Published in 2021

Perceived Benefits, Barriers, and Facilitators of a Digital Patient-Reported Outcomes Tool for Routine Diabetes Care: Protocol for a National, Multicenter, Mixed Methods Implementation Study

Skovlund, S. E., Nicolucci, A., Balk-Møller, N., Berthelsen, D. B., Glümer, C., Perrild, H., Kjær, P., Nørgaard, L. M., Troelsen, L. H., Pietraszek, A., Hessler, D., Kaplan, S. & Ejskjær, N., 3 sep. 2021, I: JMIR research protocols. 10, 9, s. e28391 e28391.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: There is growing evidence that digital patient-reported outcome (PRO) questionnaires and PRO-based decision support tools may help improve the active engagement of people with diabetes in self-care, thereby improving the quality of care. However, many barriers still exist for the real-world effectiveness and implementation of such PRO tools in routine care. Furthermore, limited research has evaluated the acceptability, feasibility, and benefits of such tools across different health care settings.

OBJECTIVE: This study aims to evaluate the acceptability, feasibility, and perceived benefits of the Danish digital PRO diabetes tool in different health care settings in Denmark and to determine the factors affecting its implementation. Furthermore, the study evaluates the psychometric characteristics of the Danish PRO Diabetes Questionnaire and the validity of the scoring algorithms for dialogue support. The objective of this study is to guide the ongoing optimization of the PRO diabetes tool, its implementation, and the design of future randomized controlled effectiveness studies.

METHODS: We designed a multicenter, mixed methods, single-arm acceptability-feasibility implementation study protocol to contribute to the real-world pilot test of a new digital PRO diabetes tool in routine diabetes care. The use of the tool involves two main steps. First, the people with diabetes will complete a digital PRO Diabetes Questionnaire in the days before a routine diabetes visit. Second, the health care professional (HCP) will use a digital PRO tool to review the PRO results together with the people with diabetes during the visit. The PRO diabetes tool is designed to encourage and support people to take an active role for the people with diabetes in their own care and to expedite the delivery of person-centered, collaborative, and coordinated care.

RESULTS: A multicenter pilot study protocol and psychometrically designed digital data collection tools for evaluation were developed and deployed as part of a national evaluation of a new digital PRO diabetes intervention. A total of 598 people with diabetes and 34 HCPs completed the study protocol by April 1, 2021.

CONCLUSIONS: A large-scale, mixed methods, multicenter study for evaluating the use of the nationally developed PRO Diabetes Questionnaire in routine care across all health care sectors in Denmark by using the RE-AIM (Reach, Efficacy, Adoption, Implementation and Maintenance) model as a framework has been designed and is ongoing. This study is expected to provide new important and detailed information about the real-world acceptability, perceived relevance, and benefits of the PRO diabetes tool among a large heterogeneous population of people with diabetes in Denmark and HCPs in different care settings. The results will be used to further improve the PRO tool, design implementation facilitation support strategies, and design future controlled effectiveness studies.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28391.

Originalsprog Engelsk
Artikelnummer e28391
Tidsskrift JMIR research protocols
Vol/bind 10
Udgave nummer 9
Sider (fra-til) e28391
ISSN 1929-0748
DOI
Status Udgivet - 3 sep. 2021

Perioperative Alcohol and Smoking Cessation Intervention: Impact on Other Lifestyles

Merzaai, B., Tonnesen, H., Rasmussen, M. & Lauridsen, S. V., feb. 2021, I: Seminars in Oncology Nursing. 37, 1, s. 151116

Publikation: Bidrag til tidsskriftReviewForskningpeer review

OBJECTIVE: Cigarette smoking and alcohol drinking are preventable risk factors in surgery. It is unknown whether intervening on these two risk factors also have an effect on other lifestyles. Therefore, the primary aim of this study was to compare the effect of an intensive alcohol and smoking cessation intervention on other lifestyles (malnutrition, obesity, and physical inactivity) with treatment as usual, among patients scheduled for radical cystectomy. The secondary aim was to evaluate associations between successful quitting and changes in other lifestyles.

DATA SOURCES: Data on 94 patients with bladder cancer undergoing radical cystectomy originated from the STOP-OP study, a randomized intervention trial that enrolled patients from four Danish hospitals. Patients were enrolled between November 2014 and July 2017.

CONCLUSION: We found no significant differences regarding the three lifestyle factors; risk of malnutrition, obesity, and physical inactivity between patients in the intervention and standard care at the end of the intervention at 6 weeks, 3 months, 6 months, and 12 months. Also, there were no significant associations between successful quitters and non-quitters for alcohol and smoking and the other three lifestyles; risk of malnutrition, obesity, and physical inactivity.

IMPLICATIONS FOR NURSING PRACTICE: Findings from this study show that cancer surgery is a good opportunity to address lifestyle changes and that more research into the effect of multimodal interventions are needed. Guidelines on how to support patients to change lifestyle in relation to surgery should be part of nursing practice.

Originalsprog Engelsk
Tidsskrift Seminars in Oncology Nursing
Vol/bind 37
Udgave nummer 1
Sider (fra-til) 151116
ISSN 0749-2081
DOI
Status Udgivet - feb. 2021

Phase angle measured by bioelectrical impedance analysis and the risk of cardiovascular disease among adult Danes

Langer, R. D., Larsen, S. C., Ward, L. C. & Heitmann, B. L., sep. 2021, I: Nutrition (Burbank, Los Angeles County, Calif.). 89, s. 111280 111280.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: This study aimed to examine associations between phase angle (PhA) and incident cardiovascular disease (CVD) morbidity and mortality in a healthy Danish subpopulation free of major chronic diseases.

METHODS: A random subset (n = 2601) of adult men and women born in 1922, 1932, 1942, and 1952 and examined in 1987 and 1988 were included, and followed over 24 y during which 643 men and 570 women developed CVD. Measures at baseline included age, weight, height, whole-body bioimpedance, from which PhA was calculated, and information on lifestyle, obtained by a self-administered questionnaire. The association between PhA and incident CVD was assessed by Cox proportional hazard model with age as the underlying time scale and with additional adjustment for covariates. To explore nonlinear associations, all results were presented using restricted cubic splines, with the median value of PhA as the reference.

RESULTS: PhA was lower among women who later developed CVD than among women who did not (6.3 vs. 6.0; P < 0.001). The highest risk of CVD was observed at the 5th percentile (hazard ratio: 1.33; 95% confidence interval, 1.11-1.60). Among men, PhA was not significantly associated with risk of CVD (7.1 vs. 7.0; P = 0.246).

CONCLUSIONS: Among apparently healthy Danish men and women, a lower PhA value was associated with a higher incidence of CVD over 24 y, also after adjusting for potential confounders, and particularly among women. These findings may encourage the future use of PhA as an additional index in predicting CVD. However, more studies are needed to confirm our results.

Originalsprog Engelsk
Artikelnummer 111280
Tidsskrift Nutrition (Burbank, Los Angeles County, Calif.)
Vol/bind 89
Sider (fra-til) 111280
ISSN 0899-9007
DOI
Status Udgivet - sep. 2021

Placebo response and effect in randomized clinical trials: meta-research with focus on contextual effects

Hafliðadóttir, S. H., Juhl, C. B., Nielsen, S. M., Henriksen, M., Harris, I. A., Bliddal, H. & Christensen, R., 26 jul. 2021, I: Trials. 22, 1, s. 493 493.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

BACKGROUND: Contextual effects (i.e., placebo response) refer to all health changes resulting from administering an apparently inactive treatment. In a randomized clinical trial (RCT), the overall treatment effect (i.e., the post-treatment effect in the intervention group) can be regarded as the true effect of the intervention plus the impact of contextual effects. This meta-research was conducted to examine the average proportion of the overall treatment effect attributable to contextual effects in RCTs across clinical conditions and treatments and explore whether it varies with trial contextual factors.

METHODS: Data was extracted from trials included in the main meta-analysis from the latest update of the Cochrane review on "Placebo interventions for all clinical conditions" (searched from 1966 to March 2008). Only RCTs reported in English having an experimental intervention group, a placebo comparator group, and a no-treatment control group were eligible.

RESULTS: In total, 186 trials (16,655 patients) were included. On average, 54% (0.54, 95%CI 0.46 to 0.64) of the overall treatment effect was attributable to contextual effects. The contextual effects were higher for trials with blinded outcome assessor and concealed allocation. The contextual effects appeared to increase proportional to the placebo effect, lower mean age, and proportion of females.

CONCLUSION: Approximately half of the overall treatment effect in RCTs seems attributable to contextual effects rather than to the specific effect of treatments. As the study did not include all important contextual factors (e.g., patient-provider interaction), the true proportion of contextual effects could differ from the study's results. However, contextual effects should be considered when assessing treatment effects in clinical practice.

TRIAL REGISTRATION: PROSPERO CRD42019130257 . Registered on April 19, 2019.

Originalsprog Engelsk
Artikelnummer 493
Tidsskrift Trials
Vol/bind 22
Udgave nummer 1
Sider (fra-til) 493
ISSN 1745-6215
DOI
Status Udgivet - 26 jul. 2021

OBJECTIVES: To investigate biomechanical changes in lumbar disc herniations.

METHODS: Patients with lumbar disc herniation verified on a 1.5-3-T magnetic resonance imaging (MRI) scanner were imaged in a weight-bearing 0.25-T MRI scanner in (1) standing position, (2) conventional supine position with relative lumbar flexion, and (3) supine position with a forced lumbar extension by adding a lumbar pillow. The L2-S1 lordosis angle, the disc cross-sectional area, the disc cross-sectional diameter, and the spinal canal cross-sectional diameter were measured for each position. Disc degeneration and nerve root compression were graded, and the pain intensity was reported during each scan position.

RESULTS: Forty-three herniated discs in 37 patients (36.7 ± 11.9 years) were analyzed in each position. The L2-S1 lumbar angle increased in the standing position (mean difference [MD]: 5.61°, 95% confidence interval [95% CI]: 3.44 to 7.78) and with the lumbar pillow in the supine position (MD: 14.63°, 95% CI: 11.71 to 17.57), both compared with the conventional supine position. The herniated disc cross-sectional area and diameter increased during standing compared with during conventional supine position. No changes were found in the spinal canal cross-sectional diameter between positions. Higher nerve root compression grades for paracentral herniations were found during standing compared with during conventional supine position. This was neither found with a lumbar pillow nor for central herniations in any position compared with conventional supine.

CONCLUSION: Disc herniations displayed dynamic behavior with morphological changes in the standing position, leading to higher nerve root compression grades for paracentral herniated discs.

KEY POINTS: • Lumbar herniated discs increased in size in the axial plane during standing. • Increased nerve root compression grades for paracentral herniated discs were found during standing. • Weight-bearing MRI may increase the diagnostic sensitivity of nerve root compression in lumbar disc herniations.

Originalsprog Engelsk
Tidsskrift European Radiology
Vol/bind 31
Udgave nummer 2
Sider (fra-til) 804-812
Antal sider 9
ISSN 0938-7994
DOI
Status Udgivet - feb. 2021

Predictors of joint damage progression and stringent remission in patients with established rheumatoid arthritis in clinical remission

Møller-Bisgaard, S., Georgiadis, S., Hørslev-Petersen, K., Ejbjerg, B., Hetland, M. L., Ørnbjerg, L. M., Glinatsi, D., Møller, J., 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., Krogh, N. S., Ellingsen, T., Nielsen, A. H., Balding, L., Jurik, A. G., Thomsen, H. S. & Østergaard, M., jan. 2021, I: Rheumatology (Oxford, England). 60, 1, s. 380-391 12 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy.

METHODS: RA patients (DAS28-CRP <3.2, no swollen joints) receiving conventional synthetic DMARDs were randomized to conventional or MRI-targeted treat-to-target strategies with predefined algorithmic treatment escalations. Potentially predictive baseline variables were tested in multivariate logistic regression analyses.

RESULTS: In the 171 patients included, baseline MRI osteitis independently predicted progression in MRI erosion [odds ratio (OR) 1.13 (95% CI 1.06, 1.22)], joint space narrowing [OR 1.15 (95% CI 1.07, 1.24)] and combined damage [OR 1.23 (95% CI 1.13, 1.37)], while tenosynovitis independently predicted MRI erosion progression [OR 1.13 (95% CI 1.03, 1.25)]. A predictor of radiographic erosion progression was age, while gender predicted progression in joint space narrowing. Following an MRI treat-to-target strategy predicted stringent remission across all remission definitions: Clinical Disease Activity Index remission OR 2.94 (95% CI 1.25, 7.52), Simplified Disease Activity Index remission OR 2.50 (95% CI 1.01, 6.66), ACR/EULAR Boolean remission OR 5.47 (95% CI 2.33, 14.13). Similarly, low tender joint count and low patient visual analogue scale pain and global independently predicted achievement of more stringent remission.

CONCLUSION: Baseline MRI osteitis and tenosynovitis were independent predictors of 2 year MRI damage progression in RA patients in clinical remission, while independent predictors of radiographic damage progression were age and gender. Following an MRI treat-to-target strategy, low scores of patient-reported outcomes and low tender joint count predicted achievement of stringent remission.

TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01656278.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 60
Udgave nummer 1
Sider (fra-til) 380-391
Antal sider 12
ISSN 1462-0324
DOI
Status Udgivet - jan. 2021

Bibliografisk note

COPECARE

Prenatal and Early Life Exposure to the Danish Mandatory Vitamin D Fortification Policy Might Prevent Inflammatory Bowel Disease Later in Life: A Societal Experiment

Duus, K. S., Moos, C., Frederiksen, P., Andersen, V. & Heitmann, B. L., 19 apr. 2021, I: Nutrients. 13, 4, 1367.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

This register-based national cohort study of 206,900 individuals investigated whether prenatal exposure to small extra doses of vitamin D from fortified margarine prevented inflammatory bowel disease (IBD) later in life; whether the risk of IBD varied according to month or season of birth; and finally, whether there was an interaction between exposure to extra D vitamin and month or season of birth. Fortification of margarine with vitamin D was mandatory in Denmark from the mid-1930s until 1st June 1985, when it was abolished. Two entire birth cohorts, each including two years, were defined: one exposed and one unexposed to the fortification policy for the entire gestation. All individuals were followed for 30 years from the day of birth for an IBD diagnosis in Danish hospital registers. Logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Odds for IBD was lower among those exposed to extra D vitamin compared to those unexposed, OR = 0.87 (95% CI: 0.79; 0.95). No association with month or season of birth was found. However, estimates suggested that particularly children born during autumn may have benefitted from the effect of small extra doses of vitamin D. This is, to our knowledge, the first study to explore if prenatal exposure to vitamin D from fortification influenced the risk of IBD. Our results suggest that prenatal exposure to small amounts of extra vitamin D from food fortification may protect against the development of IBD before 30 years of age.

Originalsprog Engelsk
Artikelnummer 1367
Tidsskrift Nutrients
Vol/bind 13
Udgave nummer 4
ISSN 2072-6643
DOI
Status Udgivet - 19 apr. 2021

Prenatal exposure to bisphenol A and autistic- and ADHD-related symptoms in children aged 2 and5 years from the Odense Child Cohort

Hansen, J. B., Bilenberg, N., Timmermann, C. A. G., Jensen, R. C., Frederiksen, H., Andersson, A-M., Kyhl, H. B. & Jensen, T. K., 12 mar. 2021, I: Environmental Health: A Global Access Science Source. 20, 1, s. 24

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive.

OBJECTIVE: To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children.

METHOD: In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score.

RESULTS: BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03).

CONCLUSION: Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.

Originalsprog Engelsk
Tidsskrift Environmental Health: A Global Access Science Source
Vol/bind 20
Udgave nummer 1
Sider (fra-til) 24
ISSN 1476-069X
DOI
Status Udgivet - 12 mar. 2021

Primary prevention of fat and weight gain among obesity susceptible healthy weight preschool children. Main results from the "Healthy Start" randomized controlled intervention

Olsen, N. J., Ängquist, L., Frederiksen, P., Lykke Mortensen, E. & Lilienthal Heitmann, B., apr. 2021, I: Pediatric obesity. 16, 4, s. e12736 e12736.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: A vital public health challenge lies in understanding the primary drivers behind excessive weight gain among healthy weight individuals.

OBJECTIVES: To examine if excessive weight and fat gain can be prevented among healthy weight, obesity susceptible children aged 2 to 6 years.

METHODS: Eligible children were identified based on information on either a high birth weight, maternal pre-pregnancy obesity or maternal low educational level from national registries, and randomized into an intervention group, a control group and a shadow control group. All children with overweight at baseline were excluded from subsequent analysis (n = 196), while healthy weight children were included (n = 926). The intervention was designed to deliver improvements in diet and physical activity habits, optimization of sleep quantity and quality, and reduction of family stress. The average intervention period was 1.3 years.

RESULTS: Intention-to-treat analyses indicated a lower gain in percentage fat mass and a higher gain in fat-free mass in the intervention group compared with the control group. However, the results should be interpreted with caution, as they were clinically small and borderline significant, only.

CONCLUSION: This primary prevention intervention among young healthy weight children with susceptibility to future obesity had clinically small effects on growth and body composition. More interventions, conducting primary obesity prevention, are urgently needed.

Originalsprog Engelsk
Artikelnummer e12736
Tidsskrift Pediatric obesity
Vol/bind 16
Udgave nummer 4
Sider (fra-til) e12736
ISSN 1524-6817
DOI
Status Udgivet - apr. 2021

Based on a large volume of observational scientific studies and many summary papers, a high consumption of meat and processed meat products has been suggested to have a harmful effect on human health. These results have led guideline panels worldwide to recommend to the general population a reduced consumption of processed meat and meat products, with the overarching aim of lowering disease risk, especially of cancer. We revisited and updated the evidence base, evaluating the methodological quality and the certainty of estimates in the published systematic reviews and meta-analyses that examined the association between processed meat consumption and the risk of cancer at different sites across the body, as well as the overall risk of cancer mortality. We further explored if discrepancies in study designs and risks of bias could explain the heterogeneity observed in meta-analyses. In summary, there are severe methodological limitations to the majority of the previously published systematic reviews and meta-analyses that examined the consumption of processed meat and the risk of cancer. Many lacked the proper assessment of the methodological quality of the primary studies they included, or the literature searches did not fulfill the methodological standards needed in order to be systematic and transparent. The primary studies included in the reviews had a potential risk for the misclassification of exposure, a serious risk of bias due to confounding, a moderate to serious risk of bias due to missing data, and/or a moderate to serious risk of selection of the reported results. All these factors may have potentially led to the overestimation of the risk related to processed meat intake across all cancer outcomes. Thus, with the aim of lowering the risk of cancer, the recommendation to reduce the consumption of processed meat and meat products in the general population seems to be based on evidence that is not methodologically strong.

Originalsprog Engelsk
Artikelnummer 3601
Tidsskrift Nutrients
Vol/bind 13
Udgave nummer 10
ISSN 2072-6643
DOI
Status Udgivet - 14 okt. 2021

INTRODUCTION: The association between chronic widespread pain (CWP) and disability is well established. Although research support large interindividual differences in functional outcomes, limited studies are available on the socio-economic consequences of offering stratified treatment based on prognostic factors. Identification of predictors of long-term functional outcomes such as work disability as a critical consequence, could assist early and targeted personalised interventions. The primary objective of this cohort study is to identify prognostic factors for the primary endpoint work status (employed and working vs not working) in patients with CWP assessed 3 years from baseline, that is, at referral for specialist care.

METHODS AND ANALYSES: Data are collected at the diagnostic unit at Department of Rheumatology, Frederiksberg Hospital. The first 1000 patients ≥18 years of age registered in a clinical research database (DANFIB registry) with CWP either 'employed and working' or 'not working' will be enrolled. Participants must meet the American College of Rheumatology 1990 definition of CWP, that is, pain in all four body quadrants and axially for more than 3 months and are additionally screened for fulfilment of criteria for fibromyalgia. Clinical data and patient-reported outcomes are collected at referral (baseline) through clinical assessment and electronic questionnaires. Data on the primary endpoint work status at baseline and 3 years from baseline will be extracted from the Integrated Labour Market Database, Statistics Denmark and the nationwide Danish DREAM database. Prognostic factor analysis will be based on multivariable logistic regression modelling with the dichotomous work status as dependent variable.

ETHICS AND DISSEMINATION: Sensitive personal data will be anonymised according to regulations by the Danish Data Protection Agency, and informed consent are obtained from all participants. Understanding and improving the prognosis of a health condition like CWP should be a priority in clinical research and practice. Results will be published in international peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT04862520.

Originalsprog Engelsk
Artikelnummer e052919
Tidsskrift BMJ Open
Vol/bind 11
Udgave nummer 12
Sider (fra-til) e052919
ISSN 2044-6055
DOI
Status Udgivet - 22 dec. 2021

Bibliografisk note

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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

Quantifying the bone marrow composition of the healthy adult wrist with dual-energy CT

Müller, F. C., Gosvig, K. K., Mikkel, Ø., Bjarne, R., Rodell, A., Henrik, B., Krauss, B., Gade, J. S. & Boesen, M., jun. 2021, I: European Journal of Radiology. 139, s. 1-8 8 s., 109725.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Purpose: Purpose of this study was to investigate Dual-energy CT (DECT) derived virtual non-calcium (VNCa) values for absolute quantification of the bone marrow composition in the wrist. Materials and Methods: We prospectively included consecutive adult participants and examined their wrists with DECT. Ranges of VNCa and calcium values were measured in the carpal bones, radius and ulna using a semi-automatic method. Bones with bone marrow edema, assessed by two blinded radiologists, were excluded. After determining optimum parameters for the three-material decomposition, the influence of calcium values, age and sex on VNCa values was assessed using multiple linear regression. Results: 41 participants (Median age 53 years, range 20 years – 88 years, 51 % men) were enrolled and 399 bones assessed. At participant level mean VNCa values were -143 HU (SD 14 HU) using the current parameters for three-material decomposition and -104HU (SD 11 HU) with optimized parameters. There was a strong and significant influence of calcium values on VNCa values with the current parameters (p < 0.001, -0.137 HU
[VNCa] / HU
[Calcium]). With optimized parameters the calcium values and sex were not statistically significant predictors of VNCa values. Age was a significant, but clinically negligible, predictor (p = 0.03, -0.225 HU / year). Conclusions: After optimizing three-material decomposition parameters, calcium values, age and sex do not substantially influence virtual non-calcium values, and DECT may therefore be used for absolute quantification of the bone marrow composition - alleviating the need for reference bones or groups.

Originalsprog Engelsk
Artikelnummer 109725
Tidsskrift European Journal of Radiology
Vol/bind 139
Sider (fra-til) 1-8
Antal sider 8
ISSN 0720-048X
DOI
Status Udgivet - jun. 2021

Bibliografisk note

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

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

Serum urate as a proposed surrogate outcome measure in gout trials: From the OMERACT working group

Morillon, M. B., Christensen, R., Singh, J. A., Dalbeth, N., Saag, K., Taylor, W. J., Neogi, T., Kennedy, M. A., Pedersen, B. M., McCarthy, G. M., Shea, B., Diaz-Torne, C., Tedeschi, S. K., Grainger, R., Abhishek, A., Gaffo, A., Nielsen, S. M., Noerup, A., Simon, L. S., Lassere, M., Tugwell, P., Stamp, L. K. & Gout Working Group, F. T. O., dec. 2021, I: Seminars in Arthritis and Rheumatism. 51, 6, s. 1378-1385 8 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms).

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 51
Udgave nummer 6
Sider (fra-til) 1378-1385
Antal sider 8
ISSN 0049-0172
DOI
Status Udgivet - dec. 2021

Bibliografisk note

Copyright © 2021 Elsevier Inc. All rights reserved.

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