Published in 2022

INTRODUCTION: Despite a trend toward the use of perforator-based flaps for autologous breast reconstruction, the m. latissimus dorsi (LD) flap remains a popular alternative. Several studies have sought to uncover the shoulder-related donor-site morbidity, but the results are inconclusive. This study aims at evaluating what impact breast reconstruction with an LD flap has on shoulder strength, range of motion (ROM), lymphedema, sensory disturbances, and patients' ability to perform activities of daily living (ADL).

MATERIALS AND METHODS: In a prospective observational study, we examined 20 female patients undergoing delayed breast reconstruction with an LD flap. The primary outcome was a change in shoulder strength, measured with the Biodex System4 Pro-dynamometer. ROM was assessed using two-dimensional photogrammetry. Furthermore, the patients' self-reported pain, lymphedema, sensory disturbances, and ability to perform ADL were assessed using a questionnaire. Measurements were performed pre-operatively at 3 months and 12 months post-operatively.

RESULTS: Of the 20 included patients, 17 completed the follow-up. At the 12 months follow-up, a significant loss of isometric shoulder strength of 17% was observed in shoulder adduction (P<0.001) and 21% in extension (P<0.001). Isometric strength and ability to perform ADL and ROM were unchanged. There was a decrease in the number of patients reporting problems with lymphedema (10 to 7) and an increase in the incidence of sensory disturbances (10 to 13).

CONCLUSION: A loss of shoulder strength was observed following the transfer of the LD flap; however, the procedure did not hinder the post-operative performance of ADLs for the patients. LD reconstruction seems to be a safe procedure.

Originalsprog Engelsk
Tidsskrift Journal of plastic, reconstructive & aesthetic surgery : JPRAS
Vol/bind 75
Udgave nummer 7
Sider (fra-til) 2205-2210
Antal sider 6
ISSN 1748-6815
DOI
Status Udgivet - jul. 2022

Bibliografisk note

Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and psoriasis - A nationwide cohort study from the DANBIO and DERMBIO registries

Egeberg, A., Rosenø, N. A. L., Aagaard, D., Lørup, E. H., Nielsen, M-L., Nymand, L., Kristensen, L. E., Thyssen, J. P., Thomsen, S. F., Cordtz, R. L., Loft, N., Skov, L., Bryld, L. E., Rasmussen, M. K., Højgaard, P., Kristensen, S. & Dreyer, L., apr. 2022, I: Seminars in Arthritis and Rheumatism. 53, 151979.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Drug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis. The objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis.

METHODS: We performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy.

FINDINGS: The study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA, drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA, tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a somewhat higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis, drug survival was generally highest for guselkumab.

INTERPRETATION: Differing treatment responses to drugs with various modes of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history.

FUNDING: None.

Originalsprog Engelsk
Artikelnummer 151979
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 53
ISSN 0049-0172
DOI
Status Udgivet - apr. 2022

Bibliografisk note

Copyright © 2022 Elsevier Inc. All rights reserved.

Effect modification by contextual factors of urate-lowering therapy on serum urate in people with gout: A systematic review with meta-regression analysis

Kampe, R. T., Nielsen, S. M., Hotea, I., van Durme, C., Christensen, R. & Boonen, A., okt. 2022, I: Seminars in Arthritis and Rheumatism. 56, s. 152049

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To synthesize evidence of the effect of contextual factors (CFs) on efficacy of urate-lowering therapy (ULT) on serum urate (SU) as outcome in gout patients.

METHODS: Randomised controlled trials (RCTs) from (updated) Cochrane reviews were the starting point. RCTs were included if they explored the role of any CF on efficacy of ULT on SU in gout patients. For CFs with sufficient data (i.e. ≥3 trials), a mixed-effects meta-regression analysis was performed with trial and comparison as random effects, whereas specific CFs were modelled as fixed factors.

RESULTS: Eight RCTs were included. Effect modification by CFs was explored for age, sex, race, renal function, cardiovascular comorbidity, tophi, thiazide-diuretic use, and previous ULT use. Crude data stratified by renal function were available for four trials (36 randomised comparisons), and suitable for meta-analysis. Pooled estimates revealed that gout patients with a normal, mildly-, or moderately impaired renal function were consistently more likely to achieve SU target with ULT compared to control. Among RCTs comparing ULT to placebo (30 comparisons), effects of ULT on achieving SU target were not statistically different for those with normal (OR:66.87;[11.39-392.75]) compared to mildly (OR:28.54;[5.11-159.46]) and moderately (OR:21.45;[3.20-143.64]) impaired renal function, but seemed lower in those with severely impaired (OR:9.13;[0.96-86.97]) renal function. Data were insufficient to draw conclusions on effect modification by other CFs.

CONCLUSION: Few RCTs report stratified analyses exploring the role of CFs. ULT seemed effective in reaching the SU target in all levels of renal function, though severely impaired renal function appeared to render a slight disadvantage.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 56
Sider (fra-til) 152049
ISSN 0049-0172
DOI
Status Udgivet - okt. 2022

Bibliografisk note

Copyright © 2022. Published by Elsevier Inc.

Effect of a Smoking and Alcohol Cessation Intervention Initiated Shortly Before Radical Cystectomy-the STOP-OP Study: A Randomised Clinical Trial

Lauridsen, S. V., Thomsen, T., Jensen, J. B., Kallemose, T., Schmidt Behrend, M., Steffensen, K., Poulsen, A. M., Jacobsen, A., Walther, L., Isaksson, A., Thind, P. & Tønnesen, H., 1 mar. 2022, (E-pub ahead of print) I: European Urology Focus. s. 1-9 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Evidence concerning the reduction of postoperative complications due to smoking and alcohol drinking in patients undergoing radical cystectomy is incomplete.

OBJECTIVE: To evaluate the efficacy of a 6-wk smoking and/or alcohol cessation intervention, initiated shortly before surgery and continued until 4 wk after, in reducing complications.

DESIGN, SETTING, AND PARTICIPANTS: Between 2014 and 2018, we enrolled 104 patients with high-risk bladder cancer who were daily smokers or consuming at least 3 units of alcohol daily in a multicentre randomised clinical trial.

INTERVENTION: Patients were randomised to a 6-wk intensive smoking and/or alcohol cessation intervention or treatment as usual.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the number of patients developing any postoperative complication, or death, within 30 d after surgery. The secondary endpoints were successful quitters, health-related quality of life, length of stay, time back to habitual activity, and mortality. An intention-to-treat analysis was applied to evaluate treatment effect.

RESULTS AND LIMITATIONS: There were some differences in baseline demographic and lifestyle characteristics. Postoperatively, 64% in the intervention group versus 70% in the control group (risk ratio [RR] 0.91, confidence interval [CI] 0.68-1.21, p = 0.51) developed complications. Significantly fewer patients developed three or more complications after 30 d (RR 0.39; CI 0.18-0.84, p = 0.01). The rates of successful quitting were 51% in the intervention group and 27% in the control group (RR 2, CI 1.14-3.51, p = 0.01). The external validity of this trial may be limited because 53% of eligible patients refused participation.

CONCLUSIONS: Despite a significant effect on the quit rate at completion of the intervention, this multimodal prehabilitation did not show a significant difference regarding our primary outcome postoperative complications.

PATIENT SUMMARY: A 6-wk smoking and alcohol cessation intervention in relation to bladder cancer surgery did not reduce postoperative complications, but it was effective in supporting people to quit in the short term.

Originalsprog Engelsk
Tidsskrift European Urology Focus
Sider (fra-til) 1-9
Antal sider 9
ISSN 2405-4569
DOI
Status E-pub ahead of print - 1 mar. 2022

Bibliografisk note

Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial

Møller-Bisgaard, S., Hørslev-Petersen, K., Ejbjerg, B., Hetland, M. L., Christensen, R., Ørnbjerg, L. M., Glinatsi, D., Møller, J. M., Boesen, M., Stengaard-Pedersen, K., Madsen, O. R., Jensen, B., Villadsen, J. A., Hauge, E. M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M., Lindegaard, H., Bliddal, H., & 7 flereKrogh, N. S., Ellingsen, T., Nielsen, A. H., Larsen, L., Jurik, A. G., Thomsen, H. S. & Østergaard, M., jul. 2022, I: Scandinavian Journal of Rheumatology. 51, 4, s. 268-278 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission.

METHOD: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models.

RESULTS: Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5).

CONCLUSIONS: Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity.

TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01656278.

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Rheumatology
Vol/bind 51
Udgave nummer 4
Sider (fra-til) 268-278
Antal sider 11
ISSN 0300-9742
DOI
Status Udgivet - jul. 2022

Bibliografisk note

Funding Information:
S Møller-Bisgaard reports grants and non-financial support from AbbVie, during the conduct of the study. ML Hetland reports grants from AbbVie, grants and personal fees from Biogen, grants from BMS, personal fees from Celltrion, grants from Eli Lilly Danmark A/S, personal fees from Janssen Biologics BV, grants from Lundbeck Fonden, personal fees from MSD, grants and personal fees from Pfizer, grants from Roche, personal fees from Samsung Biopis, grants from Sandoz, and grants from Novartis, outside the submitted work; and Dr Hetland chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies. ML Hetland co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data, and is partly funded by Novartis. R Christensen reports Lecture: Research Methods (Pfizer, DK; 2017), Lecture: GRADE, Lecture (Celgene, DK; 2017), Ad Board Lecture: CAM (Orkla Health, DK; 2017), Project Grant: ‘GreenWhistle’ (Mundipharma, 2019), Lecture: Diet in RMD (Novartis, DK; 2019), Consultancy Report: Network MA’s (Biogen, DK; 2017), Ad Board Lecture: GRADE (Lilly, DK; 2017), Consultancy Report: GRADE (Celgene, 2018), and Lecture: Network MA’s (LEO; 2020), all outside the submitted work; and Musculoskeletal Statistics Unit, The Parker Institute is grateful for the financial support received from public and private foundations, companies, and private individuals over the years. The Parker Institute is supported by a core grant from the Oak Foundation; The Oak Foundation is a group of philanthropic organizations that, since its establishment in 1983, has given grants to not-for-profit organizations around the world. LM Ørnbjerg reports grants from AbbVie during the conduct of the study. M Boesen reports grants from AbbVie during the conduct of the study; personal fees from AbbVie, personal fees from UCB, personal fees from Eli Lilly, grants and personal fees from Image Analysis Group, and grants from Esaote, outside the submitted work. M Østergaard reports grants from AbbVie, during the conduct of the study; grants, personal fees, and non-financial support from AbbVie, grants, personal fees, and non-financial support from BMS, personal fees from Boehringer-Ingelheim, personal fees from Eli Lilly, personal fees and non-financial support from Janssen, grants, personal fees, and non-financial support from Merck, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Roche, grants, personal fees, and non-financial support from UCB, grants and personal fees from Celgene, personal fees from Sanofi, personal fees from Regeneron, and grants, personal fees, and non-financial support from Novartis outside the submitted work. No other disclosures relevant to this article were reported.

Publisher Copyright:
© 2021 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation.

Effectiveness of physical activity monitors in adults: systematic review and meta-analysis

Larsen, R. T., Wagner, V., Korfitsen, C. B., Keller, C., Juhl, C. B., Langberg, H. & Christensen, J., 26 jan. 2022, I: BMJ. 376, s. e068047 e068047.

Publikation: Bidrag til tidsskriftReviewpeer review

OBJECTIVE: To estimate the effectiveness of physical activity monitor (PAM) based interventions among adults and explore reasons for the heterogeneity.

DESIGN: Systematic review and meta-analysis.

STUDY SELECTION: The electronic databases MEDLINE, Embase, SPORTDiscus, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched on 4 June 2021. Eligible randomised controlled trials compared interventions in which adults received feedback from PAMs with control interventions in which no feedback was provided. No restrictions on type of outcome measurement, publication date, or language were applied.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were used to synthesise the results. The certainty of evidence was rated by the Grading of Recommendations Assessment and Evaluation (GRADE) approach.

MAIN OUTCOME MEASURES: The three primary outcomes of interest were physical activity, moderate to vigorous physical activity, and sedentary time.

RESULTS: 121 randomised controlled trials with 141 study comparisons, including 16 743 participants, were included. The PAM based interventions showed a moderate effect (standardised mean difference 0.42, 95% confidence interval 0.28 to 0.55) on physical activity, equivalent to 1235 daily steps; a small effect (0.23, 0.16 to 0.30) on moderate to vigorous physical activity, equivalent to 48.5 weekly minutes; and a small insignificant effect (-0.12, -0.25 to 0.01) on sedentary time, equal to 9.9 daily minutes. All outcomes favoured the PAM interventions.

CONCLUSIONS: The certainty of evidence was low for the effect of PAM based interventions on physical activity and moderate for moderate to vigorous physical activity and sedentary time. PAM based interventions are safe and effectively increase physical activity and moderate to vigorous physical activity. The effect on physical activity and moderate to vigorous physical activity is well established but might be overestimated owing to publication bias.

STUDY REGISTRATION: PROSPERO CRD42018102719.

Originalsprog Engelsk
Artikelnummer e068047
Tidsskrift BMJ
Vol/bind 376
Sider (fra-til) e068047
ISSN 1756-1833
DOI
Status Udgivet - 26 jan. 2022

Bibliografisk note

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Effectiveness of tobacco cessation interventions for different groups of tobacco users in Sweden: a study protocol for a national prospective cohort study

Rasmussen, M., Larsson, M., Gilljam, H., Adami, J., Wärjerstam, S., Post, A., Björk-Eriksson, T., Helgason, A. R. & Tønnesen, H., 25 jan. 2022, I: BMJ Open. 12, 1, s. e053090

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Tobacco is still one of the single most important risk factors among the lifestyle habits that cause morbidity and mortality in humans. Furthermore, tobacco has a heavy social gradient, as the consequences are even worse among disadvantaged and vulnerable groups. To reduce tobacco-related inequity in health, those most in need should be offered the most effective tobacco cessation intervention. The aim of this study is to facilitate and improve the evaluation of already implemented national tobacco cessation efforts, focusing on 10 disadvantaged and vulnerable groups of tobacco users.

METHODS AND ANALYSIS: This is a prospective cohort study. Data will be collected by established tobacco cessation counsellors in Sweden. The study includes adult tobacco or e-cigarette users, including disadvantaged and vulnerable patients, receiving in-person interventions for tobacco or e-cigarette cessation (smoking, snus and/or e-cigarettes). Patient inclusion was initiated in April 2020. For data analyses patients will be sorted into vulnerable groups based on risk factors and compared with tobacco users without the risk factor in question.The primary outcome is continuous successful quitting after 6 months, measured by self-reporting. Secondary outcomes include abstinence at the end of the treatment programme, which could be from minutes over days to weeks, 14-day point prevalence after 6 months, and patient satisfaction with the intervention. Effectiveness of successful quitting will be examined by comparing vulnerable with non-vulnerable patients using a mixed-effect logistic regression model adjusting for potential prognostic factors and known confounders.

ETHICS AND DISSEMINATION: The project will follow the guidelines from the Swedish Data Protection Authority and have been approved by the Swedish Ethical Review Authority before patient inclusion (Dnr: 2019-02221). Only patients providing written informed consent will be included. Both positive and negative results will be published in scientific peer-reviewed journals and presented at national and international conferences. Information will be provided through media available to the public, politicians, healthcare providers and planners as these are all important stakeholders.

TRIAL REGISTRATION NUMBER: NCT04819152.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 12
Udgave nummer 1
Sider (fra-til) e053090
ISSN 2044-6055
DOI
Status Udgivet - 25 jan. 2022

Bibliografisk note

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Effectiveness of video consultations in type 1 diabetes patients treated with insulin pumps in the outpatient clinic: protocol for a randomised controlled trial

Schultz, A. N. Ø., Christensen, R., Bollig, G., Kidholm, K. & Brandt, F., 27 apr. 2022, I: BMJ Open. 12, 4, s. e058728

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: The purpose of the study is to assess the effectiveness of video consultations in patients with type 1 diabetes mellitus (DM) treated with insulin pumps in the outpatient clinic.

METHODS AND ANALYSIS: A 52 weeks' duration, open-label, randomised controlled trial will be conducted, enrolling 100 patients with type 1 DM currently treated with insulin pump.Patients will be recruited from the diabetes outpatient clinic at Hospital of Southern Jutland, Department of internal medicine, Sønderborg. Participants will be randomised to either video consultations (experimental intervention) or standard care (control comparator). Participants in the video consultation group will follow their standard care treatment but will have all of their scheduled and non-scheduled appointments by video consultation. The control group will follow their standard care treatment as usual, having all their appointments at the outpatient centre. Primary outcome will be change from baseline of time in range (3.9-10.0 mmol/L).

ETHICS AND DISSEMINATION: The study has been approved by the Regional Committe on Health Research Ethics for Southern Denmark, S-20200039G Acadre 20/12922. We will present the results of the trial at international conferences as well as publish the results of the trial in (a) peer-reviewed scientific journal(s).

TRIAL REGISTRATION NUMBER: NCT04612933.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 12
Udgave nummer 4
Sider (fra-til) e058728
ISSN 2044-6055
DOI
Status Udgivet - 27 apr. 2022

Bibliografisk note

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Effects of a 12-week supervised resistance training program, combined with home-based physical activity, on physical fitness and quality of life in female breast cancer survivors: the EFICAN randomized controlled trial

Soriano-Maldonado, A., Díez-Fernández, D. M., Esteban-Simón, A., Rodríguez-Pérez, M. A., Artés-Rodríguez, E., Casimiro-Artés, M. A., Moreno-Martos, H., Toro-de-Federico, A., Hachem-Salas, N., Bartholdy, C., Henriksen, M. & Casimiro-Andújar, A. J., 22 mar. 2022, (E-pub ahead of print) I: Journal of cancer survivorship : research and practice.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: This study assessed the effects of 12-week supervised resistance training combined with home-based physical activity on physical fitness, cancer-related fatigue, depressive symptoms, health-related quality of life (HRQoL), and life satisfaction in female breast cancer survivors.

METHODS: A parallel-group, outcome assessor-blinded, randomized controlled trial included 60 female breast cancer survivors who had completed their core treatments within the previous 10 years. Through computer-generated simple randomization, participants were assigned to resistance training (RTG; two sessions/week for 12 weeks plus instructions to undertake ≥ 10,000 steps/d) or control (CG; ≥ 10,000 steps/d only). Outcomes were evaluated at baseline and week 12. Muscular strength was assessed with electromechanical dynamometry. A standardized full-body muscular strength score was the primary outcome. Secondary outcomes included cardiorespiratory fitness, shoulder mobility, cancer-related fatigue, depressive symptoms, HRQoL, and life satisfaction.

RESULTS: Thirty-two participants were assigned to RTG (29 achieved ≥ 75% attendance) and 28 to CG (all completed the trial). Intention-to-treat analyses revealed that the standardized full-body muscular strength score increased significantly in the RTG compared to the CG (0.718; 95% CI 0.361-1.074, P < 0.001, Cohen's d = 1.04). This increase was consistent for the standardized scores of upper-body (0.727; 95% CI 0.294-1.160, P = 0.001, d = 0.87) and lower-body (0.709; 95% CI 0.324-1.094, P = 0.001, d = 0.96) strength. There was no effect on cardiorespiratory fitness, shoulder flexion, cancer-related fatigue, depressive symptoms, HRQoL, or life satisfaction. The sensitivity analyses confirmed these results.

CONCLUSION: and implication for cancer survivors. In female breast cancer survivors who had completed their core treatments within the past 10 years, adding two weekly sessions of supervised resistance training to a prescription of home-based physical activity for 12 weeks produced a large increase in upper-, lower-, and full-body muscular strength, while other fitness components and patient-reported outcomes did not improve.

TRIAL REGISTRATION NUMBER: ISRCTN14601208.

Originalsprog Engelsk
Tidsskrift Journal of cancer survivorship : research and practice
ISSN 1932-2259
DOI
Status E-pub ahead of print - 22 mar. 2022

Bibliografisk note

© 2022. The Author(s).

Effects of risankizumab on nail psoriasis in patients with active psoriatic arthritis: results from KEEPsAKE 1

Kristensen, L. E., Soliman, A. M., Papp, K., Merola, J. F., Barcomb, L., Wang, Z., Eldred, A. & Behrens, F., maj 2022, I: Journal of the European Academy of Dermatology and Venereology : JEADV. 36, 5, s. e389-e392

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Tidsskrift Journal of the European Academy of Dermatology and Venereology : JEADV
Vol/bind 36
Udgave nummer 5
Sider (fra-til) e389-e392
ISSN 0926-9959
DOI
Status Udgivet - maj 2022

Poor sleep and psychological stress are obesity determinants that are rarely included in obesity prevention programs. The aim was to report the effects of the Healthy Start randomized intervention on the secondary outcomes psychological stress and sleep duration and onset latency. Data was obtained from the Healthy Start randomized intervention conducted in 2009-2012 among Danish healthy weight children aged 2-6 years, who had either a high birth weight (>4,000 g), high maternal pre-pregnancy body mass index (>28 kg/m2), or low maternal educational level (≤10 years of schooling) and their parents. The intervention was designed to deliver improvements in diet and physical activity habits, optimization of sleep habits, and reduction of psychological family stress. The average intervention period was 15 months. Children with information on a 7-day sleep record, sleep onset latency, Strengths and Difficulties Questionnaire (SDQ), and a modified version of Parenting Stress Index (PSI) were included. The effects of the intervention on sleep habits, PSI scores, SDQ Total Difficulties (SDQ-TD) and Pro-social Behavior scores, and 95% Confidence Intervals (95% CI) were analyzed using linear regression intention-to-treat (n = 543 (intervention group n = 271, control group n = 272)) analyses. No statistically significant effects on sleep duration, sleep onset latency, PSI score, or SDQ Pro-social Behavior score were observed. Values both before and after the intervention were within the normal range both for children in the intervention and children in the control group. Mean change in SDQ-TD was 0.09 points (95% CI -0.57;0.59) in the intervention group, and -0.69 points (95% CI -1.16; -0.23) in the control group (p = 0.06). In conclusion, there were no intervention effects in relation to sleep duration, sleep onset latency, PSI score, or SDQ Pro-social behavior. There was an indication that children in the intervention group had slightly more behavioral problems than the control group after the intervention, but values were within normal range both before and after the intervention, and the difference is not considered to be clinically meaningful.

Originalsprog Engelsk
Artikelnummer e0264514
Tidsskrift PLoS One
Vol/bind 17
Udgave nummer 3
Sider (fra-til) e0264514
ISSN 1932-6203
DOI
Status Udgivet - 2022

Efficacy and Safety of Ixekizumab Versus Adalimumab in Biologic-naïve Patients With Active Psoriatic Arthritis and Moderate-to-severe Psoriasis: 52-week Results From the Randomized SPIRIT-H2H Trial

Reich, K., Kristensen, L. E., Smith, S. D., Rich, P., Sapin, C., Leage, S. L., McKenzie, R., Schuster, C., Riedl, E. & Gooderham, M., maj 2022, I: Dermatology practical & conceptual. 12, 2, s. e2022104

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: The randomized, open-label, assessor-blinded, parallel-group SPIRIT-H2H trial (NCT03151551) demonstrated superiority of ixekizumab over adalimumab in simultaneously achieving improvement in joint symptoms (American College of Rheumatology [ACR]50) and skin clearance (Psoriasis Area and Severity Index [PASI]100) in biologic-naïve patients with active psoriatic arthritis (PsA) and plaque psoriasis (PsO) at Week (W) 24. Higher efficacy of ixekizumab versus adalimumab was maintained through W52.

OBJECTIVES: This analysis investigated efficacy and safety of ixekizumab and adalimumab in the subgroup of patients with PsA and moderate-to-severe PsO through W52.

METHODS: Efficacy and safety outcomes were analyzed in patients with PsA and moderate-to-severe PsO (PASI ≥ 12, Body Surface Area ≥ 10%, static Physician Global Assessment ≥ 3) through W52. Categorical and continuous outcomes were analyzed using logistic regression models and mixed model for repeated measures, respectively.

RESULTS: More ixekizumab-versus adalimumab-treated patients simultaneously achieved PASI100 and ACR50 at W24 (40.8% versus 17.6%, P = 0.015) and W52 (38.8% versus 17.6%, P = 0.026). Likewise, more ixekizumab-versus adalimumab-treated patients achieved PASI100 (59.2% versus 25.5%, P = 0.001) and PASI90 (81.6% versus 60.8%, P = 0.028) through W52, and nail PsO clearance at W24. Joint symptom improvements were comparable between groups. No new safety findings were reported.

CONCLUSIONS: Ixekizumab had higher efficacy than adalimumab in simultaneous achievement of ACR50 and PASI100 at W24 and W52 in patients with PsA and moderate-to-severe PsO. Ixekizumab-treated patients showed higher response rates for nail PsO clearance and for reporting minimal or no impact on quality of life at W24.

Originalsprog Engelsk
Tidsskrift Dermatology practical & conceptual
Vol/bind 12
Udgave nummer 2
Sider (fra-til) e2022104
ISSN 2160-9381
DOI
Status Udgivet - maj 2022

Bibliografisk note

©2022 Reich et al.

Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial

Kristensen, L. E., Keiserman, M., Papp, K., McCasland, L., White, D., Lu, W., Wang, Z., Soliman, A. M., Eldred, A., Barcomb, L. & Behrens, F., feb. 2022, I: Annals of the Rheumatic Diseases. 81, 2, s. 225-231 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).

METHODS: In the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing.

RESULTS: At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p<0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p<0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug).

CONCLUSIONS: Risankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD.

TRIAL REGISTRATION NUMBER: NCT03675308.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 81
Udgave nummer 2
Sider (fra-til) 225-231
Antal sider 7
ISSN 0003-4967
DOI
Status Udgivet - feb. 2022

Bibliografisk note

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Evaluation of the Immediate Effects of Web-Based Intervention Modules for Goals, Planning, and Coping Planning on Physical Activity: Secondary Analysis of a Randomized Controlled Trial on Weight Loss Maintenance

Mattila, E., Horgan, G., Palmeira, A. L., O'Driscoll, R., Stubbs, R. J., Heitmann, B. L. & Marques, M. M., 14 apr. 2022, I: Journal of Medical Internet Research. 24, 4, s. e35614

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: The use of digital interventions can be accurately monitored via log files. However, monitoring engagement with intervention goals or enactment of the actual behaviors targeted by the intervention is more difficult and is usually evaluated based on pre-post measurements in a controlled trial.

OBJECTIVE: The objective of this paper is to evaluate if engaging with 2 digital intervention modules focusing on (1) physical activity goals and action plans and (2) coping with barriers has immediate effects on the actual physical activity behavior.

METHODS: The NoHoW Toolkit (TK), a digital intervention developed to support long-term weight loss maintenance, was evaluated in a 2 x 2 factorial randomized controlled trial. The TK contained various modules based on behavioral self-regulation and motivation theories, as well as contextual emotion regulation approaches, and involved continuous tracking of weight and physical activity through connected commercial devices (Fitbit Aria and Charge 2). Of the 4 trial arms, 2 had access to 2 modules directly targeting physical activity: a module for goal setting and action planning (Goal) and a module for identifying barriers and coping planning (Barriers). Module visits and completion were determined based on TK log files and time spent in the module web page. Seven physical activity metrics (steps; activity; energy expenditure; fairly active, very active and total active minutes; and distance) were compared before and after visiting and completing the modules to examine whether the modules had immediate or sustained effects on physical activity. Immediate effect was determined based on 7-day windows before and after the visit, and sustained effects were evaluated for 1 to 8 weeks after module completion.

RESULTS: Out of the 811 participants, 498 (61.4%) visited the Goal module and 406 (50.1%) visited the Barriers module. The Barriers module had an immediate effect on very active and total active minutes (very active minutes: before median 24.2, IQR 10.4-43.0 vs after median 24.9, IQR 10.0-46.3; P=.047; total active minutes: before median 45.1, IQR 22.9-74.9 vs after median 46.9, IQR 22.4-78.4; P=.03). The differences were larger when only completed Barriers modules were considered. The Barriers module completion was also associated with sustained effects in fairly active and total active minutes for most of the 8 weeks following module completion and for 3 weeks in very active minutes.

CONCLUSIONS: The Barriers module had small, significant, immediate, and sustained effects on active minutes measured by a wrist-worn activity tracker. Future interventions should pay attention to assessing barriers and planning coping mechanisms to overcome them.

TRIAL REGISTRATION: ISRCTN Registry ISRCTN88405328; https://www.isrctn.com/ISRCTN88405328.

Originalsprog Engelsk
Tidsskrift Journal of Medical Internet Research
Vol/bind 24
Udgave nummer 4
Sider (fra-til) e35614
ISSN 1439-4456
DOI
Status Udgivet - 14 apr. 2022

Bibliografisk note

©Elina Mattila, Graham Horgan, António L Palmeira, Ruairi O'Driscoll, R James Stubbs, Berit L Heitmann, Marta M Marques. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.04.2022.

Evidence-Based Research on Effectiveness of Periodontal Treatment in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis

Silva, D. S., Costa, F., Baptista, I. P., Santiago, T., Lund, H., Tarp, S., daSilva, J. A. P. & Christensen, R., okt. 2022, I: Arthritis Care & Research. 74, 10, s. 1723-1735 13 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To gauge the evidence of periodontal therapy's impact on measures of disease activity and systemic inflammatory burden in individuals with rheumatoid arthritis (RA).

METHODS: A search for randomized trials and controlled cohort studies of RA patients with periodontitis was conducted on April 7, 2019, with an update on December 17, 2020 in PubMed, Cochrane Library (CENTRAL), Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trial Registry Platform portal. Two reviewers screened titles and abstracts and selected papers for full-text review. We used Outcome Measures in Rheumatology (OMERACT)-endorsed outcome domains for RA trials and summarized continuous outcomes using standardized mean differences (SMDs) with 95% confidence intervals (95% CIs). We evaluated inconsistency using the I2 statistic and combined SMDs using random-effects models for the meta-analyses; fixed-effect meta-analyses were used for sensitivity analysis. To explore heterogeneity, we added stratified/meta-regression analyses, expressed in T2 .

RESULTS: Of the 1,909 studies identified, 9 (including 10 comparisons) were eligible for quantitative synthesis (n = 388). Evidence suggested a favorable effect of periodontal treatment on disease activity (SMD -0.88 [95% CI -1.38, -0.38]; n = 311). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to judge the estimates' certainty; evidence rated as having low or very low certainty indicated that any possible effect of periodontal treatment in RA is likely to change as more evidence is provided. Selection bias and RA medication stability were highlighted as sources of heterogeneity between studies.

CONCLUSION: There is an urgent need for a well-designed prospective cohort study (preferably a randomized controlled trial) of patients with RA and periodontitis using rigorous protocols, standardized diagnostic criteria, data collection, and adequate duration of follow-up.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
Vol/bind 74
Udgave nummer 10
Sider (fra-til) 1723-1735
Antal sider 13
ISSN 2151-464X
DOI
Status Udgivet - okt. 2022

Bibliografisk note

© 2021 American College of Rheumatology.

OBJECTIVE: To compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA).

METHODS: In this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)-100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients' global assessment of disease impact.

RESULTS: 206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI -0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups.

CONCLUSION: In individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks.

TRIAL REGISTRATION NUMBER: NCT03843931.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 81
Udgave nummer 4
Sider (fra-til) 537-543
Antal sider 7
ISSN 0003-4967
DOI
Status Udgivet - 10 mar. 2022

Bibliografisk note

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

BACKGROUND: Fatigue is a common symptom reported by patients with chronic immunoinflammatory diseases and with profound negative implications on health-related quality of life. This study aimed to delineate underlying components contributing to fatigue in patients with inflammatory bowel disease (IBD) receiving biologic therapy.

METHODS: Cross-sectional questionnaire study of all patients with IBD receiving any biologic therapy at a tertiary IBD center. Fatigue was assessed by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Disease activity and quality of life were evaluated by generic questionnaires. Principal component analysis (PCA) was used to identify components of variables explaining fatigue.

RESULTS: Three hundred patients with IBD were included. Moderate-to-severe fatigue defined as FACIT-F ≤ 39 was present in half of the included patients. PCA condensed variables associated with fatigue into three main components contributing to 49% of observed fatigue. The first component, explaining 21% of fatigue, included factors related to disease chronicity, e.g., long disease duration, high number of previously used biologic therapies, presence of previous intestinal surgery, and increasing age. The second component explained 14% of fatigue and comprised disease activity-related aspects, e.g., disease activity indices and C-reactive protein. The third explained 14% of fatigue and comprised various nutritional deficiencies.

CONCLUSION: Fatigue can partly be explained by chronicity, disease activity, and nutritional deficits. However, the cause of fatigue is unexplained in approximately half of the patients with IBD supporting that fatigue can be an independent, systemic extraintestinal disease manifestation in IBD.

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Gastroenterology
Vol/bind 57
Udgave nummer 9
Sider (fra-til) 1051-1057
Antal sider 7
ISSN 0036-5521
DOI
Status Udgivet - sep. 2022

Fostering Change Through Occupation-Based Intervention: An International Joint Group Concept Mapping Study

Wæhrens, E. E., Nielsen, K. T., Cutchin, M., Fritz, H., Jonsson, H. & la Cour, K., jan. 2022, I: OTJR : occupation, participation and health. 42, 1, s. 10-21 12 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Further consolidation and clarity regarding occupation as a means to foster change in interventions are needed. The study aimed to utilize the knowledge of occupational scholars to systematically determine what is required to use occupation as means to foster change within occupation-based interventions and to generate a conceptual model from those results. Group Concept Mapping involved the following: preparation, generation of ideas, structuring of statements, data analysis, interpretation of maps, and development of conceptual model. Fifty-two international occupational scholars brainstormed 125 ideas. A cluster rating map with nine clusters posed the foundation for a conceptual model with seven themes, namely, artful use of occupation, evidence-based use of occupation, collaboration to promote occupation, coordinating intervention fit, client factors, sociocultural context, and structural influences. The conceptual model, capturing dimensions and dynamics required for using occupation to foster change, may guide future research into occupation-based interventions.

Originalsprog Engelsk
Tidsskrift OTJR : occupation, participation and health
Vol/bind 42
Udgave nummer 1
Sider (fra-til) 10-21
Antal sider 12
ISSN 1539-4492
DOI
Status Udgivet - jan. 2022

BACKGROUND: Psoriatic Arthritis (PsA) is an immune-mediated disease with heterogenous symptoms indicating differences in the underlying immunopathogenesis. The primary objective of the study explored the dynamic mechanisms and interplay between immune cell subtypes constituting the immune response driving PsA to evaluate possible differences in immune cellular phenotypes, and secondary examined associations between emerging immune cellular phenotypes and disease outcomes.

METHODS: Peripheral blood was collected from 70 PsA patients. Frequencies of nine immune cell subtypes were determined by multicolor flow cytometry. The interplay between immune cells were examined with principal component analysis (PCA) to establish immune cellular phenotypes. Disease characteristics, Disease Activity in Psoriatic Arthritis (DAPSA) and Psoriasis Area Severity Index (PASI) were retrieved to examine associations to individual cellular phenotypes.

RESULTS: Four components were identified using PCA resembling four immune cellular phenotypes. Component 1, explaining 25.6% of the variance with contribution from T-helper 17 cells (Th17), memory T regulatory cells (mTregs), dendritic cells and monocytes, was associated with longer disease duration and higher DAPSA. Component 2, driven by Th1, naïve Tregs and mTregs, was associated with shorter disease duration. Component 3 was driven by both Th1, Th17 and CD8+ T cells, while component 4 was characterized by a reverse correlation between CD8+ T cells and natural killer cells.

CONCLUSION: Four immune cellular phenotypes of PsA were suggested at baseline demonstrating complex immune cellular mechanisms in PsA implying the possibility of improving PsA patient stratification based on both clinical and immune cellular phenotypes.

Originalsprog Engelsk
Tidsskrift Arthritis Research & Therapy
Vol/bind 24
Udgave nummer 1
Sider (fra-til) 262
ISSN 1478-6354
DOI
Status Udgivet - 29 nov. 2022

Bibliografisk note

© 2022. The Author(s).

Gut dysbiosis associated with worse disease activity and physical function in axial spondyloarthritis

Sagard, J., Olofsson, T., Mogard, E., Marsal, J., Andréasson, K., Geijer, M., Kristensen, L. E., Lindqvist, E. & Wallman, J. K., 12 feb. 2022, I: Arthritis Research & Therapy. 24, 1, s. 42 42.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain.

METHODS: Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA).

RESULTS: Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2-0.9); BASDAI 1.6 (0.8-2.4); evaluator's global disease activity assessment (Likert scale 0-4) 0.3 (0.1-0.5), BASFI 1.5 (0.6-2.4), and VAS pain (cm) 1.3 (0.4-2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis.

CONCLUSION: Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.

Originalsprog Engelsk
Artikelnummer 42
Tidsskrift Arthritis Research & Therapy
Vol/bind 24
Udgave nummer 1
Sider (fra-til) 42
ISSN 1478-6354
DOI
Status Udgivet - 12 feb. 2022

Bibliografisk note

© 2022. The Author(s).

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