Published in 2021

OBJECTIVES: The aim of this study was to determine the diagnostic performance of dual-energy computed tomography (DECT) to detect and distinguish crystal deposits in a phantom. The primary objective was to determine the cutoff DECT ratio and the cross-sectional area (CSA) of a crystal deposit necessary to differentiate monosodium urate (MSU), calcium pyrophosphate (CPP), and calcium hydroxyapatite (HA) using DECT. Our secondary objective was to determine the concentration for limit of detection for MSU, CPP, and HA crystal deposits. Exploratory objectives included the comparison between 2 generations of DECT scanners from the same manufacturer as well as different scanner settings.

MATERIALS AND METHODS: We used a cylindrical soft tissue phantom with synthetic MSU, CPP, and HA crystals suspended in resin. Crystal suspension concentration increased with similar attenuation between MSU, CPP, and HA in conventional CT. The phantom was scanned on 2 dual-source DECT scanners, at 2 dose levels and all available tube voltage combinations. Both scanners had a tin (Sn) filter at the high-energy spectra. Dual-energy CT ratios were calculated for a given tube voltage combination by dividing linear regression lines of CT numbers against concentration. Dual-energy CT ratios were compared using an analysis of covariance. Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were calculated for individual crystal suspension comparisons (HA vs CPP, MSU vs CPP, and MSU vs HA).

RESULTS: At standard clinical scan settings with 8 mGy and 80/Sn150 kV, the DECT ratios were as follows: CPP, 2.02 (95% confidence interval [CI], 1.98-2.07); HA, 2.00 (95% CI, 1.96-2.05); and MSU, 1.09 (95% CI, 1.06-1.11). Ratios varied numerically depending on the scanner and tube voltage combination. Monosodium urate crystal DECT ratios were significantly different from HA and CPP (P < 0.001), whereas DECT ratios for HA and CPP crystals did not differ significantly (P = 0.99). The differentiation of MSU crystals from both calcium crystals (HA and CPP) was excellent with an AUC of 1.00 (95% CI, 1.00-1.00) and an optimal cutoff DECT ratio of 1.43:1.40 depending on the scanner. In addition, differentiation of MSU and calcium-containing crystals (HA and CPP) required a CSA of minimum 4 pixels of crystal at standard clinical scan conditions. In contrast, differentiation between CPP and HA crystals was moderate with AUCs ranging from 0.66 (95% CI, 0.52-0.80) to 0.80 (95% CI, 0.69-0.91) and an optimal cutoff DECT ratio of 2.02:2.06 depending on the scanner. Furthermore, differentiation between CPP and HA crystals required a CSA of minimum 87 pixels of crystal at standard clinical scan conditions, corresponding to a region of interest of 3.7 mm diameter. When scanning at highest possible spectral separation and maximum dose of 50 mGy, the limit of detection for crystals within a region of interest of 50 pixels was 14 mg/cm3 for MSU and 2 mg/cm3 for both CPP and HA.

CONCLUSIONS: This phantom study shows that DECT can be used to detect MSU, CPP, and HA crystal deposits. Differentiation of CPP and HA was not possible in crystals deposits less than 3.7 mm in diameter, but MSU could accurately be differentiated from CPP and HA crystal deposits at standard clinical scan conditions.

Originalsprog Engelsk
Tidsskrift Investigative Radiology
Vol/bind 56
Udgave nummer 7
Sider (fra-til) 417-424
Antal sider 8
ISSN 0020-9996
DOI
Status Udgivet - 1 jul. 2021

STUDY DESIGN: Randomized controlled trial with 1-year follow up.

OBJECTIVE: The aim of this study was to assess whether people with low back pain (LBP) and self-reported physically demanding jobs, benefit from an occupational medicine intervention, in addition to a single hospital consultation and a magnetic resonance imaging, at 1 year of follow-up. Secondly, to examine whether the positive health effects, found in both groups at 6 months, persist at 1-year follow-up.

SUMMARY OF BACKGROUND DATA: The prevalence of LBP is high in the working population, resulting in a substantial social and economic burden. Although there are many guidelines available on the management of LBP, including multidisciplinary biopsychosocial rehabilitation, they provide limited guidance on the occupational medicine aspects.

METHODS: As reported previously, 305 participants with LBP and self-reported physically demanding jobs were enrolled in the randomized controlled study and randomly allocated to clinical care with additional occupational medicine intervention or clinical care alone. Data were collected at baseline, 6 months, and 1 year. Outcomes included in the present 1-year follow-up study are changes in neuropathic pain (painDETECT questionnaire), severity of pain (0-10 numerical rating scale), disability (Roland Morris Disability Questionnaire), fear-avoidance beliefs (FABQ), physical, and mental quality of life (short-form 36).

RESULTS: The study showed no effect of an occupational intervention on neuropathic pain, fear-avoidance beliefs, physical and mental quality of life nor disability measured after 1 year. The positive effects found at 6 months in both groups, remained at 1-year follow-up.

CONCLUSION: The results suggest that a thorough clinical consultation, with focus on explaining the cause of pain and instructions to stay active, can promote long-lasting physical and mental health in individuals with LBP. Therefore, additional occupational interventions could focus on altering occupational obstacles on a structural level.Level of Evidence: 2.

Originalsprog Engelsk
Tidsskrift Spine
Vol/bind 46
Udgave nummer 6
Sider (fra-til) 347-355
Antal sider 9
ISSN 0362-2436
DOI
Status Udgivet - 15 mar. 2021

On 11 March 2020, a lockdown to limit the spread of COVID-19 was implemented in Denmark. The pandemic and the lockdown might have caused stress, depression, and anxiety in new mothers. Individuals with high resilience to stress may have been less affected. This study aimed to investigate if changes in perceived stress, anxiety, depression, and resilience from the second trimester until two months postpartum were different before and during the COVID-19 pandemic in Denmark in spring 2020. Pregnant women enrolled in an ongoing feasibility study completed an online questionnaire measuring perceived stress, depression, anxiety, and resilience in the second trimester and two months postpartum. Changes in scores between women completing the two-month postpartum questionnaire before (n = 26) or during (n = 47) the COVID-19 pandemic were calculated. No statistically significant differences in changes from baseline to follow-up between pre- and during-pandemic groups in Cohen's Perceived Stress Scale (PSS), the Depression, Anxiety, Stress Scale (DASS), or the Connor-Davidson Resilience Scale (CD-RISC) were found. Adjusted differences in group means were as follows: PSS: 0.70 (CI-2.45; 3.85); DASS Stress: 0.76 (CI-3.59; 2.08); DASS Anxiety: 0.47 (CI-0.84; 1.77); DASS Depression: 0.88 (CI-0.95; 2.71); and CD-RISC: 1.19 (CI-3.16; 5.54). In conclusion, we did not find significant differences in the development of stress, depression, anxiety, or resilience before or during the Danish COVID-19 pandemic in spring 2020.

Originalsprog Engelsk
Artikelnummer 11734
Tidsskrift International Journal of Environmental Research and Public Health
Vol/bind 18
Udgave nummer 22
Sider (fra-til) 1-9
Antal sider 9
ISSN 1661-7827
DOI
Status Udgivet - 9 nov. 2021

Effect Modifiers and Statistical Tests for Interaction in Randomized Trials

Christensen, R., Bours, M. J. L. & Nielsen, S. M., jun. 2021, I: Journal of Clinical Epidemiology. 134, s. 174-177 4 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Statistical analyses of randomized controlled trials (RCTs) yield a causally valid estimate of the overall treatment effect, which is the contrast between the outcomes in two randomized treatment groups commonly accompanied by a confidence interval. In addition, the trial investigators may want to examine whether the observed treatment effect varies across patient subgroups (also called 'heterogeneity of treatment effects'), i.e. whether the treatment effect is modified by the value of a variable assessed at baseline. The statistical approach for this evaluation of potential effect modifiers is a test for statistical interaction to evaluate whether the treatment effect varies across levels of the effect modifier. In this article, we provide a concise and nontechnical explanation of the use of simple statistical tests for interaction to identify effect modifiers in RCTs. We explain how to calculate the test of interaction by hand, applied to a dataset with simulated data on 1,000 imaginary participants for illustration.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 134
Sider (fra-til) 174-177
Antal sider 4
ISSN 0895-4356
DOI
Status Udgivet - jun. 2021

Objectives: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. Method: One-hundred patients with established RA, Disease Activity Score based on 28-joint count–C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as ‘in clinical remission’) who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0–2.6), HAQ score (0.08, 0.03–0.1), MRI combined inflammation (2.5, 0.9–4.1), and SDAI scores (2.7, 1.9–3.5). Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. Trial registration: Clinicaltrials.gov identifier: NCT01656278.

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Rheumatology
ISSN 0300-9742
DOI
Status Accepteret/In press - 2021

Bibliografisk note

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

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

OBJECTIVE: To determine whether positive expiratory pressure (PEP) by PEP flute self-care is effective in reducing respiratory symptoms among community dwelling adults with SARS-CoV-2 infection and early stage covid-19.

DESIGN: Non-drug, open label, randomised controlled trial.

SETTING: Capital Region and Region Zealand in Denmark from 6 October 2020 to 26 February 2021.

PARTICIPANTS: Community dwelling adults, able to perform self-care, with a new SARS-CoV-2 infection (verified by reverse transcription polymerase chain reaction tests) and symptoms of covid-19.

INTERVENTION: Participants were randomised to use PEP flute self-care in addition to usual care or have usual care only. Randomisation was based on permuted random blocks in a 1:1 ratio, stratified for sex and age (<60 or ≥60 years). The PEP self-care group was instructed to use a PEP flute three times per day during the 30 day intervention.

MAIN OUTCOME MEASURES: Primary outcome was a change in symptom severity from baseline to day 30, as assessed by the self-reported COPD (chronic obstructive pulmonary disease) assessment test (CAT), which was adjusted for baseline values and stratification factors. Participants completed the CAT test questionnaire every day online. Secondary outcomes were self-reported urgent care visits due to covid-19, number of covid-19 related symptoms, and change in self-rated health, all within 30-days' follow-up.

RESULTS: 378 participants were assigned to the PEP flute self-care intervention (n=190) or usual care only (n=188). In the PEP self-care group, the median number of days with PEP flute use was 21 days (interquartile range 13-25). For the intention-to-treat population, a group difference was observed in changes from baseline in CAT scores of -1.2 points (95% confidence interval -2.1 to -0.2; P=0.017) in favour of the PEP flute self-care group. At day 30, the PEP flute self-care group also reported less chest tightness, less dyspnoea, more vigour, and higher level of daily activities, but these differences were small, and no consistent effects were seen on the secondary outcomes. No serious adverse events were reported.

CONCLUSIONS: In community dwelling adults with early covid-19, PEP flute self-care had a significant, yet marginal and uncertain clinical effect on respiratory symptom severity, as measured by CAT scores.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04530435.

Originalsprog Engelsk
Artikelnummer e066952
Tidsskrift BMJ
Vol/bind 375
Sider (fra-til) 1-9
Antal sider 9
ISSN 1756-1833
DOI
Status Udgivet - 24 nov. 2021

Bibliografisk note

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

Effect of real-time and post-event feedback in out-of-hospital cardiac arrest attended by EMS - A systematic review and meta-analysis

Lyngby, R. M., Händel, M. N., Christensen, A. M., Nikoletou, D., Folke, F., Christensen, H. C., Barfod, C. & Quinn, T., jun. 2021, I: Resuscitation plus. 6, s. 100101

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Objectives: A systematic review to determine if cardiopulmonary resuscitation (CPR) guided by either real-time or post-event feedback could improve CPR quality or patient outcome compared to unguided CPR in out-of-hospital cardiac arrest (OHCA).

Methods: Four databases were searched; PubMed, Embase, CINAHL, and Cochrane Library in August 2020 for post 2010 literature on OHCA in adults. Critical outcomes were chest compression depth, rate and fraction. Important outcomes were any return of spontaneous circulation, survival to hospital and survival to discharge.

Results: A total of 9464 studies were identified with 61 eligibility for full text screening. A total of eight studies was included in the meta-analysis. Five studies investigated real-time feedback and three investigated post-event feedback. Meta-analysis revealed that real-time feedback statistically improves compression depth and rate while post-event feedback improved depth and fraction. Feedback did not statistically improve patient outcome but an improvement in absolute numbers revealed a clinical effect of feedback. Heterogenity varied from "might not be important" to "considerable".

Conclusion: To significantly improve CPR quality real-time and post-event feedback should be combined. Neither real-time nor post event feedback could statistically be associated with patient outcome however, a clinical effect was detected. The conclusions reached were based on few studies of low to very low quality.

PROSPERO registration: CRD42019133881.

Originalsprog Engelsk
Tidsskrift Resuscitation plus
Vol/bind 6
Sider (fra-til) 100101
ISSN 2666-5204
DOI
Status Udgivet - jun. 2021

Effectiveness of a Second Biologic After Failure of a Non-tumor Necrosis Factor Inhibitor As First Biologic in Rheumatoid Arthritis

Chatzidionysiou, K., Hetland, M. L., Frisell, T., Di Giuseppe, D., Hellgren, K., Glintborg, B., Nordström, D., Peltomaa, R., Aaltonen, K., Trokovic, N., Kristianslund, E. K., Kvien, T. K., Provan, S. A., Gudbjornsson, B., Grondal, G., Dreyer, L., Kristensen, L. E., Jørgensen, T. S., Jacobsson, L. T. H. & Askling, J., okt. 2021, I: Journal of Rheumatology. 48, 10, s. 1512-1518 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: In rheumatoid arthritis (RA), evidence regarding the effectiveness of a second biologic disease-modifying antirheumatic drug (bDMARD) in patients whose first-ever bDMARD was a non-tumor necrosis factor inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of a second bDMARD (non-TNFi: rituximab [RTX], abatacept [ABA], or tocilizumab [TCZ], separately; and TNFi) after failure of a non-TNFi bDMARD as first bDMARD.

METHODS: We identified patients with RA from the 5 Nordic biologics registers who started treatment with a non-TNFi as first-ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed drug survival (at 6 and 12 months) and primary response (at 6 months).

RESULTS: We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67, and TNFi 427) following failure of a first non-TNFi bDMARD. At 6 and 12 months after start of their second bDMARD, approximately 70% and 60%, respectively, remained on treatment, and at 6 months, less than one-third of patients were still on their second bDMARD and had reached low disease activity or remission according to the Disease Activity Score in 28 joints. For those patients whose second bMDARD was a TNFi, the corresponding proportion was slightly higher (40%).

CONCLUSION: The drug survival and primary response of a second bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 48
Udgave nummer 10
Sider (fra-til) 1512-1518
Antal sider 7
ISSN 0315-162X
DOI
Status Udgivet - okt. 2021

Bibliografisk note

Copyright © 2021 by the Journal of Rheumatology.

Effectiveness of interdisciplinary combined dermatology-gastroenterology-rheumatology clinical care compared to usual care in patients with immune-mediated inflammatory diseases: a parallel group, non-blinded, pragmatic randomised trial

Hjuler, K. F., Dige, A., Agnholt, J., Laurberg, T. B., Loft, A. G., Møller, L. F., Christensen, R. & Iversen, L., 28 apr. 2021, I: BMJ Open. 11, 4, s. e041871 e041871.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Immune-mediated inflammatory diseases (IMIDs) are associated with reduced health-related quality of life (HRQol), increased risk of somatic and psychiatric comorbidities and reduced socioeconomic status. Individuals with one IMID have an increased risk for developing other IMIDs. The unmet needs in the care of patients with IMIDs may result from a lack of patient-centricity in the usual monodisciplinary siloed approach to these diseases. The advantages of novel interdisciplinary clinics towards the traditional therapeutic approach have not been investigated. The overall aim of this study is to determine the effectiveness of an interdisciplinary combined clinic intervention compared with usual care in a population of patients with the IMIDs: psoriasis, hidradenitis suppurativa, psoriatic arthritis, axial spondyloarthritis and inflammatory bowel disease. Our hypothesis is that an interdisciplinary combined clinic intervention will be more effective than usual care in improving clinical and patient-reported outcomes, and that a more effective screening and management of other IMIDs and comorbidities can be performed.

METHODS AND ANALYSIS: This is a randomised, usual care controlled, parallel-group pragmatic clinical trial. 300 consecutively enrolled participants with co-occurrence of at least two IMIDs are randomly assigned in a 2:1 ratio to either treatment in the interdisciplinary combined clinic or usual care. The study will consist of a 6-month active intervention period and a 6-month follow-up period where no intervention or incentives will be provided by the trial. The primary outcome is the change from baseline to 24 weeks on the Short-Form Health Survey (SF-36) Physical Component Summary. Additional patient-reported outcome measures and clinical measures are assessed as secondary outcomes.

ETHICS AND DISSEMINATION: Ethical approval of this study protocol was established by the institutional review board of the study site. The findings from this trial will be disseminated via conference presentations and publications in peer-reviewed journals, and by engagement with patient organisations.

TRIAL REGISTRATION NUMBER: NCT04200690.

Originalsprog Engelsk
Artikelnummer e041871
Tidsskrift BMJ Open
Vol/bind 11
Udgave nummer 4
Sider (fra-til) e041871
ISSN 2044-6055
DOI
Status Udgivet - 28 apr. 2021

Effectiveness of Mind-Body Intervention for Inflammatory Conditions: Results from a 26-Week Randomized, Non-Blinded, Parallel-Group Trial

Nguyen, T. T., Jensen, C. G., Khoury, L., Deleuran, B., Blom, E. S., Breinholt, T., Christensen, R. & Skov, L., 14 jul. 2021, I: Journal of Clinical Medicine. 10, 14, 3107.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Biopsychosocial intervention has been suggested as a complementary treatment strategy for patients with chronic conditions. We compared the effect of a mind-body intervention (MBI), relative to treatment-as-usual (TAU) on WHO-5 Well-being Index during an intensive period of 12 weeks and follow-up at week 26 among patients with either psoriasis (PsO) or rheumatoid arthritis (RA). The MBI was based on the 'Relaxation Response Resiliency Program' and the 'Open and Calm Program', as well as 'Mindfulness Based Stress Reduction' (MBSR). The trial was randomized, management-as-usual, and controlled. Statistical analyses were based on the intention-to-treat population using repeated measures and mixed effects models (NCT03888261). We screened 39 potential participants, 35 of which (PsO, n = 20; RA, n = 15) met the eligibility criteria and were randomized: 17 in the MBI group and 18 in the TAU group. Attrition from the intervention program was 19%, with 65% of MBI patients and 71% of TAU patients completing the outcome assessments. After 12 weeks, a statistically significant difference in WHO-5 was observed between the groups (p = 0.019). However, according to the protocol, during the entire trial period, the average (least squares mean values) WHO-5 score was higher although not statistically significant in the MBI group (65.3) compared with the TAU group (59.1), corresponding to a between-group difference over 26 weeks of 6.15 (95% CI: -0.26 to 12.56; p = 0.060). All things considered, adding biopsychosocial intervention to clinical practice to patients with conditions, such as PsO and RA, could potentially improve health-related quality of life.

Originalsprog Engelsk
Artikelnummer 3107
Tidsskrift Journal of Clinical Medicine
Vol/bind 10
Udgave nummer 14
ISSN 2077-0383
DOI
Status Udgivet - 14 jul. 2021

Effectiveness of Transdiagnostic Cognitive-Behavioral Psychotherapy Compared With Management as Usual for Youth With Common Mental Health Problems: A Randomized Clinical Trial

Jeppesen, P., Wolf, R. T., Nielsen, S. M., Christensen, R., Plessen, K. J., Bilenberg, N., Thomsen, P. H., Thastum, M., Neumer, S-P., Puggaard, L. B., Pedersen, M. M. A., Pagsberg, A. K., Silverman, W. K. & Correll, C. U., 1 mar. 2021, I: JAMA Psychiatry. 78, 3, s. 250-260 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Importance: Behavioral therapy and cognitive-behavioral therapy (CBT) programs targeting a single class of problems have not been widely implemented. The population of youths with common mental health problems is markedly undertreated. Objective: To determine the effectiveness of a new transdiagnostic CBT program (Mind My Mind [MMM]) compared with management as usual (MAU) in youths with emotional and behavioral problems below the threshold for referral to mental health care. Design, Setting, and Participants: This pragmatic, multisite, randomized clinical trial of MMM vs MAU was conducted from September 7, 2017, to August 28, 2019, including 8 weeks of postintervention follow-up, in 4 municipalities in Denmark. Consecutive help-seeking youths were randomized (1:1) to the MMM or the MAU group. Main inclusion criteria were age 6 to 16 years and anxiety, depressive symptoms, and/or behavioral disturbances as a primary problem. Data were analyzed from August 12 to October 25, 2019. Interventions: The MMM intervention consisted of 9 to 13 weekly, individually adapted sessions of manualized CBT delivered by local psychologists. The MAU group received 2 care coordination visits to enhance usual care. Main Outcomes and Measures: The primary outcome was change in mental health problems reported by parents at week 18, using the Strengths and Difficulties Questionnaire (SDQ) Impact scale (range, 0-10 points, with higher scores indicating greater severity of distress and impairment). Primary and secondary outcomes were assessed in the intention-To-Treat population at week 18. Maintenance effects were assessed at week 26. Results: A total of 396 youths (mean [SD] age, 10.3 [2.4] years; 206 [52.0%] boys) were randomized to MMM (n = 197) or MAU (n = 199), with primary outcome data available in 177 (89.8%) and 167 (83.9%), respectively, at 18 weeks. The SDQ Impact score decreased by 2.34 points with MMM and 1.23 with MAU, from initial scores of 4.12 and 4.21, respectively (between-group difference, 1.10 [95% CI, 0.75-1.45]; P <.001; Cohen d = 0.60). Number of responders (≥1-point reduction in SDQ Impact score) was greater with MMM than with MAU (144 of 197 [73.1%] vs 93 of 199 [46.7%]; number needed to treat, 4 [95% CI, 3-6]). Secondary outcomes indicated statistically significant benefits in parent-reported changes of anxiety, depressive symptoms, daily functioning, school attendance, and the principal problem. All benefits were maintained at week 26 except for school attendance. Conclusions and Relevance: In this randomized clinical trial, the scalable transdiagnostic cognitive-behavioral intervention MMM outperformed MAU in a community setting on multiple, clinically relevant domains in youth with emotional and behavioral problems. Trial Registration: ClinicalTrials.gov Identifier: NCT03535805.

Originalsprog Engelsk
Tidsskrift JAMA Psychiatry
Vol/bind 78
Udgave nummer 3
Sider (fra-til) 250-260
Antal sider 11
ISSN 2168-622X
DOI
Status Udgivet - 1 mar. 2021

BACKGROUND: Traumatic full-thickness rotator cuff tears are typically managed surgically, followed by rehabilitation, but the load progression to reach an optimal clinical outcome during postoperative rehabilitation is unknown.

PURPOSE: To evaluate whether there was a superior effect of 12 weeks of progressive active exercise therapy on shoulder function, pain, and quality of life compared with usual care.

STUDY DESIGN: Randomized controlled trial; Level of evidence, 1.

METHODS: Patients with surgically repaired traumatic full-thickness rotator cuff tears were recruited from 2 orthopaedic departments and randomized to progressive active exercise therapy (PR) or limited passive exercise therapy (UC [usual care]). The primary outcome was the change in the Western Ontario Rotator Cuff Index (WORC) score between groups from before surgery to 12 weeks after surgery. Secondary outcomes included changes in the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire score, pain, range of motion, and strength. Adverse events were registered during the intervention period.

RESULTS: A total of 82 patients were randomized to the PR (n = 41) or UC (n = 41) group. All 82 patients (100%) participated in the 12-week assessment and 79 in the 1-year follow-up. At 12 weeks, there was no significant difference between the groups in the change in the WORC score from baseline adjusted for age, sex, and center (physical symptoms:
P = .834; sports and recreation:
P = .723; work:
P = .541; lifestyle:
P = .508; emotions:
P = .568). Additionally, there was no between-group difference for the secondary outcomes including the WORC score at 1 year and the DASH score, pain, range of motion, and strength at 12 weeks and 1 year. Both groups showed significant improvements over time in all outcomes. In total, there were 13 retears (16%) at 1-year follow-up: 6 in the PR group and 7 in the UC group.

CONCLUSION: PR did not result in superior patient-reported and objective outcomes compared with UC at either short- or long-term follow-up (12 weeks and 1 year).

REGISTRATION: NCT02969135 (ClinicalTrials.gov identifier).

Originalsprog Engelsk
Tidsskrift The American journal of sports medicine
Vol/bind 49
Udgave nummer 2
Sider (fra-til) 321-331
Antal sider 11
ISSN 0363-5465
DOI
Status Udgivet - feb. 2021
Background: Traumatic full-thickness rotator cuff tears are typically managed surgically, followed by rehabilitation, but the load progression to reach an optimal clinical outcome during postoperative rehabilitation is unknown.

Purpose: To evaluate whether there was a superior effect of 12 weeks of progressive active exercise therapy on shoulder function, pain, and quality of life compared with usual care.

Study design: Randomized controlled trial; Level of evidence, 1.

Methods: Patients with surgically repaired traumatic full-thickness rotator cuff tears were recruited from 2 orthopaedic departments and randomized to progressive active exercise therapy (PR) or limited passive exercise therapy (UC [usual care]). The primary outcome was the change in the Western Ontario Rotator Cuff Index (WORC) score between groups from before surgery to 12 weeks after surgery. Secondary outcomes included changes in the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire score, pain, range of motion, and strength. Adverse events were registered during the intervention period.

Results: A total of 82 patients were randomized to the PR (n = 41) or UC (n = 41) group. All 82 patients (100%) participated in the 12-week assessment and 79 in the 1-year follow-up. At 12 weeks, there was no significant difference between the groups in the change in the WORC score from baseline adjusted for age, sex, and center (physical symptoms: P = .834; sports and recreation: P = .723; work: P = .541; lifestyle: P = .508; emotions: P = .568). Additionally, there was no between-group difference for the secondary outcomes including the WORC score at 1 year and the DASH score, pain, range of motion, and strength at 12 weeks and 1 year. Both groups showed significant improvements over time in all outcomes. In total, there were 13 retears (16%) at 1-year follow-up: 6 in the PR group and 7 in the UC group.

Conclusion: PR did not result in superior patient-reported and objective outcomes compared with UC at either short- or long-term follow-up (12 weeks and 1 year).

Originalsprog Engelsk
Tidsskrift The American journal of sports medicine
ISSN 0363-5465
Status Udgivet - feb. 2021

Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A post hoc Analysis of the U-TURN Trial

Abildgaard, J., Johansen, M. Y., Skov-Jeppesen, K., Andersen, L. B., Karstoft, K., Hansen, K. B., Hartmann, B., Holst, J. J., Pedersen, B. K. & Ried-Larsen, M., 24 aug. 2021, (E-pub ahead of print) I: Medicine and Science in Sports and Exercise.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION/PURPOSE: The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D.

METHODS: Persons with T2D were randomized to either a 12-month lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin, N-terminal propeptide of type-I procollagen, reflecting bone formation, and carboxyterminal collagen I crosslinks, reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up.

RESULTS: From baseline to follow-up, s-propeptide of type-I procollagen increased by 34% (95% confidence interval [CI], 17%-50%), serum-carboxyterminal collagen I crosslink by 36% (95% CI, 1%-71%), and s-osteocalcin by 31% (95% CI, 11-51%) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. Bone mineral density was unaffected by the intervention (ΔBMD, 0.1%; 95% CI, -1.1% to 1.2%).

CONCLUSIONS: A 12-month intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.

Originalsprog Engelsk
Tidsskrift Medicine and Science in Sports and Exercise
ISSN 0195-9131
DOI
Status E-pub ahead of print - 24 aug. 2021

Effects of whey protein and dietary fiber intake on insulin sensitivity, body composition, energy expenditure, blood pressure, and appetite in subjects with abdominal obesity

Fuglsang-Nielsen, R., Rakvaag, E., Langdahl, B., Knudsen, K. E. B., Hartmann, B., Holst, J. J., Hermansen, K. & Gregersen, S., apr. 2021, I: European Journal of Clinical Nutrition. 75, 4, s. 611-619 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Recently, we demonstrated that whey protein (WP) combined with low dietary fiber improved lipemia, a risk factor for cardiovascular disease in subjects with abdominal obesity. In the present study, we investigated the effects of intake of WP and dietary fiber from enzyme-treated wheat bran on other metabolic parameters of the metabolic syndrome.

METHODS: The study was a 12-week, double-blind, randomized, controlled, parallel intervention study. We randomized 73 subjects with abdominal obesity to 1 of 4 iso-energetic dietary interventions: 60 g per day of either WP hydrolysate or maltodextrin (MD) combined with high-fiber (HiFi; 30 g dietary fiber/day) or low-fiber (LoFi; 10 g dietary fiber/day) cereal products. We assessed changes in insulin sensitivity, gut hormones (GLP-1, GLP-2, GIP, and peptide YY), body composition, 24-h BP, resting energy expenditure and respiratory exchange ratio (RER), and appetite.

RESULTS: Sixty-five subjects completed the trial. Subjective hunger ratings were lower after 12 weeks of WP compared with MD, independent of fiber content (P = 0.02). We found no effects on ratings of satiety, fullness or prospective food consumption for either of the interventions. Intake of WP combined with LoFi increased the postprandial peptide YY response. There were no effects of WP or fiber on insulin sensitivity, body composition, energy expenditure, incretins, or 24-h BP.

CONCLUSIONS: WP consumption for 12 weeks reduced subjective ratings of hunger in subjects with abdominal obesity. Neither WP nor dietary fiber from wheat bran affected insulin sensitivity, 24-h BP, gut hormone responses, body composition, or energy expenditure compared with MD and low dietary fiber.

Originalsprog Engelsk
Tidsskrift European Journal of Clinical Nutrition
Vol/bind 75
Udgave nummer 4
Sider (fra-til) 611-619
Antal sider 9
ISSN 0954-3007
DOI
Status Udgivet - apr. 2021

Efficacy and safety of intra-articular therapies in rheumatic and musculoskeletal diseases: an overview of systematic reviews

Rodriguez-García, S. C., Castellanos-Moreira, R., Uson, J., Naredo, E., O'Neill, T. W., Doherty, M., Boesen, M., Pandit, H., Möller Parera, I., Vardanyan, V., Terslev, L., Kampen, W. U., D'Agostino, M. A., Berenbaum, F., Nikiphorou, E., Pitsillidou, I., de la Torre-Aboki, J. & Carmona, L., jun. 2021, I: RMD Open. 7, 2, 001658.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To summarise the evidence on intra-articular therapies (IAT) to inform the 2020 EULAR recommendations.

METHODS: An overview of systematic reviews (SR) including randomised-controlled trials (RCTs) of IAT in adults with arthropathies was performed up to July 2020. Pain, function, and frequency of adverse events were the main efficacy and safety outcomes, respectively. Quality was assessed with the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool.

RESULTS: Of 184 references identified, 16 met the inclusion criteria, and a search of their reference lists identified 16 additional SRs. After quality assessment, 29 were finally included. Of these, 18 focused on knee osteoarthritis (KOA), 6 on hip osteoarthritis (HOA), 3 on shoulder capsulitis (SC), and 3 on rheumatoid arthritis. Overall, hyaluronic acid showed a small effect on pain and function in KOA but not in HOA or shoulder capsulitis. Intra-articular glucocorticoids showed a small effect in pain and function in KOA and function in HOA and SC. Platelet-rich plasma showed benefit in pain and function in KOA but not in HOA. Mesenchymal stem cells behaved similarly. Most SR results were of moderate quality and RCTs included often presented a high risk of bias, mainly due to inadequate blinding and heterogeneous results. All interventions were well tolerated with no clear safety differences.

CONCLUSIONS: This overview underlines that most IAT currently used in KOA, HOA, and SC exert small effects and are well tolerated. However, no firm conclusions can be drawn for inflammatory arthritis due to the limited data found.

Originalsprog Engelsk
Artikelnummer 001658
Tidsskrift RMD Open
Vol/bind 7
Udgave nummer 2
ISSN 2056-5933
DOI
Status Udgivet - jun. 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.

Efficacy and Safety of Polyunsaturated Fatty Acids Supplementation in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Children and Adolescents: A Systematic Review and Meta-Analysis of Clinical Trials

Händel, M. N., Rohde, J. F., Rimestad, M. L., Bandak, E., Birkefoss, K., Tendal, B., Lemcke, S. & Callesen, H. E., 8 apr. 2021, I: Nutrients. 13, 4, 1226.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Based on epidemiological and animal studies, the rationale for using polyunsaturated fatty acids (PUFAs) as a treatment for Attention Deficit Hyperactivity Disorder (ADHD) seems promising. Here, the objective was to systematically identify and critically assess the evidence from clinical trials. The primary outcome was ADHD core symptoms. The secondary outcomes were behavioral difficulties, quality of life, and side effects. We performed a systematic search in Medline, Embase, Cinahl, PsycInfo, and the Cochrane Library up to June 2020. The overall certainty of evidence was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). We identified 31 relevant randomized controlled trials including 1755 patients. The results showed no effect on ADHD core symptoms rated by parents (k = 23; SMD: -0.17; 95% CI: -0.32, -0.02) or teachers (k = 10; SMD: -0.06; 95% CI: -0.31, 0.19). There was no effect on behavioral difficulties, rated by parents (k = 7; SMD: -0.02; 95% CI: -0.17, 0.14) or teachers (k = 5; SMD: -0.04; 95% CI: -0.35, 0.26). There was no effect on quality of life (SMD: 0.01; 95% CI: -0.29, 0.31). PUFA did not increase the occurrence of side effects. For now, there seems to be no benefit of PUFA in ADHD treatment; however, the certainty of evidence is questionable, and thus no conclusive guidance can be made. The protocol is registered in PROSPERO ID: CRD42020158453.

Originalsprog Engelsk
Artikelnummer 1226
Tidsskrift Nutrients
Vol/bind 13
Udgave nummer 4
ISSN 2072-6643
DOI
Status Udgivet - 8 apr. 2021

Endorsement of the OMERACT core domain set for shared decision making interventions in rheumatology trials: Results from a multi-stepped consensus-building approach

Toupin-April, K., Décary, S., de Wit, M., Meara, A., Barton, J. L., Fraenkel, L., Li, L. C., Brooks, P., Shea, B., Stacey, D., Légaré, F., Lydiatt, A., Hofstetter, C., Proulx, L., Christensen, R., Voshaar, M., Suarez-Almazor, M. E., Boonen, A., Meade, T., March, L., Jull, J. E., Campbell, W., Alten, R., Morgan, E. M., Kelly, A., Kaufman, J., Hill, S., Maxwell, L. J., Guillemin, F., Beaton, D., El-Miedany, Y., Mittoo, S., Westrich Robertson, T., Bartlett, S. J., Singh, J. A., Mannion, M., Nasef, S. I., de Souza, S., Boel, A., Adebajo, A., Arnaud, L., Gill, T. K., Moholt, E., Burt, J., Jayatilleke, A., Hmamouchi, I., Carrott, D., Blanco, F. J., Mather, K., Maharaj, A., Sharma, S., Caso, F., Fong, C., Fernandez, A. P., Mackie, S., Nikiphorou, E., Jones, A., Greer-Smith, R., Sloan, V. S., Akpabio, A., Strand, V., Umaefulam, V., Monti, S., Melburn, C., Abaza, N., Schultz, K., Stones, S., Kiwalkar, S., Srinivasalu, H., Constien, D., King, L. K. & Tugwell, P., jun. 2021, I: Seminars in Arthritis and Rheumatism. 51, 3, s. 593-600 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions.

METHODS: The process followed the OMERACT Filter 2.1 methodology, and used consensus-building methods, with patients involved since the inception. After developing the draft core domain set in previous research, we conducted five steps: (i) improving the draft core domain set; (ii) developing and disseminating white-board videos to promote its understanding; (iii) conducting an electronic survey to gather feedback on the draft core domain set; (iv) finalizing the core domain set and developing summaries, a plenary session video and discussion boards to promote its understanding; and (v) conducting virtual workshops with voting to endorse the core domain set.

RESULTS: A total of 167 participants from 28 countries answered the survey (62% were patients/caregivers). Most participants rated domains as relevant (81%-95%) and clear (82%-93%). A total of 149 participants (n = 48 patients/caregivers, 101 clinicians/researchers) participated in virtual workshops and voted on the proposed core domain set which received endorsement by 95%. Endorsed domains are: 1- Knowledge of options, their potential benefits and harms; 2- Chosen option aligned with each patient's values and preferences; 3- Confidence in the chosen option; 4- Satisfaction with the decision-making process; 5- Adherence to the chosen option and 6- Potential negative consequences of the SDM intervention.

CONCLUSION: We achieved consensus among an international group of stakeholders on the OMERACT core domain set for rheumatology trials of SDM interventions. Future research will develop the Core Outcome Measurement Set.

CLINICAL SIGNIFICANCE: Prior to this study, there had been no consensus on the OMERACT core domain set for SDM interventions. The current study shows that the OMERACT core domain set achieved a high level of endorsement by key stakeholders, including patients/caregivers, clinicians and researchers.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 51
Udgave nummer 3
Sider (fra-til) 593-600
Antal sider 8
ISSN 0049-0172
DOI
Status Udgivet - jun. 2021

Knee pain is an early sign of later incident radiographic knee osteoarthritis (OA). However, the prevalence of knee pain in the general population is unknown. Additionally, it is unknown how people with knee pain choose to self-manage the condition and if the perception of the illness affects these choices. In this study, 9086 citizens between 60-69 years old in the municipality of Frederiksberg, Copenhagen, Denmark, were surveyed, of which 4292 responded. The prevalence of knee pain was estimated, and associations between illness perceptions (brief illness perception questionnaire [B-IPQ]), self-management strategies, and knee symptoms were assessed. The prevalence of knee pain was 21.4% of which 40.5% reported to use no self-management strategies (non-users). These non-users perceived their knee pain as less threatening and reported less severe symptoms than users of self-management strategies. Further, we found that a more positive illness perception was associated with less severe knee symptoms. In conclusion, among Danes aged 60-69 years, the knee pain prevalence is 21.4%, of which 40.5% use no treatment and perceive the condition as non-threatening. These non-users with knee pain represent a subpopulation being at increased risk of developing knee OA later in life, and there is a potential preventive gain in identifying these persons.

Originalsprog Engelsk
Artikelnummer 668
Tidsskrift Journal of Clinical Medicine
Vol/bind 10
Udgave nummer 4
Antal sider 18
ISSN 2077-0383
DOI
Status Udgivet - 9 feb. 2021

EULAR recommendations for intra-articular therapies

Uson, J., Rodriguez-García, S. C., Castellanos-Moreira, R., O'Neill, T. W., Doherty, M., Boesen, M., Pandit, H., Möller Parera, I., Vardanyan, V., Terslev, L., Kampen, W. U., D'Agostino, M-A., Berenbaum, F., Nikiphorou, E., Pitsillidou, I. A., de la Torre-Aboki, J., Carmona, L. & Naredo, E., okt. 2021, I: Annals of the Rheumatic Diseases. 80, 10, s. 1299-1305 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To establish evidence-based recommendations to guide health professionals using intra-articular therapies (IAT) in adult patients with peripheral arthropathies.

METHODS: A multidisciplinary international task force established the objectives, users and scope and the need for background information, including systematic literature reviews) and two surveys addressed to healthcare providers and patients throughout Europe. The evidence was discussed in a face-to-face meeting, recommendations were formulated and subsequently voted for anonymously in a three-round Delphi process to obtain the final agreement. The level of evidence was assigned to each recommendation with the Oxford levels of evidence.

RESULTS: Recommendations focus on practical aspects to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles and 11 recommendations were established, addressing issues related to patient information, procedure and setting, accuracy, routine and special aseptic care, safety issues and precautions to be addressed in special populations, efficacy and safety of repeated joint injections, use of local anaesthetics and aftercare.

CONCLUSION: We have developed the first evidence and expert opinion-based recommendations to guide health professionals using IAT. We hope that these recommendations will be included in different educational programmes, used by patient associations and put into practice via scientific societies to help improve uniformity and quality of care when performing IAT in peripheral adult joints.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 80
Udgave nummer 10
Sider (fra-til) 1299-1305
Antal sider 7
ISSN 0003-4967
DOI
Status Udgivet - okt. 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.

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