Published in 2021

BACKGROUND: Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the 'active' ingredients are unknown. Designing and executing an adequate and 'blindable placebo' version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used 'state-of-art' exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA.

METHODS: In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients' global assessment of disease impact, physical performance tests, and presence of knee joint swelling.

DISCUSSION: This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA.

TRIAL REGISTRATION: www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019.

Originalsprog Engelsk
Tidsskrift Trials
Vol/bind 22
Udgave nummer 1
Sider (fra-til) 18
ISSN 1745-6215
DOI
Status Udgivet - 6 jan. 2021

Inflammatory hallmarks of lesser prominence in psoriatic arthritis patients starting biologics: a Nordic population-based cohort study

Lund Hansen, R., Schoedt Jørgensen, T., Dreyer, L., Hetland, M. L., Glintborg, B., Askling, J., Di Giuseppe, D., Jacobsson, L. T. H., Wallman, J. K., Nordstrom, D., Aaltonen, K., Kristianslund, E. K., Kvien, T. K., Provan, S. A., Gudbjornsson, B., Love, T. J. & Kristensen, L. E., 5 jan. 2021, I : Rheumatology (Oxford, England). 60, 1, s. 140-146 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries.

METHODS: PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment.

RESULTS: A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association.

CONCLUSION: Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 60
Udgave nummer 1
Sider (fra-til) 140-146
Antal sider 7
ISSN 1462-0324
DOI
Status Udgivet - 5 jan. 2021

Bibliografisk note

COPECARE

INTRODUCTION: The effects of lifestyle interventions in persons with type 2 diabetes (T2D) on health-related quality of life (HRQoL) and subjective well-being are ambiguous, and no studies have explored the effect of exercise interventions that meet or exceed current recommended exercise levels. We investigated whether a 1-year intensive lifestyle intervention is superior in improving HRQoL compared with standard care in T2D persons.

RESEARCH DESIGN AND METHODS: We performed secondary analyses of a previously conducted randomized controlled trial (April 2015 to August 2016). Persons with non-insulin-dependent T2D (duration ≤10 years) were randomized to 1-year supervised exercise and individualized dietary counseling (ie, 'U-TURN'), or standard care. The primary HRQoL outcome was change in the 36-item Short Form Health Survey (SF-36) physical component score (PCS) from baseline to 12 months of follow-up, and a key secondary outcome was changes in the SF-36 mental component score (MCS).

RESULTS: We included 98 participants (U-TURN group=64, standard care group=34) with a mean age of 54.6 years (SD 8.9). Between-group analyses at 12-month follow-up showed SF-36 PCS change of 0.8 (95% CI -0.7 to 2.3) in the U-TURN group and deterioration of 2.4 (95% CI -4.6 to -0.1) in the standard care group (difference of 3.2, 95% CI 0.5 to 5.9, p=0.02) while no changes were detected in SF-36 MCS. At 12 months, 19 participants (30%) in the U-TURN group and 6 participants (18%) in the standard care group achieved clinically significant improvement in SF-36 PCS score (adjusted risk ratio 2.6, 95% CI 1.0 to 4.5 corresponding to number needed to treat of 4, 95% CI 1.6 to infinite).

CONCLUSION: In persons with T2D diagnosed for less than 10 years, intensive lifestyle intervention improved the physical component of HRQoL, but not the mental component of HRQoL after 1 year, compared with standard care.

TRIAL REGISTRATION NUMBER: NCT02417012.

Originalsprog Engelsk
Tidsskrift BMJ open diabetes research & care
Vol/bind 9
Udgave nummer 1
ISSN 2052-4897
DOI
Status Udgivet - jan. 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.

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

Møller-Bisgaard, S., Georgiadis, S., Hørslev-Petersen, K., Ejbjerg, B., Hetland, M. L., Ørnbjerg, L. M., Glinatsi, D., Møller, J., Boesen, M., Stengaard-Pedersen, K., Madsen, O. R., Jensen, B., Villadsen, J. A., Hauge, E-M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M., Lindegaard, H., Bliddal, H., Krogh, N. S., Ellingsen, T., Nielsen, A. H., Balding, L., Jurik, A. G., Thomsen, H. S. & Østergaard, M., 2021, I : Rheumatology (Oxford, England). 60, 1, s. 380-391

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

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

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

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

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

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

Bibliografisk note

COPECARE

Published in 2020

'Standing together - at a distance': Documenting changes in mental-health indicators in Denmark during the COVID-19 pandemic

Clotworthy, A., Dissing, A. S., Nguyen, T-L., Jensen, A. K., Andersen, T. O., Bilsteen, J. F., Elsenburg, L. K., Keller, A., Kusumastuti, S., Mathisen, J., Mehta, A., Pinot de Moira, A., Rod, M. H., Skovdal, M., Strandberg-Larsen, K., Tapager, I. W., Varga, T. V., Vinther, J. L., Xu, T., Hoeyer, K. & Hulvej Rod, N., 10 sep. 2020, I : Scandinavian Journal of Public Health. Supplement.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Aims: There is a need to document the mental-health effects of the COVID-19 pandemic and its associated societal lockdowns. We initiated a large mixed-methods data collection, focusing on crisis-specific worries and mental-health indicators during the lockdown in Denmark. Methods: The study incorporated five data sources, including quantitative surveys and qualitative interviews. The surveys included a time series of cross-sectional online questionnaires starting on 20 March 2020, in which 300 (3×100) Danish residents were drawn every three days from three population groups: the general population (N=1046), families with children (N=1032) and older people (N=1059). These data were analysed by trend analysis. Semi-structured interviews were conducted with 32 people aged 24-83 throughout Denmark to provide context to the survey results and to gain insight into people's experiences of the lockdown. Results: Absolute level of worries, quality of life and social isolation were relatively stable across all population groups during the lockdown, although there was a slight deterioration in older people's overall mental health. Many respondents were worried about their loved ones' health (74-76%) and the potential long-term economic consequences of the pandemic (61-66%). The qualitative interviews documented significant variation in people's experiences, suggesting that the lockdown's effect on everyday life had not been altogether negative. Conclusions: People in Denmark seem to have managed the lockdown without alarming changes in their mental health. However, it is important to continue investigating the effects of the pandemic and various public-health measures on mental health over time and across national contexts.

Originalsprog Engelsk
Bogserie Scandinavian Journal of Public Health. Supplement
ISSN 1403-4956
DOI
Status E-pub ahead of print - 10 sep. 2020

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., 2020, I : PLoS One. 15, 6, s. e0235144

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Commercial physical activity monitors have wide utility in the assessment of physical activity in research and clinical settings, however, the removal of devices results in missing data and has the potential to bias study conclusions. This study aimed to evaluate methods to address missingness in data collected from commercial activity monitors.

METHODS: This study utilised 1526 days of near complete data from 109 adults participating in a European weight loss maintenance study (NoHoW). We conducted simulation experiments to test a novel scaling methodology (NoHoW method) and alternative imputation strategies (overall/individual mean imputation, overall/individual multiple imputation, Kalman imputation and random forest imputation). Methods were compared for hourly, daily and 14-day physical activity estimates for steps, total daily energy expenditure (TDEE) and time in physical activity categories. In a second simulation study, individual multiple imputation, Kalman imputation and the NoHoW method were tested at different positions and quantities of missingness. Equivalence testing and root mean squared error (RMSE) were used to evaluate the ability of each of the strategies relative to the true data.

RESULTS: The NoHoW method, Kalman imputation and multiple imputation methods remained statistically equivalent (p<0.05) for all physical activity metrics at the 14-day level. In the second simulation study, RMSE tended to increase with increased missingness. Multiple imputation showed the smallest RMSE for Steps and TDEE at lower levels of missingness (<19%) and the Kalman and NoHoW methods were generally superior for imputing time in physical activity categories.

CONCLUSION: Individual centred imputation approaches (NoHoW method, Kalman imputation and individual Multiple imputation) offer an effective means to reduce the biases associated with missing data from activity monitors and maximise data retention.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 15
Udgave nummer 6
Sider (fra-til) e0235144
ISSN 1932-6203
DOI
Status Udgivet - 2020

Acoustic Myography in Assessment of Isokinetic and Isometric Muscle Strength in a Healthy Danish Population

Bartels, E. M., 2020, I : Journal of Biomedical Science and Engineering.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Dansk
Tidsskrift Journal of Biomedical Science and Engineering
ISSN 1937-6871
Status Udgivet - 2020

OBJECTIVES: Glucocorticoid treatment is fundamental in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but carries a risk of glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency can cause reluctance to stop glucocorticoid treatment after disease remission as symptoms can resemble PMR/GCA flare. We aimed to determine the prevalence of adrenal insufficiency in prednisolone-treated patients with PMR/GCA.

METHODS: We included 47 patients with PMR (n = 37), GCA (n = 1) or both (n = 9), treated with prednisolone for ≥5.4 months, current dose 2.5-10 mg/day. Adrenal function was evaluated using a corticotropin (Synacthen®) stimulation test following 48 h prednisolone pause. Two years' clinical follow-up data are provided.

RESULTS: Seven patients (15%) had adrenal insufficiency, 4 (11%) of the 37 patients with PMR alone, and 3 (30%) of the 10 patients with GCA. Corticotropin-stimulated P-cortisol was significantly associated with current prednisolone dose, mean daily dose the last 3 and 6 months before testing, and basal P-cortisol, but not with total dose or treatment duration. Adrenal insufficiency occurred with all current prednisolone doses (2.5-10 mg/day). Five (71%) of the glucocorticoid-insufficient patients could discontinue prednisolone treatment; two of them recovered glucocorticoid function, whereas three still needed hydrocortisone replacement 2 years later. Two patients experienced in total four acute hospital admissions with symptoms of adrenal crises.

CONCLUSION: Glucocorticoid-induced adrenal insufficiency occurred in 15% of patients with PMR/GCA. Mean prednisolone dose the last 3 months and basal P-cortisol were the best and simplest predictors of adrenal function. Most of the glucocorticoid-insufficient patients could discontinue prednisolone with appropriate treatment for adrenal insufficiency.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 59
Udgave nummer 10
Sider (fra-til) 2764-2773
ISSN 1462-0332
DOI
Status Udgivet - 1 okt. 2020

Bibliografisk note

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Antibiotic containing bone cement in prevention of hip and knee prosthetic joint infections: A systematic review and meta-analysis

Sebastian, S., Liu, Y., Christensen, R., Raina, D. B., Tägil, M. & Lidgren, L., jul. 2020, I : Journal of orthopaedic translation. 23, s. 53-60 8 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Background: Prosthetic joint infection (PJI) is the most serious total joint arthroplasty (TJA) complication despite several aseptic and antiseptic preventive measures. There is no clear evidence or even consensus, whether antibiotic-loaded bone cement (ALBC) should be used, in addition to systemic short-term routine antibiotic prophylaxis, to reduce the risk of PJI in primary TJA. We aimed to analyze the efficacy of ALBC for prevention of PJI in patients undergoing primary TJA.

Methods: We searched systematically for randomized controlled trials (RCTs) in PubMed, Scopus, Embase, Web of Science and Cochrane library. Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. PJI was prespecified as the primary outcome of interest. The meta-analyses were based on risk ratios using random-effects model per default. For the purpose of sensitivity, the corresponding fixed effects model odds ratios were calculated with the use of the Peto method as well. To evaluate a potential difference in effect sizes using different types (subgroups) of antibiotics used in bone cement, and at different follow-up periods, we performed stratified meta-analyses.

Results: Thirty-seven studies were eligible for the systematic review and qualitative synthesis, and 9 trials (6507 total joint arthroplasties) were included in this meta-analysis. Overall ALBC significantly reduced the risk of PJI following primary TJAs (RRs, 0.36; 95% CIs, 0.16 to 0.80; P = 0.01) with a moderate degree of inconsistency (I2 = 47%). Based on stratified meta-analyses the use of gentamicin appeared to have a better effect (P = 0.0005) in the total hip arthroplasty. Pooled data of different antibiotics used in knee arthroplasties showed a significant association of cefuroxime (RRs, 0.08; 95% CIs, 0.01 to 0.63; P = 0.02). Further, ALBCs significantly reduced the PJI at one and two years of follow-up (P = 0.03 and P = 0.005 respectively).

Conclusions: The evidence suggests that ALBCs are effective in reducing the PJI following primary TJA; i.e. between 20 and 84% reduced risk. However, the clear limitations of the available trial evidence highlight the need for joint-specific confirmatory trials, that will need to be designed as cluster-randomized trials of clinics in countries with well-functioning arthroplasty registries.The translational potential of this article: This meta-analysis highlights the prophylactic potential of ALBCs in lowering the risk of infection following primary hip or knee arthroplasties but emphasizes the need for more recent confirmatory trials.

Originalsprog Engelsk
Tidsskrift Journal of orthopaedic translation
Vol/bind 23
Sider (fra-til) 53-60
Antal sider 8
ISSN 2214-031X
DOI
Status Udgivet - jul. 2020

Bibliografisk note

© 2020 The Author(s).

OBJECTIVE: To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse.

METHODS: Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests.

RESULTS: Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P < .01), independent of clinical and radiographic measures, and was also associated with most of the hand-related HAQ items (P < .03). In multivariate models including MRI, SvH scores were not associated with PROs. MRI-assessed inflammation was not associated with PROs at remission or relapse.

CONCLUSION: Magnetic resonance imaging-assessed wrist/hand damage, but not inflammation, in patients with established RA is associated with patient-reported physical impairment at remission and relapse. The amount of damage in the wrist/hand is associated with reduced hand function.

Originalsprog Engelsk
Tidsskrift International Journal of Rheumatic Diseases
Vol/bind 23
Udgave nummer 4
Sider (fra-til) 488-498
ISSN 1756-1841
DOI
Status Udgivet - 2020

Bibliografisk note

COPECARE

Association between objectively measured sleep duration, adiposity and weight loss history

Larsen, S. C., Horgan, G., Mikkelsen, M-L. K., Palmeira, A. L., Scott, S., Duarte, C., Santos, I., Encantado, J., Driscoll, R. O., Turicchi, J., Michalowska, J., Stubbs, J. & Heitmann, B. L., jul. 2020, I : International journal of obesity (2005). 44, 7, s. 1577-1585 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: An association between sleep and obesity has been suggested in several studies, but many previous studies relied on self-reported sleep and on BMI as the only adiposity measure. Moreover, a relationship between weight loss history and attained sleep duration has not been thoroughly explored.

DESIGN: The study comprised of 1202 participants of the European NoHoW trial who had achieved a weight loss of ≥5% and had a BMI of ≥25 kg/m2 prior to losing weight. Information was available on objectively measured sleep duration (collected during 14 days), adiposity measures, weight loss history and covariates. Regression models were conducted with sleep duration as the explanatory variable and BMI, fat mass index (FMI), fat-free mass index (FFMI) and waist-hip ratio (WHR) as response variables. Analyses were conducted with 12-month weight loss, frequency of prior weight loss attempts or average duration of weight maintenance after prior weight loss attempts as predictors of measured sleep duration.

RESULTS: After adjusting for physical activity, perceived stress, smoking, alcohol consumption, education, sex and age, sleep duration was associated to BMI (P < 0.001), with the highest BMI observed in the group of participants sleeping <6 h a day [34.0 kg/m2 (95% CI: 31.8-36.1)]. Less difference in BMI was detected between the remaining groups, with the lowest BMI observed among participants sleeping 8-<9 h a day [29.4 kg/m2 (95% CI: 28.8-29.9)]. Similar results were found for FMI (P = 0.008) and FFMI (P < 0.001). We found no association between sleep duration and WHR. Likewise, we found no associations between weight loss history and attained sleep duration.

CONCLUSION: In an overweight population who had achieved a clinically significant weight loss, short sleep duration was associated with higher BMI, with similar associations for fat and lean mass. We found no evidence of association between weight loss history and attained sleep duration.

Originalsprog Engelsk
Tidsskrift International journal of obesity (2005)
Vol/bind 44
Udgave nummer 7
Sider (fra-til) 1577-1585
Antal sider 9
ISSN 0307-0565
DOI
Status Udgivet - jul. 2020

Association Between Participant Retention and the Proportion of Included Elderly People in Rheumatology Trials: Results From a Series of Exploratory Meta-Regression Analyses

Palmowski, A., Nielsen, S. M., Buttgereit, T., Palmowski, Y., Boers, M., Christensen, R. & Buttgereit, F., okt. 2020, I : Arthritis Care & Research. 72, 10, s. 1490-1496 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The elderly, a population defined by an age of ≥65 years, are underrepresented in rheumatology trials, possibly due to investigators' concerns of increased premature discontinuations in higher age groups. The present study was undertaken to evaluate whether the proportion of included elderly individuals (PE) is independently associated with participant retention in rheumatology trials.

METHODS: Medline was searched for randomized controlled trials (RCTs) in rheumatoid arthritis (RA) and osteoarthritis (OA) of any intervention (years 2016 and 2017). PE was either extracted from the research manuscript or estimated from an assumed (truncated) normal distribution. We used mixed-effects meta-regression models including several covariates to assess whether there is an independent association between PE and participant retention. Using sensitivity analyses, we evaluated whether associations were connected to attrition due to lack of efficacy (LoE) or adverse events (AE).

RESULTS: In total, 243 RCTs comprising >48,000 participants were included. Pooled participant retention was 88%. PE was not associated with retention in the unadjusted (P = 0.97) or adjusted (all: P ≥ 0.14) models. Of all covariates, only study duration and type of intervention were associated with retention (both: P < 0.001). Post hoc analyses allowing for interaction revealed a small but statistically significant positive association between PE and retention in pharmacologic interventions and a negative association in physical/physiotherapeutic interventions (overall P for interaction = 0.05). No associations were found for PE and attrition due to LoE or AE.

CONCLUSION: Participant retention in RA and OA trials is high and not associated with PE. These findings should motivate investigators to include more elderly participants in rheumatology trials.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
Vol/bind 72
Udgave nummer 10
Sider (fra-til) 1490-1496
Antal sider 7
ISSN 2151-464X
DOI
Status Udgivet - okt. 2020

Bibliografisk note

© 2019 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

OBJECTIVE: To describe spontaneous changes in time spent physically inactive measured continuously by accelerometry during an 8-week weight loss intervention in overweight/obese individuals with knee osteoarthritis.

METHOD: This study was designed as an observational cohort study including individuals with concomitant overweight/obesity and symptomatic knee osteoarthritis from an osteoarthritis outpatient clinic. Participants completed an 8-week dietary intervention previously shown to induce substantial weight loss. The main outcome was accelerometer-based measurement of physical inactivity for 24 hours daily during the 8-week intervention period presented as change in the average daily time spent inactive (sitting, reclined or sleeping) from one week prior to intervention to the last week of the intervention.

RESULTS: A total of 124 participants completed the dietary intervention and had valid accelerometer recordings. The mean weight loss was 12.7 kg [95% CI -13.2 to -12.1; P<.0001] after 8 weeks corresponding to a decrease in BMI of 4.3 kg/m2 [95%CI -4.5 to -4.2; P<.0001]. Significant improvements in osteoarthritis symptoms (assessed by the Knee Injury and Osteoarthritis Outcome Score) was found across all subscales; for KOOS pain an improvement of 12.8 points [95% CI, 10.6 to 15.0; P<.0001] was observed. No statistically significant change occurred in the average daily time spent inactive from baseline to follow-up (mean change: 8.8 minutes/day [95% CI, -12.1 to 29.7]; P=0.41).

CONCLUSION: Physical inactivity remains stable despite a clinically significant weight loss and improvements in knee osteoarthritis symptoms. Change in inactivity does not seem to occur spontaneously, suggesting that focused efforts to reduce inactive behaviors are needed. This article is protected by copyright. All rights reserved.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
Vol/bind 72
ISSN 2151-464X
DOI
Status Udgivet - 2020

Bibliografisk note

This article is protected by copyright. All rights reserved.

Exposure to prenatal stress is linked to health consequences in the offspring. The objective of this systematic review was to synthesize and critically appraise primary human studies that have examined the association between prenatal exposure to psychosocial stress, or adverse life events, stress hormones, and later risk of developing obesity. We searched Medline, Embase, ScienceDirect, WorldCat, and OpenGrey up to January 2019 to identify relevant literature. We critically appraised the identified studies, assessed their quality, and summarized their findings. From a total of 5930 search results and references of studies that authors considered pertinent, we identified 15 relevant studies among which three were of high quality and the rest were medium-quality studies. We found direct association between exposure to stress in fetal life and different measures of obesity in the offspring in eight studies. The direct association was usually observed in studies that involved measurement of stress among mothers exposed to natural disasters. Due to lack of adequate and comparable data from the included studies, we did not conduct a meta-analysis. We concluded that there may be direct association between prenatal stress and later obesity, but further research with more comparable sources of stressors is recommended.

Originalsprog Engelsk
Tidsskrift Obesity reviews : an official journal of the International Association for the Study of Obesity
Vol/bind 21
Udgave nummer 2
Sider (fra-til) e12951
ISSN 1467-7881
DOI
Status Udgivet - feb. 2020

Bibliografisk note

© 2019 World Obesity Federation.

Associations between objective measures of physical activity, sleep and stress levels among preschool children

Eythorsdottir, D. Y., Frederiksen, P., Larsen, S. C., Olsen, N. J. & Heitmann, B. L., 27 maj 2020, I : BMC Pediatrics. 20, 1, s. 258

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Cortisol is often used as a biological marker for stress. When measured in urine or serum, representing a short-term measurement of the hormone, it has been associated with unfavorable sleep characteristics and both low and high physical activity levels. However, cortisol in hair represents a long-term stress measure and has been suggested as a promising new marker for chronic stress. Therefore, we aimed to examine the association between objectively measured sleep, physical activity and hair cortisol levels in preschool children.

METHODS: In order to obtain objective measures of physical activity and sleep habits, 54 children aged 2-6 years wore an ActiGraph for 5 consecutive days and nights. For chronic stress measurements of each child, hair was cut from the back of the head close to the scalp for analysis of cortisol levels. Associations between measured sleep quality and quantity and level of physical activity and hair cortisol levels were estimated using linear regression analysis, presented as β. Results were adjusted for sex, age and BMI z-score.

RESULTS: We found no significant association between log-transformed cortisol (pg/mg) and sleep duration (hours) (β = - 0.0016, p = 0.99), sleep efficiency (β = - 3.1, p = 0.18), sleep latency (β = 0.015, p = 0.16) or physical activity level (100 counts per min) (β = 0.014, p = 0.22). However, sleep latency (min) was directly associated with physical activity (counts per min) levels (β = 35.2, p = 0.02), while sleep duration (hours) (β = - 142.1, p = 0.55) and sleep efficiency (%) (β = - 4087, p = 0.26) showed no significant associations.

CONCLUSIONS: In our study, a high physical activity level was associated with poorer sleep habits. Neither sleep quality nor physical activity were related to long term cortisol exposure. These results are among the first to study associations between objectively measured sleep, physical activity and chronic cortisol levels among preschool children. More and larger studies are therefore needed.

Originalsprog Engelsk
Tidsskrift BMC Pediatrics
Vol/bind 20
Udgave nummer 1
Sider (fra-til) 258
ISSN 1471-2431
DOI
Status Udgivet - 27 maj 2020

Associations between shoulder symptoms and concomitant pathology in patients with traumatic supraspinatus tears

Kjær, B. H., Juul-Kristensen, B., Warming, S., Magnusson, S. P., Krogsgaard, M. R., Boyle, E. & Henriksen, M., mar. 2020, I : JSES international. 4, 1, s. 85-90 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: The association between concomitant pathologic characteristics and preoperative symptoms in patients identified as eligible for surgical rotator cuff repair has been sparsely evaluated. The purpose was to explore the associations between preoperative shoulder symptoms and additional structural pathology or injuries identified during surgery in patients with traumatic supraspinatus tears.

Methods: This was a cross-sectional study including patients with traumatic supraspinatus tears. Preoperatively, patients reported pain and disability using a numeric pain rating scale from 0 to 10 and the Western Ontario Rotator Cuff Index. During surgery, the presence of prespecified structural injuries and pathologies including a full-thickness or partial supraspinatus tear, infraspinatus tear, subscapularis tear, hooked acromion, acromioclavicular joint osteoarthritis, biceps tendon pathology, labral tear, and cartilage lesion was recorded. Linear regression and analysis of covariance were used to assess associations.

Results: A total of 87 patients (52 male patients, 60%) were included (mean age, 60 years; standard deviation, 9.2 years). Of these patients, 69 (79%) had a full-thickness supraspinatus tear and 18 (21%) had a partial-thickness tear. Concomitant structural pathology was found in 79 patients (91%). No association was found between the number of structural shoulder pathologies and preoperative numeric pain rating scale or Western Ontario Rotator Cuff Index score, and no particular concomitant pathology was associated with worse patient-reported symptoms.

Conclusion: Pathology of the infraspinatus and subscapularis and other structural joint pathologies concomitant with supraspinatus tears were not correlated with preoperative self-reported pain and disability in patients scheduled to undergo rotator cuff surgery, suggesting that concomitant pathology adds little to the symptoms in patients with a traumatic supraspinatus tear.

Originalsprog Engelsk
Tidsskrift JSES international
Vol/bind 4
Udgave nummer 1
Sider (fra-til) 85-90
Antal sider 6
ISSN 2666-6383
DOI
Status Udgivet - mar. 2020

Bibliografisk note

© 2019 The Author(s).

Biomarkers for length of hospital stay, changes in muscle mass, strength and physical function in older medical patients: protocol for the Copenhagen PROTECT study-a prospective cohort study

Kamper, R. S., Schultz, M., Hansen, S. K., Andersen, H., Ekmann, A., Nygaard, H., Helland, F., Wejse, M. R., Rahbek, C. B., Noerst, T., Pressel, E., Nielsen, F. E. & Suetta, C., 29 dec. 2020, I : BMJ Open. 10, 12, s. e042786

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Sarcopenia is generally used to describe the age-related loss of muscle mass and strength believed to play a major role in the pathogenesis of physical frailty and functional impairment that may occur with old age. The knowledge surrounding the prevalence and determinants of sarcopenia in older medical patients is scarce, and it is unknown whether specific biomarkers can predict physical deconditioning during hospitalisation. We hypothesise that a combination of clinical, functional and circulating biomarkers can serve as a risk stratification tool and can (i) identify older acutely ill medical patients at risk of prolonged hospital stays and (ii) predict changes in muscle mass, muscle strength and function during hospitalisation.

METHOD AND ANALYSIS: The Copenhagen PROTECT study is a prospective cohort study consisting of acutely ill older medical patients admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. Assessments are performed within 24 hours of admission and include blood samples, body composition, muscle strength, physical function and questionnaires. A subgroup of patients transferred to the Geriatric Department are included in a smaller geriatric cohort and have additional assessments at discharge to evaluate the relative change in circulating biomarker concentrations, body composition, muscle strength and physical function during hospitalisation. Enrolment commenced 4 November 2019, and proceeds until August 2021.

ETHICS AND DISSEMINATION: The study protocol has been approved by the local ethics committee of Copenhagen and Frederiksberg (H-19039214) and the Danish Data Protection Agency (P-2019-239) and all experimental procedures were performed in accordance with the Declaration of Helsinki. Findings from the project, regardless of the outcome, will be published in relevant peer-reviewed scientific journals in online (www.clinicaltrials.gov).

TRIAL REGISTRATION NUMBER: NCT04151108.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 10
Udgave nummer 12
Sider (fra-til) e042786
ISSN 2044-6055
DOI
Status Udgivet - 29 dec. 2020

Bibliografisk note

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chances of live birth after exposure to vitamin D-fortified margarine in women with fertility problems: results from a Danish population-based cohort study

Jensen, A., Nielsen, M. L., Guleria, S., Kjaer, S. K., Heitmann, B. L. & Kesmodel, U. S., 2020, I : Fertility and Sterility. 113, 2, s. 383-391 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To study the association between extra vitamin D from a mandatory margarine fortification program and chance of live birth among infertile women.

DESIGN: Nationwide cohort study.

SETTING: Not applicable.

PATIENT(S): The study population consisted of 16,212 women diagnosed with infertility from June 1, 1980, to August 31, 1991.

INTERVENTIONS(S): We took advantage of the mandatory vitamin D fortification program of margarine in Denmark that was abruptly stopped on May 31, 1985. The termination of the vitamin D fortification served as a cutoff point to separate the study population into various exposure groups.

MAIN OUTCOME MEASURE(S): Odds ratios and 95% confidence intervals for the association between vitamin D exposure status and chance of a live birth within 12, 15, and 18 months after first infertility diagnosis.

RESULT(S): Women who were diagnosed with infertility during the vitamin D-exposed period had an increased chance of a live birth compared with women diagnosed with infertility during the nonexposed period. For women diagnosed with infertility during the wash-out period, the chance of a live birth was also increased, but somewhat lower. Similar estimates were obtained with longer follow-up, in women with anovulatory infertility, and little seasonal variation was observed when calendar period of conception was applied.

CONCLUSION(S): Our findings suggest that infertile women exposed to extra vitamin D from a margarine fortification program had an increased chance of live birth compared with women not exposed to extra vitamin D from fortification.

Originalsprog Engelsk
Tidsskrift Fertility and Sterility
Vol/bind 113
Udgave nummer 2
Sider (fra-til) 383-391
Antal sider 9
ISSN 0015-0282
DOI
Status Udgivet - 2020

Bibliografisk note

Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Changes in physical inactivity during supervised educational and exercise therapy in patients with knee osteoarthritis: A prospective cohort study

Bartholdy, C., Skou, S. T., Bliddal, H. & Henriksen, M., 1 dec. 2020, I : The Knee. 27, 6, s. 1848-1856 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Physical inactivity is a global problem and patients with knee osteoarthritis (OA) are predisposed to inactivity and its health-related consequences. Current guidelines recommend exercise as primary treatment but whether this affects time spent physically inactive is unknown. The objective was to investigate changes in physical inactivity among individuals with knee OA following an educational and exercise program.

METHODS: Pragmatic prospective cohort study performed in six physical therapy clinics in Denmark offering a nationwide education and exercise program for knee OA. The program consists of physiotherapy guided education and group-based or home exercise sessions, performed biweekly for approximately eight weeks. The exercises target knee and hip joint stability as well as focus on increasing muscle strength. Primary outcome was time spent physically inactive (min/day), measured with a tri-axial accelerometer mounted on the lateral side of the thigh during the entire exercise program duration. OA symptoms were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS).

RESULTS: Thirty-two individuals with knee OA were analyzed. From baseline to post-intervention, no changes occurred in average time spent physically inactive (mean change: +16.2 min [95% CI -15.7 to 48.1]; P = 0.31), but statistically significant improvements in KOOS pain (+6.7 points [95% CI 2.3 to 11.0]; P = 0.0032) and KOOS function (+5.8 points [95% CI 1.9 to 9.7]; P = 0.0046) were found.

CONCLUSIONS: Participating and completing a widely adopted education and exercise program are not associated with spontaneous improvements in physical inactivity despite changes in self-reported pain and function. Interventions specifically targeting physical inactivity are needed. Registration number: www.clinicaltrials.gov: NCT03125954.

Originalsprog Engelsk
Tidsskrift The Knee
Vol/bind 27
Udgave nummer 6
Sider (fra-til) 1848-1856
Antal sider 9
ISSN 0968-0160
DOI
Status Udgivet - 1 dec. 2020

Bibliografisk note

Copyright © 2020 Elsevier B.V. All rights reserved.

Clinical trial discrimination of physical function instruments for psoriatic arthritis: A systematic review

Leung, Y-Y., Holland, R., Mathew, A. J., Lindsay, C., Goel, N., Ogdie, A., Orbai, A-M., Hojgaard, P., Chau, J., Coates, L. C., Strand, V., Gladman, D. D., Christensen, R., Tillett, W. & Mease, P., okt. 2020, I : Seminars in Arthritis and Rheumatism. 50, 5, s. 1158-1181 24 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: Physical function (PF) is a core domain to be measured in randomized controlled trials (RCTs) of psoriatic arthritis (PsA), yet the discriminative performance of patient reported outcome measures (PROMs) for PF in RCTs has not been evaluated systematically. In this systematic review, we aimed to evaluate the clinical trial discrimination of PF-PROMs in PsA RCTs.

METHODS: We searched PubMed and Scopus databases in English to identify all original RCTs on biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) conducted in PsA. We assessed quality in each article using the OMERACT good method checklist. Effect sizes (ES) for the PF-PROMs were calculated and appraised using a priori hypotheses. Evidence supporting clinical trial discrimination for each PF-PROM was summarized to derive recommendations.

RESULTS: 35 articles from 31 RCTs were included. Four PF-PROMs had data for evaluation: HAQ-Disability Index (DI), HAQ-Spondyloarthritis (S), and Short Form 36-item Health Survey Physical Component Summary (SF-36 PCS) and Physical Functioning domain (SF-36 PF). As anticipated, higher ES values were observed for intervention groups than the control groups. Across all studies, for HAQ-DI, the median ES were -0.73 and -0.24 for intervention and control groups, respectively. Whereas for SF-36 PCS, the median ES were 0.77 and 0.23. For intervention and control groups, respectively.

CONCLUSION: Clinical trial discrimination was supported for HAQ-DI and SF-36 PCS in PsA with low risk of bias; and for SF-36 PF and HAQ-S with some caution. More studies are required for HAQ-S.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 50
Udgave nummer 5
Sider (fra-til) 1158-1181
Antal sider 24
ISSN 0049-0172
DOI
Status Udgivet - okt. 2020

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

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