinatsi, D. E., Møller, J. M., Boesen, M., Christensen, R., Stengaard-Petersen, K., Madsen, O. R., Jensen, B., Villadsen, J., Hauge, E-M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M., Lindegaard, H., Nielsen, S. M., Bliddal, H., Krogh, N., Ellingsen, T., Nielsen, A. H., Balding, L., Jurik, A. G., Thomsen, H. & Østergaard, M., 2018, I : Annals of the Rheumatic Diseases. 77, Suppl. 2, s. 58-9 2 s., OP0018.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer OP0018
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Udgave nummer Suppl. 2
Sider (fra-til) 58-9
Antal sider 2
ISSN 0003-4967
Status Udgivet - 2018

The Value of Adding MRI to a Clinical Treat-to-Target Strategy in Rheumatoid Arthritis Patients in Clinical Remission: Clinical and Radiographic Outcomes from the Imagine-RA Randomized Controlled Trial

Møller-Bisgaard, S. K., Hørslev-Petersen, K., Ejbjerg, B. J., Hetland, M. L., Glinatsi, D. E., Ørnbjerg, L. M., Møller, J. M., Boesen, M., Christensen, R. D. K., Stengaard-Petersen, K., Madsen, O. R., Jensen, B., Villadsen, J. A., Hauge, E-M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M. R., Lindegaard, H., Nielsen, S. M., Bliddal, H., Krogh, N. S., Ellingsen, T., Nielsen, A., Balding, L., Jurik, A. G., Thomsen, H. S. & Østergaard, M., 2018, I : Arthritis & Rheumatology. 70, S9, 3 s., 1451.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer 1451
Tidsskrift Arthritis & Rheumatology
Vol/bind 70
Udgave nummer S9
Antal sider 3
ISSN 1537-2960
Status Udgivet - 2018

TISSUE PERFUSION IN KNEE OSTEOARTHRITIS: IMPLICATIONS FOR EXERCISE THERAPY

Bandak, E., 31 mar. 2018, Eget forlag, København. 66 s.

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

Originalsprog Engelsk
Forlag Eget forlag, København
Antal sider 66
Status Udgivet - 31 mar. 2018

To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry

Glintborg, B., Loft, A. G., Omerovic, E., Hendricks, O., Linauskas, A., Espesen, J., Danebod, K., Jensen, D. V., Nordin, H., Dalgaard, E. B., Chrysidis, S., Kristensen, S., Raun, J. L., Lindegaard, H., Manilo, N., Jakobsen, S. H., Hansen, I. M. J., Dalsgaard Pedersen, D., Sørensen, I. J., Andersen, L. S., Grydehøj, J., Mehnert, F., Krogh, N. S. & Hetland, M. L. 5 nov. 2018 I : Annals of the Rheumatic Diseases.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: Real-world evidence on effectiveness of switching to biosimila r etanercept is scarce. In Denmark, a nationwide guideline of mandatory switch from 50 mg originator (ETA) to biosimilar (SB4) etanercept was issued for patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) in 2016. Clinical characteristics and treatment outcomes were studied in ETA-treated patients, who switched to SB4 (switchers) or maintained ETA (non-switchers). Retention rates were compared with that of a historic cohort of ETA-treated patients. Switchers who resumed ETA treatment (back-switchers) were characterised.

METHODS: Observational cohort study based on the DANBIO registry. Treatment retention was explored by Kaplan-Meier plots and Cox regression (crude, adjusted).

RESULTS: 1621 (79%) of 2061 ETA-treated patients switched to SB4. Disease activity was unchanged 3 months' preswitch/postswitch. Non-switchers often received 25 mg ETA (ETA 25 mg pens/syringes and powder solution were still available). One-year adjusted retention rates were: non-switchers: 77% (95% CI: 72% to 82%)/switchers: 83% (79% to 87%)/historic cohort: 90% (88% to 92%). Patients not in remission had lower retention rates than patients in remission, both in switchers (crude HR 1.7 (1.3 to 2.2)) and non-switchers (2.4 (1.7 to 3.6)). During follow-up, 120 patients (7% of switchers) back-switched to ETA. Back-switchers' clinical characteristics were similar to switchers, and reasons for SB4 withdrawal were mainly subjective.

CONCLUSION: Seventy-nine per cent of patients switched from ETA to SB4. After 1 year, adjusted treatment retention rates were lower in switchers versus the historic ETA cohort, but higher than in non-switchers. Withdrawal was more common in patients not in remission. The results suggest that switch outcomes in routine care are affected by patient-related factors and non-specific drug effects.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
ISSN 0003-4967
DOI
Status E-pub ahead of print - 5 nov. 2018

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II

Thorlacius, L., Garg, A., Ingram, J. R., Villumsen, B., Theut Riis, P., Gottlieb, A. B., Merola, J. F., Dellavalle, R., Ardon, C., Baba, R., Bechara, F. G., Cohen, A. D., Daham, N., Davis, M., Emtestam, L., Fernández-Peñas, P., Filippelli, M., Gibbons, A., Grant, T., Guilbault, S., Gulliver, S., Harris, C., Harvent, C., Houston, K., Kirby, J. S., Matusiak, L., Mehdizadeh, A., Mojica, T., Okun, M., Orgill, D., Pallack, L., Parks-Miller, A., Prens, E. P., Randell, S., Rogers, C., Rosen, C. F., Choon, S. E., van der Zee, H. H., Christensen, R. & Jemec, G. B. E., mar. 2018, I : British Journal of Dermatology. 178, 3, s. 715-721 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items.

OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains.

METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey.

RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments.

CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Originalsprog Engelsk
Tidsskrift British Journal of Dermatology
Vol/bind 178
Udgave nummer 3
Sider (fra-til) 715-721
Antal sider 7
ISSN 0007-0963
DOI
Status Udgivet - mar. 2018

Treating Early Undifferentiated Arthritis: A Systematic Review and Meta-Analysis of Direct and Indirect Trial Evidence

Lopez-Olivo, M. A., Kakpovbia-Eshareturi, V., des Bordes, J. K., Barbo, A., Christensen, R. & Suarez-Almazor, M. E., sep. 2018, I : Arthritis Care & Research. 70, 9, s. 1355-1365 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: We undertook a systematic review and meta-analysis of direct and indirect trial evidence to evaluate the efficacy of treatments for patients with undifferentiated arthritis (UA).

METHODS: We searched 4 electronic databases from inception to January 2016, clinicaltrials.gov, and bibliographies of relevant articles. Two reviewers independently screened and evaluated the studies. The primary outcome was development of rheumatoid arthritis (RA).

RESULTS: Nine studies were included. Interventions included methotrexate, abatacept, infliximab, intraarticular or intramuscular glucocorticoids, and radiation synovectomy. Treating patients resulted in lower rates of RA at 12 months compared to placebo or no treatment (odds ratio [OR] 0.49 [95% confidence interval (95% CI) 0.26, 0.90]). From direct meta-analysis, patients treated with methotrexate were less likely to develop RA at 12 months compared to patients treated without methotrexate (OR 0.13 [95% CI 0.03, 0.48]). This difference was no longer significant at 30 or 60 months. From indirect comparisons, most interventions showed decreased risk of developing RA compared to placebo at 12 months, reaching statistical significance for methotrexate (OR 0.16 [95% CI 0.08, 0.33]) and intramuscular methylprednisolone (OR 0.72 [95% CI 0.53, 0.99]). Most individual interventions included a limited number of studies.

CONCLUSION: Treating patients with UA resulted in a statistically significant delay in the development of RA, with the largest effect observed for methotrexate. These findings suggest that there is a window of opportunity to treat patients with UA early, to delay subsequent progression to RA.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
Vol/bind 70
Udgave nummer 9
Sider (fra-til) 1355-1365
Antal sider 11
ISSN 2151-464X
DOI
Status Udgivet - sep. 2018

Trends in the incidence of rheumatoid arthritis in Denmark from 1995–2016: A nationwide register-based study

Cordtz, R. L., Højgaard, P., Zobbe, K. & Dreyer, L., 2018, I : Annals of the Rheumatic Diseases. 77, Suppl. 2, s. 1201-1202 2 s., SAT0707.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer SAT0707
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Udgave nummer Suppl. 2
Sider (fra-til) 1201-1202
Antal sider 2
ISSN 0003-4967
Status Udgivet - 2018

Trial Characteristics as Contextual Factors when Evaluating Targeted Therapies in Patients with Psoriatic Disease: A Meta-Epidemiological Study

Ballegaard, C., Jørgensen, T. S., Skougaard, M., Strand, V., Mease, P. J., Kristensen, L. E., Dreyer, L., Gottlieb, A., de Wit, M., Christensen, R. & Tarp, S., 2018, I : Arthritis Care & Research. 70, 8, s. 1206-1217

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To assess the importance of trial characteristics as contextual factors when evaluating treatment effect of targeted therapies for patients with psoriatic disease.

METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the two psoriatic conditions combined by using drug retention as common outcome, and separately by using ACR20 for PsA and PASI75 for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta-regression analyses. Odds ratios (OR) were calculated and compared among the trial eligibility criteria via the Ratio of Odds Ratios (ROR).

RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons, 17,737 patients) were eligible. Overall retention was OR 2.16 (1.70 to 2.75) with higher odds for PsA trials compared with psoriasis trials (ROR = 2.55 [1.64 to 3.97]). The eligibility criteria "targeted therapy history", "minimum required disease duration", "required negative rheumatoid factor", and "required CASPAR criteria" were of importance for achieving ACR20 in PsA. The eligibility criterion "minimum required disease duration" was of importance for achieving PASI75 in psoriasis. 7 PsA trials had rescue before time point of retention reporting (adaptive trials).

CONCLUSION: From this exploratory meta-epidemiological study we now have evidence from RCTs to support that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials. This article is protected by copyright. All rights reserved.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
Vol/bind 70
Udgave nummer 8
Sider (fra-til) 1206-1217
ISSN 2151-464X
DOI
Status Udgivet - 2018

Bibliografisk note

COPECARE

Unilateral Ultrasound Scoring Methods for Synovitis in Rheumatoid Arthritis: An Agreement Study Exploring the Most Inflammatory Active Side

Terslev, L., Christensen, R. D. K., Aga, A-B., Sexton, J., Haavardsholm, E. A. & Hammer, H. B., 2018, I : Arthritis & Rheumatology. 70, S9, 2 s., 1200.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer 1200
Tidsskrift Arthritis & Rheumatology
Vol/bind 70
Udgave nummer S9
Antal sider 2
ISSN 1537-2960
Status Udgivet - 2018

Variability in the Reporting of Serum Urate and Flares in Gout Clinical Trials: Need for Minimum Reporting Requirements

Stamp, L. K., Morillon, M. B., Taylor, W. J., Dalbeth, N., Singh, J. A., Lassere, M. & Christensen, R., mar. 2018, I : Journal of Rheumatology. 45, 3, s. 419-424 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To describe the ways in which serum urate (SU) and gout flares are reported in clinical trials, and to propose minimum reporting requirements.

METHODS: This analysis was done as part of a systematic review aiming to validate SU as a biomarker for gout. The ways in which SU and flares were reported were extracted from each study by 2 reviewers.

RESULTS: A total of 22 studies (10 randomized controlled trials, 3 open-label extension studies, and 9 observational studies) were identified. There were 3 broad categories of SU reporting: percentage at target SU, mean SU, and change in SU. A median of 2 (range 1-3) categories were reported across all studies. The most common method of reporting SU was percentage at target in 17/22 (77.3%) studies, with all studies reporting a target of SU < 6 mg/dl. There were 12/22 (54.5%) studies reporting mean SU at some time after study entry, with 7 (58.3%) of these reporting at more than just the final study visit. Two ways of reporting gout flares were identified: mean flare rate and percentage of participants with flares. There was variability in time periods over which flares rates were reported.

CONCLUSION: There is inconsistent reporting of SU and flares in gout studies. Reporting the percentage of participants who achieve a target SU reflects international treatment guidelines. SU should also be reported as a continuous variable with a relevant central and dispersion estimate. Gout flares should be reported as both percentage of participants and mean flare rates at each timepoint.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 45
Udgave nummer 3
Sider (fra-til) 419-424
Antal sider 6
ISSN 0315-162X
DOI
Status Udgivet - mar. 2018

Background and purpose - Obesity is a rising issue worldwide and growing evidence supports poor outcome amongst obese patients following total knee arthroplasty (TKA). Using nationwide registries we investigated the association between bodyweight and risk of revision of primary TKA. Patients and methods - All primary TKA performed during 1997-2015, weight at time of primary TKA and subsequent TKA revisions were identified in the Danish Knee Arthroplasty Register (DKR). Data on comorbidities and a priori selected confounding variables were collected from nationwide registries. The association between weight and 1st time TKA revision was calculated as both crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) using Cox regression. Results - Of 67,810 identified primary TKAs, 4.8% were revised within a median follow-up time of 5.4 years. No association between weight and risk of any revision in patients aged 18-54 and 55-70 years was found. Increased risk of any revision was seen in patients >70 years, 80-89 kg (aHR =1.5, CI 1.2-1.8), 90-99 kg (aHR =1.7, CI 1.3-2.1) and patients >99 kg (aHR =1.6, CI 1.3-2.1), as well as those weighing 45-60 kg (aHR =1.4, CI 1.1-1.9) compared with same aged patients weighing 70-79 kg. Interpretation - We found a complex association between weight and knee arthroplasty survival. There was an increased risk of any revision in patients older than 70 years of age weighing <60 kg and >80 kg. Patients aged 18-55 years weighing 60-69 kg had a lower risk of revision compared with all other weight groups, whereas weight was not found to affect risk of any revision in patients aged 55-70 years.

Originalsprog Engelsk
Tidsskrift Acta Orthopaedica (Print Edition)
ISSN 1745-3674
DOI
Status E-pub ahead of print - 1 dec. 2018

OBJECTIVE: To investigate whether adalimumab (ADA) reduces whole-body (WB-) magnetic resonance imaging (MRI) indices for inflammation in the entheses, peripheral joints, sacroiliac joints, spine, and the entire body in patients with axial spondyloarthritis (axSpA).

METHODS: An investigator-initiated, randomized, placebo-controlled, double-blinded 48-week followup trial included 49 patients with axSpA, who had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4.0 despite treatment with nonsteroidal antiinflammatory drugs and a clinical indication for tumor necrosis factor inhibitor treatment. Patients were randomized to subcutaneous ADA 40 mg or placebo every other week for 6 weeks; thereafter, all patients received ADA. Conventional MRI and WBMRI were performed at weeks 0, 6, 24, and 48. The primary WBMRI endpoint was the proportion of patients with an improvement in WBMRI total inflammation index above the smallest detectable change (SDC) at Week 6.

RESULTS: The primary WBMRI endpoint (improvement of SDC > 2.3) was met in 11 (44%) patients in the ADA group and 3 (13%) patients in the placebo group (p = 0.025, Fisher's exact test). The primary conventional MRI endpoint, the minimally important change in Spondyloarthritis Research Consortium of Canada Spine MRI Inflammation Index at Week 6, was achieved by 9 (36%) patients in the ADA group and 4 (17%) patients in the placebo group (p = 0.20). The primary clinical endpoint, BASDAI reduction > 50% or 2.0 at Week 24, was attained by 32 (65%) patients.

CONCLUSION: ADA provided significant reductions in WBMRI indices of peripheral, axial, and whole-body inflammation in patients with axSpA. WBMRI is promising for objective assessment and monitoring of peripheral and axial disease activity in future clinical trials.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 45
Tidsskriftsnummer 5
Sider (fra-til) 621-629
Antal sider 9
ISSN 0315-162X
DOI
Status Udgivet - maj 2018

The majority of T2D cases are preventable through a healthy lifestyle, leaving little room for questions that lifestyle should be the first line of defence in the fight against the development of T2D. However, when it comes to the clinical care of T2D, the potential efficacy of lifestyle is much less clear-cut, both in terms of impacting the pathological metabolic biomarkers of the disease, and long-term complications. A healthy diet, high leisure-time physical activity, and exercise are considered to be cornerstones albeit adjunct to drug therapy in the management of T2D. The prescription and effective implementation of structured exercise and other lifestyle interventions in the treatment of T2D have not been routinely used. In this article, we critically appraise and debate our reflections as to why exercise and physical activity may not have reached the status of a viable and effective treatment in the clinical care of T2D to the same extent as pharmaceutical drugs. We argue that the reason why exercise therapy is not utilized to a satisfactory degree is multifaceted and primarily relates to a "vicious cycle" with lack of proven efficacy on T2D complications and a lack of proven effectiveness on risk factors in the primary care of T2D. Furthermore, there is a lack of experimental research establishing the optimal dose of exercise. This precludes widespread and sustained implementation of physical activity and exercise in the clinical treatment of T2D will not succeed.

Originalsprog Engelsk
Tidsskrift Diabetes - Metabolism: Research and Reviews (Print Edition)
Vol/bind 34
Udgave nummer 5
Sider (fra-til) e2999
ISSN 1520-7552
DOI
Status Udgivet - jul. 2018

Published in 2017

A neuromuscular exercise programme versus standard care for patients with traumatic anterior shoulder instability: study protocol for a randomised controlled trial (the SINEX study)

Eshoj, H., Rasmussen, S., Frich, L. H., Hvass, I., Christensen, R., Jensen, S. L., Søndergaard, J., Søgaard, K. & Juul-Kristensen, B., 28 feb. 2017, I : Trials. 18, 1, s. 90

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme with standard care in patients with traumatic anterior shoulder dislocations (TASD).

METHODS/DESIGN: Randomised, assessor-blinded, controlled, multicentre trial. Eighty patients with a TASD will be recruited from three orthopaedic departments in Denmark. Patients with primary or recurrent anterior shoulder dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status (primary or recurrent). Primary outcome will be change from baseline to 12 weeks in the patient-reported QoL outcome questionnaire, the Western Ontario Shoulder Instability Index (WOSI).

DISCUSSION: This trial will be the first study to compare the efficacy and safety of two different nonoperative exercise treatment strategies for patients with TASD. Moreover, this is also the first study to investigate nonoperative treatment effects in patients with recurrent shoulder dislocations. Lastly, this study will add knowledge to the shared decision-making process of treatment strategies for clinical practice.

TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02371928 . Registered on 9 February 2015 at the National Institutes of Health Clinical Trials Protocol Registration System.

Originalsprog Engelsk
Tidsskrift Trials
Vol/bind 18
Udgave nummer 1
Sider (fra-til) 90
ISSN 1745-6215
DOI
Status Udgivet - 28 feb. 2017

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine

Andersen, V., Holmskov, U., Sørensen, S. B., Jawhara, M., Andersen, K. W., Bygum, A., Hvid, L., Grauslund, J., Wied, J., Glerup, H., Fredberg, U., Villadsen, J. A., Kjær, S. G., Fallingborg, J., Moghadd, S. A. G. R., Knudsen, T., Brodersen, J. B., Frøjk, J., Dahlerup, J. F., Nielsen, O. H., Christensen, R., Bojesen, A. B., Sorensen, G. L., Thiel, S., Færgeman, N. J., Brandslund, I., Stensballe, A., Schmidt, E. B., Franke, A., Ellinghaus, D., Rosenstiel, P., Raes, J., Heitmann, B., Boyé, M., Nielsen, C. L., Werner, L., Kjeldsen, J. & Ellingsen, T., 15 maj 2017, I : Nutrients. 9, 5, 499.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

Originalsprog Engelsk
Artikelnummer 499
Tidsskrift Nutrients
Vol/bind 9
Udgave nummer 5
ISSN 2072-6643
DOI
Status Udgivet - 15 maj 2017

Vitamin A deficiency has been associated with impaired fetal pancreatic development and increased risk of developing type 2 diabetes mellitus (T2DM). In 1962, mandatory margarine fortification with vitamin A was increased by 25 % in Denmark. We aimed to determine whether offspring of mothers who had been exposed to the extra vitamin A from fortification during pregnancy had a lower risk of developing T2DM in adult life, compared with offspring of mothers exposed to less vitamin A. Individuals from birth cohorts with the higher prenatal vitamin A exposure (born 1 December 1962-31 March 1964) and those with lower prenatal exposure (born 1 September 1959-31 December 1960) were followed up with regard to development of T2DM before 31 December 2012 in the Danish National Diabetes Registry and National Patient Register. Logistic and Cox regression analyses were performed to determine the risk of T2DM by vitamin A exposure level. A total of 193 803 individuals were followed up until midlife. Our results showed that individuals exposed prenatally to extra vitamin A from fortified margarine had a lower risk of developing T2DM than those exposed to lower levels: OR 0·88; 95 % CI 0·81, 0·95, P=0·001, after adjustment for sex. Fetal exposure to small, extra amounts of vitamin A from food fortification may reduce the risk of T2DM. These results may have public health relevance, as they demonstrate that one of the most costly chronic diseases may be prevented by food fortification - a simple and affordable public health nutrition intervention.

Originalsprog Engelsk
Tidsskrift The British journal of nutrition
Vol/bind 117
Udgave nummer 5
Sider (fra-til) 731-736
Antal sider 6
ISSN 0007-1145
DOI
Status Udgivet - mar. 2017

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