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.

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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

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

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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

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.

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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

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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

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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.

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

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

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

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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
DOI
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
DOI
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
DOI
Status Udgivet - jan. 2019

Bibliografisk note

© 2018 British Association of Dermatologists.

OBJECTIVE: To study the association between extra vitamin D from a mandatory margarine fortification program and chance of live birth among infertile women.

DESIGN: Nationwide cohort study.

SETTING: Not applicable.

PATIENT(S): The study population consisted of 16,212 women diagnosed with infertility from June 1, 1980, to August 31, 1991.

INTERVENTIONS(S): We took advantage of the mandatory vitamin D fortification program of margarine in Denmark that was abruptly stopped on May 31, 1985. The termination of the vitamin D fortification served as a cutoff point to separate the study population into various exposure groups.

MAIN OUTCOME MEASURE(S): Odds ratios and 95% confidence intervals for the association between vitamin D exposure status and chance of a live birth within 12, 15, and 18 months after first infertility diagnosis.

RESULT(S): Women who were diagnosed with infertility during the vitamin D-exposed period had an increased chance of a live birth compared with women diagnosed with infertility during the nonexposed period. For women diagnosed with infertility during the wash-out period, the chance of a live birth was also increased, but somewhat lower. Similar estimates were obtained with longer follow-up, in women with anovulatory infertility, and little seasonal variation was observed when calendar period of conception was applied.

CONCLUSION(S): Our findings suggest that infertile women exposed to extra vitamin D from a margarine fortification program had an increased chance of live birth compared with women not exposed to extra vitamin D from fortification.

Originalsprog Engelsk
Tidsskrift Fertility and Sterility
ISSN 0015-0282
DOI
Status E-pub ahead of print - 20 nov. 2019

Bibliografisk note

Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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
ISSN 1661-7827
DOI
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
DOI
Status Udgivet - jul. 2019

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