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., 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

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)
ISSN 1462-0332
DOI
Status Udgivet - 7 feb. 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).

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).

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.

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.

Background: More than half of patients with rheumatoid arthritis complain of insomnia, which is predominantly treated with hypnotic drugs. However, cognitive behavioural therapy for insomnia is recommended as the first-line treatment in international guidelines on sleep. Patients with rheumatoid arthritis suffer from debilitating symptoms, such as fatigue and pain, which can also be linked to sleep disturbance. It remains to be determined whether cognitive behavioural therapy for insomnia can be effective in patients with rheumatoid arthritis. The aim of the Sleep-RA trial is to investigate the efficacy of cognitive behavioural therapy for insomnia on sleep and disease-related symptoms in patients with rheumatoid arthritis. The primary objective is to compare the effect of cognitive behavioural therapy for insomnia relative to usual care on changes in sleep efficiency from baseline to week 7 in patients with rheumatoid arthritis. The key secondary objectives are to compare the effect of cognitive behavioural therapy for insomnia relative to usual care on changes in sleep onset latency, wake after sleep onset, total sleep time, insomnia, sleep quality, fatigue, impact of rheumatoid arthritis and depressive symptoms from baseline to week 26 in patients with rheumatoid arthritis. Methods: The Sleep-RA trial is a randomised controlled trial with a two-group parallel design. Sixty patients with rheumatoid arthritis, insomnia and low-to-moderate disease activity will be allocated 1:1 to treatment with cognitive behavioural therapy for insomnia or usual care. Patients in the intervention group will receive nurse-led, group-based cognitive behavioural therapy for insomnia once a week for 6 weeks. Outcome assessments will be carried out at baseline, after treatment (week 7) and at follow-up (week 26). Discussion: Data on treatment of insomnia in patients with rheumatoid arthritis are sparse. The Sleep-RA trial is the first randomised controlled trial to investigate the efficacy of cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis. Because symptoms of rheumatoid arthritis and insomnia have many similarities, we also find it relevant to investigate the secondary effects of cognitive behavioural therapy for insomnia on fatigue, impact of rheumatoid arthritis, depressive symptoms, pain, functional status, health-related quality of life and disease activity. If we find cognitive behavioural therapy for insomnia to be effective in patients with rheumatoid arthritis this will add weight to the argument that evidence-based non-pharmacological treatment for insomnia in rheumatological outpatient clinics is eligible in accordance with the existing international guidelines on sleep. Trial registration: ClinicalTrials.gov: NCT03766100. Registered on 30 November 2018.

Originalsprog Engelsk
Artikelnummer 440
Tidsskrift Trials
Vol/bind 21
Udgave nummer 1
ISSN 1745-6215
DOI
Status Udgivet - 29 maj 2020

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

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

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

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

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

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

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

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

Publikation: Bidrag til tidsskriftReviewForskningpeer review

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

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

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

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

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

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

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

O'Driscoll, R., Turicchi, J., Duarte, C., Michalowska, J., Larsen, S. C., Palmeira, A. L., Heitmann, B. L., Horgan, G. W. & Stubbs, R. J., 2020, I : PLoS One. 15, 9, s. e0238965

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 15
Udgave nummer 9
Sider (fra-til) e0238965
ISSN 1932-6203
DOI
Status Udgivet - 2020

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

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

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

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

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

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

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

Bibliografisk note

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

Definition, pathology and pathogenesis of osteoarthritis

Henriksen, M. & Skou, S. T., 12 okt. 2020, I : Ugeskrift for Laeger. 182, 42

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Therapeutic exercise for knee osteoarthritis is recommended globally, based on more than 100 randomised, controlled trials documenting beneficial effects on pain and function. There are adverse effects of exercise and symptom exacerbations may occur in the first 4-6 weeks of an exercise programme, but will most often decline with time. If pain and function do not improve after a structured exercise program, other treatments must be considered. The effects of exercise decline over time, if regular exercise is not implemented in the daily life of the patient.

Bidragets oversatte titel Exercise for knee osteoarthritis
Originalsprog Dansk
Tidsskrift Ugeskrift for Laeger
Vol/bind 182
Udgave nummer 42
ISSN 0041-5782
Status Udgivet - 12 okt. 2020

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

Originalsprog Engelsk
Tidsskrift Mayo Clinic Proceedings
ISSN 0025-6196
DOI
Status Udgivet - 1 jan. 2020

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

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

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

Bibliografisk note

© 2019 Federation of American Societies for Experimental Biology.

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