Published in 2019

Improving Benefit-harm Assessment of Therapies from the Patient Perspective: OMERACT Premeeting Toward Consensus on Core Sets for Randomized Controlled Trials

Andersen, K. M., Cheah, J. T. L., March, L., Bartlett, S. J., Beaton, D., Bingham, C. O., Brooks, P. M., Christensen, R., Conaghan, P. G., D'Agostino, M-A., de Wit, M., Dueck, A. C., Goodman, S. M., Grosskleg, S., Hill, C. L., Howell, M., Mackie, S. L., Richards, B., Shea, B., Singh, J. A., Strand, V., Tugwell, P., Wells, G. A. & Simon, L. S., aug. 2019, I : Journal of Rheumatology. 46, 8, s. 1053-1058 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Outcome Measures in Rheumatology (OMERACT) convened a premeeting in 2018 to bring together patients, regulators, researchers, clinicians, and consumers to build upon previous OMERACT drug safety work, with patients fully engaged throughout all phases.

METHODS: Day 1 included a brief introduction to the history of OMERACT and methodology, and an overview of current efforts within and outside OMERACT to identify patient-reported medication safety concerns. On Day 2, two working groups presented results; after each, breakout groups were assembled to discuss findings.

RESULTS: Five themes pertaining to drug safety measurement emerged.

CONCLUSION: Current approaches have failed to include data from the patient's perspective. A better understanding of how individuals with rheumatic diseases view potential benefits and harms of therapies is essential.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 8
Sider (fra-til) 1053-1058
Antal sider 6
ISSN 0315-162X
DOI
Status Udgivet - aug. 2019

Incidence and time trends of joint surgery in patients with psoriatic arthritis: a register-based time series and cohort study from Denmark

Guldberg-Møller, J., Cordtz, R. L., Kristensen, L. E. & Dreyer, L., nov. 2019, I : Annals of the Rheumatic Diseases. 78, 11, s. 1517-1523 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To investigate time-trends and cumulative incidence of joint surgery among patients with psoriatic arthritis (PsA) compared with the general population.

METHODS: In this nationwide register-based cohort study, The Danish National Patient Registry was used to identify incident PsA patients. The 5-year incidence rates (IR) and incidence rate ratios (IRR) of joint surgery were calculated in four calendar-period defined cohorts. Each patient was matched with ten non-PsA individuals from the general population cohort (GPC). The cumulative incidences of any joint and joint-sacrificing surgery, respectively, were estimated using the Aalen-Johansen method.

RESULTS: From 1996 to 2017, 11 960 PsA patients (mean age 50 years; 57% female) were registered. The IRR of any joint surgery was twice as high for PsA patients compared with GPCs across all calendar periods. Among patients with PsA, 2, 10 and 29% required joint surgery at 5, 10 and 15 years after diagnosis. The risk of surgery in PsA patients diagnosed at 18-40 years was higher (22%) than in GPC 60+ year old (20%) after 15 years of follow-up.

CONCLUSIONS: The use of joint surgery among PsA patients remained around twofold higher from 1996 to 2012 compared with GPC. After 15 years of follow-up, nearly 30% of the PsA patients had received any surgery, and even a person diagnosed with PsA at the age of 18-40 years had a higher risk of surgery than GPCs of 60+ year old. Thus, the high surgical rates represent an unmet need in the current treatment of PsA.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 78
Udgave nummer 11
Sider (fra-til) 1517-1523
Antal sider 7
ISSN 0003-4967
DOI
Status Udgivet - nov. 2019

Bibliografisk note

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Inflammation and Hypervascularization in a Large Animal Model of Knee Osteoarthritis: Imaging with Pathohistologic Correlation

Korchi, A. M., Cengarle-Samak, A., Okuno, Y., Martel-Pelletier, J., Pelletier, J. P., Boesen, M., Doyon, J., Bodson-Clermont, P., Lussier, B., Héon, H., Sapoval, M., Bureau, N. J. & Soulez, G., jul. 2019, I : Journal of vascular and interventional radiology : JVIR. 30, 7, s. 1116-1127 12 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: To evaluate if synovial inflammation and hypervascularization are present in a dog model of knee osteoarthritis and can be detected on conventional magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), contrast-enhanced magnetic resonance imaging (CE-MRI), and quantitative digital subtraction angiography (Q-DSA) imaging.

MATERIALS AND METHODS: Six dogs underwent MRI and angiography of both knees before and 12 weeks after right knee anterior cruciate ligament injury. Synovial vascularity was evaluated on CE-MRI, DCE-MRI, and Q-DSA by 2 independent observers. Synovial inflammation and vascularity were histologically scored independently. Cartilage lesions and osteophytes were analyzed macroscopically, and cartilage volumetry was analyzed by MRI. Vascularity and osteoarthritis markers on imaging were compared before and after osteoarthritis generation, and between the osteoarthritis model and the control knee, using linear mixed models accounting for within-dog correlation.

RESULTS: In all knees, baseline imaging showed no abnormalities. Control knees did not develop significant osteoarthritis changes, synovial inflammation, or hypervascularization. In osteoarthritis knees, mean synovial enhancement score on CE-MR imaging increased by 13.1 ± 0.59 (P < .0001); mean synovial inflammation variable increased from 47.33 ± 18.61 to 407.97 ± 18.61 on DCE-MR imaging (P < .0001); and area under the curve on Q-DSA increased by 1058.58 ± 199.08 (P = .0043). Synovial inflammation, hypervascularization, and osteophyte formations were present in all osteoarthritis knees. Histology scores showed strong correlation with CE-MR imaging findings (Spearman correlation coefficient [SCC] = 0.742; P = .0002) and Q-DSA findings (SCC = 0.763; P < .0001) and weak correlation with DCE-MR imaging (SCC = -0.345; P = .329). Moderate correlation was found between CE-MR imaging and DSA findings (SCC = 0.536; P = .0004).

CONCLUSIONS: In this early-stage knee osteoarthritis dog model, synovial inflammation and hypervascularization were found on imaging and confirmed by histology.

Originalsprog Engelsk
Tidsskrift Journal of vascular and interventional radiology : JVIR
Vol/bind 30
Udgave nummer 7
Sider (fra-til) 1116-1127
Antal sider 12
ISSN 1051-0443
DOI
Status Udgivet - jul. 2019

Bibliografisk note

Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

Inter-rater agreement and reliability of outcome measurement instruments and staging systems used in hidradenitis suppurativa

Thorlacius, L., Garg, A., Riis, P. T., Nielsen, S. M., Bettoli, V., Ingram, J. R., Del Marmol, V., Matusiak, L., Pascual, J. C., Revuz, J., Sartorius, K., Tzellos, T., van der Zee, H. H., Zouboulis, C. C., Saunte, D. M., Gottlieb, A. B., Christensen, R. & Jemec, G. B. E., sep. 2019, I : British Journal of Dermatology. 181, 3, s. 483-491 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Monitoring disease activity over time is a prerequisite for clinical practice and research. Valid and reliable outcome measurement instruments (OMIs) and staging systems provide researchers and clinicians with benchmark tools to assess the primary and secondary outcomes of interventional trials and to guide treatment selection properly.

OBJECTIVES: To investigate inter-rater reliability and agreement in instruments currently used in hidradenitis suppurativa (HS), with dermatologists experienced in HS as the rater population of interest.

METHODS: In a prospective completely balanced design, 24 patients with HS underwent a physical examination by 12 raters (288 assessments) using nine instruments. The results were analysed using generalized linear mixed models.

RESULTS: For the staging systems, the study found good inter-rater reliability for Hurley staging in the axillae and gluteal region, moderate inter-rater reliability for Hurley staging in the groin and for Physician's Global Assessment, and fair inter-rater reliability for refined Hurley staging and the International HS Severity Scoring System. For all the tested OMIs, the observed intervals for limits of agreement were very wide relative to the ranges of the scales.

CONCLUSIONS: The very wide intervals for limits of agreement imply that substantial changes are needed in clinical research in order to rule out measurement error. The results illustrate a difficulty, even for experienced HS experts, to agree on the type and number of lesions when evaluating disease severity. The apparent caveats call for global efforts, such as the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) to reach consensus on how best to measure physical signs of HS reliably in randomized trials. What's already known about this topic? Without valid and reliable instruments to measure outcomes, researchers and clinicians lack the necessary benchmarks to assess primary and secondary end points of interventional trials properly. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Several outcome measure instruments exist for HS, but their validation is generally incomplete or of relatively low methodological quality. What does this study add? Using a prospective completely balanced design this study examined inter-rater reliability with HS-experienced dermatologists as the rater population of interest. The study did not find very good reliability for any included instrument or lesion counts. This study illustrates the difficulty in finding agreement on the type and number of HS lesions, even among experts. The results question whether physical signs are best measured by a traditional physician lesion count instrument. What are the clinical implications of this work? For staging, Hurley staging and physician global visual analogue scale proved to be acceptable instruments in terms of inter-rater reliability. For the instruments designed to measure changes in health status, our study illustrates how difficult it is, even for experts, to measure the physical signs of HS using a simple rater counting. Consequently, other assessment methods of physicals signs, such as ultrasound evaluation, require consideration.

Originalsprog Engelsk
Tidsskrift British Journal of Dermatology
Vol/bind 181
Udgave nummer 3
Sider (fra-til) 483-491
Antal sider 9
ISSN 0007-0963
DOI
Status Udgivet - sep. 2019

Bibliografisk note

© 2019 British Association of Dermatologists.

Intratympanic Steroid for Menière's Disease: A Systematic Review

Devantier, L., Djurhuus, B. D., Hougaard, D. D., Händel, M. N., Guldfred, F. L-A., Schmidt, J. H. & Edemann-Callesen, H., jul. 2019, I : Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 40, 6, s. 806-812 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To investigate the beneficial effects and safety of intratympanic steroid installation compared with placebo in patients with Menière's disease.

METHODS: We performed a systematic literature search in MEDLINE and EMBASE for existing systematic reviews and individual randomized controlled trials (RCTs). Studies were included if they investigated the usage intratympanic steroids in patients aged 18 and above, with definite or probable Menière's disease. The quality of the identified existing reviews was assessed using the AMSTAR tool. The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool and overall quality of the individual outcomes was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method.

RESULTS: The literature search provided four systematic reviews, from which one yielded a sufficient AMSTAR evaluation and subsequently provided three RCTs relevant for inclusion. Due to the lack of sufficient reporting of the data, quantitative synthesis was not applicable. In the qualitative synthesis for the primary outcome, the results from the RCTs showed that there was a slight indication of steroid treatment reducing the frequency of vertiginous attacks. No serious adverse events were reported. Based on the GRADE approach the quality for both findings is very low. No studies reported on the secondary outcomes.

CONCLUSION: The effect of intratympanic steroid treatment in Menière's disease is questionable. There is a great need for further research to sufficiently assess whether steroid treatment may be considered as a safe and effective treatment for patients with Menière's disease.

Originalsprog Engelsk
Tidsskrift Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
Vol/bind 40
Udgave nummer 6
Sider (fra-til) 806-812
Antal sider 7
ISSN 1531-7129
DOI
Status Udgivet - jul. 2019

Long-Term Exposure to Road Traffic Noise and Incidence of Diabetes in the Danish Nurse Cohort

Jørgensen, J. T., Bräuner, E. V., Backalarz, C., Laursen, J. E., Pedersen, T. H., Jensen, S. S., Ketzel, M., Hertel, O., Lophaven, S. N., Simonsen, M. K. & Andersen, Z. J., maj 2019, I : Environmental Health Perspectives. 127, 5, s. 57006

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Evidence on the association between road traffic noise and diabetes risk is sparse and inconsistent with respect to how confounding by air pollution was treated.

OBJECTIVES: In this study, we aimed to examine whether long-term exposure to road traffic noise over 25 years is associated with incidence of diabetes, independent of air pollution.

METHODS: A total of 28,731 female nurses from the Danish Nurse cohort ([Formula: see text] at recruitment in 1993 or 1999) were linked to the Danish National Diabetes Register with information on incidence of diabetes from 1995 until 2013. The annual mean weighted levels of 24-h average road traffic noise ([Formula: see text]) at nurses' residences from 1970 until 2013 were estimated with the Nord2000 method and annual mean levels of particulate matter (PM) with diameter [Formula: see text] and [Formula: see text] ([Formula: see text] and [Formula: see text]), nitrogen dioxide ([Formula: see text]), and nitrogen oxide ([Formula: see text]) with the Danish AirGIS modeling system. Cox proportional hazards regression models were used to examine the association between residential [Formula: see text] in four different exposure windows (1-, 5-, 10-, and 25-years) and the incidence of diabetes, adjusted for lifestyle factors and air pollutants.

RESULTS: Of 23,762 nurses free of diabetes at the cohort baseline, 1,158 developed diabetes during a mean follow-up of 15.2 years. We found weak positive associations between 5-y mean exposure to [Formula: see text] (per [Formula: see text] increase) and diabetes incidence in a crude model [hazard ratio (HR): 1.07; 95% confidence interval (CI): 0.99, 1.12], which attenuated in a model adjusted for lifestyle factors (HR:1.04; 95% CI: 0.97, 1.12), and reached unity after additional adjustment for [Formula: see text] (HR: 0.99; 0.91, 1.08). In analyses by level of urbanization, we found a positive association between noise and diabetes in urban areas (HR:1.27; 95% CI: 0.98, 1.63) that was unchanged after adjusting for [Formula: see text] (HR: 1.25; 95% CI: 0.97, 1.62), but we found no apparent association in provincial (HR: 1.02; 95% CI: 0.88, 1.18) or rural areas (HR: 0.97; 95% CI: 0.87, 1.08).

CONCLUSION: In the nationwide cohort of Danish nurses 44 years of age and older, we found no association between long-term exposure to road traffic noise and diabetes incidence after adjustment for [Formula: see text] but found suggestive evidence of an association limited to urban areas. https://doi.org/10.1289/EHP4389.

Originalsprog Engelsk
Tidsskrift Environmental Health Perspectives
Vol/bind 127
Udgave nummer 5
Sider (fra-til) 57006
ISSN 0091-6765
DOI
Status Udgivet - maj 2019

Long-term wind turbine noise exposure and the risk of incident atrial fibrillation in the Danish Nurse cohort

Bräuner, E. V., Jørgensen, J. T., Duun-Henriksen, A. K., Backalarz, C., Laursen, J. E., Pedersen, T. H., Simonsen, M. K. & Andersen, Z. J., sep. 2019, I : Environment International. 130, s. 104915

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: The potential health effects related to wind turbine noise (WTN) have received increased focus during the past decades, but evidence is sparse. We examined the association between long-term exposure to wind turbine noise and incidence of atrial fibrillation (AF).

METHODS: First ever hospital admission of AF amongst 28,731 female nurses in the Danish Nurse Cohort were identified in the Danish National Patient register until ultimo 2013. WTN levels at residential addresses between 1982 and 2013 were estimated using the Nord2000 noise propagation model, as the annual means of Lden, Lday, Levening and Lnight at the most exposed façade. Time-varying Cox proportional hazard regression models were used to examine the association between the 11-, 5- and 1-year rolling means of WTN levels and AF incidence.

RESULTS: 1430 nurses developed AF by end of follow-up in 2013. Mean (standard deviation) baseline residential noise levels amongst exposed nurses were 26.3 (6.7) dB and slightly higher in those who developed AF (27.3 (7.31) dB), than those who didn't (26.2 (6.6)). We observed a 30% statistically significant increased risk (95% CI: 1.05-1.61) of AF amongst nurses exposed to long-term (11-year running mean) WTN levels ≥20 dB(A) at night compared to nurses exposed to levels <20 dB(A). Similar effects were observed with day (HR 1.25; 95% CI: 1.01-1.54), and evening (HR 1.25; 95% CI: 1.01-1.54) noise levels.

CONCLUSIONS: We found suggestive evidence of an association between long-term exposure to WTN and AF amongst female nurses. However, interpretation should be cautious as exposure levels were low.

Originalsprog Engelsk
Tidsskrift Environment International
Vol/bind 130
Sider (fra-til) 104915
ISSN 0160-4120
DOI
Status Udgivet - sep. 2019

Bibliografisk note

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

LOW SERUM LEVEL OF VITAMIN D AT TIME OF DIAGNOSIS IS ASSOCIATED WITH HIGHER ONE-YEAR REMISSION RATE IN PATIENTS WITH NEWLY DIAGNOSED RA, TREATED AGGRESSIVELY DURING FOLLOW-UP: POST-HOC ANALYSES OF THE CIMESTRA TRIAL

Herly, M., Steengaard-Pedersen, K., Vestergaard, P., Christensen, R. D. K., Østergaard, M., Junker, P., Hetland, M. L., Hørslev-Petersen, K. & Ellingsen, T., 2019, I : Annals of the Rheumatic Diseases. 78, Suppl. 2, s. 1112 1 s.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 78
Udgave nummer Suppl. 2
Sider (fra-til) 1112
Antal sider 1
ISSN 0003-4967
Status Udgivet - 2019

MAGNETIC RESONANCE IMAGING TENOSYNOVITIS AND OSTEITIS ARE INDEPENDENT PREDICTORS OF RADIOGRAPHIC AND MRI DAMAGE PROGRESSION IN RHEUMATOID ARTHRITIS PATIENTS IN CLINICAL REMISSION

Møller-Bisgaard, S. K., Hørslev-Petersen, K., Ejbjerg, B., Hetland, M. L., Ørnbjerg, L. M., Glinatsi, D. E., Møller, J. M., Boesen, M., Stengaard-Pedersen, K., Madsen, O., Jensen, B., Villadsen, J., Hauge, E. M., Bennett, P., Hendricks, O., Asmussen, K., Kowalski, M., Lindegaard, H. M., Bliddal, H., Krogh, N. S., Ellingsen, T., Nielsen, A., Larsen, L., Jurik, A. G., Thomsen, H. S. & Østergaard, M., 2019, I : Annals of the Rheumatic Diseases. 78, Suppl. 2, s. 248-249 2 s.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 78
Udgave nummer Suppl. 2
Sider (fra-til) 248-249
Antal sider 2
ISSN 0003-4967
Status Udgivet - 2019

Management of skin, mucosa and joint involvement of Behçet's syndrome: A systematic review for update of the EULAR recommendations for the management of Behçet's syndrome

Leccese, P., Ozguler, Y., Christensen, R., Esatoglu, S. N., Bang, D., Bodaghi, B., Celik, A. F., Fortune, F., Gaudric, J., Gül, A., Kötter, I., Mahr, A., Moots, R. J., Richter, J., Saadoun, D., Salvarani, C., Scuderi, F., Sfikakis, P. P., Siva, A., Stanford, M., Tugal-Tutkun, I., West, R., Yurdakul, S., Olivieri, I., Yazici, H. & Hatemi, G., feb. 2019, I : Seminars in Arthritis and Rheumatism. 48, 4, s. 752-762 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS.

METHODS: A systematic literature search, data extraction, statistical analyses and assessment of the quality of evidence were performed according to a pre-specified protocol using the PRISMA guidelines. Studies that assessed the efficacy of an intervention in comparison to an active comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions, nodular lesions or arthritis were included. Where possible, risk ratios were calculated for binary outcomes and mean difference for continuous outcomes.

RESULTS: Among the 3927 references that were screened, 37 were included in the analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint involvement. Twenty-one of these studies were randomised controlled trials (RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide, etanercept and apremilast showed beneficial results with some differences according to lesion type and gender. These agents were generally well tolerated with few adverse events causing withdrawal from the study.

CONCLUSIONS: RCTs comprised more than a half (21/37, 57%) of the sources included in the evidence synthesis related to skin, mucosa and joint involvement applicable for the EULAR Recommendations for the management of BS. Differences in the outcome measures that were used across the included studies often made it difficult to combine and compare the results.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 48
Udgave nummer 4
Sider (fra-til) 752-762
Antal sider 11
ISSN 0049-0172
DOI
Status Udgivet - feb. 2019

Bibliografisk note

Copyright © 2018 Elsevier Inc. All rights reserved.

BACKGROUND: Few studies have examined the relationship between eating frequency and long-term change in body weight, and the results have been inconsistent.

OBJECTIVE: We examined the associations between eating frequency and 6-y changes in body mass index (BMI; in kg/m2), fat mass, fat-free mass, body fat percentage, and waist circumference.

METHODS: The study consisted of Danish men (n = 1080) and women (n = 1044) aged 35-67 y with repeated measures of eating frequency, adiposity, and covariates during 11 y. Multiple linear regression was used to assess the associations between baseline eating frequency and subsequent change in BMI, fat mass, fat-free mass, fat percentage, and waist circumference, as well as the association between initial change in eating frequency and subsequent change in the same outcomes.

RESULTS: Total baseline eating frequency was not associated with change in outcomes. However, when separately examining regular meals and snacks, each additional daily meal was associated with a subsequent 6-y change in BMI of -0.14 (95% CI: -0.27, -0.00). Similar tendencies of inverse associations were found for change in fat mass (P = 0.04), fat-free mass (P = 0.07), and waist circumference (P = 0.05). We found no association between initial change in total eating frequency and subsequent change in outcomes. However, each additional daily regular meal after 5 y was associated with a subsequent 6-y change in BMI of -0.16 (95% CI: -0.30, -0.01). Inverse associations were also seen for fat (P = 0.04) and fat-free mass (P = 0.05). In contrast, an increase in daily frequency of snacking was associated with an increase in fat mass (P = 0.04) and fat percentage (P = 0.02).

CONCLUSIONS: Our results indicate that total frequency of eating has little or no influence on adiposity among middle-aged Danish men and women. Consumption of regular meals, but not snack consumption, showed a weak inverse association with longitudinal gains in BMI.

Originalsprog Engelsk
Tidsskrift The Journal of Nutrition
Vol/bind 149
Udgave nummer 5
Sider (fra-til) 824-830
Antal sider 7
ISSN 0022-3166
DOI
Status Udgivet - 1 maj 2019

Bibliografisk note

Copyright © American Society for Nutrition 2019.

The condition of active muscles determines an individual's ability to carry out daily activities and has implications for an athlete's performance. Multi-frequency bioimpedance (mfBIA) is a non-invasive, well-known, validated, and much used method to assess muscle condition. However, it is rarely used to its full potential. Our aim was to apply mfBIA fully in the assessment of an adult healthy population, to compare muscle condition in different functional rested muscle groups, with age, and between men and women, and establish a control data set. Fifty healthy subjects (25 men/25 women) aged 20-69 years, participated. mfBIA measurements at a frequency range of 4-1000 kHz were taken from muscles of the lower and the upper extremities, the upper back, and the hand. Data were analyzed using ImpediMed software, giving Impedance, Resistance, Reactance, Phase Angle, Center Frequency, external and internal Resistance, and Membrane Capacitance. Differences between means were tested for statistical significance. A P value >0.05 was considered nonsignificant. While no difference in the mfBIA parameters was seen with age, a highly significant gender difference was seen. At rest, women's muscles cf men's showed a significantly higher center frequency and intra- and extra-cellular resistance, while the membrane capacitance was lower. A set of values for mfBIA parameters for healthy adult individuals are given for some of the main muscles which are frequently part of muscle assessment. The documented gender difference in muscle condition at rest has important implications in work situations, during physical rehabilitation and when training for competitive sports.

Originalsprog Engelsk
Tidsskrift Physiological Reports
Vol/bind 7
Udgave nummer 11
Sider (fra-til) e14109
ISSN 2051-817X
DOI
Status Udgivet - jun. 2019

Bibliografisk note

© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Night work and miscarriage: a Danish nationwide register-based cohort study

Begtrup, L. M., Specht, I. O., Hammer, P. E. C., Flachs, E. M., Garde, A. H., Hansen, J., Hansen, Å. M., Kolstad, H. A., Larsen, A. D. & Bonde, J. P., maj 2019, I : Occupational and Environmental Medicine. s. 302-308 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Observational studies indicate an association between working nights and miscarriage, but inaccurate exposure assessment precludes causal inference. Using payroll data with exact and prospective measurement of night work, the objective was to investigate whether working night shifts during pregnancy increases the risk of miscarriage.

METHODS: A cohort of 22 744 pregnant women was identified by linking the Danish Working Hour Database (DWHD), which holds payroll data on all Danish public hospital employees, with Danish national registers on births and admissions to hospitals (miscarriage). The risk of miscarriage during pregnancy weeks 4-22 according to measures of night work was analysed using Cox regression with time-varying exposure adjusted for a fixed set of potential confounders.

RESULTS: In total 377 896 pregnancy weeks (average 19.7) were available for follow-up. Women who had two or more night shifts the previous week had an increased risk of miscarriage after pregnancy week 8 (HR 1.32 (95% CI 1.07 to 1.62) compared with women, who did not work night shifts. The cumulated number of night shifts during pregnancy weeks 3-21 increased the risk of miscarriages in a dose-dependent pattern.

CONCLUSIONS: The study corroborates earlier findings that night work during pregnancy may confer an increased risk of miscarriage and indicates a lowest observed threshold level of two night shifts per week.

Originalsprog Engelsk
Tidsskrift Occupational and Environmental Medicine
Sider (fra-til) 302-308
Antal sider 7
ISSN 1351-0711
DOI
Status Udgivet - maj 2019

Bibliografisk note

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Night work and sick leave during pregnancy: a national register-based within-worker cohort study

Hammer, P. E. C., Garde, A. H., Begtrup, L. M., Flachs, E. M., Hansen, J., Hansen, Å. M., Hougaard, K. S., Kolstad, H. A., Larsen, A. D., Pinborg, A. B., Specht, I. O. & Bonde, J. P., mar. 2019, I : Occupational and Environmental Medicine. 76, 3, s. 163-168 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The aim of our study was to investigate the acute effect of night work during pregnancy on the risk of calling in sick the following day using register-based information and the workers as their own controls.

METHODS: Using the payroll-based national Danish Working Hour Database, including all public hospital employees in Denmark, we identified 9799 pregnant women with ≥1 day shift and ≥1 night shift and ≥1 day of sick leave during the first 32 pregnancy weeks from January 2007 to December 2013. We performed fixed effects logistic regression, that is, within-worker comparisons, of the risk of sick leave of any duration starting within 24 hours after night shifts of different length versus day shifts.

RESULTS: Most of the participants were nurses (64%) or physicians (16%). We found an increased relative risk of sick leave following night shifts compared with day shifts during all pregnancy trimesters. The risk was highest for night shifts lasting >12 hours (OR 1.37, 95% CI 1.15 to 1.63 for nurses; OR 1.87, 95% CI 1.69 to 2.08 for physicians) and among women aged >35 years (OR 1.42, 95% CI 1.24 to 1.63).

CONCLUSION: Among Danish public hospital employees night shifts during pregnancy, especially shifts longer than 12 hours, increased the risk of calling in sick the following day independent of personal factors and time-invariant confounders in all pregnancy trimesters.

Originalsprog Engelsk
Tidsskrift Occupational and Environmental Medicine
Vol/bind 76
Udgave nummer 3
Sider (fra-til) 163-168
Antal sider 6
ISSN 1351-0711
DOI
Status Udgivet - mar. 2019

Night work during pregnancy and preterm birth-A large register-based cohort study

Specht, I. O., Hammer, P. E. C., Flachs, E. M., Begtrup, L. M., Larsen, A. D., Hougaard, K. S., Hansen, J., Hansen, Å. M., Kolstad, H. A., Rugulies, R., Garde, A. H. & Bonde, J. P., 2019, I : PLoS One. 14, 4, s. e0215748

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Melatonin stimulates the production of progesterone, which is essential for the maintenance of pregnancy. Since melatonin in blood is reduced due to work under illuminated conditions during night work, it has been hypothesized that night work may increase the risk of preterm birth. Previous meta-analyses have not revealed increased risk of preterm birth in women working night shifts during pregnancy. Still, these studies might have been limited by inaccurate self-reports of timing, intensity and duration of night work most likely causing bias towards the null. The aim of this is study was to investigate if the frequency and duration of night work during the first (week 1-12) and second (week 13-22) trimester of pregnancy were associated with risk of preterm birth when objective and prospective data on night work are used.

METHOD: In a register-based prospective cohort study, we obtained individual day-to-day information on working hours from The Danish Working Hour Database (DWHD, a payroll database including all public service employees in administrative Danish Regions from 2007-2013) and information on preterm birth from the Danish Medical Birth Registry. Night-shift was defined as at least three working hours between 23:00 and 06:00. Preterm birth was defined as giving birth during gestational weeks 23-37. Odds of preterm birth according to working night shifts were analysed by logistic regression.

RESULTS: We identified 16,501 pregnant women eligible for the study, of which 10,202 women (61.8%) had at least one night-shift during the first 22 gestational weeks. The risk of preterm birth was not elevated among women working night shifts compared to women working only day shifts during either the first or second trimester. Within night-shift workers, the risk was not related to the number of night shifts, the duration of night shifts, consecutive night shifts or quick returns defined as short intervals between shifts. Odds of preterm birth was not related to change of working schedule from the first to second trimester, although women changing from night shifts in the first trimester to day work only in the second trimester displayed a weak increased odds of preterm birth (OR 1.21, 95%CI 0.98-1.49) compared to women working night shifts in both trimesters.

CONCLUSION: Our results, which are without bias from self-report of either exposure or outcome, are in line with the results of previous meta-analyses. Due to the detailed information on hours worked during pregnancy, we were able to investigate several dimensions of night work not previously investigated, of which none were associated with elevated risk of preterm birth.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 14
Udgave nummer 4
Sider (fra-til) e0215748
ISSN 1932-6203
DOI
Status Udgivet - 2019

OMERACT Development of a Core Domain Set of Outcomes for Shared Decision-making Interventions

Toupin-April, K., Barton, J. L., Fraenkel, L., Meara, A., Li, L. C., Brooks, P., de Wit, M., Stacey, D., Légaré, F., Shea, B., Lyddiatt, A., Hofstetter, C., Christensen, R., Scholte Voshaar, M., Suarez-Almazor, M. E., Boonen, A., Meade, T., March, L., Jull, J. E., Campbell, W., Alten, R., Karuranga, S., Morgan, E. M., Kelly, A., Kaufman, J., Hill, S., Maxwell, L. J., Beaton, D., El-Miedany, Y., Mittoo, S., Bartlett, S. J., Singh, J. A. & Tugwell, P. S., okt. 2019, I : Journal of Rheumatology. 46, 10, s. 1409-1414 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Shared Decision Making (SDM) Working Group aims to determine the core outcome domain set for measuring the effectiveness of SDM interventions in rheumatology trials.

METHODS: A white paper was developed to clarify the draft core domain set. It was then used to prepare for interviews to investigate reasons for lack of consensus on it and to suggest further improvements.

RESULTS: OMERACT scientists/clinicians (n = 13) and patients (n = 10) suggested limiting the core domain set to outcome domains, removing process domains, and clarifying remaining domains.

CONCLUSION: A revised core domain set will undergo further consensus-building.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 10
Sider (fra-til) 1409-1414
Antal sider 6
ISSN 0315-162X
DOI
Status Udgivet - okt. 2019

Opioid-Induced Reductions in Gait Variability in Healthy Volunteers and Individuals with Knee Osteoarthritis

Henriksen, M., Alkjær, T., Raffalt, P. C., Jørgensen, L., Bartholdy, C., Hansen, S. H. & Bliddal, H., 12 jan. 2019, I : Pain medicine (Malden, Mass.).

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Objective: To investigate differences in gait variability induced by two different single-dose opioid formulations and an inert placebo in healthy volunteers and knee osteoarthritis patients.

Design: Experimental, randomized, double-blinded, crossover study of inert placebo (calcium tablets), 50 mg of tapentadol, and 100 mg of tramadol.

Setting: Laboratory setting.

Subjects: Healthy volunteers and knee osteoarthritis patients.

Methods: At three visits, separated by seven days, one tablet was administered per visit according to the randomization code. At each visit, a baseline measurement was done before tablet administration, after which hourly measurements were performed for six hours, yielding a total of seven measurements per visit. Gait variability was measured by three-dimensional gait analysis, recorded during six minutes of continuous treadmill walking at self-selected speed. One hundred seventy gait cycles were identified from detection of clear events of the knee joint angle trajectories. Gait variability was assessed as average standard deviations over a gait cycle of the sacrum displacements and accelerations; sagittal plane ankle, knee, and hip joint angles; step widths; and stride times.

Results: Twenty-four opioid-naïve and neurologically intact participants (12 healthy volunteers and 12 knee osteoarthritis patients) were included and completed the experiment. Tapentadol reduced the variability of sacrum displacements and accelerations compared with placebo and tramadol. There were no differences between experimental conditions regarding the variability in lower-extremity joint angle variability, step widths, or stride times.

Conclusions: In opioid-naïve and neurologically intact individuals, tapentadol seems to reduce movement variability during treadmill walking, compared with placebo and tramadol. This can be interpreted as a loss of adaptability that might increase the risk of falling if the system is perturbed.

Originalsprog Engelsk
Tidsskrift Pain medicine (Malden, Mass.)
ISSN 1526-2375
DOI
Status E-pub ahead of print - 12 jan. 2019

Osteoarthritis phenotypes and novel therapeutic targets

Van Spil, W. E., Kubassova, O., Boesen, M., Bay-Jensen, A-C. & Mobasheri, A., jul. 2019, I : Biochemical Pharmacology. 165, s. 41-48 8 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

The success of disease-modifying osteoarthritis drug (DMOAD) development is still elusive. While there have been successes in preclinical and early clinical studies, phase 3 clinical trials have failed so far and there is still no approved, widely available DMOAD on the market. The latest research suggests that, among other causes, poor trial outcomes might be explained by the fact that osteoarthritis (OA) is a heterogeneous disease with distinct phenotypes. OA trials might be more successful if they would address and target a specific phenotype. The increasing availability of advanced techniques to detect particular OA characteristics expands the possibilities to distinguish between such potential OA phenotypes. Magnetic resonance imaging is among the key imaging techniques to stratify and monitor patients with changes in bone, cartilage and inflammation. Biochemical markers have mainly used as secondary parameters and could further delineate phenotypes. Moreover, post-hoc analyses of trial data have suggested the existence of distinct pain phenotypes and their relevance in the design of clinical trials. Although ongoing work in the field supports the concept of OA heterogeneity, this has not yet resulted in more effective treatment options. This paper reviews the current knowledge about potential OA phenotypes and suggests that combining patient clinical data, quantitative imaging, biochemical markers and utilizing data-driven approaches in patient selection and efficacy assessment will allow for more successful development of effective DMOADs.

Originalsprog Engelsk
Tidsskrift Biochemical Pharmacology
Vol/bind 165
Sider (fra-til) 41-48
Antal sider 8
ISSN 0006-2952
DOI
Status Udgivet - jul. 2019

Bibliografisk note

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Pain Measurement in Rheumatic and Musculoskeletal Diseases: Where To Go from Here? Report from a Special Interest Group at OMERACT 2018

Chiarotto, A., Kaiser, U., Choy, E., Christensen, R., Conaghan, P. G., Cowern, M., Gill, M., de Wit, M., Gargon, E., Horgan, B., Kirkham, J. J., Simon, L. S., Singh, J. A., Tugwell, P., Turk, D. C. & Mease, P. J., okt. 2019, I : Journal of Rheumatology. 46, 10, s. 1355-1359 5 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Establishing a research agenda on standardizing pain measurement in clinical trials in rheumatic and musculoskeletal diseases (RMD).

METHODS: Discussion during a meeting at the Outcome Measures in Rheumatology (OMERACT) 2018, prepared by a systematic review of existing core outcome sets and a patient online survey.

RESULTS: Several key questions were debated: Is pain a symptom or a disease? Are pain core (sub)domains consistent across RMD? How to account for pain mechanistic descriptors (e.g., central sensitization) in pain measurement?

CONCLUSION: Characterizing and assessing the spectrum of pain experience across RMD in a standardized fashion is the objective of the OMERACT Pain Working Group.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 10
Sider (fra-til) 1355-1359
Antal sider 5
ISSN 0315-162X
DOI
Status Udgivet - okt. 2019

OBJECTIVE: To study the prognostic value of widespread pain and of musculoskeletal ultrasound (US) examination for subsequent treatment outcomes in patients with psoriatic arthritis (PsA).

METHODS: An exploratory prospective cohort study enrolled patients with PsA initiating biologic or conventional synthetic disease-modifying antirheumatic drugs in routine care. Clinical, US, and patient-reported measures were collected at baseline and after 4 months. Widespread nonarthritic pain (WP) was defined as a Widespread Pain Index score of ≥4 with pain in ≥4 of 5 regions. PsA activity by US was defined as color Doppler (yes/no) in selected entheses, joints, or tendons. The main response criteria included the American College of Rheumatology 20% improvement, the Disease Activity in Psoriatic Arthritis 50% improvement, and minimal disease activity. The primary analyses were age- and sex-adjusted logistic regression.

RESULTS: WP was present in 24 of 69 included patients (35%) and was associated with worse patient-reported and composite baseline measures, while US and other objective findings were similar to those in patients without WP. The odds of reaching minimal disease activity after 4 months were significantly greater for patients enrolled without WP (odds ratio 18.43 [95% confidence interval 1.51, 224.41]; P = 0.022), while WP did not impair other response measures. Patients with baseline color Doppler activity (n = 42 [61%]) had a worse objective PsA burden, but their chance of treatment response was comparable to those without color Doppler.

CONCLUSION: More than one-third of patients with PsA presented with WP, which was associated with worse patient-reported scores and failure to achieve minimal disease activity following conventional synthetic or biologic disease-modifying antirheumatic drug therapy. PsA activity by color Doppler US had no influence on subsequent treatment response in this PsA cohort.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
Vol/bind 71
Udgave nummer 6
Sider (fra-til) 798-810
Antal sider 13
ISSN 2151-464X
DOI
Status Udgivet - jun. 2019

Bibliografisk note

© 2018, American College of Rheumatology.

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