Published in 2021

Determining a healthy reference range and factors potentially influencing PRO-C3 - A biomarker of liver fibrosis

Erhardtsen, E., Rasmussen, D. G. K., Frederiksen, P., Leeming, D. J., Shevell, D., Gluud, L. L., Karsdal, M. A., Aithal, G. P. & Schattenberg, J. M., aug. 2021, I: JHEP reports : innovation in hepatology. 3, 4, 100317.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background & Aims: Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical studies in NAFLD/NASH patients support the utility of PRO-C3, a marker of type III collagen formation, as a marker for the degree of fibrosis, disease activity, and effect of treatment. Here we establish the healthy reference range, optimal sample handling conditions for both short- and long-term serum storage, and robustness for the PRO-C3 assay.

Methods: PRO-C3 was measured in 269 healthy volunteers and in 222 NAFLD patients. Robustness of the PRO-C3 assay was measured according to Clinical and Laboratory Standards Institute standards and included validation of interference, precision, and reagent stability, whilst sample stability was defined for storage at different temperatures and for 3 freeze-thaw cycles. Fibrosis scoring was based on histological assessments and used as a reference for the diagnostic ability of PRO-C3 to discriminate between patients with different levels of fibrosis.

Results: Robustness of the PRO-C3 analysis validated by interference, precision, and reagent stability was found to be within the predefined acceptance criteria. The healthy reference range was determined to be 6.1-14.7 ng/ml. Levels of PRO-C3 were not affected by sex, age, BMI, or ethnicity. Levels of PRO-C3 were able to identify patients with clinically significant fibrosis and advanced fibrosis (AUC = 0.83 (95% CI [0.77-0.88], p <0.0001), and AUC = 0.79 (95% CI [0.73-0.85], p <0.0001), respectively).

Conclusions: The assay proved to be robust and sample stability was found to comply with hospital sample handling requirements. PRO-C3 measured in samples from patients with NAFLD/NASH was diagnostic for significant and advanced liver fibrosis.

Lay summary: We showed that PRO-C3 levels were stable under conditions conforming with hospital sample-handling requirements. We determined a healthy reference range and showed that PRO-C3 levels were not associated with sex, age, BMI, or ethnicity. Finally, we provide further evidence of an association of PRO-C3 with increasing liver fibrosis.

Originalsprog Engelsk
Artikelnummer 100317
Tidsskrift JHEP reports : innovation in hepatology
Vol/bind 3
Udgave nummer 4
ISSN 2589-5559
DOI
Status Udgivet - aug. 2021

Dietary trans-fatty acid intake in relation to cancer risk: a systematic review and meta-analysis

Michels, N., Specht, I. O., Heitmann, B. L., Chajès, V. & Huybrechts, I., 4 jun. 2021, I: Nutrition Reviews. 79, 7, s. 758-776 19 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

CONTEXT: Apart from ruminant fat, trans-fatty acids are produced during the partial hydrogenation of vegetable oils, (eg, in the production of ultraprocessed foods). Harmful cardiovascular effects of trans-fatty acids are already proven, but the link with cancer risk has not yet been summarized.

OBJECTIVE: A systematic review (following PRISMA guidelines) - including observational studies on the association of trans-fatty acid intake with any cancer risk - was conducted, with no limitations on population types.

DATA SOURCES: The electronic databases PubMed and Embase were searched to identify relevant studies.

DATA EXTRACTION: This systematic review included 46 articles. Quality was assessed via the Newcastle-Ottawa scale. Meta-analyses were conducted if at least 4 articles exploring the same transfat-cancer pairings were found.

DATA ANALYSIS: Nineteen cancer types have been researched in cohort and case-control studies on trans-fatty acids, with breast cancer (n = 17), prostate cancer (n = 11), and colorectal cancer (n = 9) as the most researched. The meta-analyses on total trans-fat showed a significant positive association for prostate cancer (odds ratio [OR] 1.49; 95%CI, 1.13-1.95) and colorectal cancer (OR 1.26; 95%CI, 1.08-1.46) but not for breast cancer (OR 1.12; 95%CI, 0.99-1.26), ovarian cancer (OR 1.10; 95%CI, 0.94-1.28), or non-Hodgkin lymphoma (OR 1.32; 95%CI, 0.99-1.76). Results were dependent on the fatty acid subtype, with even cancer-protective associations for some partially hydrogenated vegetable oils. Enhancing moderators in the positive transfat-cancer relation were gender (direction was cancer-site specific), European ancestry, menopause, older age, and overweight.

CONCLUSION: Despite heterogeneity, higher risk of prostate and colorectal cancer by high consumption of trans-fatty acids was found. Future studies need methodological improvements (eg, using long-term follow-up cancer data and intake biomarkers). Owing to the lack of studies testing trans-fatty acid subtypes in standardized ways, it is not clear which subtypes (eg, ruminant sources) are more carcinogenic.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42018105899.

Originalsprog Engelsk
Tidsskrift Nutrition Reviews
Vol/bind 79
Udgave nummer 7
Sider (fra-til) 758-776
Antal sider 19
ISSN 0029-6643
DOI
Status Udgivet - 4 jun. 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

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

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 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

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-months 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 (OC), N-terminal propeptide of type-I procollagen (PINP), reflecting bone formation, and carboxyterminal collagen I crosslinks (CTX-I), reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up.

RESULTS: From baseline to follow-up, s-PINP increased by 34 % (95 % CI: 17 - 50 %), s-CTX-I by 36 % (95 % CI: 1 - 71 %), and s-OC 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. BMD was unaffected by the intervention ([INCREMENT] BMD: 0.1 %, 95 % CI: -1.1 to 1.2 %).

CONCLUSIONS: A 12-months 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 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 the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs)

Costantino, F., Carmona, L., Boers, M., Backhaus, M., Balint, P. V., Bruyn, G. A., Christensen, R., Conaghan, P. G., Ferreira, R. J. O., Garrido-Castro, J. L., Guillemin, F., Hammer, H. B., van der Heijde, D., Iagnocco, A., Kortekaas, M. C., Landewé, R. B., Mandl, P., Naredo, E., Schmidt, W. A., Terslev, L., Terwee, C. B., Thiele, R. & D'Agostino, M-A., jul. 2021, I: Annals of the Rheumatic Diseases. 80, 7, s. 840-847 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To produce European League Against Rheumatism (EULAR) recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs).

METHODS: Based on the literature reviews and expert opinion (through Delphi surveys), a taskforce of 23 members (12 experts in ultrasound in RMDs, 9 in methodology and biostatistics together with a patient research partner and a health professional in rheumatology) developed a checklist of items to be reported in every RMD study using ultrasound. This checklist was further refined by involving a panel of 79 external experts (musculoskeletal imaging experts, methodologists, journal editors), who evaluated its comprehensibility, feasibility and comprehensiveness. Agreement on each proposed item was assessed with an 11-point Likert scale, grading from 0 (total disagreement) to 10 (full agreement).

RESULTS: Two face-to-face meetings, as well as two Delphi rounds of voting, resulted in a final checklist of 23 items, including a glossary of terminology. Twenty-one of these were considered 'mandatory' items to be reported in every study (such as blinding, development of scoring systems, definition of target pathologies) and 2 'optional' to be reported only if applicable, such as possible confounding factors (ie, ambient conditions) or experience of the sonographers.

CONCLUSION: An EULAR taskforce developed a checklist to ensure transparent and comprehensive reporting of aspects concerning research and procedures that need to be presented in studies using ultrasound in RMDs. This checklist, if widely adopted by authors and editors, will greatly improve the interpretability of study development and results, including the assessment of validity, generalisability and applicability.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 80
Udgave nummer 7
Sider (fra-til) 840-847
Antal sider 8
ISSN 0003-4967
DOI
Status Udgivet - jul. 2021

Evidence-Based Digital Tools for Weight Loss Maintenance: The NoHoW Project

Stubbs, R. J., Duarte, C., Palmeira, A. L., Sniehotta, F. F., Horgan, G., Larsen, S. C., Marques, M. M., Evans, E. H., Ermes, M., Harjumaa, M., Turicchi, J., O'Driscoll, R., Scott, S. E., Pearson, B., Ramsey, L., Mattila, E., Matos, M., Sacher, P., Woodward, E., Mikkelsen, M-L., Sainsbury, K., Santos, I., Encantado, J., Stalker, C., Teixeira, P. J. & Heitmann, B. L., 2021, I: Obesity Facts. 14, 3, s. 320-333 14 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Effective interventions and commercial programmes for weight loss (WL) are widely available, but most people regain weight. Few effective WL maintenance (WLM) solutions exist. The most promising evidence-based behaviour change techniques for WLM are self-monitoring, goal setting, action planning and control, building self-efficacy, and techniques that promote autonomous motivation (e.g., provide choice). Stress management and emotion regulation techniques show potential for prevention of relapse and weight regain. Digital technologies (including networked-wireless tracking technologies, online tools and smartphone apps, multimedia resources, and internet-based support) offer attractive tools for teaching and supporting long-term behaviour change techniques. However, many digital offerings for weight management tend not to include evidence-based content and the evidence base is still limited. The Project: First, the project examined why, when, and how many European citizens make WL and WLM attempts and how successful they are. Second, the project employed the most up-to-date behavioural science research to develop a digital toolkit for WLM based on 2 key conditions, i.e., self-management (self-regulation and motivation) of behaviour and self-management of emotional responses for WLM. Then, the NoHoW trial tested the efficacy of this digital toolkit in adults who achieved clinically significant (≥5%) WL in the previous 12 months (initial BMI ≥25). The primary outcome was change in weight (kg) at 12 months from baseline. Secondary outcomes included biological, psychological, and behavioural moderators and mediators of long-term energy balance (EB) behaviours, and user experience, acceptability, and cost-effectiveness.

IMPACT: The project will directly feed results from studies on European consumer behaviour, design and evaluation of digital toolkits self-management of EB behaviours into development of new products and services for WLM and digital health. The project has developed a framework and digital architecture for interventions in the context of EB tracking and will generate results that will help inform the next generation of personalised interventions for effective self-management of weight and health.

Originalsprog Engelsk
Tidsskrift Obesity Facts
Vol/bind 14
Udgave nummer 3
Sider (fra-til) 320-333
Antal sider 14
ISSN 1662-4025
DOI
Status Udgivet - 2021

Evidence-Based Research Series-Paper 1: What Evidence-Based Research is and why is it important?

Robinson, K. A., Brunnhuber, K., Ciliska, D., Juhl, C. B., Christensen, R. & Lund, H., jan. 2021, I: Journal of Clinical Epidemiology. 129, s. 151-157 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: There is considerable actual and potential waste in research. Evidence-based research ensures worthwhile and valuable research. The aim of this series, which this article introduces, is to describe the evidence-based research approach.

STUDY DESIGN AND SETTING: In this first article of a three-article series, we introduce the evidence-based research approach. Evidence-based research is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner.

RESULTS: We describe evidence-based research and provide an overview of the approach of systematically and transparently using previous research before starting a new study to justify and design the new study (article #2 in series) and-on study completion-place its results in the context with what is already known (article #3 in series).

CONCLUSION: This series introduces evidence-based research as an approach to minimize unnecessary and irrelevant clinical health research that is unscientific, wasteful, and unethical.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 129
Sider (fra-til) 151-157
Antal sider 7
ISSN 0895-4356
DOI
Status Udgivet - jan. 2021

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

Evidence-Based Research Series-Paper 2: Using an Evidence-Based Research approach before a new study is conducted to ensure value

Evidence-Based Research Network, jan. 2021, I: Journal of Clinical Epidemiology. 129, s. 158-166 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background and Objectives: There is considerable actual and potential waste in research. The aim of this article is to describe how using an evidence-based research approach before conducting a study helps to ensure that the new study truly adds value. Study Design and Setting: Evidence-based research is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner. In this second article of the evidence-based research series, we describe how to apply an evidence-based research approach before starting a new study. Results: Before a new study is performed, researchers need to provide a solid justification for it using the available scientific knowledge as well as the perspectives of end users. The key method for both is to conduct a systematic review of earlier relevant studies. Conclusion: Describing the ideal process illuminates the challenges and opportunities offered through the suggested evidence-based research approach. A systematic and transparent approach is needed to provide justification for and to optimally design a relevant and necessary new study.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 129
Sider (fra-til) 158-166
Antal sider 9
ISSN 0895-4356
DOI
Status Udgivet - jan. 2021

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

Evidence-Based Research Series-Paper 3: Using an Evidence-Based Research approach to place your results into context after the study is performed to ensure usefulness of the conclusion

Evidence-Based Research Network, jan. 2021, I: Journal of Clinical Epidemiology. 129, s. 167-171 5 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background and Objective: There is considerable actual and potential waste in research. Using evidence-based research (EBR) can ensure the value of a new study. The aim of this article, the third in a series, is to describe an EBR approach to putting research results into context. Study Design and Setting: EBR is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner. In this third and final article of a series, we describe how to use the context of existing evidence to reach and present a trustworthy and useful conclusion when reporting results from a new clinical study. Results: We describe a method, the EBR approach, that by using a systematic and transparent consideration of earlier similar studies when interpreting and presenting results from a new original study will ensure usefulness of the conclusion. Conclusion: Using an EBR approach will improve the usefulness of a clinical study by providing the context to draw more valid conclusions and explicit information about new research needs.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 129
Sider (fra-til) 167-171
Antal sider 5
ISSN 0895-4356
DOI
Status Udgivet - jan. 2021

Bibliografisk note

Funding Information:
This work has been prepared as part of the Evidence-Based Research Network (ebrnetwork.org). The EBRNetwork is an international network that promotes the use of systematic reviews when prioritizing, designing, and interpreting research. Evidence-based research is the use of prior research in a systematic and transparent way to inform the new study so that it is answering questions that matter in a valid, efficient, and accessible manner. The authors thank the Centre for Evidence-Based Practice, Western Norway University of Applied Sciences for their very generous support of the EBRNetwork. The Parker Institute, Bispebjerg and Frederiksberg Hospital (Professor Christensen and Professor Henriksen) are supported by a core grant from the Oak Foundation USA (OCAY-18-774-OFIL). Financial support, This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Funding Information:
The Parker Institute, Bispebjerg and Frederiksberg Hospital (Professor Christensen and Professor Henriksen) are supported by a core grant from the Oak Foundation USA ( OCAY-18-774-OFIL ).

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