Published in 2020

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 59
Udgave nummer 10
Sider (fra-til) e78
ISSN 1462-0324
DOI
Status Udgivet - 1 okt. 2020

Comorbidity Clusters and Healthcare Use in Individuals With COPD

Hansen, N. S., Ängquist, L., Lange, P. & Jacobsen, R., aug. 2020, I: Respiratory Care. 65, 8, s. 1120-1127 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Individuals who share the same comorbidity profile are usually similar with regard to their disease severity, use of health care, and clinical outcomes. The identification of comorbidity clusters therefore bears prognostic information. The objective of this study was to identify and characterize comorbidity clusters in individuals with COPD in Denmark.

METHODS: Data from the Danish national registers were used. The study population included all individuals ≥16 y old who lived in the Danish Capital Region on January 1, 2012, and were diagnosed with COPD (N = 70,274). Comorbid chronic conditions were identified using diagnostic algorithms. A 2-step cluster analysis was performed.

RESULTS: 81% of subjects with COPD had chronic comorbidities; the most common was hypertension (47.6%), and the least common was anxiety (0.1%). Three comorbidity clusters were identified. Cluster 1 contained 16% of the studied individuals with COPD, with all having heart disease in addition to the remaining comorbidities. Cluster 2 contained 30% of the studied individuals with COPD, of whom approximately 1 in 3 suffered from allergies, while the rest had no comorbidities. Cluster 3 contained 54% of the studied individuals with COPD, where all comorbidities but heart disease were represented. Cluster 1 contained the highest proportion of individuals over the age of 65 y, as well as the individuals with the lowest education. After adjusting for sociodemographic characteristics, individuals in Cluster 1 had the highest rates of hospitalizations and bed days.

CONCLUSIONS: The presence of heart disease in individuals with COPD is a strong prognostic factor for socioeconomic and health vulnerability.

Originalsprog Engelsk
Tidsskrift Respiratory Care
Vol/bind 65
Udgave nummer 8
Sider (fra-til) 1120-1127
Antal sider 8
ISSN 0020-1324
DOI
Status Udgivet - aug. 2020

Bibliografisk note

Copyright © 2020 by Daedalus Enterprises.

Consistent sleep onset and maintenance of body weight after weight loss: An analysis of data from the NoHoW trial

Larsen, S. C., Horgan, G., Mikkelsen, M-L. K., Palmeira, A. L., Scott, S., Duarte, C., Santos, I., Encantado, J., O'Driscoll, R., Turicchi, J., Michalowska, J., Stubbs, R. J. & Heitmann, B. L., jul. 2020, I: PLOS Medicine. 17, 7, s. e1003168

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Several studies have suggested that reduced sleep duration and quality are associated with an increased risk of obesity and related metabolic disorders, but the role of sleep in long-term weight loss maintenance (WLM) has not been thoroughly explored using prospective data.

METHODS AND FINDINGS: The present study is an ancillary study based on data collected on participants from the Navigating to a Healthy Weight (NoHoW) trial, for which the aim was to test the efficacy of an evidence-based digital toolkit, targeting self-regulation, motivation, and emotion regulation, on WLM among 1,627 British, Danish, and Portuguese adults. Before enrolment, participants had achieved a weight loss of ≥5% and had a BMI of ≥25 kg/m2 prior to losing weight. Participants were enrolled between March 2017 and March 2018 and followed during the subsequent 12-month period for change in weight (primary trial outcome), body composition, metabolic markers, diet, physical activity, sleep, and psychological mediators/moderators of WLM (secondary trial outcomes). For the present study, a total of 967 NoHoW participants were included, of which 69.6% were women, the mean age was 45.8 years (SD 11.5), the mean baseline BMI was 29.5 kg/m2 (SD 5.1), and the mean weight loss prior to baseline assessments was 11.4 kg (SD 6.4). Objectively measured sleep was collected using the Fitbit Charge 2 (FC2), from which sleep duration, sleep duration variability, sleep onset, and sleep onset variability were assessed across 14 days close to baseline examinations. The primary outcomes were 12-month changes in body weight (BW) and body fat percentage (BF%). The secondary outcomes were 12-month changes in obesity-related metabolic markers (blood pressure, low- and high-density lipoproteins [LDL and HDL], triglycerides [TGs], and glycated haemoglobin [HbA1c]). Analysis of covariance and multivariate linear regressions were conducted with sleep-related variables as explanatory and subsequent changes in BW, BF%, and metabolic markers as response variables. We found no evidence that sleep duration, sleep duration variability, or sleep onset were associated with 12-month weight regain or change in BF%. A higher between-day variability in sleep onset, assessed using the standard deviation across all nights recorded, was associated with weight regain (0.55 kg per hour [95% CI 0.10 to 0.99]; P = 0.016) and an increase in BF% (0.41% per hour [95% CI 0.04 to 0.78]; P = 0.031). Analyses of the secondary outcomes showed that a higher between-day variability in sleep duration was associated with an increase in HbA1c (0.02% per hour [95% CI 0.00 to 0.05]; P = 0.045). Participants with a sleep onset between 19:00 and 22:00 had the greatest reduction in diastolic blood pressure (DBP) (P = 0.02) but also the most pronounced increase in TGs (P = 0.03). The main limitation of this study is the observational design. Hence, the observed associations do not necessarily reflect causal effects.

CONCLUSION: Our results suggest that maintaining a consistent sleep onset is associated with improved WLM and body composition. Sleep onset and variability in sleep duration may be associated with subsequent change in different obesity-related metabolic markers, but due to multiple-testing, the secondary exploratory outcomes should be interpreted cautiously.

TRIAL REGISTRATION: The trial was registered with the ISRCTN registry (ISRCTN88405328).

Originalsprog Engelsk
Tidsskrift PLOS Medicine
Vol/bind 17
Udgave nummer 7
Sider (fra-til) e1003168
ISSN 1549-1277
DOI
Status Udgivet - jul. 2020

Consumption of nutrients and insulin resistance suppress markers of bone turnover in subjects with abdominal obesity

Fuglsang-Nielsen, R., Rakvaag, E., Vestergaard, P., Hartmann, B., Holst, J. J., Hermansen, K., Gregersen, S. & Starup-Linde, J., apr. 2020, I: Bone. 133, s. 115230

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Abdominal obesity and type 2 diabetes are associated with insulin resistance and low bone turnover along with an increased fracture risk. The mode of action is poorly understood. The bone resorption marker, C-terminal telopeptide type 1 collagen (CTX), and to a lesser extent, the bone formation marker, Procollagen type 1 N-terminal propeptide (P1NP) appear to be inhibited by food consumption. The link between food consumption, insulin resistance and bone turnover remains to be clarified. Primarily we aimed to compare the postprandial CTX, P1NP and PTH responses by two frequently applied methods in assessing metabolic health; oral glucose tolerance test (OGTT) and mixed meal tolerance test. Secondly, we explored the effect of insulin resistance on bone marker responses.

METHODS: We enrolled 64 subjects with abdominal obesity. Following 10 h of fasting, subjects initially underwent a standard OGTT (300 kcal) and approximately one week later a mixed meal tolerance test (1130 kcal). Circulating CTX, P1NP and PTH were assessed on both days at time = 0, after 30 min and after 90 min for comparison of the two interventions. We analyzed glucose and insulin levels for the assessment of insulin resistance. Additionally, we measured plasma calcium levels along with the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 2 (GLP-2) in an attempt to identify possible mediators of the postprandial bone response.

RESULTS: CTX, P1NP and PTH were suppressed by OGTT and the mixed meal; the latter induced a more pronounced suppression after 90 min. Calcium levels were similar between OGTT and meal. GIP and GLP-2 levels increased after both interventions, although only the meal induced a sustained increase after 90 min. Fasting P1NP was inversely associated with insulin resistance. The meal-induced suppression of P1NP (but not CTX or PTH) was inversely associated with level of insulin resistance.

CONCLUSION: The acute postprandial suppression of bone turnover markers is extended after ingestion of a mixed meal compared to an OGTT. The response appears to be independent of gender and prompted by a reduction in PTH. The study additionally indicates a possible link between the development of insulin resistance and low bone turnover - which may be of key essence in the development of the fragile bone structure and increased fracture risk demonstrated in subjects with abdominal obesity and T2D.

Originalsprog Engelsk
Tidsskrift Bone
Vol/bind 133
Sider (fra-til) 115230
ISSN 8756-3282
DOI
Status Udgivet - apr. 2020

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

Controversy and Debate on Meta-epidemiology. Paper 1: Treatment effect sizes vary in randomized trials depending on the type of outcome measure

Berthelsen, D. B., Ginnerup-Nielsen, E., Juhl, C., Lund, H., Henriksen, M., Hróbjartsson, A., Nielsen, S. M., Voshaar, M. & Christensen, R., jul. 2020, I: Journal of Clinical Epidemiology. 123, s. 27-38 12 s.

Publikation: Bidrag til tidsskriftReviewpeer review

OBJECTIVE: To compare estimated treatment effects of physical therapy (PT) between patient-reported outcome measures (PROMs) and outcomes measured in other ways.

STUDY DESIGN AND SETTING: We selected randomized trials of PT with both a PROM and a non-PROM included in Cochrane systematic reviews (CSRs). Two reviewers independently extracted data and risk-of-bias assessments. Our primary outcome was the ratio of odds ratios (RORs), used to quantify how effect varies between PROMs and non-PROMs; an ROR > 1 indicates larger effect when assessed by using PROMs. We used REML-methods to estimate associations of trial characteristics with effects and between-trial heterogeneity.

RESULTS: From 90 relevant CSRs, 205 PT trials were included. The summary ROR across all the comparisons was not statistically significant (ROR, 0.88 [95% CI: 0.70-1.12]; P = 0.30); however, the heterogeneity was substantial (I2 = 88.1%). When stratifying non-PROMs further into clearly objective non-PROMs (e.g., biomarkers) and other non-PROMs (e.g., aerobic capacity), the PROMs appeared more favorable than did clearly objective non-PROMs (ROR, 1.92 [95% CI: 0.99-3.72]; P = 0.05).

CONCLUSION: Estimated treatment effects based on PROMs are generally comparable with treatment effects measured in other ways. However, in our study, PROMs indicate a more favorable treatment effect compared with treatment effects based on clearly objective outcomes.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 123
Sider (fra-til) 27-38
Antal sider 12
ISSN 0895-4356
DOI
Status Udgivet - jul. 2020

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

Controversy and Debate on Meta-epidemiology. Paper 3: Causal inference from meta-epidemiology: a reasonable goal, or wishful thinking?

Christensen, R. & Berthelsen, D. B., jul. 2020, I: Journal of Clinical Epidemiology. 123, s. 131-132 2 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 123
Sider (fra-til) 131-132
Antal sider 2
ISSN 0895-4356
DOI
Status Udgivet - jul. 2020

Correction: A novel scaling methodology to reduce the biases associated with missing data from commercial activity monitors

O'Driscoll, R., Turicchi, J., Duarte, C., Michalowska, J., Larsen, S. C., Palmeira, A. L., Heitmann, B. L., Horgan, G. W. & Stubbs, R. J., 3 sep. 2020

Publikation: AndetAndet bidragForskning

[This corrects the article DOI: 10.1371/journal.pone.0235144.].

Originalsprog Engelsk
Publikationsdato 3 sep. 2020
Udgave 9
Vol/bind 15
DOI
Status Udgivet - 3 sep. 2020
Navn PLoS One
ISSN 1932-6203

Corrigendum to 'EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort Under the Auspices of the EAU-ESMO Guidelines Committees' [European Urology 77 (2020) 223-250]

Witjes, J. A., Babjuk, M., Bellmunt, J., Bruins, H. M., De Reijke, T. M., De Santis, M., Gillessen, S., James, N., Maclennan, S., Palou, J., Powles, T., Ribal, M. J., Shariat, S. F., Van Der Kwast, T., Xylinas, E., Agarwal, N., Arends, T., Bamias, A., Birtle, A., Black, P. C., Bochner, B. H., Bolla, M., Boormans, J. L., Bossi, A., Briganti, A., Brummelhuis, I., Burger, M., Castellano, D., Cathomas, R., Chiti, A., Choudhury, A., Compérat, E., Crabb, S., Culine, S., De Bari, B., De Blok, W., De Visschere, P. J. L., Decaestecker, K., Dimitropoulos, K., Dominguez-Escrig, J. L., Fanti, S., Fonteyne, V., Frydenberg, M., Futterer, J. J., Gakis, G., Geavlete, B., Gontero, P., Grubmüller, B., Hafeez, S., Hansel, D. E., Hartmann, A., Hayne, D., Henry, A. M., Hernandez, V., Herr, H., Herrmann, K., Hoskin, P., Huguet, J., Jereczek-Fossa, B. A., Jones, R., Kamat, A. M., Khoo, V., Kiltie, A. E., Krege, S., Ladoire, S., Lara, P. C., Leliveld, A., Linares-Espinós, E., Løgager, V., Lorch, A., Loriot, Y., Meijer, R., Mir, M. C., Moschini, M., Mostafid, H., Müller, A-C., Müller, C. R., N'Dow, J., Necchi, A., Neuzillet, Y., Oddens, J. R., Oldenburg, J., Osanto, S., Oyen, W. J. G., Pacheco-Figueiredo, L., Pappot, H., Patel, M. I., Pieters, B. R., Plass, K., Remzi, M., Retz, M., Richenberg, J., Rink, M., Roghmann, F., Rosenberg, J. E., Rouprêt, M., Rouvière, O., Salembier, C., Salminen, A., Sargos, P., Sengupta, S., Sherif, A., Smeenk, R. J., Smits, A., Stenzl, A., Thalmann, G. N., Tombal, B., Turkbey, B., Lauridsen, S. V., Valdagni, R., Van Der Heijden, A. G., Van Poppel, H., Vartolomei, M. D., Veskimäe, E., Vilaseca, A., Rivera, F. A. V., Wiegel, T., Wiklund, P., Willemse, P-P. M., Williams, A., Zigeuner, R. & Horwich, A., jul. 2020, I: European Urology. 78, 1, s. e48-e50

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Tidsskrift European Urology
Vol/bind 78
Udgave nummer 1
Sider (fra-til) e48-e50
ISSN 0302-2838
DOI
Status Udgivet - jul. 2020
Originalsprog Engelsk
Tidsskrift Muscles, Ligaments and Tendons Journal
ISSN 2240-4554
Status Udgivet - 2020

Data Imputation and Body Weight Variability Calculation Using Linear and Nonlinear Methods in Data Collected From Digital Smart Scales: Simulation and Validation Study

Turicchi, J., O'Driscoll, R., Finlayson, G., Duarte, C., Palmeira, A. L., Larsen, S. C., Heitmann, B. L. & Stubbs, R. J., 11 sep. 2020, I: JMIR mHealth and uHealth. 8, 9, s. e17977

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Body weight variability (BWV) is common in the general population and may act as a risk factor for obesity or diseases. The correct identification of these patterns may have prognostic or predictive value in clinical and research settings. With advancements in technology allowing for the frequent collection of body weight data from electronic smart scales, new opportunities to analyze and identify patterns in body weight data are available.

OBJECTIVE: This study aims to compare multiple methods of data imputation and BWV calculation using linear and nonlinear approaches.

METHODS: In total, 50 participants from an ongoing weight loss maintenance study (the NoHoW study) were selected to develop the procedure. We addressed the following aspects of data analysis: cleaning, imputation, detrending, and calculation of total and local BWV. To test imputation, missing data were simulated at random and using real patterns of missingness. A total of 10 imputation strategies were tested. Next, BWV was calculated using linear and nonlinear approaches, and the effects of missing data and data imputation on these estimates were investigated.

RESULTS: Body weight imputation using structural modeling with Kalman smoothing or an exponentially weighted moving average provided the best agreement with observed values (root mean square error range 0.62%-0.64%). Imputation performance decreased with missingness and was similar between random and nonrandom simulations. Errors in BWV estimations from missing simulated data sets were low (2%-7% with 80% missing data or a mean of 67, SD 40.1 available body weights) compared with that of imputation strategies where errors were significantly greater, varying by imputation method.

CONCLUSIONS: The decision to impute body weight data depends on the purpose of the analysis. Directions for the best performing imputation methods are provided. For the purpose of estimating BWV, data imputation should not be conducted. Linear and nonlinear methods of estimating BWV provide reasonably accurate estimates under high proportions (80%) of missing data.

Originalsprog Engelsk
Tidsskrift JMIR mHealth and uHealth
Vol/bind 8
Udgave nummer 9
Sider (fra-til) e17977
ISSN 2291-5222
DOI
Status Udgivet - 11 sep. 2020

Bibliografisk note

©Jake Turicchi, Ruairi O'Driscoll, Graham Finlayson, Cristiana Duarte, A L Palmeira, Sofus C Larsen, Berit L Heitmann, R James Stubbs. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 11.09.2020.

Definition, pathology and pathogenesis of osteoarthritis

Bliddal, H., 12 okt. 2020, I: Ugeskrift for Laeger. 182, 42

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Osteoarthritis (OA) is defined by clinical symptoms and radiological signs. Cartilage is crucial in the development, but all tissue components in and around the joint are affected by the disease. OA aetiopathogenesis is multifactorial and may be primary (idiopathic) or secondary, with an influence of heritable factors. Contributing to OA development are age, joint trauma, other joint diseases, and overweight/obesity. The latter is of special interest being modifiable, and weight loss has proven very effective on symptoms of OA. Over the course of OA, inflammatory flares may be experienced, some associated with crystal formation in the joint, which opens for possible treatments, as argued in this review.

Bidragets oversatte titel Definition, pathology and pathogenesis of osteoarthritis
Originalsprog Dansk
Tidsskrift Ugeskrift for Laeger
Vol/bind 182
Udgave nummer 42
ISSN 0041-5782
Status Udgivet - 12 okt. 2020

Dose-Response Effects of Exercise on Glucose-Lowering Medications for Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial

MacDonald, C. S., Johansen, M. Y., Nielsen, S. M., Christensen, R., Hansen, K. B., Langberg, H., Vaag, A. A., Karstoft, K., Lieberman, D. E., Pedersen, B. K. & Ried-Larsen, M., mar. 2020, I: Mayo Clinic Proceedings. 95, 3, s. 488-503 16 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Objective: To investigate whether a dose-response relationship exists between volume of exercise and discontinuation of glucose-lowering medication treatment in patients with type 2 diabetes. Patients and Methods: Secondary analyses of a randomized controlled exercise-based lifestyle intervention trial (April 29, 2015 to August 17, 2016). Patients with non–insulin-dependent type 2 diabetes were randomly assigned to an intensive lifestyle intervention (U-TURN) or standard-care group. Both groups received lifestyle advice and objective target-driven medical regulation. Additionally, the U-TURN group received supervised exercise and individualized dietary counseling. Of the 98 randomly assigned participants, 92 were included in the analysis (U-TURN, n=61, standard care, n=31). Participants in the U-TURN group were stratified into tertiles based on accumulated volumes of exercise completed during the 1-year intervention. Results: Median exercise levels of 178 (interquartile range [IQR], 121-213; lower tertile), 296 (IQR, 261-310; intermediate tertile), and 380 minutes per week (IQR, 355-446; upper tertile) were associated with higher odds of discontinuing treatment with glucose-lowering medication, with corresponding odds ratios of 12.1 (95% CI, 1.2-119; number needed to treat: 4), 30.2 (95% CI, 2.9-318.5; 3), and 34.4 (95% CI, 4.1-290.1; 2), respectively, when comparing with standard care. Cardiovascular risk factors such as glycated hemoglobin A1c levels, fitness, 2-hour glucose levels, and triglyceride levels were improved significantly in the intermediate and upper tertiles, but not the lower tertile, compared with the standard-care group. Conclusion: Exercise volume is associated with discontinuation of glucose-lowering medication treatment in a dose-dependent manner, as are important cardiovascular risk factors in well-treated participants with type 2 diabetes and disease duration less than 10 years. Further studies are needed to support these findings. Study Registration: ClinicalTrials.gov registration (NCT02417012).

Originalsprog Engelsk
Tidsskrift Mayo Clinic Proceedings
Vol/bind 95
Udgave nummer 3
Sider (fra-til) 488-503
Antal sider 16
ISSN 0025-6196
DOI
Status Udgivet - mar. 2020

Dual-Energy CT for Suspected Radiographically Negative Wrist Fractures: A Prospective Diagnostic Test Accuracy Study

Müller, F. C., Gosvig, K. K., Børgesen, H., Gade, J. S., Brejnebøl, M., Rodell, A., Nèmery, M. & Boesen, M., sep. 2020, I: Radiology. 296, 3, s. 596-602 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background Patients with wrist trauma and negative findings on radiographs often undergo additional MRI examinations to assess for radiographically occult fractures. Dual-energy CT may be more readily available than MRI in some settings. Purpose To evaluate the diagnostic test accuracy of dual-energy CT in helping detect bone marrow edema and fracture in participants with wrist trauma and clinical suspicion of a wrist fracture but with negative findings on radiographs. Materials and Methods Adults were prospectively enrolled between January 2018 and November 2018. Wrists were examined with dual-energy CT and MRI, and images were read by four readers who were blinded to clinical information. The presence of bone marrow edema and fracture was rated per bone. The reference standard for bone marrow edema was the combined reading of MRI scans. The reference standard for fracture was a combined reading of MRI and dual-energy CT scans. A fifth radiologist arbitrated results in case of discrepancies. Diagnostic test accuracy was calculated per reader and for readers combined using exact binomial tests. Results Forty-six participants (mean age, 47 years ± 19 [standard deviation]; 24 men [52%]) were enrolled, and 750 bones (50 wrists) were assessed. Dual-energy CT had an average sensitivity of 94% (95% confidence interval [CI]: 80%, 99%; 31 of 33 wrists) and specificity of 65% (95% CI: 38%, 86%; 11 of 17 wrists) in the detection of wrists with bone marrow edema and a sensitivity of 69% (95% CI: 55%, 81%; 36 of 52 bones) and a specificity of 98% (95% CI: 97%, 99%; 682 of 696 bones) in the detection of edema in individual bones. MRI had a sensitivity of 80% (95% CI: 63%, 91%; 28 of 35 wrists) and a specificity of 93% (95% CI: 68%, 100%; 14 of 15 wrists) in helping detect wrists with fractures. Dual-energy CT had a sensitivity of 91% (95% CI: 77%, 98%; 32 of 35 wrists) and a specificity of 87% (95% CI: 60%, 98%; 53 of 60 wrists) in helping detect wrists with fractures. McNemar tests showed no significant differences between MRI and dual-energy CT (P = .07 to >.99) for all readers. Conclusion Dual-energy CT had a high sensitivity and a moderate specificity in the detection of bone marrow edema of the wrist. Dual-energy CT had high sensitivity and specificity in depicting fractures of the wrist in patients with suspected wrist fractures and negative findings on radiographs. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Fukuda in this issue.

Originalsprog Engelsk
Tidsskrift Radiology
Vol/bind 296
Udgave nummer 3
Sider (fra-til) 596-602
Antal sider 7
ISSN 0033-8419
DOI
Status Udgivet - sep. 2020

Early development of tendinopathy in humans: Sequence of pathological changes in structure and tissue turnover signaling

Tran, P. H. T., Malmgaard-Clausen, N. M., Puggaard, R. S., Svensson, R. B., Nybing, J. D., Hansen, P., Schjerling, P., Zinglersen, A. H., Couppé, C., Boesen, M., Magnusson, S. P. & Kjaer, M., jan. 2020, I: FASEB Journal. 34, 1, s. 776-788 13 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Overloading of tendon tissue with resulting chronic pain (tendinopathy) is a common disorder in occupational-, leisure- and sports-activity, but its pathogenesis remains poorly understood. To investigate the very early phase of tendinopathy, Achilles and patellar tendons were investigated in 200 physically active patients and 50 healthy control persons. Patients were divided into three groups: symptoms for 0-1 months (T1), 1-2 months (T2) or 2-3 months (T3). Tendinopathic Achilles tendon cross-sectional area determined by ultrasonography (US) was ~25% larger than in healthy control persons. Both Achilles and patellar anterior-posterior diameter were elevated in tendinopathy, and only later in Achilles was the width increased. Increased tendon size was accompanied by an increase in hypervascularization (US Doppler flow) without any change in mRNA for angiogenic factors. From patellar biopsies taken bilaterally, mRNA for most growth factors and tendon components remained unchanged (except for TGF-beta1 and substance-P) in early tendinopathy. Tendon stiffness remained unaltered over the first three months of tendinopathy and was similar to the asymptomatic contra-lateral tendon. In conclusion, this suggests that tendinopathy pathogenesis represents a disturbed tissue homeostasis with fluid accumulation. The disturbance is likely induced by repeated mechanical overloading rather than a partial rupture of the tendon.

Originalsprog Engelsk
Tidsskrift FASEB Journal
Vol/bind 34
Udgave nummer 1
Sider (fra-til) 776-788
Antal sider 13
ISSN 0892-6638
DOI
Status Udgivet - jan. 2020

Bibliografisk note

© 2019 Federation of American Societies for Experimental Biology.

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

OBJECTIVE: 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 an MRI, 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 was 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 (SF-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 one year. The positive effects found at 6 months in both groups, remained at 1-year follow-up.

CONCLUSIONS: 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
ISSN 0362-2436
DOI
Status E-pub ahead of print - 10 nov. 2020

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort†: Under the Auspices of the EAU-ESMO Guidelines Committees

Witjes, J. A., Babjuk, M., Bellmunt, J., Bruins, H. M., De Reijke, T. M., De Santis, M., Gillessen, S., James, N., Maclennan, S., Palou, J., Powles, T., Ribal, M. J., Shariat, S. F., Der Kwast, T. V., Xylinas, E., Agarwal, N., Arends, T., Bamias, A., Birtle, A., Black, P. C., Bochner, B. H., Bolla, M., Boormans, J. L., Bossi, A., Briganti, A., Brummelhuis, I., Burger, M., Castellano, D., Cathomas, R., Chiti, A., Choudhury, A., Compérat, E., Crabb, S., Culine, S., De Bari, B., De Blok, W., J L De Visschere, P., Decaestecker, K., Dimitropoulos, K., Dominguez-Escrig, J. L., Fanti, S., Fonteyne, V., Frydenberg, M., Futterer, J. J., Gakis, G., Geavlete, B., Gontero, P., Grubmüller, B., Hafeez, S., Hansel, D. E., Hartmann, A., Hayne, D., Henry, A. M., Hernandez, V., Herr, H., Herrmann, K., Hoskin, P., Huguet, J., Jereczek-Fossa, B. A., Jones, R., Kamat, A. M., Khoo, V., Kiltie, A. E., Krege, S., Ladoire, S., Lara, P. C., Leliveld, A., Linares-Espinós, E., Løgager, V., Lorch, A., Loriot, Y., Meijer, R., Mir, M. C., Moschini, M., Mostafid, H., Müller, A-C., Müller, C. R., N'Dow, J., Necchi, A., Neuzillet, Y., Oddens, J. R., Oldenburg, J., Osanto, S., J G Oyen, W., Pacheco-Figueiredo, L., Pappot, H., Patel, M. I., Pieters, B. R., Plass, K., Remzi, M., Retz, M., Richenberg, J., Rink, M., Roghmann, F., Rosenberg, J. E., Rouprêt, M., Rouvière, O., Salembier, C., Salminen, A., Sargos, P., Sengupta, S., Sherif, A., Smeenk, R. J., Smits, A., Stenzl, A., Thalmann, G. N., Tombal, B., Turkbey, B., Lauridsen, S. V., Valdagni, R., Van Der Heijden, A. G., Van Poppel, H., Vartolomei, M. D., Veskimäe, E., Vilaseca, A., Rivera, F. A. V., Wiegel, T., Wiklund, P., Williams, A., Zigeuner, R. & Horwich, A., feb. 2020, I: European Urology. 77, 2, s. 223-250 28 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.

OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.

DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.

SETTING: Online Delphi survey and consensus conference.

PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).

RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.

CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.

PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Originalsprog Engelsk
Tidsskrift European Urology
Vol/bind 77
Udgave nummer 2
Sider (fra-til) 223-250
Antal sider 28
ISSN 0302-2838
DOI
Status Udgivet - feb. 2020

Bibliografisk note

Copyright © 2019 European Society of Medical Oncology and European Association of Urology. Published by Elsevier B.V. All rights reserved.

Effect of aerobic exercise training on asthma in adults - A systematic review and meta-analysis

Hansen, E. S. H., Pitzner-Fabricius, A., Toennesen, L. L., Rasmusen, H. K., Hostrup, M., Hellsten, Y., Backer, V. & Henriksen, M., 2020, I: European Respiratory Journal. Supplement. 56, 1, s. 2000146

Publikation: Bidrag til tidsskriftReviewpeer review

Objective: To evaluate the effect of aerobic exercise training on asthma control, lung function and airway inflammation in adults with asthma. Design: Systematic review and meta-analysis. Methods: Randomised controlled trials investigating the effect of ≥8 weeks of aerobic exercise training on outcomes for asthma control, lung function and airway inflammation in adults with asthma were eligible for study. MEDLINE, Embase, CINAHL, PEDro and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to April 3, 2019. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Results: We included 11 studies with a total of 543 adults with asthma. Participants' mean (range) age was 36.5 (22-54) years; 74.8% of participants were female and the mean (range) body mass index was 27.6 (23.2-38.1) kg·m-2. Interventions had a median (range) duration of 12 (8-12)weeks and included walking, jogging, spinning, treadmill running and other unspecified exercise training programmes. Exercise training improved asthma control with a standard mean difference (SMD) of -0.48 (-0.81 - -0.16). Lung function slightly increased with an SMD of -0.36 (-0.72-0.00) in favour of exercise training. Exercise training had no apparent effect on markers of airway inflammation (SMD -0.03 (-0.41-0.36)). Conclusions: In adults with asthma, aerobic exercise training has potential to improve asthma control and lung function, but not airway inflammation.

Originalsprog Engelsk
Bogserie European Respiratory Journal. Supplement
Vol/bind 56
Udgave nummer 1
Sider (fra-til) 2000146
ISSN 0904-1850
DOI
Status Udgivet - 2020

Bibliografisk note

Funding Information:
Support statement: The Centre for Physical Activity Research (CFAS) is supported by TrygFonden (grants ID 101390 and ID 20045).

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., 23 dec. 2020, (E-pub ahead of print) I: JAMA Psychiatry.

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
ISSN 2168-622X
DOI
Status E-pub ahead of print - 23 dec. 2020

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., 18 sep. 2020, I: European Journal of Clinical Nutrition.

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
ISSN 0954-3007
DOI
Status Udgivet - 18 sep. 2020

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