Published in 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
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
Status Udgivet - mar. 2019

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
Sider (fra-til) A5578
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
Status Udgivet - jun. 2019

Bibliografisk note

Copyright © 2018 Elsevier Inc. All rights reserved.


Terslev, L., Christensen, R. D. K., Aga, A-B., Sexton, J., Haavardsholm, E. A. & Hammer, H. B., 2019, I: Annals of the Rheumatic Diseases. 78, Suppl. 2, s. 1009-1010 2 s., FRI0625.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer FRI0625
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 78
Udgave nummer Suppl. 2
Sider (fra-til) 1009-1010
Antal sider 2
ISSN 0003-4967
Status Udgivet - 2019

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
Status Udgivet - 5 jul. 2019

Bibliografisk note

Funding Information:
The Parker Institute, Bispebjerg and Frederiksberg Hospital, is supported by a core grant from the Oak Foundation (OCAY-13-309). For the ULRABIT study, we acknowledge our study nurses Anne Katrine Kongtorp and Britt Birketvedt who were important in the organization of the study and performed clinical joint assessments. For the ARCTIC study, we wish to thank the following for the participation in the study: the patients and the ARCTIC investigators Hallvard Fremstad, Tor Magne Madland, Åse Stavland Lexberg, Hilde Haukeland, Erik Rødevand, Christian Høili, Hilde Stray, Anne Lindter Noraas, Dag Magnar Soldal, and Gunnstein Bakland, as well as all other study personnel.

Funding Information:
The ULRABIT trial was supported by AbbVie, Pfizer, and Roche in form of study grants to the Department of Rheumatology, DiakonHjmmet Hospital, Oslo, Norway. The ARTIC trial was supported by Pfizer, UCB, Roche, MSD, and AbbVie.

BACKGROUND AND PURPOSE: Older adults acutely hospitalized for medical illness typically have comorbidity and disability, and inhospital physical inactivity greatly increases the likelihood of developing new disability. Thus, assessment of the patients' mobility status is crucial for planning and carrying out targeted interventions that ensure mobilization during hospital admission. The aim of this study was to determine convergent validity, known group validity, floor and ceiling effects, and anchor-based minimal clinically important difference (MCID) of the more time-consuming de Morton Mobility Index (DEMMI) and the less time-consuming Cumulated Ambulation Score (CAS) in older adults acutely hospitalized for medical illness.

METHODS: In this multicenter cohort study, 235 older hospitalized adults, with a mean (standard deviation) age of 84.8 (7.1) years, were consecutively included. Assessments of mobility using the DEMMI (score range 0-100), the CAS (score range 0-6), and the Barthel Index (BI, score range 0-100) were performed by physical or occupational therapists at hospital admission and discharge. In addition, at discharge patients and therapists were independently asked to assess the patients' current mobility status compared with their mobility status at hospital admission using the Global Rating of Change scale.

RESULTS AND DISCUSSION: Complete data sets were obtained for 155 patients. Baseline characteristics of those with complete data sets did not differ from those with incomplete data sets, except for the number of secondary diagnoses, which was lower in the latter. Significant and moderate relationships existed both at admission and at discharge between scores in the DEMMI and the BI (rs = 0.68, P < .0001, and rs = 0.71, P < .0001), and between scores in the CAS and the BI (rs = 0.60, P < .0001, and rs = 0.57, P < .0001). Use of a gait aid and discharge to inpatient rehabilitation or nursing home were associated with significantly lower DEMMI and CAS scores. No floor or ceiling effects were present in the DEMMI, while a ceiling effect was present in the CAS. The MCID scores based on patients' assessments were 10.7 points for the DEMMI and 0.67 for the CAS.

CONCLUSIONS: These data show that the DEMMI is valid and responsive to changes in mobility and can be considered to have the required properties for measuring mobility in older adults who are hospitalized in medical and geriatric wards. In contrast, the CAS appears to be appropriate to identify whether a patient is independently mobile or needs assistance, while the measure is less suitable for measuring improvements in mobility.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Originalsprog Engelsk
Tidsskrift Journal of geriatric physical therapy
ISSN 1539-8412
Status Udgivet - 15 dec. 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
Artikelnummer e0213573
Tidsskrift PLoS One
Vol/bind 14
Udgave nummer 3
Sider (fra-til) e0213573
ISSN 1932-6203
Status Udgivet - 1 mar. 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
Status Udgivet - 16 jul. 2019

Bibliografisk note

Funding Information:
This work was supported by the Danish Heart Foundation and Danish Council for Independent Research (DFF‐4183‐00353).

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.


Originalsprog Engelsk
Tidsskrift Nutrition Reviews
Vol/bind 77
Udgave nummer 5
Sider (fra-til) 330-349
Antal sider 20
ISSN 0029-6643
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:

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
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 tidsskriftReviewpeer 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
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
Status Udgivet - 1 apr. 2019

Calcium and vitamin D supplementation and/or periodontal therapy in the treatment of periodontitis among Brazilian pregnant women: protocol of a feasibility randomised controlled trial (the IMPROVE trial)

Cocate, P. G., Kac, G., Heitmann, B. L., Nadanovsky, P., da Veiga Soares Carvalho, M. C., Benaim, C., Schlüssel, M. M., de Castro, M. B. T., Alves-Santos, N. H., Baptista, A. F., Holick, M. F., Mokhtar, R. R., Bomfim, A. R. & Adegboye, A. R. A., 2019, I: Pilot and Feasibility Studies. 5, s. 38

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: Periodontitis is a common oral inflammation, which is a risk factor for adverse pregnancy outcomes. Intakes of vitamin D and calcium are inversely associated with occurrence and progression of periodontitis. This study aims to assess the feasibility of a multi-component intervention, including provision of milk powder supplemented with calcium and vitamin D and periodontal therapy (PT), for improving maternal periodontal health and metabolic and inflammatory profiles of low-income Brazilian pregnant women with periodontitis.

Methods: The IMPROVE trial is a feasibility randomised controlled trial (RCT) with a 2 × 2 factorial design with a parallel process evaluation. Pregnant women with periodontitis, aged 18-40 years and with < 20 gestational weeks (n = 120) were recruited and randomly allocated into four groups: (1) fortified sachet (vitamin D and calcium) and powdered milk plus PT during pregnancy, (2) placebo sachet and powdered milk plus PT during pregnancy, (3) fortified sachet (vitamin D and calcium) and powdered milk plus PT after delivery and (4) placebo sachet and powdered milk plus PT after delivery. Dentists and participants are blinded to fortification. Acceptability of study design, recruitment strategy, random allocation, data collection procedures, recruitment rate, adherence and attrition rate will be evaluated. Data on serum levels of vitamin D, calcium and inflammatory biomarkers; clinical periodontal measurements; anthropometric measurements; and socio-demographic questionnaires are collected at baseline, third trimester and 6-8 weeks postpartum. Qualitative data are collected using focus group, for analysis of favourable factors and barriers related to study adherence.

Discussion: Oral health and mineral/vitamin supplementation are much overlooked in the public prenatal assistance in Brazil and of scarcity of clinical trials addressing these issues in low and middle-income countries,. To fill this gap the present study was designed to assess the feasibility of a RCT on acceptability of a multi-component intervention combining conventional periodontal treatment and consumption of milk fortified with calcium-vitamin D for improving periodontal conditions and maternal metabolic and inflammation status, among Brazilian low-income pregnant women with periodontitis. Thus, we hope that this relatively low-cost and safe multicomponent intervention can help reduce inflammation, improve maternal periodontal health and metabolic profile and consequently prevent negative gestational outcomes.

Trial registration: NCT, NCT03148483. Registered on May 11, 2017.

Originalsprog Engelsk
Tidsskrift Pilot and Feasibility Studies
Vol/bind 5
Sider (fra-til) 38
ISSN 2055-5784
Status Udgivet - 2019

Can legal restrictions of prenatal exposure to industrial trans-fatty acids reduce risk of childhood hematopoietic neoplasms? A population-based study

Specht, I. O., Huybrechts, I., Frederiksen, P., Steliarova-Foucher, E., Chajes, V. & Heitmann, B. L., feb. 2019, I: European Journal of Clinical Nutrition. 73, 2, s. 311-318 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Causes of most childhood hematopoietic neoplasms are unknown. Early age of occurrence suggests prenatal etiology. Positive associations have been reported between industrially produced trans-fatty acids (iTFAs) and risks of some cancers in adults. iTFAs are pro-inflammatory and adversely affect the beneficial effects of essential fatty acids, the latter is diminishing tumor growth. In 2004 Denmark legislated against the use of iTFA in foodstuffs. Using the entire population, we investigated if the changes in the legislation as a proxy to the reduced exposure to iTFA had affected the incidence of childhood hematopoietic neoplasms.

METHODS: We used a Cox proportional hazard model to compare the hazard of childhood hematopoietic neoplasms among children born before and after the iTFA ban, as a proxy for fetal iTFA exposure. To take the potential secular trend in hematopoietic neoplasms into account, we modeled the variation in cancer risk across birth cohorts by a piecewise linear spline with a knot in 2004, which allowed a comparison of the hazard of childhood hematopoietic neoplasms between the time before and after the iTFA ban.

RESULTS: Among children born in 1988-2008 in Denmark, 720 were diagnosed with hematopoietic neoplasms before the age of 7 years, corresponding to an overall incidence rate of 7.6 per 100 000 person years. The incidence rates increased by 2% per cohort in 1988-2004 (hazard ratio: 1.02 [1.01; 1.04]) and in 2004-2008 (hazard ratio: 1.02 [0.95; 1.11]).

CONCLUSIONS: No apparent benefit of the iTFA legislation in reducing childhood hematopoietic neoplasms was observed on population basis. Individual-level data are needed to investigate any possible associations between biomarkers of iTFA intake and risk of childhood hematopoietic neoplasms.

Originalsprog Engelsk
Tidsskrift European Journal of Clinical Nutrition
Vol/bind 73
Udgave nummer 2
Sider (fra-til) 311-318
Antal sider 8
ISSN 0954-3007
Status Udgivet - feb. 2019

Cause-specific mortality in patients with psoriasis and psoriatic arthritis

Skov, L., Thomsen, S. F., Kristensen, L. E., Dodge, R., Hedegaard, M. S. & Kjellberg, J., jan. 2019, I: British Journal of Dermatology. 180, 1, s. 100-107 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: There are limited data regarding causes of mortality in patients with psoriasis or psoriatic arthritis (PsA).

OBJECTIVES: This retrospective cohort study evaluated the risk and leading causes of mortality in patients with psoriasis or PsA.

METHODS: Individuals with a hospital-based diagnosis of PsA or psoriasis were identified using the Danish National Patient Registry. Matched control individuals were identified from the general population. The main outcome measures were risk of death and cause-specific mortality in patients with psoriasis or PsA.

RESULTS: Death rates per 1000 patient-years (with 95% confidence intervals) vs. controls were 22·3 (19·7-24·9) vs. 13·9 (11·8-16·0) for patients with psoriasis and 10·8 (8·9-12·8) vs. 11·6 (9·6-13·6) for patients with PsA. Survival, according to stratified hazard ratios (HRs), was significantly lower in patients with psoriasis than in controls (HR 1·74, P < 0·001), but not in patients with PsA (HR 1·06, P = 0·19). Significantly increased risk of death was observed in patients with psoriasis vs. controls due to a number of causes; the highest risks were observed for diseases of the digestive system; endocrine, nutritional and metabolic diseases; and certain infectious and parasitic diseases (HRs 3·61, 3·02 and 2·71, respectively). In patients with PsA, increased mortality was observed only for certain infectious and parasitic diseases (HR 2·80) and diseases of the respiratory system (HR 1·46). Patients with psoriasis died at a younger age than controls (mean age 71·0 vs. 74·5 years, P < 0·001).

CONCLUSIONS: Patients with severe psoriasis have increased mortality risk compared with matched controls, due to a number of causes. Evidence to support an increased risk for patients with PsA was less convincing.

Originalsprog Engelsk
Tidsskrift British Journal of Dermatology
Vol/bind 180
Udgave nummer 1
Sider (fra-til) 100-107
Antal sider 8
ISSN 0007-0963
Status Udgivet - jan. 2019

Bibliografisk note

© 2018 British Association of Dermatologists.

Child behaviour and subsequent changes in body weight, composition and shape

Christensen, K. G., Nielsen, S. G., Olsen, N. J., Dalgård, C., Heitmann, B. L. & Larsen, S. C., 2019, I: PLoS One. 14, 12, s. e0226003

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Studies have found an association between child behavioural problems and overweight, but the existing evidence for this relationship is inconsistent, and results from longitudinal studies are sparse. Thus, we examined the association between behavioural problems and subsequent changes in body mass index (BMI) and anthropometry over a follow-up period of 1.3 years among children aged 2-6 years.

DESIGN: The study was based on a total of 345 children from The Healthy Start Study; all children were healthy weight but predisposed to develop overweight. The Danish version of the Strengths and Difficulties Questionnaire (SDQ), classified as SDQ Total Difficulties (SDQ-TD) and SDQ Prosocial Behaviour (SDQ-PSB), was used to assess child behaviour. Linear regression analyses were used to examine associations between SDQ scores and subsequent change in BMI z-score, body fat percentage, waist circumference and waist-hip ratio, while taking possible confounding factors into account.

RESULTS: We found an association between SDQ-PSB and subsequent change in BMI z-score (β: 0.040 [95% CI: 0.010; 0.071, p = 0.009]). However, there was no evidence of an association between SDQ-PSB and measures of body composition or body shape.

CONCLUSIONS: Among 2 to 6 years old children predisposed to overweight, the association between SDQ-scores and weight gain is either absent or marginal. The SDQ-PSB score may be associated with subsequent increases in BMI z-score, but this association does not seem driven by an increased relative fat accumulation.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 14
Udgave nummer 12
Sider (fra-til) e0226003
ISSN 1932-6203
Status Udgivet - 2019

Compliance with the Very Integrated Program (VIP) for Smoking Cessation, Nutrition, Physical Activity and Comorbidity Education Among Patients in Treatment for Alcohol and Drug Addiction

Hovhannisyan, K., Günther, M., Raffing, R., Wikström, M., Adami, J. & Tønnesen, H., 28 jun. 2019, I: International Journal of Environmental Research and Public Health. 16, 13, s. E2285

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Meeting adherence is an important element of compliance in treatment programmes. It is influenced by several factors one being self-efficacy. We aimed to investigate the association between self-efficacy and meeting adherence and other factors of importance for adherence among patients with alcohol and drug addiction who were undergoing an intensive lifestyle intervention. The intervention consisted of a 6-week Very Integrated Programme. High meeting adherence was defined as >75% participation. The association between self-efficacy and meeting adherence were analysed. The qualitative analyses identified themes important for the patients and were performed as text condensation. High self-efficacy was associated with high meeting adherence (ρ = 0.24, p = 0.03). In the multivariate analyses two variables were significant: avoid complications (OR: 0.51, 95% CI: 0.29-0.90) and self-efficacy (OR: 1.28, 95% CI: 1.00-1.63). Reflections on lifestyle change resulted in the themes of Health and Wellbeing, Personal Economy, Acceptance of Change, and Emotions Related to Lifestyle Change. A higher level of self-efficacy was positively associated with meeting adherence. Patients score high on avoiding complications but then adherence to the intervention drops. There was no difference in the reflections on lifestyle change between the group with high adherence and the group with low adherence.

Originalsprog Engelsk
Tidsskrift International Journal of Environmental Research and Public Health
Vol/bind 16
Udgave nummer 13
Sider (fra-til) E2285
ISSN 1661-7827
Status Udgivet - 28 jun. 2019

Continuous glucose monitoring in pregnant women with type 1 diabetes: an observational cohort study of 186 pregnancies

Kristensen, K., Ögge, L. E., Sengpiel, V., Kjölhede, K., Dotevall, A., Elfvin, A., Knop, F. K., Wiberg, N., Katsarou, A., Shaat, N., Kristensen, L. & Berntorp, K., jul. 2019, I: Diabetologia. 62, 7, s. 1143-1153 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

AIMS/HYPOTHESIS: The aim of this study was to analyse patterns of continuous glucose monitoring (CGM) data for associations with large for gestational age (LGA) infants and an adverse neonatal composite outcome (NCO) in pregnancies in women with type 1 diabetes.

METHODS: This was an observational cohort study of 186 pregnant women with type 1 diabetes in Sweden. The interstitial glucose readings from 92 real-time (rt) CGM and 94 intermittently viewed (i) CGM devices were used to calculate mean glucose, SD, CV%, time spent in target range (3.5-7.8 mmol/l), mean amplitude of glucose excursions and also high and low blood glucose indices (HBGI and LBGI, respectively). Electronic records provided information on maternal demographics and neonatal outcomes. Associations between CGM indices and neonatal outcomes were analysed by stepwise logistic regression analysis adjusted for confounders.

RESULTS: The number of infants born LGA was similar in rtCGM and iCGM users (52% vs 53%). In the combined group, elevated mean glucose levels in the second and the third trimester were significantly associated with LGA (OR 1.53, 95% CI 1.12, 2.08, and OR 1.57, 95% CI 1.12, 2.19, respectively). Furthermore, a high percentage of time in target in the second and the third trimester was associated with lower risk of LGA (OR 0.96, 95% CI 0.94, 0.99 and OR 0.97, 95% CI 0.95, 1.00, respectively). The same associations were found for mean glucose and for time in target and the risk of NCO in all trimesters. SD was significantly associated with LGA in the second trimester and with NCO in the third trimester. Glucose patterns did not differ between rtCGM and iCGM users except that rtCGM users had lower LBGI and spent less time below target.

CONCLUSIONS/INTERPRETATION: Higher mean glucose levels, higher SD and less time in target range were associated with increased risk of LGA and NCO. Despite the use of CGM throughout pregnancy, the day-to-day glucose control was not optimal and the incidence of LGA remained high.

Originalsprog Engelsk
Tidsskrift Diabetologia
Vol/bind 62
Udgave nummer 7
Sider (fra-til) 1143-1153
Antal sider 11
ISSN 0012-186X
Status Udgivet - jul. 2019

Core Outcome Sets Specifically for Longterm Observational Studies: OMERACT Special Interest Group Update in Rheumatoid Arthritis

Lopez-Olivo, M. A., Negrón, J. B., Zogala, R. J., Carmona, L., Criner, K., Goel, N., Gonzalez-Lopez, L., Ingegnoli, F., Leong, A., March, L., Shea, B., Strand, V., Tugwell, P., Westrich-Robertson, T., Zamora, N. V., Christensen, R. & Suarez-Almazor, M. E., sep. 2019, I: Journal of Rheumatology. 46, 9, s. 1164-1167 4 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: This is an update from the Outcome Measures in Rheumatology (OMERACT) Core Outcomes in Longterm Observational Studies Special Interest Group with a focus on rheumatoid arthritis.

METHODS: Preliminary data and proposed next steps were outlined and discussed by participants.

RESULTS: Domains identified after initial steps (systematic review and qualitative research) were pain, physical functioning, participation (i.e., work, social), longterm symptoms, fertility/family planning, emotional well-being, coping, financial status, and adverse events including death.

CONCLUSION: The group agreed conceptually that short-term core outcomes could be different from longer term ones. Participants emphasized the importance of analyzing the need for core domains specifically for longterm longitudinal observational studies.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 9
Sider (fra-til) 1164-1167
Antal sider 4
ISSN 0315-162X
Status Udgivet - sep. 2019