Published in 2021

Proposal for capturing patient experience through extended value frameworks of health technologies

Inotai, A., Jakab, I., Brixner, D., Campbell, J. D., Hawkins, N., Kristensen, L. E., Charokopou, M., Mountian, I., Szegvari, B. & Kaló, Z., jul. 2021, I: Journal of managed care & specialty pharmacy. 27, 7, s. 936-947 12 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

BACKGROUND: Inclusion of patient experience (PEx) in health technology assessment (HTA) has become increasingly important; however, no harmonized approach exists to help manufacturers or decision makers ensure PEx considerations are fair, consistent, and thorough within global HTA frameworks. OBJECTIVE: To develop a proposal for including PEx in the HTA frameworks of health technologies. METHODS: A systematic literature review (SLR) on existing value frameworks (VFs) was conducted to capture how PEx-related value judgment is currently considered. Guided by the results of the SLR, a research group including HTA experts and patient representatives used an iterative process to develop potential value domains to capture PEx, in accordance with international guidelines. Subsequently, a panel of international payer experts was used to challenge the proposed PEx domains and provide recommendations for implementation. RESULTS: The SLR found 61 VFs and multi-criteria decision analyses (MCDAs) that considered PEx; however, PEx-related value elements were often referred to superficially, without clear definitions. Five potential PEx domains, with proposed measures for each, were developed and refined using expert feedback: (1) responsiveness to patient's individual needs, (2) improved health literacy and empowerment, (3) patient and caregiver reported outcomes, (4) household's financial burden, and (5) improved access for vulnerable patient populations. A flexible approach for framework implementation was proposed. CONCLUSIONS: Proposed PEx domains could be implemented at multiple levels of healthcare decision making to formalize consideration of PEx in the assessment of value, either through the extension of existing VFs or to create new PEx-focused VFs and more holistic decision making tools. DISCLOSURES: This study was funded and sponsored by UCB Pharma. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. Charokopou, Mountain, and Szegvari are employed by UCB Pharma. Inotai, Jakab, and Kalo are employed by Syreon Research Institute, which received funding from UCB Pharma for this research. Brixner has received fees from AbbVie, Elevar, Millcreek Outcomes Group, Novartis, Sanofi, UCB Pharma, and Xcenda. Campbell has received grants and contracts from the PhRMA Foundation and the Institute for Clinical and Economic Review. During a sabbatical leave, Campbell collaborated with Syreon Research Institute on research projects that included funding from UCB Pharma. Hawkins has received consultancy fees from UCB Pharma. Kristensen has received speakers bureau fees from Pfizer, AbbVie, Amgen, UCB Pharma, Celgene, Bristol-Myers Squibb, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals and consultancy fees from UCB Pharma.

Originalsprog Engelsk
Tidsskrift Journal of managed care & specialty pharmacy
Vol/bind 27
Udgave nummer 7
Sider (fra-til) 936-947
Antal sider 12
DOI
Status Udgivet - jul. 2021

Protein Intake During Infancy and Subsequent Body Mass Index in Early Childhood: Results from the Melbourne InFANT Program

Zheng, M., Yu, H-J., He, Q-Q., Heitmann, B. L., Rangan, A., McNaughton, S. A. & Campbell, K. J., sep. 2021, I: Journal of the Academy of Nutrition and Dietetics. 121, 9, s. 1775-1784 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: The link between high protein intake during infancy and obesity later in childhood has been much debated, and the association with differing protein sources remains unclear.

OBJECTIVE: This study aimed to examine the associations between total protein intake and protein from different sources (ie, nondairy animal, dairy, and plant) reported at age 9 months and development in body mass index (BMI) z scores until age 5 years.

DESIGN: This study involved a secondary data analysis of the Melbourne InFANT (Infant Feeding, Activity and Nutrition Trial) program, an observational prospective cohort study that was conducted from 2008 to 2013.

PARTICIPANTS/SETTING: Participants were children (n = 345) who completed both the 9-month and 5-year follow-up visits within the Melbourne InFANT program.

MAIN OUTCOME MEASURES: BMI z score was measured at age 5 years.

STATISTICAL ANALYSES PERFORMED: Linear mixed models with a random effect for clusters of mother's group and with adjustment for baseline child and maternal covariates were conducted.

RESULTS: With adjustment for covariates, every 1 g or 1% energy increase in total protein intake at age 9 months was associated with a 0.016-unit (95% CI 0.003 to 0.029) or 0.034-unit (95% CI 0.005 to 0.063) increase in BMI z score at age 5 years, respectively. With respect to protein sources, associations of similar magnitude were found for nondairy animal protein. No evidence of an association with BMI z score was found for dairy (including milk, yogurt, cheese, breast milk, and infant formula) and plant proteins.

CONCLUSIONS: High intakes of total protein, nondairy animal protein, but not dairy or plant proteins, during infancy were associated with higher BMI z score in early childhood. These findings can inform dietary recommendations regarding protein intakes during infancy.

CLINICAL TRIAL REGISTRATION: The InFANT program was registered with Current Controlled Trials (ISRCTN81847050); http://www.isrctn.com/ISRCTN81847050.

Originalsprog Engelsk
Tidsskrift Journal of the Academy of Nutrition and Dietetics
Vol/bind 121
Udgave nummer 9
Sider (fra-til) 1775-1784
Antal sider 10
ISSN 2212-2672
DOI
Status Udgivet - sep. 2021

Real-life drug persistence in patients with rheumatic diseases treated with CT-P13: a prospective observational cohort study (PERSIST)

Taylor, P. C., Christensen, R., Moosavi, S., Selema, P., Guilatco, R., Fowler, H., Mueller, M., Liau, K. F. & Haraoui, B., 2021, I: Rheumatology Advances in Practice. 5, 2, s. rkab026

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Objective: The aim was to report results from PERSIST, a real-life, observational, prospective cohort study of CT-P13, an infliximab (IFX) biosimilar, for treatment of patients with RA, AS or PsA who were biologic naïve or switched from an IFX reference product (IFX-RP; Remicade).

Methods: Adult patients were recruited during usual care at 38 sites in Europe and Canada and enrolled by their physicians after meeting eligibility criteria according to the country-approved label for CT-P13. Primary outcomes were to determine drug utilization and treatment persistence and to assess safety. Patients were followed for up to 2 years. Data were analysed and reported descriptively.

Results: Of 351 patients enrolled, 334 were included in the analysis (RA, 40.4%; AS, 34.7%; PsA, 24.9%). The safety analysis set comprised all 328 patients treated with CT-P13. The majority (58.2%) of patients received CT-P13 monotherapy, most (72.6%) by dosing every 6 or 8 weeks. The mean treatment persistence was 449.2 days; 62.3% of patients completed 2 years of treatment. In all, 214 treatment-emergent adverse events (TEAEs) were reported in 38.4% of patients. Most TEAEs were of mild or moderate intensity; 13 were severe. The most commonly reported TEAEs were drug ineffective (9.5%) and infusion-related reactions (5.2%). The most frequently reported infection-related TEAEs were upper respiratory tract infections (3.0%), nasopharyngitis (2.1%) and bronchitis (1.5%). No patients experienced tuberculosis.

Conclusion: Drug utilization and treatment persistence with CT-P13 were consistent with historical reports of IFX-RP in this patient population. Safety findings did not identify new concerns for CT-P13 in the treatment of patients with RA, AS or PsA.

Trial registration: ClinicalTrials.gov: NCT02605642.

Originalsprog Engelsk
Tidsskrift Rheumatology Advances in Practice
Vol/bind 5
Udgave nummer 2
Sider (fra-til) rkab026
ISSN 2514-1775
DOI
Status Udgivet - 2021

OBJECTIVE: The objective of this population-based cohort study was to investigate the association between fatigue with disease activity and drug survival in patients with psoriatic arthritis (PsA) receiving their first tumor necrosis factor inhibitor (TNFi).

METHODS: Data on patient characteristics, disease activity, and drug survival were obtained from the DANBIO database on all patients with PsA from 2006 through 2015. Information on comorbidities was obtained through linkage with the Danish National Patient Registry.

RESULTS: A total of 880 patients were eligible for analyses. Patients with upper median fatigue scores had statistically significant higher disease activity measures (Disease Activity Score in 28 joints based on C-reactive protein), pain, and Health Assessment Questionnaire (HAQ) scores; tender joint counts; comorbidities (Charlson Comorbidity Index ≥ 2); and current smoking status at baseline compared to patients with lower median fatigue scores (P < 0.05). In the upper median fatigue group, fewer patients achieved American College of Rheumatology (ACR) responses and improvements in visual analog scale (VAS) fatigue compared to patients in the lower median fatigue group. Kaplan-Meier curves showed shorter drug survival in patients in the upper median fatigue group compared with the lower median fatigue group at 6-month follow-up.

CONCLUSION: Fatigue remains a dominating symptom after TNFi treatment, and is associated with higher baseline disease activity, pain, and HAQ scores; more comorbidities; and increased risk of TNFi treatment discontinuation in a cohort of Danish patients with PsA. The agreement between ACR and VAS fatigue responses is weak to moderate, suggesting heterogeneity between experienced fatigue and joint inflammation.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 48
Udgave nummer 6
Sider (fra-til) 829-835
Antal sider 7
ISSN 0315-162X
DOI
Status Udgivet - jun. 2021

Risk of harm in synthetic and biological intervention trials in patients with inflammatory arthritis: protocol for a metaepidemiological study focusing on contextual factors

Malm, E., Nielsen, S. M., Berg, J., Ioannidis, J. P. A., Furst, D., Smolen, J. S., Taylor, P. C., Kristensen, L. E., Tarp, S., Ellingsen, T. & Christensen, R., 6 sep. 2021, I: BMJ Open. 11, 9, s. e049850 e049850.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Inflammatory arthritis (IA) conditions, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, are characterised by inflammatory infiltration of the joints. Biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively, reduce the effects of proinflammatory cytokines and immune cells to ameliorate disease. However, immunosuppression can be associated with high rates of serious adverse events (SAEs), including serious infections, and maybe an increased risk of malignancies and cardiovascular events. Currently, there is no empirical evidence on the extent to which contextual factors and risk of bias (RoB) domains may modify these harm signals in randomised trials.

METHODS AND ANALYSIS: We will search MEDLINE (via PubMed) for systematic reviews published since April 2015 and all Cochrane reviews. From these reviews, randomised trials will be eligible if they include patients with an IA condition with at least one group randomly allocated to bDMARD and/or tsDMARD treatments. A predefined form will be used for extracting data on population characteristics (eg, baseline characteristics or eligibility criteria, such as medication background) and specific harm outcome measures, such as number of withdrawals, numbers of patients discontinuing due to adverse events and number of patients having SAEs. RoB in individual trials will be assessed using a modified Cochrane RoB tool. We will estimate the potentially causal harm effects related to the experimental intervention compared with control comparator as risk ratios, and heterogeneity across randomised comparisons will be assessed statistically and evaluated as inconsistency using the I2 Index. Our metaregression analyses will designate population and trial characteristics and each RoB domain as independent variables, whereas the three harm domains will serve as dependent variables.

ETHICS AND DISSEMINATION: Ethics approval is not required for this study. Results will be disseminated through publication in international peer-reviewed journals.

PROSPERO REGISTRATION NUMBER: CRD42020171124.

Originalsprog Engelsk
Artikelnummer e049850
Tidsskrift BMJ Open
Vol/bind 11
Udgave nummer 9
Sider (fra-til) e049850
ISSN 2044-6055
DOI
Status Udgivet - 6 sep. 2021

Risk of solid cancers overall and by subtypes in patients with psoriatic arthritis treated with TNF inhibitors - a Nordic cohort study

Hellgren, K., Ballegaard, C., Delcoigne, B., Cordtz, R., Nordström, D., Aaltonen, K., Gudbjornsson, B., Love, T. J., Aarrestad Provan, S., Sexton, J., Zobbe, K., Kristensen, L. E., Askling, J. & Dreyer, L., 2 aug. 2021, I: Rheumatology (Oxford, England). 60, 8, s. 3656-3668 13 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To investigate whether TNF inhibitors (TNFi) are associated with increased risk of solid cancer in patients with psoriatic arthritis (PsA).

METHODS: From the Nordic clinical rheumatology registers (CRR) here: SRQ/ARTIS (Sweden), DANBIO (Denmark), NOR-DMARD (Norway), ROB-FIN (Finland) and ICEBIO (Iceland) we identified PsA patients who started a first TNFi 2001-2017 (n = 9655). We identified patients with PsA not treated with biologics from (i) the CRR (n = 14 809) and (ii) the national patient registers (PR, n = 31 350). By linkage to the national cancer registers, we collected information on incident solid cancer overall and for eight cancer types. We used Cox regression to estimate hazard ratio (HR) with 95% CI of cancer (per country and pooled) in TNFi-exposed vs biologics-naïve, adjusting for age, sex, calendar period, comorbidities and disease activity. We also assessed standardized incidence ratios (SIR) in TNFi-exposed PsA vs the general population (GP).

RESULTS: We identified 296 solid cancers among the TNFi-exposed PsA patients (55 850 person-years); the pooled adjusted HR for solid cancer overall was 1.0 (0.9-1.2) for TNFi-exposed vs biologics-naïve PsA from the CRR, and 0.8 (0.7-1.0) vs biologics-naïve PsA from the PRs. There were no significantly increased risks for any of the cancer types under study. The pooled SIR of solid cancer overall in TNFi treated PsA vs GP was 1.0 (0.9-1.1).

CONCLUSION: In this large cohort study from five Nordic countries, we found no increased risk of solid cancer in TNFi-treated PsA patients, neither for solid cancer overall nor for eight common cancer types.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 60
Udgave nummer 8
Sider (fra-til) 3656-3668
Antal sider 13
ISSN 1462-0324
DOI
Status Udgivet - 2 aug. 2021

Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial

Kragsnaes, M. S., Kjeldsen, J., Horn, H. C., Munk, H. L., Pedersen, J. K., Just, S. A., Ahlquist, P., Pedersen, F. M., de Wit, M., Möller, S., Andersen, V., Kristiansen, K., Kinggaard Holm, D., Holt, H. M., Christensen, R. & Ellingsen, T., sep. 2021, I: Annals of the Rheumatic Diseases. 80, 9, s. 1158-1167 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA).

METHODS: In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26.

RESULTS: Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)).

CONCLUSIONS: In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA.

TRIAL REGISTRATION NUMBER: NCT03058900.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 80
Udgave nummer 9
Sider (fra-til) 1158-1167
Antal sider 10
ISSN 0003-4967
DOI
Status Udgivet - sep. 2021

Similar lipid level changes in early rheumatoid arthritis patients following 1-year treat-to-target strategy with adalimumab plus methotrexate versus placebo plus methotrexate: secondary analyses from the randomised controlled OPERA trial

Mašić, D., Stengaard-Pedersen, K., Løgstrup, B. B., Hørslev-Petersen, K., Hetland, M. L., Junker, P., Østergaard, M., Ammitzbøll, C., Möller, S., Christensen, R. & Ellingsen, T., mar. 2021, I: Rheumatology International. 41, 3, s. 543-549 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

To compare changes in low-density lipoprotein cholesterol and other lipids in patients with rheumatoid arthritis (RA) randomised to a 1-year treat-to-target strategy with either adalimumab plus methotrexate or placebo plus methotrexate. Prespecified secondary analyses from the OPERA trial, where 180 early and treatment-naïve RA patients received methotrexate 20 mg once weekly in combination with either placebo or subcutaneous adalimumab 40 mg every other week. Serum lipid levels were measured at baseline and after 1 year. Changes in lipid levels were analysed using mixed linear models based on the intention-to-treat (ITT) population. Overall, 174 patients were included in the ITT population (adalimumab plus methotrexate n = 86; placebo plus methotrexate n = 88). Differences between changes in lipid levels were low-density lipoprotein cholesterol 0.18 mmol/l [95% CI - 0.05 to 0.42], total cholesterol 0.27 mmol/l [- 0.002 to 0.54], high-density lipoprotein cholesterol 0.05 mmol/l [- 0.06 to 0.15], triglycerides 0.11 mmol/l [- 0.08 to 0.29], very-low-density lipoprotein cholesterol 0.03 mmol/l [- 0.05 to 0.12], and non-high-density lipoprotein cholesterol 0.22 mmol/l [- 0.02 to 0.46]. In early RA patients treated to tight control of inflammation over a period of 1 year with either adalimumab plus methotrexate or placebo plus methotrexate, changes in lipid levels were similar. Trial registration number: NCT00660647.

Originalsprog Engelsk
Tidsskrift Rheumatology International
Vol/bind 41
Udgave nummer 3
Sider (fra-til) 543-549
Antal sider 7
ISSN 0172-8172
DOI
Status Udgivet - mar. 2021

OBJECTIVE: To study the effects of supervised training in adults with subacromial pain syndrome.

DATA SOURCES: Embase, MEDLINE, Cochrane Library, Cumulative Index to Nursing and Allied Health, and Physiotherapy Evidence Database were searched from inception to March 2020.

STUDY SELECTION: Independent reviewers selected randomized controlled trials comparing supervised training with (1) no training or (2) self-training in adults with subacromial pain syndrome lasting for at least 1 month. Critical outcomes were shoulder pain, function, and patient-perceived effect. Important outcomes included other potential benefits and adverse events at 3-month follow-up.

DATA EXTRACTION: Two independent reviewers extracted data for the meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool 1, and certainty of evidence was evaluated using the Grades of Recommendation Assessment, Development, and Evaluation (GRADE).

DATA SYNTHESIS: Ten studies (n=597, 43% female) were included. Supervised training resulted in larger improvements than no training on pain (at rest: n=286; mean difference [MD], 1.68; 95% confidence interval [CI], 0.31-3.06 on 0-10 scale; during movement: n=353; MD, 1.84; 95% CI,0.91-2.76), function (n=396; standardized MD, 0.30; 95% CI, 0.07-0.52), and patient-perceived effect (n=118; risk ratio, 1.43; 95% CI, 0.87-2.34). Supervised training had potential benefits regarding quality of life, return to work, dropout, and training adherence, albeit more patients reported mild, transient pain after training. Supervised training and self-training showed equal improvements on pain (n=44) and function (n=76), with no data describing patient-perceived effect. Certainty of evidence was low for critical outcomes and low-moderate for other outcomes.

CONCLUSIONS: Supervised training might be superior to no training and equally effective as self-training on critical and important outcomes. Based on low-moderate certainty of evidence, these findings support a weak recommendation for supervised training in adults with subacromial pain syndrome.

Originalsprog Engelsk
Tidsskrift Archives of Physical Medicine and Rehabilitation
ISSN 0003-9993
DOI
Status E-pub ahead of print - 28 apr. 2021

Systematic Literature Review and Meta-Analysis of the Relationship Between Polyunsaturated and Trans Fatty Acids During Pregnancy and Offspring Weight Development

Ren, X., Vilhjálmsdóttir, B. L., Rohde, J. F., Walker, K. C., Runstedt, S. E., Lauritzen, L., Heitmann, B. L. & Specht, I. O., 25 mar. 2021, I: Frontiers in nutrition. 8, s. 625596 625596.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and trans fatty acids (TFAs) may have an impact on offspring weight development. We conducted a systematic review and meta-analysis according to PRISMA guidelines to evaluate whether levels of these fatty acids during pregnancy influenced offspring weight development. Randomized controlled trials (RCTs) with DHA and/or EPA supplementation or cohort studies, which examined levels of DHA, EPA, or TFAs in maternal or neonatal blood samples and recorded offspring weight, were included. Overall, 27 RCTs and 14 observational studies were identified. The results showed that DHA and/or EPA supplementation doses >650 mg/day resulted in slightly higher birth weight (MD 87.5 g, 95% CI 52.3-122.6, n = 3,831) and combined BMI and BMI z score at 5-10 years (SMD 0.11, 95% CI 0.04-0.18, n = 3,220). These results were rated as moderate quality. Results from the observational studies were generally inconsistent. High TFA levels during pregnancy seemed to be associated with lower birth weight. Finally, this review and meta-analysis supports a relationship between high maternal or neonatal DHA and/or EPA levels and higher offspring birth weight and weight in childhood. More high-quality long-term studies are still needed.

Originalsprog Engelsk
Artikelnummer 625596
Tidsskrift Frontiers in nutrition
Vol/bind 8
Sider (fra-til) 625596
ISSN 2296-861X
DOI
Status Udgivet - 25 mar. 2021

The Effect of a Combined Gluten- and Casein-Free Diet on Children and Adolescents with Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

Keller, A., Rimestad, M. L., Friis Rohde, J., Holm Petersen, B., Bruun Korfitsen, C., Tarp, S., Briciet Lauritsen, M. & Händel, M. N., feb. 2021, I: Nutrients. 13, 2, s. 1-18 18 s., 470.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

There has been a growing interest in the gastrointestinal system and its significance for autism spectrum disorder (ASD), including the significance of adopting a gluten-free and casein-free (GFCF) diet. The objective was to investigate beneficial and safety of a GFCF diet among children with a diagnosis of ASD. We performed a systematic literature search in Medline, Embase, Cinahl, and the Cochrane Library up to January 2020 for existing systematic reviews and individual randomized controlled trials (RCTs). Studies were included if they investigated a GFCF diet compared to a regular diet in children aged 3 to 17 years diagnosed with ASD, with or without comorbidities. The quality of the identified existing reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR). The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool, and overall quality of evidence was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). We identified six relevant RCTs, which included 143 participants. The results from a random effect model showed no effect of a GFCF diet on clinician-reported autism core symptoms (standardized mean difference (SMD) -0.31 (95% Cl. -0.89, 0.27)), parent-reported functional level (mean difference (MD) 0.61 (95% Cl -5.92, 7.14)) or behavioral difficulties (MD 0.80 (95% Cl -6.56, 10.16)). On the contrary, a GFCF diet might trigger gastrointestinal adverse effects (relative risk (RR) 2.33 (95% Cl 0.69, 7.90)). The quality of evidence ranged from low to very low due to serious risk of bias, serious risk of inconsistency, and serious risk of imprecision. Clinical implications of the present findings may be careful consideration of introducing a GFCF diet to children with ASD. However, the limitations of the current literature hinder the possibility of drawing any solid conclusion, and more high-quality RCTs are needed. The protocol is registered at the Danish Health Authority website.

Originalsprog Engelsk
Artikelnummer 470
Tidsskrift Nutrients
Vol/bind 13
Udgave nummer 2
Sider (fra-til) 1-18
Antal sider 18
ISSN 2072-6643
DOI
Status Udgivet - feb. 2021

OBJECTIVE: This study investigated the effect of exercise therapy on inflammatory activity in synovitis and bone marrow lesions (BMLs) assessed by magnetic resonance imaging (MRI) in patients with knee OA.

METHODS: 60 patients with knee OA were randomized 1:1 to 12 weeks of supervised exercise therapy 3 times/week (ET) or a no-attention control group (CG). Synovitis and BMLs were assessed with static MRI with and without contrast and with dynamic contrast enhanced MRI (DCE-MRI). DCE-MRI data was quantified using pixel-by-pixel methodology based on analysis of signal intensity curves. Pain was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses of covariance were used assessing group differences in changes from baseline to week 12.

RESULTS: 33 patients adhered to the protocol and had valid MRI and KOOS data (ET, n = 16, CG, n = 17). Statistically significant and clinically relevant group difference in favour of ET was seen in KOOS pain change (-11.7 points, 95%CI: -20.1 to -3.4). There were statistically significant group differences in DCE-MRI assessed synovitis in the anterior synovium with unchanged inflammatory activity in the ET group compared to the CG. There were no group differences in BMLs and static MRI.

CONCLUSION: Inflammatory activity was unchanged, and pain was reduced in patients with knee OA adhering to 12 weeks of exercise therapy compared to a no-attention control group. The reduction in pain was not explained by changes in inflammatory activity. Overall, the results suggest that exercise is not harmful in knee OA. ClinicalTrials.gov number: NCT01545258.

Originalsprog Engelsk
Tidsskrift The Knee
Vol/bind 28
Udgave nummer 1
Sider (fra-til) 256-265
Antal sider 10
ISSN 0968-0160
DOI
Status Udgivet - jan. 2021

Bibliografisk note

Copyright © 2021 Elsevier B.V. All rights reserved.

The Effect of Metformin on Self-Selected Exercise Intensity in Healthy, Lean Males: A Randomized, Crossover, Counterbalanced Trial

Pilmark, N. S., Petersen-Bønding, C., Holm, N. F. R., Johansen, M. Y., Pedersen, B. K., Hansen, K. B. & Karstoft, K., 25 feb. 2021, I: Frontiers in Endocrinology. 12, s. 599164 599164.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Introduction: In general, patients with type 2 diabetes have lower cardiorespiratory fitness levels and perform exercise at lower intensities compared to healthy controls. Since metformin (MET) has been shown to increase the rate of perceived exertion (RPE) during exercise with a fixed intensity, MET per se may reduce self-selected exercise intensity. The aim of this study was to assess the effect of MET on self-selected exercise intensity.

Methods: Healthy males were eligible for this crossover, counterbalanced study with two treatment periods: MET and placebo (PLA), each lasting 17 days. Treatment dose was gradually increased and reached 2 g/day on treatment day 9, and continued at that level for the rest of the treatment period. The two periods were performed in randomized order. Two experimental days (A+B) were conducted on Day 15 (A) and Day 17 (B) of each period, respectively. Day A consisted of an exercise bout with self-selected exercise intensity (equal to RPE = 14-15 on the Borg Scale). Day B consisted of an exercise bout with fixed intensity (70% of VO2peak). Oxygen consumption rate was assessed continuously during both exercise bouts.

Results: Fifteen males (age 23.7 ± 0.6 years, BMI 22.3 ± 2.0, VO2peak 3.5 ± 0.6 L/min) were included in the study. On Day B, RPE was higher in MET compared to PLA (14.8 ± 0.4 vs. 14.0 ± 0.3, P = 0.045). On Day A, no difference in self-selected exercise intensity measured by oxygen consumption rate (PLA 2.33 ± 0.09 L O2/min, MET 2.42 ± 0.10 L O2/min, P = 0.09) was seen between treatment periods.

Conclusions: Self-selected exercise intensity was not reduced by MET in healthy males, despite the fact that MET increased RPE during an exercise bout with fixed intensity.

Originalsprog Engelsk
Artikelnummer 599164
Tidsskrift Frontiers in Endocrinology
Vol/bind 12
Sider (fra-til) 599164
ISSN 1664-2392
DOI
Status Udgivet - 25 feb. 2021

BACKGROUND: Lifestyle intervention, i.e. diet and physical activity, forms the basis for care of type 2 diabetes (T2D). The current physical activity recommendation for T2D is aerobic training for 150 min/week of moderate to vigorous intensity, supplemented with resistance training 2-3 days/week, with no more than two consecutive days without physical activity. The rationale for the recommendations is based on studies showing a reduction in glycated haemoglobin (HbA1c). This reduction is supposed to be caused by increased insulin sensitivity in muscle and adipose tissue, whereas knowledge about effects on abnormalities in the liver and pancreas are scarce, with the majority of evidence stemming from in vitro and animal studies. The aim of this study is to investigate the role of the volume of exercise training as an adjunct to dietary therapy in order to improve the pancreatic β-cell function in T2D patients less than 7 years from diagnosis. The objective of this protocol for the DOSE-EX trial is to describe the scientific rationale in detail and to provide explicit information about study procedures and planned analyses.

METHODS/DESIGN: In a parallel-group, 4-arm assessor-blinded randomised clinical trial, 80 patients with T2D will be randomly allocated (1:1:1:1, stratified by sex) to 16 weeks in either of the following groups: (1) no intervention (CON), (2) dietary intervention (DCON), (3) dietary intervention and supervised moderate volume exercise (MED), or (4) dietary intervention and supervised high volume exercise (HED). Enrolment was initiated December 15th, 2018, and will continue until N = 80 or December 1st, 2021. Primary outcome is pancreatic beta-cell function assessed as change in late-phase disposition index (DI) from baseline to follow-up assessed by hyperglycaemic clamp. Secondary outcomes include measures of cardiometabolic risk factors and the effect on subsequent complications related to T2D. The study was approved by The Scientific Ethical Committee at the Capital Region of Denmark (H-18038298).

TRIAL REGISTRATION: The Effects of Different Doses of Exercise on Pancreatic β-cell Function in Patients With Newly Diagnosed Type 2 Diabetes (DOSE-EX), NCT03769883, registered 10 December 2018 https://clinicaltrials.gov/ct2/show/NCT03769883 ). Any modification to the protocol, study design, and changes in written participant information will be approved by The Scientific Ethical Committee at the Capital Region of Denmark before effectuation.

DISCUSSION: The data from this study will add knowledge to which volume of exercise training in combination with a dietary intervention is needed to improve β-cell function in T2D. Secondarily, our results will elucidate mechanisms of physical activity mitigating the development of micro- and macrovascular complications correlated with T2D.

Originalsprog Engelsk
Artikelnummer 244
Tidsskrift Trials
Vol/bind 22
Udgave nummer 1
Sider (fra-til) 244
ISSN 1745-6215
DOI
Status Udgivet - 1 apr. 2021

The H2020 "NoHoW Project": A Position Statement on Behavioural Approaches to Longer-Term Weight Management

The EASO Obesity Management Task Force, apr. 2021, I: Obesity Facts. 14, 2, s. 246-258 13 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

There is substantial evidence documenting the effects of behavioural interventions on weight loss (WL). However, behavioural approaches to initial WL are followed by some degree of longer-term weight regain, and large trials focusing on evidence-based approaches to weight loss maintenance (WLM) have generally only demonstrated small beneficial effects. The current state-of-the-art in behavioural interventions for WL and WLM raises questions of (i) how we define the relationship between WL and WLM, (ii) how energy balance (EB) systems respond to WL and influence behaviours that primarily drive weight regain, (iii) how intervention content, mode of delivery and intensity should be targeted to keep weight off, (iv) which mechanisms of action in complex interventions may prevent weight regain and (v) how to design studies and interventions to maximise effective longer-term weight management. In considering these issues a writing team within the NoHoW Consortium was convened to elaborate a position statement, and behaviour change and obesity experts were invited to discuss these positions and to refine them. At present the evidence suggests that developing the skills to self-manage EB behaviours leads to more effective WLM. However, the effects of behaviour change interventions for WL and WLM are still relatively modest and our understanding of the factors that disrupt and undermine self-management of eating and physical activity is limited. These factors include physiological resistance to weight loss, gradual compensatory changes in eating and physical activity and reactive processes related to stress, emotions, rewards and desires that meet psychological needs. Better matching of evidence-based intervention content to quantitatively tracked EB behaviours and the specific needs of individuals may improve outcomes. Improving objective longitudinal tracking of energy intake and energy expenditure over time would provide a quantitative framework in which to understand the dynamics of behaviour change, mechanisms of action of behaviour change interventions and user engagement with intervention components to potentially improve weight management intervention design and evaluation.

Originalsprog Engelsk
Tidsskrift Obesity Facts
Vol/bind 14
Udgave nummer 2
Sider (fra-til) 246-258
Antal sider 13
ISSN 1662-4025
DOI
Status Udgivet - apr. 2021

The impact of early body-weight variability on long-term weight maintenance: exploratory results from the NoHoW weight-loss maintenance intervention

Turicchi, J., O'Driscoll, R., Lowe, M., Finlayson, G., Palmeira, A. L., Larsen, S. C., Heitmann, B. L. & Stubbs, J., mar. 2021, I: International journal of obesity (2005). 45, 3, s. 525-534 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Weight-loss programmes often achieve short-term success though subsequent weight regain is common. The ability to identify predictive factors of regain early in the weight maintenance phase is crucial.

OBJECTIVE: To investigate the associations between short-term weight variability and long-term weight outcomes in individuals engaged in a weight-loss maintenance intervention.

METHODS: The study was a secondary analysis from The NoHoW trial, an 18-month weight maintenance intervention in individuals who recently lost ≥5% body weight. Eligible participants (n = 715, 64% women, BMI = 29.2 (SD 5.0) kg/m2, age = 45.8 (SD 11.5) years) provided body-weight data by smart scale (Fitbit Aria 2) over 18 months. Variability in body weight was calculated by linear and non-linear methods over the first 6, 9 and 12 weeks. These estimates were used to predict percentage weight change at 6, 12, and 18 months using both crude and adjusted multiple linear regression models.

RESULTS: Greater non-linear weight variability over the first 6, 9 and 12 weeks was associated with increased subsequent weight in all comparisons; as was greater linear weight variability measured over 12 weeks (up to AdjR2 = 4.7%). Following adjustment, 6-week weight variability did not predict weight change in any model, though greater 9-week weight variability by non-linear methods was associated with increased body-weight change at 12 (∆AdjR2 = 1.2%) and 18 months (∆AdjR2 = 1.3%) and by linear methods at 18 months (∆AdjR2 = 1.1%). Greater non-linear weight variability measured over 12 weeks was associated with increased weight at 12 (∆AdjR2 = 1.4%) and 18 (∆AdjR2 = 2.2%) months; and 12-week linear variability was associated with increased weight at 12 (∆AdjR2 = 2.1%) and 18 (∆AdjR2 = 3.6%) months.

CONCLUSION: Body-weight variability over the first 9 and 12 weeks of a weight-loss maintenance intervention weakly predicted increased weight at 12 and 18 months. These results suggest a potentially important role in continuously measuring body weight and estimating weight variability.

Originalsprog Engelsk
Tidsskrift International journal of obesity (2005)
Vol/bind 45
Udgave nummer 3
Sider (fra-til) 525-534
Antal sider 10
ISSN 0307-0565
DOI
Status Udgivet - mar. 2021

The Prognostic Value of Pain Phenotyping in Relation to Treatment Outcomes in Patients with Axial Spondyloarthritis Treated in Clinical Practice: A Prospective Cohort Study

Andreasen, R. A., Kristensen, L. E., Egstrup, K., Baraliakos, X., Strand, V., Horn, H. C., Wied, J., Schiøttz-Christensen, B., Aalykke, C., Jensen Hansen, I. M., Ellingsen, T. & Christensen, R., 1 apr. 2021, I: Journal of Clinical Medicine. 10, 7, 1469.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Despite the control of inflammation, many patients with axial spondyloarthritis (axSpA) still report pain as a significant concern. Our objective was to explore the prognostic value of the painDETECT questionnaire (PDQ) in relation to treatment outcomes in axSpA patients treated in clinical practice. AxSpA patients with high disease activity initiating or switching a biological Disease-Modifying Antirheumatic Drug (bDMARD) were eligible. The PDQ score (range: -1 to 38) was used to distinguish participants with nociceptive pain (NcP) mechanisms from participants with a mixed pain mechanism (MP). The primary outcome was the proportion of individuals achieving a 50% improvement of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 12 weeks; logistic regression analysis models were used to determine the prognostic value of the nociceptive pain phenotype. Changes in continuous outcomes such as the Assessment of SpondyloArthritis International Society (ASAS) core outcome domains were analyzed using analysis of covariance (ANCOVA). Health-related quality of life (HR-QoL) was addressed using the Medical Outcomes Study SF-36. During a period of 22 months, 49 axSpA patients were included. Twenty (41%) had an NcP phenotype according to the PDQ score. BASDAI50 responses were reported by 40% (8/20) and 28% (8/29) NcP and MP groups, respectively. However, a prognostic value was not found in relation to the primary outcome (crude odds ratio [95% confidence interval]: 1.75 [0.52 to 5.87]). Across most of the secondary outcomes, axSpA NcP phenotype patients were reported having the most improvements in the HR-QoL measures. These data indicate the influence of personalized management strategies according to patients' pain phenotypes for stratification of axSpA patients in randomized controlled trials.

Originalsprog Engelsk
Artikelnummer 1469
Tidsskrift Journal of Clinical Medicine
Vol/bind 10
Udgave nummer 7
ISSN 2077-0383
DOI
Status Udgivet - 1 apr. 2021

The right to smoke and the right to smoke-free surroundings: international comparison of smoke-free psychiatric clinic implementation experiences

Freiburghaus, T., Raffing, R., Ballbè, M., Gual, A. & Tönnesen, H., 16 apr. 2021, I: BJPsych Open. 7, 3, s. e81 e81.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: In Scandinavia, people with a severe mental disorder have a reduced life expectancy of 15-20 years compared with the general public. Smoking is a major contributor, and smoke-free policies are increasingly adopted in psychiatric clinics around the world. We compared potential facilitators and barriers among staff and management, for the implementation of smoke-free psychiatric clinics.

AIMS: To investigate the attitudes and experiences regarding smoke-free policies among managers and staff involved in the implementation processes of smoke-free psychiatric clinics at hospitals in Malmö (Sweden) and Barcelona (Spain).

METHOD: We used a qualitative methodology, with 15 semi-structured interviews. The interviews were conducted with each participant individually, and were subsequently transcribed. The data were analysed with systematic text condensation.

RESULTS: There were notable differences in how the smoke-free policies were carried out and experienced, and attitudes regarding the policy changes differed in the two settings. Key differences were the views on the right to smoke in compulsory care and to stay in smoke-free surroundings supported by smoking cessation intervention; the prioritisation of staff facilitation of smoking breaks; and views on smoking and smoke-free psychiatry. In contrast, participants agreed on the importance of staff education and management support. A smoking ban by law and belonging to a network of smoke-free hospitals were also relevant.

CONCLUSIONS: Staff education, and support from staff and management for the patients' right to stay in smoke-free surroundings, facilitated successful implementation of smoke-free policies in the psychiatric clinics, whereas supporting the right to smoke was a barrier.

Originalsprog Engelsk
Artikelnummer e81
Tidsskrift BJPsych Open
Vol/bind 7
Udgave nummer 3
Sider (fra-til) e81
ISSN 2056-4724
DOI
Status Udgivet - 16 apr. 2021

The diet of Danish children is often not in accordance with dietary guidelines. We aimed to evaluate changes in the intake of selected foods and beverages during a multi-component school-based physical activity intervention, and to investigate if changes were modified by socioeconomic status (SES). The study included 307 children (intervention group: 184; comparison group: 123) with information on dietary intake pre- and post-intervention as well as on SES. Linear regression models were conducted to assess the effect of the intervention on changes in dietary factors. Children from the intervention group increased their intake of whole-grain bread during the intervention (group means: 6.1 g/d (95% CI: 2.2 to 10.0) vs. 0.3 g/d (95% CI: -3.1 to 3.7) in the comparison group, p = 0.04). A significant interaction between SES and group allocation was observed to change in fruit intake (p = 0.01). Among children from low SES families, only those from the comparison group decreased their fruit intake (group means: -40.0 g/d (95% CI: -56.0 to -23.9) vs. 9.3 g/d (95% CI: -16.1 to 94) in the intervention group, p = 0.006). The present study found no convincing effect of introducing a multi-component intervention on dietary intake except a small beneficial effect on whole-grain bread consumption. However, beneficial intervention effects in fruit intake were found particularly among children from low SES families.

Originalsprog Engelsk
Tidsskrift International Journal of Environmental Research and Public Health
Vol/bind 18
Udgave nummer 19
Sider (fra-til) 10543
ISSN 1661-7827
DOI
Status Udgivet - 8 okt. 2021

Towards consensus in defining and handling contextual factors within rheumatology trials: an initial qualitative study from an OMERACT working group

Nielsen, S. M., Uggen Rasmussen, M., Boers, M., A van der Windt, D., de Wit, M., G Woodworth, T., A Flurey, C., Beaton, D., Shea, B., Escorpizo, R., Furst, D. E., Smolen, J. S., Toupin-April, K., Boonen, A., Voshaar, M., Ellingsen, T., Wells, G. A., Reeves, B. C., March, L., Tugwell, P. & Christensen, R., feb. 2021, I: Annals of the Rheumatic Diseases. 80, 2, s. 242-249 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: The Outcome Measures in Rheumatology Initiative established the Contextual Factors Working Group to guide the understanding, identification and handling of contextual factors for clinical trials. In clinical research, different uses of the term 'contextual factors' exist. This study explores the perspectives of researchers (including clinicians) and patients in defining 'contextual factor' and its related terminology, identifying such factors and accounting for them in trials across rheumatology.

METHODS: We conducted individual semistructured interviews with researchers (including clinicians) who have experience within the field of contextual factors in clinical trials or other potentially relevant areas, and small focus group interviews with patients with rheumatic conditions. We transcribed the interviews and applied qualitative content analysis.

RESULTS: We interviewed 12 researchers and 7 patients. Researcher's and patient's descriptions of contextual factors were categorised into two broad themes, each comprising two contextual factors types. The 'treatment effect' theme focused on factors explaining variations in treatment effects (A) among patients and (B) among studies. The 'outcome measurement' theme focused on factors that explain (C) variations in the measurement result itself (apart from actual changes/differences in the outcome) and (D) variations in the outcome itself (beside treatment of interest). Methods for identifying and handling contextual factors differed among these themes and types.

CONCLUSIONS: Two main themes for contextual factors with four types of contextual factors were identified based on input from researchers and patients. This will guide operationalisation of contextual factors. Further research should refine our findings and establish consensus among relevant stakeholders.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 80
Udgave nummer 2
Sider (fra-til) 242-249
Antal sider 8
ISSN 0003-4967
DOI
Status Udgivet - feb. 2021

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