Published in 2019

The Importance of the World Health Organization Sugar Guidelines for Dental Health and Obesity Prevention

Breda, J., Jewell, J. & Keller, A., 2019, I : Caries Research. 53, 2, s. 149-152 4 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

The World Health Organization (WHO) recommends a reduced intake of free sugars throughout the life course (strong recommendation) with a reduction of free sugars intake to less than 10% of the total energy intake (strong recommendation) and preferably below 5% of the total energy intake (conditional recommendation) in both adults and children. Available data clearly show that people already consume significantly more sugar than they should, increasing the risk for dental caries, overweight and obesity. The WHO recommendations are intended for use by the policy makers as a benchmark for assessing intake of sugars by populations and as a driving force for policy change. To create a favorable environment, enabling the overall amount of free sugar intake to be as low as possible and to reduce the frequency of consumption of sugar-rich foods, a range of public health interventions is advised.

Originalsprog Engelsk
Tidsskrift Caries Research
Vol/bind 53
Udgave nummer 2
Sider (fra-til) 149-152
Antal sider 4
ISSN 0008-6568
DOI
Status Udgivet - 2019

Bibliografisk note

The Author(s). Published by S. Karger AG, Basel.

The NoHoW protocol: a multicentre 2×2 factorial randomised controlled trial investigating an evidence-based digital toolkit for weight loss maintenance in European adults

Scott, S. E., Duarte, C., Encantado, J., Evans, E. H., Harjumaa, M., Heitmann, B. L., Horgan, G. W., Larsen, S. C., Marques, M. M., Mattila, E., Matos, M., Mikkelsen, M-L., Palmeira, A. L., Pearson, B., Ramsey, L., Sainsbury, K., Santos, I., Sniehotta, F., Stalker, C., Teixeira, P. J. & Stubbs, R. J., 30 sep. 2019, I : BMJ Open. 9, 9, s. e029425

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Obesity and associated diseases place a severe burden on healthcare systems. Behavioural interventions for weight loss (WL) are successful in the short term but often result in weight regain over time. Self-regulation of eating and activity behaviours may significantly enhance weight loss maintenance (WLM) and may be effectively augmented by contextual behavioural approaches to emotion regulation. The NoHoW trial tests the efficacy of a theoretically informed, evidence-based digital toolkit using a mobile-enabled website, activity trackers and Wi-Fi scales for WLM aiming to target (1) self-regulation and motivation, and (2) emotion regulation in adults who achieved clinically significant (≥5%) WL in the previous 12 months (initial body mass index (BMI) ≥25 kg/m2).

METHODS AND ANALYSIS: The study is an 18-month, 3-centre, 2×2 factorial single-blind, randomised controlled trial, which recruited 1627 participants achieving ≥5% WL between March 2017 and March 2018. Participants are randomly allocated to one of four arms: (1) self-monitoring only (self-weighing and activity tracker), (2) self-regulation and motivation, (3) emotion regulation or (4) combined self-regulation, motivation and emotion regulation. Participants attend four clinical investigation days at 0, 6, 12 and 18 months and are instructed to use the digital toolkit for 18 weeks during the first 6 months and at their discretion for the remaining 12 months. The primary outcome is change in weight (kg) at 12 months from baseline. Secondary outcomes are body composition (eg, bioimpedance analysis), health biomarkers (glycated haemoglobin, lipids, blood pressure, hair cortisol), dietary intake, physical activity, sleep, motivational, self-regulatory, emotion regulatory moderators/mediators of WLM, engagement, user experience, acceptability and cost-effectiveness of the interventions.

ETHICS AND DISSEMINATION: Ethical approval was granted by Institutional Ethics Committees at the Universities of Leeds (17-0082; 27 February 2017), Lisbon (17/2016; 20 February 2017) and Capital Region of Denmark (H-16030495, 8 March 2017). Results will be published in scientific journals.

TRIAL REGISTRATION NUMBER: ISRCTN88405328.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 9
Udgave nummer 9
Sider (fra-til) e029425
ISSN 2044-6055
DOI
Status Udgivet - 30 sep. 2019

Bibliografisk note

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

The OMERACT-OARSI Core Domain Set for Measurement in Clinical Trials of Hip and/or Knee Osteoarthritis

Smith, T. O., Hawker, G. A., Hunter, D. J., March, L. M., Boers, M., Shea, B. J., Christensen, R., Guillemin, F., Terwee, C. B., Williamson, P. R., Dodd, S., Roos, E. M., Loeser, R. F., Schnitzer, T. J., Kloppenburg, M., Neogi, T., Ladel, C. H., Kalsi, G., Kaiser, U., Buttel, T. W., Ashford, A. E., Mobasheri, A., Arden, N. K., Tennant, A., Hochberg, M. C., de Wit, M., Tugwell, P. & Conaghan, P. G., aug. 2019, I : Journal of Rheumatology. 46, 8, s. 981-989 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To update the 1997 OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) core domain set for clinical trials in hip and/or knee osteoarthritis (OA).

METHODS: An initial review of the COMET database of core outcome sets (COS) was undertaken to identify all domains reported in previous COS including individuals with hip and/or knee OA. These were presented during 5 patient and health professionals/researcher meetings in 3 continents (Europe, Australasia, North America). A 3-round international Delphi survey was then undertaken among patients, healthcare professionals, researchers, and industry representatives to gain consensus on key domains to be included in a core domain set for hip and/or knee OA. Findings were presented and discussed in small groups at OMERACT 2018, where consensus was obtained in the final plenary.

RESULTS: Four previous COS were identified. Using these, and the patient and health professionals/researcher meetings, 50 potential domains formed the Delphi survey. There were 426 individuals from 25 different countries who contributed to the Delphi exercise. OMERACT 2018 delegates (n = 129) voted on candidate domains. Six domains gained agreement as mandatory to be measured and reported in all hip and/or knee OA clinical trials: pain, physical function, quality of life, and patient's global assessment of the target joint, in addition to the mandated core domain of adverse events including mortality. Joint structure was agreed as mandatory in specific circumstances, i.e., depending on the intervention.

CONCLUSION: The updated core domain set for hip and/or knee OA has been agreed upon. Work will commence to determine which outcome measurement instrument should be recommended to cover each core domain.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 8
Sider (fra-til) 981-989
Antal sider 9
ISSN 0315-162X
DOI
Status Udgivet - aug. 2019

Total, Added, and Free Sugar Consumption and Adherence to Guidelines in Switzerland: Results from the First National Nutrition Survey menuCH

Chatelan, A., Gaillard, P., Kruseman, M. & Keller, A., 19 maj 2019, I : Nutrients. 11, 5

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

The World Health Organization (WHO) recommends reducing free sugars to less than 10% of total energy intake (TEI) due to their potential implications in weight gain and dental caries. Our objectives were to (1) estimate the intake of total, added, and free sugars, (2) define the main sugar sources, and (3) evaluate the adherence to sugar guidelines. The first national nutrition survey 2014-2015 included non-institutional adults aged 18-75 years. Diet was assessed with two non-consecutive 24-hour dietary recalls in 2057 participants. Added and free sugar content was systematically estimated by two dietitians using available information from the manufacturer and/or standard recipe/composition. Usual daily intake distributions were modeled and weighted for sampling design, non-response, weekdays, and seasons. Total, added, and free sugar intake was respectively 107 g (±44), 53 g (±36), and 65 g (±40), representing 19%, 9%, and 11% of TEI. Sugar consumption was higher among younger adults and lower among people living in the Italian-speaking region. The three main food sources of free sugars were: (1) sweet products (47% of total free sugars), in particular sweet spreads (15%) and cakes/cookies (11%); (2) beverages (29%), mainly fruit and vegetable juices (13%), and sugar-sweetened beverages (12%, but 20% in younger adults); and (3) dairy products (9%), with yogurt accounting for 6%. Respectively, 44% of women and 45% of men had free sugar intake below 10% of TEI. Of people aged between 18-29, 30-64, and 65-75 years, 36%, 45%, and 53% had free sugar intake below 10% of TEI, respectively. The prevalence of Swiss people with free sugar intake that was <5% of the TEI was 8%. Adherence to the WHO recommendations guidelines was generally low in Switzerland, particularly among young adults, and in line with other high-income countries.

Originalsprog Engelsk
Tidsskrift Nutrients
Vol/bind 11
Udgave nummer 5
ISSN 2072-6643
DOI
Status Udgivet - 19 maj 2019

AIMS: To investigate whether intensive lifestyle intervention induce partial or complete type 2 diabetes (T2D) remission.

MATERIALS AND METHODS: In a secondary analysis of a randomized, assessor-blinded, single-center trial, patients with non-insulin dependent T2D (duration<10 years), were randomly assigned (2:1, stratified by sex, from April 2015 to August 2016) to a lifestyle intervention group (n=64) or a standard care group (n=34). The primary outcome was partial or complete T2D remission defined as non-diabetic glycemia with no glucose-lowering medications at the outcome assessments at both 12- and 24-months from baseline. All participants received standard care with a standardized, blinded, target-driven medical therapy during the initial 12-months. The lifestyle intervention moreover included 5-6 weekly aerobic and combined aerobic and strength training sessions (30-60 min) and individual dietary plans aiming for BMI ≤ 25 kg/m2 . No intervention was provided during the 12 months follow-up period.

RESULTS: Among 98 randomized participants, 93 (mean [SD] age, 54.6 [8.9] years; 46 [43%] women; mean [SD] baseline HbA1c 49.3 [9.3] mmol/mol) completed follow-up. At follow-up, 23%(14) in the intervention and 7%(2) in the standard care group met the criteria for any T2D remission (odds ratio (OR) [95% CI] 4.4 [0.8 to 21.4], p=0.08). Assuming participants lost-to-follow-up (N=5) had relapsed, the OR [95% CI] for T2D remission was 4.4 [1.0 to 19.8] (p=0.048).

CONCLUSIONS: The statistically non-significant three-fold increased remission rate of T2D in the lifestyle intervention group calls for further large-scale studies to understand how to implement sustainable lifestyle interventions in T2D.

STUDY REGISTRATION: ClinicalTrials.gov registration (NCT02417012). This article is protected by copyright. All rights reserved.

Originalsprog Engelsk
Tidsskrift Diabetes, Obesity and Metabolism
ISSN 1462-8902
DOI
Status E-pub ahead of print - 5 jun. 2019

Bibliografisk note

This article is protected by copyright. All rights reserved.

OBJECTIVES: Ultrasound (US) examination of the entheses is increasingly used. However, little is known about US findings in the entheses in asymptomatic persons. The aim of this study was to investigate the appearance of US signs in the enthuses of the lower limb in asymptomatic subjects.

METHODS: We recruited 64 subjects, eight women and eight men whose ages covered four decades, from 20 to 60 years. None had tendon or joint disease in the lower limbs. Participants were examined by a rheumatologist and blood samples were collected to rule out enthesis pathology. The enthesis of the dominant leg were examined with grey-scale and Doppler US to evaluate increased thickness, changed structure, enthesophytes/calcifications, erosions, and colour Doppler signal.

RESULTS: Ultrasound examination of 320 entheses was made. At enthesis level, elementary lesions were seen at 73 (22.8%) sites, at subject-level 47 (73.4%) persons showed elementary lesions, in 27 (57%) only one enthesis was affected. Doppler activity was seen in four sites, three at the quadriceps insertion. Most common US elementary lesion was enthesophytes at the Achilles and quadriceps tendon insertion. A tendency towards more elementary lesions was seen in men, and a slight increase was seen with increasing age, however, not statistically significance.

CONCLUSIONS: Our findings suggest that US can be used to diagnose/examine subjects in adulthood for pathological changes in the entheses; however, caution should be taken regarding enthesophytes of the quadriceps and Achilles tendon.

Originalsprog Engelsk
Tidsskrift Clinical and Experimental Rheumatology
Vol/bind 37
Udgave nummer 3
Sider (fra-til) 408-413
Antal sider 6
ISSN 0392-856X
Status Udgivet - 9 jan. 2019

Uptake of the OMERACT-OARSI Hip and Knee Osteoarthritis Core Outcome Set: Review of Randomized Controlled Trials from 1997 to 2017

Smith, T. O., Mansfield, M., Hawker, G. A., Hunter, D. J., March, L. M., Boers, M., Shea, B. J., Christensen, R., Guillemin, F., Terwee, C. B., Williamson, P. R., Roos, E. M., Loeser, R. F., Schnitzer, T. J., Kloppenburg, M., Neogi, T., Ladel, C. H., Kalsi, G., Kaiser, U., Buttel, T. W., Ashford, A. E., Mobasheri, A., Arden, N. K., Tennant, A., Hochberg, M. C., de Wit, M., Tugwell, P. & Conaghan, P. G., aug. 2019, I : Journal of Rheumatology. 46, 8, s. 976-980 5 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To assess the uptake of the OMERACT-OARSI (Outcome Measures in Rheumatology- Osteoarthritis Research Society International) core outcome set (COS) domains in hip and/or knee osteoarthritis (OA) trials.

METHODS: There were 382 trials of hip and/or knee OA identified from the ClinicalTrial.gov registry from 1997 to 2017. Frequency of COS adoption was assessed by year and per 5-yearly phases.

RESULTS: COS adoption decreased from 61% between 1997 and 2001 to 38% between 2012 and 2016. Pain (95%) and physical function (86%) were most consistently adopted. Patient's global assessment (48%) was the principal missing domain.

CONCLUSION: Limited adoption of the COS domains indicates that further consideration to improve uptake is required.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 8
Sider (fra-til) 976-980
Antal sider 5
ISSN 0315-162X
DOI
Status Udgivet - aug. 2019

Vitamin D in early life and later risk of multiple sclerosis-A systematic review, meta-analysis

Ismailova, K., Poudel, P., Parlesak, A., Frederiksen, P. & Heitmann, B. L., 2019, I : PLoS One. 14, 8, s. e0221645

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

The study examined results from previous studies of early life vitamin D exposure and risk of MS in adulthood, including studies on season or month of birth and of migration. A systematic review was conducted using PubMed and Web of Science databases as well as checking references cited in articles. The quality of studies was assessed using the Newcastle-Ottawa scale and the AMSTAR score. Twenty-eight studies were selected for analysis. Of these, six population studies investigated early life vitamin D exposure and risk of MS, and three found inverse while the remaining found no associations. A consistent seasonal tendency for MS seemed evident from 11/15 studies, finding a reduced occurrence of MS for Northern hemisphere children who were born late autumn, and late fall for children born in the Southern hemisphere. This was also confirmed by pooled analysis of 6/15 studies. Results of the migration studies showed an increased risk of MS if migration from high to low-MS-risk areas had occurred after age 15 years, while risk of MS was reduced for those migrating earlier in life (<15years). A similar, but inverse risk pattern was observed among migrants from low to high-MS-risk areas. One study found an increased risk of MS in the second generation of migrants when migrating from low to high-MS-risk areas. An association between early life vitamin D and later risk of MS seems possible, however evidence is still insufficient to conclude that low vitamin D exposure in early life increases the risk of MS in adulthood. PROSPERO register number: CRD 42016043229.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 14
Udgave nummer 8
Sider (fra-til) e0221645
ISSN 1932-6203
DOI
Status Udgivet - 2019

Published in 2018

2018 update of the EULAR recommendations for the management of Behçet's syndrome

Hatemi, G., Christensen, R., Bang, D., Bodaghi, B., Celik, A. F., Fortune, F., Gaudric, J., Gul, A., Kötter, I., Leccese, P., Mahr, A., Moots, R., Ozguler, Y., Richter, J., Saadoun, D., Salvarani, C., Scuderi, F., Sfikakis, P. P., Siva, A., Stanford, M., Tugal-Tutkun, I., West, R., Yurdakul, S., Olivieri, I. & Yazici, H., jun. 2018, I : Annals of the Rheumatic Diseases. 77, 6, s. 808-818 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Udgave nummer 6
Sider (fra-til) 808-818
Antal sider 11
ISSN 0003-4967
DOI
Status Udgivet - jun. 2018

A core domain set for hidradenitis suppurativa trial outcomes: an international Delphi process

HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC), sep. 2018, I : British Journal of Dermatology. 179, 3, s. 642-650 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: There is no consensus on core outcome domains for hidradenitis suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials likely leads to outcome-reporting bias and limits the ability to synthesize evidence.

OBJECTIVES: To achieve global multistakeholder consensus on a core outcome set (COS) of domains regarding what to measure in clinical trials for HS.

METHODS: Six stakeholder groups participated in a Delphi process that included five anonymous e-Delphi rounds and four face-to-face consensus meetings to reach consensus on the final COS. The aim was for a 1 : 1 ratio of patients to healthcare professionals (HCPs).

RESULTS: A total of 41 patients and 52 HCPs from 19 countries in four continents participated in the consensus process, which yielded a final COS that included five domains: pain, physical signs, HS-specific quality of life, global assessment and progression of course. A sixth domain, symptoms, was highly supported by patients and not by HCPs but is recommended for the core domain set.

CONCLUSIONS: Routine adoption of the COS in future HS trials should ensure that core outcomes of importance to both patients and HCPs are collected.

Originalsprog Engelsk
Tidsskrift British Journal of Dermatology
Vol/bind 179
Udgave nummer 3
Sider (fra-til) 642-650
Antal sider 9
ISSN 0007-0963
DOI
Status Udgivet - sep. 2018

A 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, Y. Y., Goel, N., de Wit, M., Gladman, D. D., Mease, P., Dreyer, L., Kristensen, L. E., FitzGerald, O., Tillett, W., Gossec, L., Helliwell, P., Strand, V., Ogdie, A., Terwee, C. B. & Christensen, R., 2018, I : Seminars in Arthritis and Rheumatism. 47, 5, s. 654-665

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 47
Udgave nummer 5
Sider (fra-til) 654-665
ISSN 0049-0172
DOI
Status Udgivet - 2018

Bibliografisk note

COPECARE

Acute sensory and motor response to 45-s heavy isometric holds for the plantar flexors in patients with Achilles tendinopathy

O'Neill, S., Radia, J., Bird, K., Rathleff, M. S., Bandholm, T., Jorgensen, M. & Thorborg, K. 1 aug. 2018 I : Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: The purpose of this study was to explore the immediate effects of heavy isometric plantar flexor exercise on sensory output (pain during a functional task and mechanical pain sensitivity) and motor output (plantar flexor torque) in individuals with Achilles tendinopathy.

METHODS: Sixteen subjects with Achilles tendinopathy participated in the study, mean (SD) age 48.6 (8.9) years and Victorian institute assessment-Achilles (VISA-A) score 61.3 (23.0). Sensory testing assessing pain during a functional task, mechanical pain sensitivity and motor output, and plantar flexor peak torque was completed prior to the intervention. All subjects completed a 45-s heavy isometric plantar flexor contraction and were then re-tested using the same sensory and motor tests. Motor output was assessed using isokinetic dynamometry at speeds previously identified as of interest in subjects with Achilles tendinopathy.

RESULTS: Only 9 of the 16 subjects experienced pain during a functional task, self-reported pain was 4.2 (1.9) numerical rating scale (NRS) pre-intervention and 4.9 (3.2) NRS postintervention (n.s.). Mechanical pressure sensitivity was 446.5 (± 248.5) g/mm2 pre-intervention and 411.8 (± 211.8) g/mm2 post-intervention (n.s.). Mean concentric plantar flexor torque at 90 and 225°/s was 47.1 (14.5) and 33.6 (11.6) Nm, respectively, pre-intervention and 53.0 (18.5) and 33.4 (6.6) Nm post-intervention (p = 0.039 and n.s.). Eccentric torque at 90°/s was 98.5 (34.2) Nm preintervention versus 106.0 (41.4) Nm post-intervention (n.s.).

CONCLUSION: In this exploratory study, patients with Achilles tendinopathy had a varied sensory and motor output response to heavy isometric contractions. Using the recommended approach of heavy 45-s isometric contractions did not offer a meaningful acute benefit for sensory or motor output for subjects with Achilles tendinopathy. Based on this study, heavy 45-s isometric contractions cannot be recommended for immediate pain relief or improved motor output for patients with Achilles tendinopathy.

LEVEL OF EVIDENCE: IV, prospective cohort study.

Originalsprog Engelsk
Tidsskrift Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
ISSN 0942-2056
DOI
Status E-pub ahead of print - 1 aug. 2018
Originalsprog Engelsk
Artikelnummer P19
Tidsskrift Endocrine Abstracts
Vol/bind 56
ISSN 1479-6848
DOI
Status Udgivet - 2018

An MRI guided treat-to-target strategy in rheumatoid arthritis patients in clinical remission improved MRI inflammation but not damage progression – Results from the IMAGINE-RA randomised controlled trial

Møller-Bisgaard, S. K., Hørslev-Petersen, K., Ejbjerg, B., Glinatsi, D. E., Hetland, M. L., Ørnbjerg, L. M., Møller, J. M., Boesen, M., Christensen, R. D. K., Stengaard-Pedersen, K., Madsen, O. R., Jensen, B., Villadsen, J., Hauge, E. M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M. R., 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. 126 1 s., OP0149.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer OP0149
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Udgave nummer Suppl. 2
Sider (fra-til) 126
Antal sider 1
ISSN 0003-4967
Status Udgivet - 2018

An MRI Guided Treat-to-Target Strategy in Rheumatoid Arthritis Patients in Clinical Remission Improved MRI Inflammation but Not Damage Progression – Results from the Imagine-RA Randomized Controlled Trial

Møller-Bisgaard, S. K., Hørslev-Petersen, K., Ejbjerg, B. J., Glinatsi, D. E., Hetland, M. L., 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, 2 s., 867.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer 867
Tidsskrift Arthritis & Rheumatology
Vol/bind 70
Udgave nummer S9
Antal sider 2
ISSN 1537-2960
Status Udgivet - 2018

Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

Almholt, K., Hebsgaard, J. B., Nansen, A., Andersson, C., Pass, J., Rønø, B., Thygesen, P., Pelzer, H., Loftager, M., Lund, I. K., Høyer-Hansen, G., Frisch, T., Jensen, C. H., Otte, K. S., Søe, N. H., Bartels, E. M., Andersen, M., Bliddal, H. & Usher, P. A., 1 feb. 2018, I : Journal of immunology (Baltimore, Md. : 1950). 200, 3, s. 957-965

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target-mediated drug disposition consistent with a high turnover of endogenous uPA. The cellular expression patterns of uPA and uPAR were characterized by double immunofluorescence in the inflamed synovium from patients with rheumatoid arthritis and compared with synovium from healthy donors. The arthritic synovium showed expression of uPA and uPAR in neutrophils, macrophages, and a fraction of endothelial cells, whereas there was little or no expression in synovium from healthy donors. The data from animal models and human material provide preclinical proof-of-principle that validates uPA as a novel therapeutic target in rheumatic diseases.

Originalsprog Engelsk
Tidsskrift Journal of immunology (Baltimore, Md. : 1950)
Vol/bind 200
Udgave nummer 3
Sider (fra-til) 957-965
ISSN 0022-1767
DOI
Status Udgivet - 1 feb. 2018

Knee osteoarthritis (KOA) is one of the most common causes of physical disability in the elderly population. With an increasing ageing and obese population, the prevalence of KOA is expected to rise substantially. The needs for a better understanding of the disease and tools that can predict the course of the disease, for example following treatment, are therefore imperative. 

Inflammation has over the last years been recognised as an important factor for both the symptomatology and disease course in KOA. Synovitis, inflammation of the synovium, is the hallmark of intra-articular inflammation and has been associated with pain, symptoms and disease progression. Synovitis can be visualised on conventional static MRI. However, the addition of a dynamic contrast-enhanced (DCE) MRI-sequence enables the assessment of the synovium both in regards of its morphology and perfusion. Studies in both KOA and rheumatoid arthritis have shown that DCE-MRI measures of synovitis are more sensitive than conventional static MRI in regards of microscopic synovitis and patient-reported outcome measures (PROMs).

 The aims of this PhD project were to characterise synovitis in KOA with conventional static and DCE MRI in regards of histology (study I), its association with PROMs (studies II-III) and changes following a symptoms-improving intervention (study III). We found that DCE-MRI-measures of synovitis seem to be superior to conventional static MRI in their association with histological synovitis (study I) and pain (study II) in a cross-sectional setting. However, the use of DCE-MRI over conventional static CE-MRI cannot be justified when assessing the long-term changes in synovitis following an intervention with intra-articular corticosteroids/placebo and exercise (study III). 

Evidence is mounting that KOA is constituted of different phenotypes. There is an urgent need to define these in order to improve and individualise treatment and management. It is essential to gain a better understanding of the different pro-cesses taking place in KOA, on an individual level and in the different stages of the disease. DCE-MRI may very well be a useful tool in facing these challenges especially in regards of the role of perfusion and inflammation in KOA and osteoarthri-tis in general.

Originalsprog Engelsk
Tidsskrift Danish Medical Journal
Vol/bind 65
Udgave nummer 4
ISSN 1603-9629
Status Udgivet - apr. 2018

Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study

Andersen, M., Boesen, M., Ellegaard, K., Söderström, K., Søe, N. H., Spee, P., Mørch, U. G. W., Torp-Pedersen, S., Bartels, E. M., Danneskiold-Samsøe, B., Karlsson, L. & Bliddal, H., 2018, I : PLoS One. 13, 5, s. e0197001

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline.

METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant.

RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit.

CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 13
Udgave nummer 5
Sider (fra-til) e0197001
ISSN 1932-6203
DOI
Status Udgivet - 2018

Association between NICE guidance on biologic therapies with rates of hip and knee replacement among rheumatoid arthritis patients in England and Wales: An interrupted time-series analysis

Hawley, S., Cordtz, R., Dreyer, L., Edwards, C. J., Arden, N. K., Delmestri, A., Silman, A., Cooper, C., Judge, A. & Prieto-Alhambra, D. 2018 I : Seminars in Arthritis and Rheumatism. 47, 5, s. 605-610

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To estimate the impact of NICE approval of tumor necrosis factor inhibitor (TNFi) therapies on the incidence of total hip replacement (THR) and total knee replacement (TKR) among rheumatoid arthritis (RA) patients in England and Wales.

METHODS: Primary care data [Clinical Practice Research Datalink (CPRD)] for the study period (1995-2014) were used to identify incident adult RA patients. The age and sex-standardised 5-year incidence of THR and TKR was calculated separately for RA patients diagnosed in each six-months between 1995-2009. We took a natural experimental approach, using segmented linear regression to estimate changes in level and trend following the publication of NICE TA 36 in March 2002, incorporating a 1-year lag. Regression coefficients were used to calculate average change in rates, adjusted for prior level and trend.

RESULTS: We identified 17,505 incident RA patients of whom 465 and 650 underwent THR and TKR surgery, respectively. The modeled average incidence of THR and TKR over the biologic-era was 6.57/1000 person years (PYs) and 8.51/1000 PYs, respectively, with projected (had pre-NICE TA 36 level and trend continued uninterrupted) figures of 5.63/1000 PYs and 12.92 PYs, respectively. NICE guidance was associated with a significant average decrease in TKR incidence of -4.41/1000 PYs (95% C.I. -6.88 to -1.94), equating to a relative 34% reduction. Overall, no effect was seen on THR rates.

CONCLUSIONS: Among incident RA patients in England and Wales, NICE guidance on TNFi therapies for RA management was temporally associated with reduced rates of TKR but not THR.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 47
Tidsskriftsnummer 5
Sider (fra-til) 605-610
ISSN 0049-0172
DOI
Status Udgivet - 2018

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