Published in 2021

UTE T2* mapping of tendinopathic patellar tendons: an MRI reproducibility study

Agergaard, A-S., Malmgaard-Clausen, N. M., Svensson, R. B., Nybing, J. D., Boesen, M., Kjaer, M., Magnusson, S. P. & Hansen, P., feb. 2021, I: Acta Radiologica. 62, 2, s. 215-224 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: There is currently a lack of imaging modalities that can be used as a sensitive measure in tendinopathy. Recent findings suggest the applicability of ultra-short echo time (UTE) magnetic resonance imaging (MRI) T2* mapping in tendons, but the reproducibility remains unknown. Purpose: To evaluate test–retest reproducibility of UTE MRI T2* mapping of tendinopathic patellar tendons and to evaluate the intra- and inter-observer reproducibility of the measurement. Material and Methods: Fifteen patients with chronic patellar tendinopathy were evaluated with UTE MRI twice in a 3.0-T scanner on the same day. Manual segmentation of the patellar tendon was performed by two blinded investigators and automated T2*map reconstruction was performed in custom-made software. Results: There was a significant and numerically small difference in test–retest T2* values (T2*mean
diff = 0.06 ± 0.07 ms ≈ 3.7%; P = 0.006) with an ICC = 0.91 (95% confidence interval [CI] 0.58–0.98; typical error of 3.0%). The intra- and inter-observer reproducibility showed no significant bias (P = 0.493 and P = 0.052), and generally substantial reproducibility was demonstrated for T2* (intra-observer ICC = 0.99; 95% CI 0.98–1.00 and inter-observer ICC = 0.99; 95% CI 0.96–1.00, and typical error 1.3% and 1.3%, respectively). Conclusion: These data demonstrate a small bias between repeated measurements for UTE T2*, but with a very low associated mean difference (3.7%) between the two tests. The high ICC values and low typical error % demonstrate reproducibility of repeated T2*-mapping sessions. Further, the method showed substantial intra- and inter-observer reproducibility for T2* values proving feasibility for use of UTE T2* mapping in research and clinical practice.

Originalsprog Engelsk
Tidsskrift Acta Radiologica
Vol/bind 62
Udgave nummer 2
Sider (fra-til) 215-224
Antal sider 10
ISSN 0284-1851
DOI
Status Udgivet - feb. 2021

Vertiginous Episodes in Menière Disease following Transmyringeal Ventilation Tube Insertion: A Systematic Review on the Current State of Evidence

Grønlund, C., Devantier, L., Callesen, H. E., Hougaard, D. D., Händel, M. N., Schmidt, J. H., Guldfred, F. L-A. & Djurhuus, B. D., jul. 2021, I: International Archives of Otorhinolaryngology. 25, 3, s. e463-e470 190098SR.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Introduction  Menière disease (MD) is a disorder characterized by episodes of vertigo, sensorineural hearing loss, tinnitus and aural fullness. Objectives  To assess the effect of ventilation tube insertion (VTI) on vertiginous episodes in patients (≥ 18 years old) with MD. Data Synthesis  A systematic literature search on randomized clinical trials (RCTs), nonrandomized trials and other systematic reviews was performed. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to assess the overall certainty of evidence. Two RCTs and four nonrandomized studies were identified. Data extraction was only possible for one RCT. Results showed that the number of patients with no vertigo attacks significantly increased following active treatment (relative risk 1.52; [95% confidence interval: 1.19-1.94]). The quality of evidence was rated as low. None of the nonrandomized trials included a proper control group, which hindered data extraction and quality assessment. Conclusion  There are currently no RCTs that specifically assess the efficacy of VTI in patients with MD. Current limited data suggest a considerable positive effect on the number of vertiginous episodes in patients with MD. However, due to poor evidence, a fluctuating course and a substantial placebo-effect associated with MD-treatment, no solid conclusion(s) regarding the efficacy of VTI can be made. There is a need for high-quality RCTs.

Originalsprog Engelsk
Artikelnummer 190098SR
Tidsskrift International Archives of Otorhinolaryngology
Vol/bind 25
Udgave nummer 3
Sider (fra-til) e463-e470
ISSN 1809-9777
DOI
Status Udgivet - jul. 2021

Vitamin D concentrations from neonatal dried blood spots and the risk of early-onset type 2 diabetes in the Danish D-tect case-cohort study

Keller, A., Thorsteinsdottir, F., Stougaard, M., Cardoso, I., Frederiksen, P., Cohen, A. S., Vaag, A., Jacobsen, R. & Heitmann, B. L., jul. 2021, I: Diabetologia. 64, 7, s. 1572-1582 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

AIMS/HYPOTHESIS: The aim of this study was to examine the influence of neonatal vitamin D concentration on the development of early-onset type 2 diabetes in a large population sample.

METHODS: We conducted a case-cohort study utilising data from the Danish biobank and registers. Neonatal vitamin D was assessed measuring 25-hydroxyvitamin D3 [25(OH)D3] concentrations on the dried blood spot samples from the Biological Specimen Bank for Neonatal Screening. Cases of type 2 diabetes (n = 731) were retrieved from the Danish National Patient Register for all individuals born in Denmark between 1 May 1981 and 31 December 1992. The sub-cohort (n = 1765) was randomly selected from all children born in the same period. We used a weighted Cox proportional hazard model assessing the hazard of first type 2 diabetes diagnoses by quintiles of 25(OH)D3 and restricted cubic spline.

RESULTS: The median 25(OH)D3 concentration (IQR) among cases was 21.3 nmol/l (13.3-34.1) and 23.9 nmol/l (13.7-35.7) in the sub-cohort. There was no indication of a potential lower risk of early-onset type 2 diabetes among individuals in the higher quintile of vitamin D concentration compared with the lowest (HRcrude 0.97 [95% CI 0.71, 1.33] p = 0.85; HRadjusted 1.29 [95% CI 0.92, 1.83] p = 0.14).

CONCLUSIONS/INTERPRETATION: The results of this study do not support the hypothesis that higher neonatal vitamin D concentrations are associated with a lower risk of early-onset type 2 diabetes in adulthood.

Originalsprog Engelsk
Tidsskrift Diabetologia
Vol/bind 64
Udgave nummer 7
Sider (fra-til) 1572-1582
Antal sider 11
ISSN 0012-186X
DOI
Status Udgivet - jul. 2021

Published in 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., 24 jun. 2020, I: PLoS One. 15, 6, s. e0235144 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
Artikelnummer e0235144
Tidsskrift PLoS One
Vol/bind 15
Udgave nummer 6
Sider (fra-til) e0235144
ISSN 1932-6203
DOI
Status Udgivet - 24 jun. 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

Adrenal insufficiency in prednisolone-treated patients with polymyalgia rheumatica or giant cell arteritis-prevalence and clinical approach

Borresen, S. W., Thorgrimsen, T. B., Jensen, B., Hilsted, L., Bartels, E. M., Feldt-Rasmussen, U. & Locht, H., 1 okt. 2020, I: Rheumatology (Oxford, England). 59, 10, s. 2764-2773 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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
Antal sider 10
ISSN 1462-0324
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).

Assessing the effect of interventions for axial spondyloarthritis according to the endorsed ASAS/OMERACT core outcome set: a meta-research study of trials included in Cochrane reviews

Andreasen, R. A., Kristensen, L. E., Baraliakos, X., Strand, V., Mease, P. J., de Wit, M., Ellingsen, T., Hansen, I. M. J., Kirkham, J., Wells, G. A., Tugwell, P., Maxwell, L., Boers, M., Egstrup, K. & Christensen, R., 25 jul. 2020, I: Arthritis Research & Therapy. 22, 1, s. 177

Publikation: Bidrag til tidsskriftReviewForskningpeer review

The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: "physical function," "pain," "spinal mobility," "spinal stiffness," and "patient's global assessment" (PGA). The core set for clinical record keeping further includes the domains "peripheral joints/entheses" and "acute phase reactants," and the core set for DC-ART further includes the domains "fatigue" and "spine radiographs/hip radiographs." The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998.Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to meta-analyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log [OR], dependent variable) across all trials.Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcome domains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and "missing data") should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain provide a valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation.

Originalsprog Engelsk
Tidsskrift Arthritis Research & Therapy
Vol/bind 22
Udgave nummer 1
Sider (fra-til) 177
ISSN 1478-6354
DOI
Status Udgivet - 25 jul. 2020

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
Antal sider 10
ISSN 1756-1841
DOI
Status Udgivet - apr. 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.

Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease: A Pooled Analysis of Individual Patient Data From 12 Studies

Mishra, S. R., Chung, H-F., Waller, M., Dobson, A. J., Greenwood, D. C., Cade, J. E., Giles, G. G., Bruinsma, F., Simonsen, M. K., Hardy, R., Kuh, D., Gold, E. B., Crawford, S. L., Derby, C. A., Matthews, K. A., Demakakos, P., Lee, J. S., Mizunuma, H., Hayashi, K., Sievert, L. L., Brown, D. E., Sandin, S., Weiderpass, E. & Mishra, G. D., 1 dec. 2020, I: JAMA Cardiology. 5, 12, s. 1410-1418 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Importance: Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD.

Objective: To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause.

Design, Setting, and Participants: Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019.

Exposures: Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older.

Main Outcomes and Measures: First nonfatal CVD event, including coronary heart disease and stroke events.

Results: A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (<30 years) were at 1.71 (95% CI, 1.58-1.84) times higher risk of incident CVD events than women with a reproductive life span of 36 to 38 years after adjustment for covariates. This association remained unchanged when adjusted for age at menarche but was attenuated to 1.26 (95% CI, 1.09-1.46) when adjusted for age at menopause. There was a significant interaction between reproductive life span and age at menarche associated with CVD risk (P < .001). Women who had both short reproductive life span (<33 years) and early menarche (age ≤11 years) had the highest risk of CVD (hazard ratio, 2.06; 95% CI, 1.76-2.41) compared with those with a reproductive life span of 36 to 38 years and menarche at age 13 years.

Conclusions and Relevance: Short reproductive life span was associated with an increased risk of nonfatal CVD events in midlife, and the risk was significantly higher for women with early age at menarche.

Originalsprog Engelsk
Tidsskrift JAMA Cardiology
Vol/bind 5
Udgave nummer 12
Sider (fra-til) 1410-1418
Antal sider 9
ISSN 2380-6583
DOI
Status Udgivet - 1 dec. 2020

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

METHODS: This study was designed as an observational cohort study including individuals from an OA outpatient clinic who were concomitantly overweight/obese and had symptomatic knee OA. Participants completed an 8-week dietary intervention that had been previously shown to induce substantial weight loss. The main outcome was accelerometer-based measurement of daily physical inactivity for 24 hours during the 8-week intervention period that was presented as change in the average daily time spent inactive (sitting, reclined, or sleeping) from 1 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% confidence interval [95% CI] -13.2, -12.1; P < 0.0001) after 8 weeks, which corresponded to a decrease in body mass index of 4.3 kg/m
2 (95% CI -4.5, -4.2; P < 0.0001). Significant improvements in OA symptoms (assessed by the Knee Injury and Osteoarthritis Outcome Score [KOOS]) was found across all subscales; an improvement of 12.8 points (95% CI 10.6, 15.0; P < 0.0001) was observed for pain using the KOOS. 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, 29.7]; P = 0.41).

CONCLUSION: Physical inactivity remains stable despite a clinically significant weight loss and improvements in knee OA symptoms. Change in inactivity does not seem to occur spontaneously, suggesting that focused efforts to reduce inactive behaviors are needed.

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.

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

METHODS: This study was designed as an observational cohort study including individuals from an OA outpatient clinic who were concomitantly overweight/obese and had symptomatic knee OA. Participants completed an 8-week dietary intervention that had been previously shown to induce substantial weight loss. The main outcome was accelerometer-based measurement of daily physical inactivity for 24 hours during the 8-week intervention period that was presented as change in the average daily time spent inactive (sitting, reclined, or sleeping) from 1 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% confidence interval [95% CI] -13.2, -12.1; P < 0.0001) after 8 weeks, which corresponded to a decrease in body mass index of 4.3 kg/m
2 (95% CI -4.5, -4.2; P < 0.0001). Significant improvements in OA symptoms (assessed by the Knee Injury and Osteoarthritis Outcome Score [KOOS]) was found across all subscales; an improvement of 12.8 points (95% CI 10.6, 15.0; P < 0.0001) was observed for pain using the KOOS. 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, 29.7]; P = 0.41).

CONCLUSION: Physical inactivity remains stable despite a clinically significant weight loss and improvements in knee OA symptoms. Change in inactivity does not seem to occur spontaneously, suggesting that focused efforts to reduce inactive behaviors are needed.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
Vol/bind 72
Udgave nummer 3
Sider (fra-til) 397-404
Antal sider 8
ISSN 2151-464X
DOI
Status Udgivet - mar. 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
Artikelnummer e12951
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. 258 258.

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
Artikelnummer 258
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.

Body weight variability is not associated with changes in risk factors for cardiometabolic disease

Turicchi, J., O'Driscoll, R., Horgan, G., Duarte, C., Santos, I., Encantado, J., Palmeira, A. L., Larsen, S. C., Olsen, J. K., Heitmann, B. L. & Stubbs, R. J., sep. 2020, I: International Journal of Cardiology. Hypertension. 6, s. 100045

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Context: Weight loss is known to improve health, however the influence of variability in body weight around the overall trajectory on these outcomes is unknown. Few studies have measured body weight frequently enough to accurately estimate the variability component.

Objective: To investigate the association of 12-month weight variability and concurrent weight change with changes in health markers and body composition.

Methods: This study was a secondary analysis of the NoHoW trial, a 2 × 2 factorial randomised controlled trial promoting evidence-based behaviour change for weight loss maintenance. Outcome measurements related to cardiometabolic health and body composition were taken at 0, 6 and 12 months. Participants were provided with Wi-Fi connected smart scales (Fitbit Aria 2) and asked to self-weigh regularly over this period. Associations of weight variability and weight change with change in outcomes were investigated using multiple linear regression with multiple levels of adjustment in 955 participants.

Results: Twelve models were generated for each health marker. Associations between weight variability and changes in health markers were inconsistent between models and showed no evidence of a consistent relationship, with all effects explaining <1% of the outcome, and most 0%. Weight loss was consistently associated with improvements in health and body composition, with the greatest effects seen in percent body fat (R2 = 10.4-11.1%) followed by changes in diastolic (4.2-4.7%) and systolic (3-4%) blood pressure.

Conclusion: Over 12-months, weight variability was not consistently associated with any measure of cardiometabolic health or body composition, however weight loss consistently improved all outcomes.

Trial registration number: ISRCTN88405328.

Originalsprog Engelsk
Tidsskrift International Journal of Cardiology. Hypertension
Vol/bind 6
Sider (fra-til) 100045
ISSN 2590-0862
DOI
Status Udgivet - sep. 2020

Bibliografisk note

© 2020 The Authors.

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.

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