Published in 2020

OBJECTIVE: To evaluate the structural effects of weight loss on hip or knee osteoarthritis (OA) and to summarize which structural joint pathologies have been examined and the evidence for the outcome measurement instruments applied.

DESIGN: Based on a pre-specified protocol (available: PROSPERO CRD42017065263), we conducted a systematic search of the bibliographic databases, Medline, Embase and Web of Science identifying longitudinal articles reporting the effects of weight loss on structural imaging outcomes in OA of the hip or knee in people who are overweight or obese.

RESULTS: From 1625 potentially eligible records, 14 articles (from 6 cohorts) were included. 2 cohorts were derived from RCTs. Evaluated pathologies were: articular cartilage (n = 7), joint space width (n = 3), bone marrow lesions (n = 5), synovitis (n = 2), effusion (n = 1), meniscus (n = 3), bone marrow density (n = 1) and infrapatellar fat pad (IPFP; n = 2). Cartilage showed conflicting results when evaluating cartilage thickness by direct thickness measurements. Compositional dGEMRIC and T2 mapping measures in early knee OA showed trends towards reduced cartilage degeneration. Joint space width on conventional radiographs showed no change. Weight loss reduced the size of the IPFP. Synovitis and effusion were not affected. Following weight loss DXA showed bone loss at the hip.

CONCLUSION: We did not find consistent evidence of the effects of weight loss on OA structural pathology in people who are overweight or obese. There is a need to achieve consensus on which structural pathologies and measurements to apply in weight loss and OA research.

Originalsprog Engelsk
Tidsskrift Osteoarthritis and Cartilage
Vol/bind 28
Udgave nummer 1
Sider (fra-til) 10-21
Antal sider 12
ISSN 1063-4584
DOI
Status Udgivet - jan. 2020

Bibliografisk note

Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Published in 2019

A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis

Fleischmann, R. M., Bliddal, H., Blanco, F. J., Schnitzer, T. J., Peterfy, C., Chen, S., Wang, L., Feng, S., Conaghan, P. G., Berenbaum, F., Pelletier, J-P., Martel-Pelletier, J., Vaeterlein, O., Kaeley, G. S., Liu, W., Kosloski, M. P., Levy, G., Zhang, L., Medema, J. K. & Levesque, M. C., jul. 2019, I : Arthritis & rheumatology (Hoboken, N.J.). 71, 7, s. 1056-1069 14 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To assess the efficacy and safety of the anti-interleukin-1α/β (anti-IL-1α/β) dual variable domain immunoglobulin lutikizumab (ABT-981) in patients with knee osteoarthritis (OA) and evidence of synovitis.

METHODS: Patients (n = 350; 347 analyzed) with Kellgren/Lawrence grade 2-3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or ultrasound) were randomized to receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at week 16 and change from baseline in MRI-assessed synovitis at week 26.

RESULTS: The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg (P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab-treated and placebo-treated patients. Changes from baseline in MRI-assessed synovitis at week 26 and other key symptom- and most structure-related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high-sensitivity C-reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations.

CONCLUSION: The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL-1 inhibitors, suggest that IL-1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis.

Originalsprog Engelsk
Tidsskrift Arthritis & rheumatology (Hoboken, N.J.)
Vol/bind 71
Udgave nummer 7
Sider (fra-til) 1056-1069
Antal sider 14
ISSN 2326-5191
DOI
Status Udgivet - jul. 2019

Bibliografisk note

© 2019, American College of Rheumatology.

A portfolio of biologic self-injection devices in rheumatology: how patient involvement in device design can improve treatment experience

van den Bemt, B. J. F., Gettings, L., Domańska, B., Bruggraber, R., Mountian, I. & Kristensen, L. E., dec. 2019, I : Drug Delivery . 26, 1, s. 384-392 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Biologic drugs (e.g. anti-tumor necrosis factors) are effective treatments for multiple chronic inflammatory diseases including rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis. Administration of biologic drugs is usually via subcutaneous self-injection, which provides many patient benefits compared to infusions including increased flexibility, reduced costs, and reduced caregiver burden. However, it is also associated with challenges such as needle phobia, patient treatment misconceptions and incorrect drug administration, and can be impacted by dexterity problems. Evidence suggests these problems, along with other drug administration challenges (e.g. patient forgetfulness, busy lifestyles, and polypharmacy), can reduce patient adherence to treatment. To combat these challenges, patient feedback has been used to develop a range of self-injection devices, including pre-filled syringes, pre-filled pens, and electronic injection devices. Providing different devices for drug administration gives patients the opportunity to choose a device that addresses the challenges they face as an individual. Research suggests involving patients in medical device development, providing patients with a choice of devices and enrolling individuals in patient support programs can empower patients to take control of their treatment journey. By providing a portfolio of self-injection devices, designed based on patient needs, patient experience will improve, potentially improving adherence and hence, long-term treatment outcomes.

Originalsprog Engelsk
Tidsskrift Drug Delivery
Vol/bind 26
Udgave nummer 1
Sider (fra-til) 384-392
Antal sider 9
ISSN 1071-7544
DOI
Status Udgivet - dec. 2019

A systematic literature review of the relation between iron status/anemia in pregnancy and offspring neurodevelopment

Janbek, J., Sarki, M., Specht, I. O. & Heitmann, B. L., dec. 2019, I : European Journal of Clinical Nutrition. 73, 12, s. 1561-1578 18 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

BACKGROUND: The fetal brain starts developing early and animal studies have suggested that iron plays several roles for the development, but results from epidemiological studies investigating associations between gestational iron and offspring neurodevelopment are inconsistent.

OBJECTIVE: To systematically examine results from observational studies and RCTs on gestational iron and offspring neurodevelopment, with focus on the importance of four domains: iron status indicators, exposure timing, neurodevelopmental outcomes, and offspring age.

METHODS: PRISMA guidelines were followed. Embase, PsychInfo, Scopus, and The Cochrane library were searched in September 2017 and February 2018. Overall, 3307 articles were identified and 108 retrieved for full-text assessment. Pre-specified eligibility criteria were used to select studies and 27 articles were included;19 observational and 8 RCTs.

RESULTS: Iron status in pregnancy was associated with offspring behavior, cognition, and academic achievement. The direction of associations with behavioral outcomes were unclear and the conclusions related to cognition and academic achievement were based on few studies, only. Little evidence was found for associations with motor development. Observed associations were shown to persist beyond infancy into adolescence, and results depended on iron status indicator type but not on the timing of exposure.

CONCLUSION: We conclude that there is some evidence that low pregnancy iron, possibly particularly in the 3rd trimester, may be associated with adverse offspring neurodevelopment. As most previous research used Hemoglobin, inferring results to iron deficiency should be done with caution. No conclusions could be reached regarding associations beyond early childhood, and supplementation with iron during pregnancy did not seem to influence offspring neurodevelopment.

Originalsprog Engelsk
Tidsskrift European Journal of Clinical Nutrition
Vol/bind 73
Udgave nummer 12
Sider (fra-til) 1561-1578
Antal sider 18
ISSN 0954-3007
DOI
Status Udgivet - dec. 2019

Adaptive Trial Designs in Rheumatology: Report from the OMERACT Special Interest Group

Pickles, T., Alten, R., Boers, M., Bykerk, V., Christensen, J., Christensen, R., van Hoogstraten, H., Simon, L. S., Tam, L-S. & Choy, E. H., okt. 2019, I : Journal of Rheumatology. 46, 10, s. 1406-1408 3 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Adaptive trial design was developed initially for oncology to improve trial efficiency. If optimized for rheumatology, it may improve trial efficiency by reducing sample size and time.

METHODS: A systematic review assessed design of phase II clinical trials in rheumatoid arthritis.

RESULTS: Fifty-six trials were reviewed. Most trials had 4 groups (1 control and 3 intervention), with an average group size of 34 patients. American College of Rheumatology 20 measured at 16 weeks was the most commonly used primary endpoint.

CONCLUSION: The next step is to undertake a systematic review of adaptive designs used in early-phase trials in nonrheumatic conditions.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 10
Sider (fra-til) 1406-1408
Antal sider 3
ISSN 0315-162X
DOI
Status Udgivet - okt. 2019

Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials

Tarp, S., Jørgensen, T. S., Furst, D. E., Dossing, A., Taylor, P. C., Choy, E. H., Suarez-Almazor, M. E., Lyddiatt, A., Kristensen, L. E., Bliddal, H. & Christensen, R., jun. 2019, I : Seminars in Arthritis and Rheumatism. 48, 6, s. 958-966 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA).

METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates.

RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence.

CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 48
Udgave nummer 6
Sider (fra-til) 958-966
Antal sider 9
ISSN 0049-0172
DOI
Status Udgivet - jun. 2019

Bibliografisk note

Copyright © 2018 Elsevier Inc. All rights reserved.

Adolescent wine consumption is inversely associated with long-term weight gain: results from follow-up of 20 or 22 years

Poudel, P., Ismailova, K., Andersen, L. B., Larsen, S. C. & Heitmann, B. L., 10 sep. 2019, I : Nutrition Journal. 18, 1, s. 56

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Several studies have suggested a link between the type of alcoholic beverage consumption and body weight. However, results from longitudinal studies have been inconsistent, and the association between adolescent alcohol consumption long-term weight gain has generally not been examined.

METHODS: The study was based on data from 720 Danish adolescents aged between 15 to 19 years at baseline from the Danish Youth and Sports Study (YSS). Self-reported alcohol use, height, weight, smoking, social economic status (SES) and physical activity levels were assessed in baseline surveys conducted in 1983 and 1985, and in the follow up survey which was conducted in 2005. Multiple linear regression analyses were used to examine the association between alcohol consumption in adolescence and subsequent weight gain later in midlife.

RESULTS: There was no significant association between total alcohol consumption during adolescence and change in BMI into midlife (P = 0.079) (β - 0.14; 95% CI -0.28, 0.005). Wine consumption was found to be inversely associated to subsequent BMI gain (P = 0.001) (β - 0.46; 95% CI -0.82, - 0.09) while the results were not significant for beer and spirit. The relationship did not differ by gender, but smoking status was found to modify the relationship, and the inverse association between alcohol and BMI gain was seen only among non-smokers (P = 0.01) (β - 0.24; 95% CI -0.41, - 0.06) while no association was found among smokers. Neither adolescent nor attained socioeconomic status in adulthood modified the relationship between alcohol intake and subsequent BMI gain.

CONCLUSION: Among non-smoking adolescents, consumption of alcohol, and in particular wine, seems to be associated with less weight gain until midlife.

TRIAL REGISTRATION: The YSS cohort was retrospectively registered on August 2017. (Study ID number: NCT03244150 ).

Originalsprog Engelsk
Tidsskrift Nutrition Journal
Vol/bind 18
Udgave nummer 1
Sider (fra-til) 56
ISSN 1475-2891
DOI
Status Udgivet - 10 sep. 2019
Originalsprog Engelsk
Artikelnummer P19
Tidsskrift Endocrine Abstracts
Vol/bind 58
Antal sider 1
ISSN 0804-4643
Status Udgivet - 2019

Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data

Zhu, D., Chung, H-F., Dobson, A. J., Pandeya, N., Giles, G. G., Bruinsma, F., Brunner, E. J., Kuh, D., Hardy, R., Avis, N. E., Gold, E. B., Derby, C. A., Matthews, K. A., Cade, J. E., Greenwood, D. C., Demakakos, P., Brown, D. E., Sievert, L. L., Anderson, D., Hayashi, K., Lee, J. S., Mizunuma, H., Tillin, T., Simonsen, M. K., Adami, H-O., Weiderpass, E. & Mishra, G. D., nov. 2019, I : The Lancet Public Health. 4, 11, s. e553-e564

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease.

METHODS: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early), 50-51 years (reference category), 52-54 years (relatively late), and 55 years or older (late menopause).

FINDINGS: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50-51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age <40 years; HR 1·55, 95% CI 1·38-1·73; p<0·0001), early menopause (age 40-44 years; 1·30, 1·22-1·39; p<0·0001), and relatively early menopause (age 45-49 years; 1·12, 1·07-1·18; p<0·0001), with a significantly reduced risk of cardiovascular disease following menopause after age 51 years (p<0·0001 for trend). The associations persisted in never smokers, and were strongest before age 60 years for women with premature menopause (HR 1·88, 1·62-2·20; p<0·0001) and early menopause (1·40, 1·27-1·54; p<0·0001), but were attenuated at age 60-69 years, with no significant association observed at age 70 years and older.

INTERPRETATION: Compared with women who had menopause at age 50-51 years, women with premature and early menopause had a substantially increased risk of a non-fatal cardiovascular disease event before the age of 60 years, but not after age 70 years. Women with earlier menopause need close monitoring in clinical practice, and age at menopause might also be considered as an important factor in risk stratification of cardiovascular disease for women.

FUNDING: Australian National Health and Medical Research Council.

Originalsprog Engelsk
Tidsskrift The Lancet Public Health
Vol/bind 4
Udgave nummer 11
Sider (fra-til) e553-e564
ISSN 2468-2667
DOI
Status Udgivet - nov. 2019

Bibliografisk note

© 2019 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY NC ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

An acoustic myography functional assessment of cerebral palsy subjects compared to healthy controls during physical exercise

Pingel, J., Andersen, I. T., Broholm, R., Harder, A., Bartels, E. M., Bülow, J. & Harrison, A., mar. 2019, I : Journal of muscle research and cell motility. 40, 1, s. 53-58 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Individuals with cerebral palsy (CP) participate in reduced levels of physical activity and spend an increased amount of time in a sedentary state compared with healthy control subjects. Whether this in part can be explained by impaired muscle function is still unclear. The aim of the present study was to elucidate differences in muscle fibre recruitment during treadmill exercise between CP subjects and healthy age-, sex- and BMI-matched controls. This is a case-control study. Acoustic myography (AMG), a method recording fibre use and efficiency from contracting muscles, was applied during a period of treadmill exercise. The recorded AMG parameters revealed that the CP subjects had a significantly lower initial S-score (spatial summation) than the controls (P < 0.01). However, the T-score (temporal summation) and the E-score (efficiency) showed no significant differences between individuals with CP and the healthy control subjects. The present findings indicate that CP subjects use a higher degree of spatial summation (more fibres recruited) to keep up the same speed during treadmill exercise when compared to healthy matched control subjects. Our results suggest that individuals with CP have a tendency to recruit far more muscle fibres during bouts of exercise than healthy individuals. This may partly explain why CP subjects experience premature fatigue.

Originalsprog Engelsk
Tidsskrift Journal of muscle research and cell motility
Vol/bind 40
Udgave nummer 1
Sider (fra-til) 53-58
Antal sider 6
ISSN 0142-4319
DOI
Status Udgivet - mar. 2019

Analgesics use and withdrawal in people with dementia - a register-based Danish study and a systematic review

Sørensen, A. M. S., Tarp, S., Johannsen, P., Lolk, A., Bandak, E., Pedersen, H., Saxtrup, N., Kallehauge, H., Solem, E. J. & Christensen, M. B., dec. 2019, I : Danish Medical Journal. 66, 12

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Pain assessment in people with dementia is difficult, and withdrawal of analgesics may allow for assessment of treatment efficacy whilst decreasing pill burden, adverse events and interactions. We aimed to describe the use of analgesics among elderly in Denmark and to compile the evidence for withdrawal of analgesics among people with dementia.

METHODS: With respect to analgesics use, we employed data from national registries on the analgesic prescription use (opioids, nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen) in 2017 among elderly people with and without dementia. Trial evidence was produced by performing a systematic search in MEDLINE, Embase and Cinahl for trials evaluating withdrawal of analgesics in people with dementia.

RESULTS: Opioids were prescribed more frequently (p = 0.026) and NSAIDs less frequently (p = 0.026) to people with dementia. With respect to trial evidence, we identified two studies: An observational cross-over study (n = 3) reporting acetaminophen withdrawal leading to increases in pain frequency and duration, and a cluster-randomised clinical trial (n = 352) reporting changes in mobilization-observation-behaviour-intensity-dementia-2 (MOBID-2) pain score during a four-week withdrawal period (acetaminophen, opioids and/or pregabaline) from a mean ± standard deviation of 2.3 ± 2.1 to 2.9 ± 2.6 compared with 3.5 ± 2.6 to 3.5 ± 2.5 in the control group.

CONCLUSIONS: In Denmark, use of opioids is higher in elderly with dementia compared to elderly without dementia. The evidence suggests that withdrawal of analgesics may aggravate pain but increases in pain scores may be of little clinical relevance in most people. Clinical trials investigating analgesics withdrawal are warranted.

Originalsprog Engelsk
Tidsskrift Danish Medical Journal
Vol/bind 66
Udgave nummer 12
ISSN 1603-9629
Status Udgivet - dec. 2019

Bibliografisk note

Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Applicability of trials in rheumatoid arthritis and osteoarthritis: A systematic review and meta-analysis of trial populations showing adequate proportion of women, but underrepresentation of elderly people

Palmowski, A., Buttgereit, T., Palmowski, Y., Nielsen, S. M., Boers, M., Christensen, R. & Buttgereit, F., jun. 2019, I : Seminars in Arthritis and Rheumatism. 48, 6, s. 983-989 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To evaluate whether elderly people and women are adequately represented in randomized controlled trials (RCT) in rheumatoid arthritis (RA) and osteoarthritis (OA).

METHODS: Four systematic searches in MEDLINE yielded RCT in RA and OA on any intervention published in 2016 and 2017 and population-based studies (PBS) in RA and OA published between 2013 and 2017. Random effects meta-analyses estimated the pooled proportion of elderly people (defined as being ≥ 65 years old), the mean age, its standard deviation (SD), and the proportion of women stratified by disease (RA and OA) and study type (RCT and PBS). Stratified estimates were subsequently compared.

RESULTS: 265 RCT comprising 51,240 participants and 53 PBS comprising 523,630 participants were included. In both RA and OA, RCT included lower proportions of elderly people than PBS: RA -0.18 (95% confidence interval -0.22 to -0.13); OA -0.20 (-0.30 to -0.09); had lower mean ages: RA -5.2 years (-6.8 to -3.5); OA -4.7 years (-7.5 to -2.0); and smaller SD: RA -1.9 years (-2.6 to -1.3); OA -2.7 years (-4.2 to -1.2); (all comparisons: p ≤ 0.001). Proportions of women were comparable in RCT compared to PBS in both RA and OA.

CONCLUSIONS: While women are adequately represented in RA and OA trials, the elderly are underrepresented, probably limiting applicability of current evidence to this growing subgroup. It is urgent to improve the inclusion of elderly people in clinical trials and study age as a determinant for outcome.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 48
Udgave nummer 6
Sider (fra-til) 983-989
Antal sider 7
ISSN 0049-0172
DOI
Status Udgivet - jun. 2019

Bibliografisk note

Copyright © 2018 Elsevier Inc. All rights reserved.

Assessing synovitis in the hands in patients with rheumatoid arthritis by ultrasound: an agreement study exploring the most inflammatory active side from two Norwegian trials

Terslev, L., Christensen, R., Aga, A-B., Sexton, J., Haavardsholm, E. A. & Hammer, H. B., 5 jul. 2019, I : Arthritis Research & Therapy. 21, 1, s. 166

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To assess if the right hand, the dominant hand, or the hand with more clinically swollen joints (SwJ) is per se the most inflamed and exhibits the greatest change during treatment and hence preferred for unilateral scoring of synovitis by ultrasound in rheumatoid arthritis (RA) patients.

METHODS: Using data from two previously published Norwegian RA patient cohorts initiating treatment, bilateral metacarpophalangeal joint 1-5, proximal phalangeal joint 2+3, and wrists were evaluated by ultrasound. Using a 0-3 scoring system a grey-scale (GS), power Doppler (PD) and global synovitis score (GLOESS) was calculated for each hand (0-30). For precision, a difference of < ± 3 in sum score was pre-specified as indicating clinically insignificant difference in inflammatory activity for all three scores.

RESULTS: Four hundred thirty-seven RA patients were included. Baseline ultrasound inflammation was statistically significantly higher in hands with more vs fewer SwJ ([mean difference, 95%CI] GS sum score 2.21[1.30 to 3.12], PD sum score 1.70 [0.94 to 2.47] and GLOESS 2.31[1.36 to 3.26]) and also exhibited significantly more change for all sum scores at 3 months follow-up (GS sum score 1.34 [0.60 to 2.08], PD sum score 1.17 [0.44 to 1.91], and GLOESS 1.43 [0.63 to 2.22]). No such differences were found between the dominant and the non-dominant or the right and the left hands at any time points.

CONCLUSION: The hand with clinically more SwJ is statistically more inflammatory active according to GS, Doppler, and GLOESS sum scores, exhibits a change during treatment, and is potentially the best choice for unilateral scoring systems.

Originalsprog Engelsk
Tidsskrift Arthritis Research & Therapy
Vol/bind 21
Udgave nummer 1
Sider (fra-til) 166
ISSN 1478-6354
DOI
Status Udgivet - 5 jul. 2019

BACKGROUND: The association between chronically elevated cortisol, as measured by hair cortisol concentration (HCC), and dietary intake among children has generally not been explored. Moreover, it is unknown whether there is an association between parental HCC and dietary intake among their children.

OBJECTIVE: To examine associations between HCC and dietary intake among children, and to explore the association between parental HCC and dietary intake among their children.

METHODS: We conducted a cross-sectional study based on 296 children predisposed to overweight and obesity who participated in the Healthy Start study. Multiple Linear regression analyses were conducted to assess the association between HCC and total energy intake, macronutrients, fruit and vegetables, added sugar, sugar-sweetened beverages (SSB), and a diet quality index (DQI).

RESULTS: Among the children, we found that higher HCC was associated with a lower consumption of dietary fat (β: -0.7 g/day [95% CI: -1.3, -0.0] per 100 pg/mg HCC). We found no statistically significant association between HCC and intake of total energy, protein, carbohydrate, fruit and vegetables, added sugar, SSB or DQI. We found no association between parental HCC and intake of total energy, added sugar, selected food groups or DQI among their children. However, stratified analyses showed that paternal HCC was associated with a borderline significant lower total energy intake and significantly lower protein intake, but only among daughters (adjusted β: -42 kcal/day [95% CI: -85, 0] and -2.6 g/day [95% CI: -4.4, -0.8] per 100 pg/mg HCC, respectively).

CONCLUSION: Among children, chronic stress as measured by HCC may be associated with a lower fat consumption, and paternal HCC may be associated with a lower intake of energy and protein among their daughters. However, the associations observed were weak, and any clinical relevance of these findings remains questionable.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 14
Udgave nummer 3
Sider (fra-til) e0213573
ISSN 1932-6203
DOI
Status Udgivet - 2019

Association Between Long-Term Exposure to Wind Turbine Noise and the Risk of Stroke: Data From the Danish Nurse Cohort

Bräuner, E. V., Jørgensen, J. T., Duun-Henriksen, A. K., Backalarz, C., Laursen, J. E., Pedersen, T. H., Simonsen, M. K. & Andersen, Z. J., 16 jul. 2019, I : Journal of the American Heart Association. 8, 14, s. e013157

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background Epidemiological studies suggest that road traffic noise increases the risk of stroke. Similar effects may be expected from wind turbine noise (WTN) exposure, but epidemiological evidence is lacking. The present study investigated the association between long-term exposure to WTN and the risk for stroke. Methods and Results First-ever stroke in 28 731 female nurses in the Danish Nurse Cohort was identified in the Danish National Patient register until the end of 2013. WTN, traffic noise, and air pollution exposures were estimated for all historic and present residential addresses between 1982 and 2013. Time-varying Cox proportional hazard regression was used to examine the associations between the 11-, 5-, and 1-year rolling means of WTN levels and stroke incidence. Of 23 912 nurses free of stroke at the cohort baseline, 1097 nurses developed stroke by the end of follow-up. At the cohort baseline, 10.3% of nurses were exposed to WTN (≥1 turbine within a 6000-meter radius of the residence) and 13.3% in 2013. Mean baseline residential noise levels among exposed nurses were 26.3 dB(A). No association between long-term WTN exposure and stroke incidence was found. The adjusted hazard ratios and 95% CIs for the 11-, 5-, and 1-year running mean residential WTN exposures preceding stroke diagnosis, comparing nurses with residential WTN levels above and below 20 dB(A) were 1.09 (0.90-1.31), 1.08 (0.89-1.31) and 1.08 (0.89-1.32), respectively. Conclusions This comprehensive cohort study lends no support to an association between long-term WTN exposure and stroke risk.

Originalsprog Engelsk
Tidsskrift Journal of the American Heart Association
Vol/bind 8
Udgave nummer 14
Sider (fra-til) e013157
ISSN 2047-9980
DOI
Status Udgivet - 16 jul. 2019

OBJECTIVE: To describe spontaneous changes in time spent physically inactive measured continuously by accelerometry during an 8-week weight loss intervention in overweight/obese individuals with knee osteoarthritis.

METHOD: This study was designed as an observational cohort study including individuals with concomitant overweight/obesity and symptomatic knee osteoarthritis from an osteoarthritis outpatient clinic. Participants completed an 8-week dietary intervention previously shown to induce substantial weight loss. The main outcome was accelerometer-based measurement of physical inactivity for 24 hours daily during the 8-week intervention period presented as change in the average daily time spent inactive (sitting, reclined or sleeping) from one week prior to intervention to the last week of the intervention.

RESULTS: A total of 124 participants completed the dietary intervention and had valid accelerometer recordings. The mean weight loss was 12.7 kg [95% CI -13.2 to -12.1; P<.0001] after 8 weeks corresponding to a decrease in BMI of 4.3 kg/m2 [95%CI -4.5 to -4.2; P<.0001]. Significant improvements in osteoarthritis symptoms (assessed by the Knee Injury and Osteoarthritis Outcome Score) was found across all subscales; for KOOS pain an improvement of 12.8 points [95% CI, 10.6 to 15.0; P<.0001] was observed. No statistically significant change occurred in the average daily time spent inactive from baseline to follow-up (mean change: 8.8 minutes/day [95% CI, -12.1 to 29.7]; P=0.41).

CONCLUSION: Physical inactivity remains stable despite a clinically significant weight loss and improvements in knee osteoarthritis symptoms. Change in inactivity does not seem to occur spontaneously, suggesting that focused efforts to reduce inactive behaviors are needed. This article is protected by copyright. All rights reserved.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
ISSN 2151-464X
DOI
Status E-pub ahead of print - 1 mar. 2019

Bibliografisk note

This article is protected by copyright. All rights reserved.

Associations between vitamin D status in pregnancy and offspring neurodevelopment: a systematic literature review

Janbek, J., Specht, I. O. & Heitmann, B. L., 1 maj 2019, I : Nutrition Reviews. 77, 5, s. 330-349 20 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

CONTEXT: Vitamin D plays an important role in the development of the brain, which is one of the earliest fetal organs to develop. Results from epidemiological studies investigating associations between maternal levels of vitamin D during pregnancy and offspring neurodevelopment are mixed and inconclusive.

OBJECTIVE: This systematic review of studies that examined vitamin D levels in pregnancy and offspring neurodevelopment used 3 specific domains-timing of exposure during pregnancy trimesters, neurodevelopmental outcomes, and offspring age at assessment of outcomes-to determine whether vitamin D status in pregnancy is associated with offspring neurodevelopment.

DATA SOURCES: A search of the Embase, PsychInfo, Scopus, and The Cochrane Library databases in September 2017 and February 2018 identified 844 articles, of which 46 were retrieved for full-text assessment.

STUDY SELECTION: Eligibility criteria were used to select studies. All authors examined the studies, and consensus was reached through discussion. Results were divided according to the 3 domains.

DATA EXTRACTION: Authors examined the studies independently, and data from eligible studies were extracted using a modified version of the Cochrane data collection form. Using the modified Downs and Black checklist, 2 authors assessed the quality of the studies independently and were blinded to each other's assessment. Consensus was reached upon discussion and with the involvement of the third author.

RESULTS: Fifteen observational studies were included. Vitamin D in pregnancy was associated with offspring language and motor skills in young children. Associations persisted into adolescence, and results were not dependent on the timing of vitamin D exposure during pregnancy. No supplementation studies were identified.

CONCLUSIONS: There is some evidence that low vitamin D status in pregnancy is associated with offspring language and motor development, particularly in young children.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42017078312.

Originalsprog Engelsk
Tidsskrift Nutrition Reviews
Vol/bind 77
Udgave nummer 5
Sider (fra-til) 330-349
Antal sider 20
ISSN 0029-6643
DOI
Status Udgivet - 1 maj 2019

Bibliografisk note

© The Author(s) 2019. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Attribution of weight regain to emotional reasons amongst European adults with overweight and obesity who regained weight following a weight loss attempt

Sainsbury, K., Evans, E. H., Pedersen, S., Marques, M. M., Teixeira, P. J., Lähteenmäki, L., Stubbs, R. J., Heitmann, B. L. & Sniehotta, F. F., apr. 2019, I : Eating and Weight Disorders. 24, 2, s. 351-361 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: Despite the wide availability of effective weight loss programmes, maintenance of weight loss remains challenging. Difficulties in emotion regulation are associated with binge eating and may represent one barrier to long-term intervention effectiveness in obesity. The purpose of this study was to determine the relationship between emotion regulation difficulties and the extent of weight regain in a sample of adults who had lost, and then regained, weight, and to examine the characteristics associated with emotional difficulties.

METHODS: 2000 adults from three European countries (UK, Portugal, and Denmark) completed an online survey assessing self-reported weight loss and regain following their most recent weight loss attempt. They also completed a binge eating disorder screening questionnaire and, if they had regained weight, were asked if they attributed it to any emotional factors (a proxy for emotion regulation difficulties). Spearman's correlations and logistic regression were used to assess the associations between emotion regulation, weight regain, and strategy use.

RESULTS: Emotion regulation difficulties were associated with greater weight regain (N = 1594 who lost and regained weight). Attribution to emotional reasons was associated with younger age, female gender, loss of control and binge eating, lower perceptions of success at maintenance, using more dietary and self-regulatory strategies in weight loss, and fewer dietary strategies in maintenance.

CONCLUSIONS: Weight-related emotion regulation difficulties are common amongst regainers and are associated with regaining more weight. Affected individuals are already making frequent use of behavioural strategies during weight loss, but do not apply these consistently beyond active attempts. Simply encouraging the use of more numerous strategies, without concurrently teaching emotion regulation skills, may not be an effective means to improving weight outcomes in this group.

LEVEL OF EVIDENCE: Level V, descriptive (cross-sectional) study.

Originalsprog Engelsk
Tidsskrift Eating and Weight Disorders
Vol/bind 24
Udgave nummer 2
Sider (fra-til) 351-361
Antal sider 11
ISSN 1124-4909
DOI
Status Udgivet - apr. 2019

Biomarkers of Whole-Grain and Cereal-Fiber Intake in Human Studies: A Systematic Review of the Available Evidence and Perspectives

Jawhara, M., Sørensen, S. B., Heitmann, B. L. & Andersen, V., 6 dec. 2019, I : Nutrients. 11, 12

Publikation: Bidrag til tidsskriftReviewForskningpeer review

High whole-grain consumption is related to better health outcomes. The specific physiological effect of these compounds is still unrevealed, partly because the accurate estimation of the intake of whole grains from dietary assessments is difficult and prone to bias, due to the complexity of the estimation of the intake by the consumer. A biomarker of whole-grain intake and type of whole-grain intake would be useful for quantifying the exposure to whole-grain intake. In this review, we aim to review the evidence on the potential biomarkers for whole-grain intake in the literature. We conducted a systematic search in Medline, Embase, Web of Science, and the Cochrane database. In total, 39 papers met the inclusion criteria following the PRISMA guidelines and were included. The relative validity, responsiveness, and reproducibility of these markers were assessed for short-, medium-, and long-term exposure as important criteria for the potential use of these biomarkers from a clinical and research perspective. We found three major groups of biomarkers: (1) alkylresorcinol, as well as its homologs and metabolites, assessed in plasma, adipose tissue biopsies, erythrocyte membranes, and urine; (2) avenacosides, assessed in urine samples; and (3) benzoxazinoid-derived phenylacetamide sulfates, assessed in blood and urine samples. The reviewed biomarkers may be used for improved assessment of associations between whole-grain intake and health outcomes.

Originalsprog Engelsk
Tidsskrift Nutrients
Vol/bind 11
Udgave nummer 12
ISSN 2072-6643
DOI
Status Udgivet - 6 dec. 2019

Brain resting-state connectivity in the development of secondary hyperalgesia in healthy men

Hansen, M. S., Becerra, L., Dahl, J. B., Borsook, D., Mårtensson, J., Christensen, A., Nybing, J. D., Havsteen, I., Boesen, M. & Asghar, M. S., 1 apr. 2019, I : Brain structure & function. 224, 3, s. 1119-1139 21 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Central sensitization is a condition in which there is an abnormal responsiveness to nociceptive stimuli. As such, the process may contribute to the development and maintenance of pain. Factors influencing the propensity for development of central sensitization have been a subject of intense debate and remain elusive. Injury-induced secondary hyperalgesia can be elicited by experimental pain models in humans, and is believed to be a result of central sensitization. Secondary hyperalgesia may thus reflect the individual level of central sensitization. The objective of this study was to investigate possible associations between increasing size of secondary hyperalgesia area and brain connectivity in known resting-state networks. We recruited 121 healthy participants (male, age 22, SD 3.35) who underwent resting-state functional magnetic resonance imaging. Prior to the scan session, areas of secondary hyperalgesia following brief thermal sensitization (3 min. 45 °C heat stimulation) were evaluated in all participants. 115 participants were included in the final analysis. We found a positive correlation (increasing connectivity) with increasing area of secondary hyperalgesia in the sensorimotor- and default mode networks. We also observed a negative correlation (decreasing connectivity) with increasing secondary hyperalgesia area in the sensorimotor-, fronto-parietal-, and default mode networks. Our findings indicate that increasing area of secondary hyperalgesia is associated with increasing and decreasing connectivity in multiple networks, suggesting that differences in the propensity for central sensitization, assessed as secondary hyperalgesia areas, may be expressed as differences in the resting-state central neuronal activity.

Originalsprog Engelsk
Tidsskrift Brain structure & function
Vol/bind 224
Udgave nummer 3
Sider (fra-til) 1119-1139
Antal sider 21
ISSN 0177-5154
DOI
Status Udgivet - 1 apr. 2019

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