Published in 2018

The relation between maximal voluntary force in m. palmaris longus and the temporal and spatial summation of muscle fiber recruitment in human subjects

Claudel, C. G., Ahmed, W., Elbrønd, V. S., Harrison, A. P. & Bartels, E. M. jan. 2018 I : Physiological Reports. 6, 1

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

This study aimed at looking at the frequency (T-score) and the amplitude (S-score) of fiber use during contraction of a forearm muscle, m. palmaris longus, as measured by acoustic myography (AMG). An additional aim was to relate the T- and S-scores to the recorded force obtained from a hand dynamometer. The hypothesis being that temporal and spatial summation of muscle fiber contraction in a given muscle during a given movement, can together describe a given obtained force. Force measurements were carried out on 12 healthy human subjects aged 19-68 years (6 men & 6 women), while their m. palmaris longus contractile function was measured using an acoustic myography CURO device. Force production was varied from 90 to 10% of assessed maximal voluntary force (MVF), and also monitored over a 1 min period of 50% MVF. Linear regression analysis was applied to relate force to spatial and temporal summation. Muscle strength was sustained by changing the frequency and/or the number of active fibere at any given point in time. Force production, whilst stronger for men than women, was regulated in a similar fashion for both sexes and was closely correlated with the AMG T- and S-scores. It is concluded that AMG is a noninvasive method which can be readily applied to accurately describe how a subject uses a given muscle during any given movement. These findings have relevance when considering training strategies in subjects with muscle trauma or disease, in the elderly, or for both amateur and top professional athletes.

Originalsprog Engelsk
Tidsskrift Physiological Reports
Vol/bind 6
Tidsskriftsnummer 1
ISSN 2051-817X
DOI
Status Udgivet - jan. 2018

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II

Thorlacius, L., Garg, A., Ingram, J. R., Villumsen, B., Theut Riis, P., Gottlieb, A. B., Merola, J. F., Dellavalle, R., Ardon, C., Baba, R., Bechara, F. G., Cohen, A. D., Daham, N., Davis, M., Emtestam, L., Fernández-Peñas, P., Filippelli, M., Gibbons, A., Grant, T., Guilbault, S., Gulliver, S., Harris, C., Harvent, C., Houston, K., Kirby, J. S., Matusiak, L., Mehdizadeh, A., Mojica, T., Okun, M., Orgill, D., Pallack, L., Parks-Miller, A., Prens, E. P., Randell, S., Rogers, C., Rosen, C. F., Choon, S. E., van der Zee, H. H., Christensen, R. & Jemec, G. B. E. mar. 2018 I : British Journal of Dermatology. 178, 3, s. 715-721 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items.

OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains.

METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey.

RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments.

CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Originalsprog Engelsk
Tidsskrift British Journal of Dermatology
Vol/bind 178
Tidsskriftsnummer 3
Sider (fra-til) 715-721
Antal sider 7
ISSN 0007-0963
DOI
Status Udgivet - mar. 2018

OBJECTIVES: To assess the importance of trial characteristics as contextual factors when evaluating treatment effect of targeted therapies for patients with psoriatic disease.

METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the two psoriatic conditions combined by using drug retention as common outcome, and separately by using ACR20 for PsA and PASI75 for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta-regression analyses. Odds ratios (OR) were calculated and compared among the trial eligibility criteria via the Ratio of Odds Ratios (ROR).

RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons, 17,737 patients) were eligible. Overall retention was OR 2.16 (1.70 to 2.75) with higher odds for PsA trials compared with psoriasis trials (ROR = 2.55 [1.64 to 3.97]). The eligibility criteria "targeted therapy history", "minimum required disease duration", "required negative rheumatoid factor", and "required CASPAR criteria" were of importance for achieving ACR20 in PsA. The eligibility criterion "minimum required disease duration" was of importance for achieving PASI75 in psoriasis. 7 PsA trials had rescue before time point of retention reporting (adaptive trials).

CONCLUSION: From this exploratory meta-epidemiological study we now have evidence from RCTs to support that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials. This article is protected by copyright. All rights reserved.

Originalsprog Engelsk
Tidsskrift Arthritis Care & Research
ISSN 2151-464X
DOI
Status E-pub ahead of print - 2018

Bibliografisk note

COPECARE

Variability in the Reporting of Serum Urate and Flares in Gout Clinical Trials: Need for Minimum Reporting Requirements

Stamp, L. K., Morillon, M. B., Taylor, W. J., Dalbeth, N., Singh, J. A., Lassere, M. & Christensen, R. mar. 2018 I : Journal of Rheumatology. 45, 3, s. 419-424 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To describe the ways in which serum urate (SU) and gout flares are reported in clinical trials, and to propose minimum reporting requirements.

METHODS: This analysis was done as part of a systematic review aiming to validate SU as a biomarker for gout. The ways in which SU and flares were reported were extracted from each study by 2 reviewers.

RESULTS: A total of 22 studies (10 randomized controlled trials, 3 open-label extension studies, and 9 observational studies) were identified. There were 3 broad categories of SU reporting: percentage at target SU, mean SU, and change in SU. A median of 2 (range 1-3) categories were reported across all studies. The most common method of reporting SU was percentage at target in 17/22 (77.3%) studies, with all studies reporting a target of SU < 6 mg/dl. There were 12/22 (54.5%) studies reporting mean SU at some time after study entry, with 7 (58.3%) of these reporting at more than just the final study visit. Two ways of reporting gout flares were identified: mean flare rate and percentage of participants with flares. There was variability in time periods over which flares rates were reported.

CONCLUSION: There is inconsistent reporting of SU and flares in gout studies. Reporting the percentage of participants who achieve a target SU reflects international treatment guidelines. SU should also be reported as a continuous variable with a relevant central and dispersion estimate. Gout flares should be reported as both percentage of participants and mean flare rates at each timepoint.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 45
Tidsskriftsnummer 3
Sider (fra-til) 419-424
Antal sider 6
ISSN 0315-162X
DOI
Status Udgivet - mar. 2018

Published in 2017

A neuromuscular exercise programme versus standard care for patients with traumatic anterior shoulder instability: study protocol for a randomised controlled trial (the SINEX study)

Eshoj, H., Rasmussen, S., Frich, L. H., Hvass, I., Christensen, R., Jensen, S. L., Søndergaard, J., Søgaard, K. & Juul-Kristensen, B. 28 feb. 2017 I : Trials. 18, 1, s. 90

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme with standard care in patients with traumatic anterior shoulder dislocations (TASD).

METHODS/DESIGN: Randomised, assessor-blinded, controlled, multicentre trial. Eighty patients with a TASD will be recruited from three orthopaedic departments in Denmark. Patients with primary or recurrent anterior shoulder dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status (primary or recurrent). Primary outcome will be change from baseline to 12 weeks in the patient-reported QoL outcome questionnaire, the Western Ontario Shoulder Instability Index (WOSI).

DISCUSSION: This trial will be the first study to compare the efficacy and safety of two different nonoperative exercise treatment strategies for patients with TASD. Moreover, this is also the first study to investigate nonoperative treatment effects in patients with recurrent shoulder dislocations. Lastly, this study will add knowledge to the shared decision-making process of treatment strategies for clinical practice.

TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02371928 . Registered on 9 February 2015 at the National Institutes of Health Clinical Trials Protocol Registration System.

Originalsprog Engelsk
Tidsskrift Trials
Vol/bind 18
Tidsskriftsnummer 1
Sider (fra-til) 90
ISSN 1745-6215
DOI
Status Udgivet - 28 feb. 2017

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine

Andersen, V., Holmskov, U., Sørensen, S. B., Jawhara, M., Andersen, K. W., Bygum, A., Hvid, L., Grauslund, J., Wied, J., Glerup, H., Fredberg, U., Villadsen, J. A., Kjær, S. G., Fallingborg, J., Moghadd, S. A. G. R., Knudsen, T., Brodersen, J. B., Frøjk, J., Dahlerup, J. F., Nielsen, O. H., Christensen, R., Bojesen, A. B., Sorensen, G. L., Thiel, S., Færgeman, N. J., Brandslund, I., Stensballe, A., Schmidt, E. B., Franke, A., Ellinghaus, D., Rosenstiel, P., Raes, J., Heitmann, B., Boyé, M., Nielsen, C. L., Werner, L., Kjeldsen, J. & Ellingsen, T. 15 maj 2017 I : Nutrients. 9, 5, 499

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

Originalsprog Engelsk
Artikelnummer 499
Tidsskrift Nutrients
Vol/bind 9
Tidsskriftsnummer 5
ISSN 2072-6643
DOI
Status Udgivet - 15 maj 2017

Vitamin A deficiency has been associated with impaired fetal pancreatic development and increased risk of developing type 2 diabetes mellitus (T2DM). In 1962, mandatory margarine fortification with vitamin A was increased by 25 % in Denmark. We aimed to determine whether offspring of mothers who had been exposed to the extra vitamin A from fortification during pregnancy had a lower risk of developing T2DM in adult life, compared with offspring of mothers exposed to less vitamin A. Individuals from birth cohorts with the higher prenatal vitamin A exposure (born 1 December 1962-31 March 1964) and those with lower prenatal exposure (born 1 September 1959-31 December 1960) were followed up with regard to development of T2DM before 31 December 2012 in the Danish National Diabetes Registry and National Patient Register. Logistic and Cox regression analyses were performed to determine the risk of T2DM by vitamin A exposure level. A total of 193 803 individuals were followed up until midlife. Our results showed that individuals exposed prenatally to extra vitamin A from fortified margarine had a lower risk of developing T2DM than those exposed to lower levels: OR 0·88; 95 % CI 0·81, 0·95, P=0·001, after adjustment for sex. Fetal exposure to small, extra amounts of vitamin A from food fortification may reduce the risk of T2DM. These results may have public health relevance, as they demonstrate that one of the most costly chronic diseases may be prevented by food fortification - a simple and affordable public health nutrition intervention.

Originalsprog Engelsk
Tidsskrift The British journal of nutrition
Vol/bind 117
Tidsskriftsnummer 5
Sider (fra-til) 731-736
Antal sider 6
ISSN 0007-1145
DOI
Status Udgivet - mar. 2017

OBJECTIVE: To determine the comparative efficacy and safety of antipsychotics for youth with early-onset schizophrenia using network meta-analytic methods combining direct and indirect trial data.

METHOD: The authors systematically searched MEDLINE, the Cochrane Library, and clinicaltrials.gov and selected randomized controlled trials allocating youth with schizophrenia spectrum disorders to a (non-clozapine) antipsychotic versus placebo or another antipsychotic. Major efficacy outcomes were Positive and Negative Syndrome Scale (PANSS) total and positive symptoms. Major safety outcomes were weight, plasma triglyceride levels, extrapyramidal symptoms, akathisia, and all-cause discontinuation. Sixteen additional outcomes were analyzed. A random-effects arm-based network meta-analysis was applied, and consistency was assessed by pairwise meta-analysis. Confidence in PANSS total estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

RESULTS: Twelve 6- to 12-week trials (N = 2,158; 8-19 years old; 61% boys) involving 8 antipsychotics (aripiprazole, asenapine, paliperidone, risperidone, quetiapine, olanzapine, molindone, and ziprasidone) were analyzed. PANSS total symptom change was comparable among antipsychotics (low- to moderate-quality evidence), except ziprasidone (very low- to low-quality evidence), and all antipsychotics were superior to placebo (low- to high-quality evidence), except ziprasidone and asenapine (low- to moderate-quality evidence). PANSS positive changes and additional efficacy outcomes were comparable among antipsychotics. Weight gain was primarily associated with olanzapine; extrapyramidal symptoms and akathisia were associated with molindone; and prolactin increased with risperidone, paliperidone, and olanzapine. Serious adverse events, discontinuation of treatment, sedation, insomnia, or change in triglycerides did not differ among antipsychotics.

CONCLUSION: This network meta-analysis showed comparable efficacy among antipsychotics for early-onset schizophrenia, except that efficacy appeared inferior for ziprasidone and unclear for asenapine. Adverse reaction profiles varied substantially among the investigated antipsychotics and were largely consistent with prior findings in adults. Protocol registration information-Antipsychotic Treatment for Children With Schizophrenia Spectrum Disorders: Network Meta-Analysis of Randomised Trials; https://www.crd.york.ac.uk/PROSPERO/; CRD42013006676.

Originalsprog Engelsk
Tidsskrift Journal of the American Academy of Child and Adolescent Psychiatry
Vol/bind 56
Tidsskriftsnummer 3
Sider (fra-til) 191-202
Antal sider 12
ISSN 0890-8567
DOI
Status Udgivet - mar. 2017

Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment

Darzi, A., Harfouche, M., Arayssi, T., Alemadi, S., Alnaqbi, K. A., Badsha, H., Al Balushi, F., Elzorkany, B., Halabi, H., Hamoudeh, M., Hazer, W., Masri, B., Omair, M. A., Uthman, I., Ziade, N., Singh, J. A., Christensen, R. D. K., Tugwell, P., Schünemann, H. J. & Akl, E. A. 21 sep. 2017 I : Health and Quality of Life Outcomes. 15, 1, s. 183

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR.

METHODS: We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software.

RESULTS: The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost (n = 5 [100%]), impact on health equities (n = 4 [80%]), the balance of benefits and harms (n = 1 [20%]) and acceptability (n = 1 [20%]).

CONCLUSION: This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.

Originalsprog Engelsk
Tidsskrift Health and Quality of Life Outcomes
Vol/bind 15
Tidsskriftsnummer 1
Sider (fra-til) 183
ISSN 1477-7525
DOI
Status Udgivet - 21 sep. 2017
Originalsprog Engelsk
Artikelnummer THU0340
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 76
Tidsskriftsnummer Suppl 2
Sider (fra-til) 332
Antal sider 1
ISSN 0003-4967
Status Udgivet - 2017

Bibliografisk note

COPECARE

BACKGROUND: Studies have suggested a link between alcohol intake and adiposity. However, results from longitudinal studies have been inconsistent, and a possible interaction with genetic predisposition to adiposity measures has often not been taken into account.

OBJECTIVE: To examine the association between alcohol intake recorded at baseline and subsequent annual changes in body weight (∆BW), waist circumference (ΔWC) and WC adjusted for BMI (ΔWCBMI), and to test for interaction with genetic predisposition scores based on single nucleotide polymorphisms (SNPs) associated with various forms of adiposity.

METHOD: This study included a total of 7028 adult men and women from MONICA, the Diet, Cancer and Health cohort (DCH), and the Inter99 studies. We combined 50 adiposity-associated SNPs into four scores indicating genetic predisposition to BMI, WC, WHRBMI and all three traits combined. Linear regression was used to examine the association of alcohol intake (drinks of 12 g (g) alcohol/day) with ΔBW, ΔWC, and ΔWCBMI, and to examine possible interactions with SNP-scores. Results from the analyses of the individual cohorts were combined in meta-analyses.

RESULTS: Each additional drink/day was associated with a ΔBW/year of -18.0 g (95% confidence interval (CI): -33.4, -2.6, P = 0.02) and a ΔWC of -0.3 mm/year (-0.5, -0.0, P = 0.03). In analyses of women only, alcohol intake was associated with a higher ΔWCBMI of 0.5 mm/year (0.2, 0.9, P = 0.002) per drink/day. Overall, we found no statistically significant interactions between the four SNP-scores and alcohol intake in relation to changes in adiposity measures. However in analyses of women separately, we found interaction between the complete score of all 50 SNPs and alcohol intake in relation to ΔBW (P for interaction = 0.03). No significant interaction was observed among the men.

CONCLUSION: Alcohol intake was associated with a decrease in BW and WC among men and women, and an increase in WCBMI among women only. We found no strong indication that these associations depend on a genetic predisposition to adiposity.

TRIAL REGISTRATION: Registry: ClinicalTrials.gov Trial number: CT00289237 , Registered: 19 September 2005 retrospectively registered.

Originalsprog Engelsk
Tidsskrift Nutrition Journal
Vol/bind 16
Tidsskriftsnummer 1
Sider (fra-til) 51
ISSN 1475-2891
DOI
Status Udgivet - 25 aug. 2017

AIM: To assess the effect of elevated basal shear stress on angiogenesis in humans and the role of enhanced skeletal muscle capillarization on blood flow and O2 extraction.

METHODS: Limb haemodynamics and O2 extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24 W) in 10 healthy untrained young men before and after 4-week treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day-1 ). Corresponding biopsies were taken from the m. vastus lateralis.

RESULTS: Resting leg blood flow was increased by 57% 6 h following Terazosin treatment (P < 0.05), while basal capillary-to-fibre ratio was 1.69 ± 0.08 and increased to 1.90 ± 0.08 after treatment (P < 0.05). Leg O2 extraction during knee-extensor exercise was higher (4-5%; P < 0.05), leg blood flow and venous lactate levels lower (6-7%; P < 0.05), while leg VO2 was not different after Terazosin treatment.

CONCLUSIONS: These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarization resulted in an increased fractional O2 extraction, a lower blood flow and venous lactate levels in the exercising leg. The increase in capillarization, and concomitant functional readouts in the exercising leg, may provide a basis for novel angiotherapy.

Originalsprog Engelsk
Tidsskrift Acta physiologica (Oxford, England)
Vol/bind 221
Tidsskriftsnummer 1
Sider (fra-til) 32-43
Antal sider 12
ISSN 1748-1708
DOI
Status Udgivet - sep. 2017

An OMERACT Initiative Toward Consensus to Identify and Characterize Candidate Contextual Factors: Report from the Contextual Factors Working Group

Finger, M. E., Boonen, A., Woodworth, T. G., Escorpizo, R., Christensen, R., Nielsen, S. M., Leong, A. L., Scholte-Voshaar, M., Flurey, C. A., Milman, N., Verstappen, S. M. M., Alten, R., Guillemin, F., Kloppenburg, M., Beaton, D. E., Tugwell, P. S., March, L. M., Furst, D. E. & Pohl, C. 1 maj 2017 I : Journal of Rheumatology.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: The importance of contextual factors (CF) for appropriate patient-specific care is widely acknowledged. However, evidence in clinical trials on how CF influence outcomes remains sparse. The 2014 Outcome Measures in Rheumatology (OMERACT) Handbook introduced the role of CF in outcome assessment and defined them as "potential confounders and/or effect modifiers of outcomes in randomized controlled trials." Subsequently, the CF Methods Group (CFMG) was formed to develop guidance on how to address CF in clinical trials.

METHODS: First, the CFMG conducted an e-mail survey of OMERACT working groups (WG) to analyze how they had addressed CF in outcome measurement so far. The results facilitated an informed discussion at the OMERACT 2016 CFMG Special Interest Group (SIG) session, with the aim of gaining preliminary consensus regarding an operational definition of CF and to make a first selection of potentially relevant CF.

RESULTS: The survey revealed that the WG had mostly used the OMERACT Handbook and/or the International Classification of Functioning, Disability and Health (ICF) definition. However, significant heterogeneity was found in the methods used to identify, refine, and categorize CF candidates. The SIG participants agreed on using the ICF as a framework along with the OMERACT Handbook definition. A list with 28 variables was collected including person-related factors and physical and social environments. Recommendations from the SIG guided the CFMG to formulate 3 preliminary projects on how to identify and analyze CF.

CONCLUSION: New methods are urgently needed to assist researchers to identify and characterize CF that significantly influence the interpretation of results in clinical trials. The CFMG defined first steps to develop further guidance.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
ISSN 0315-162X
DOI
Status Udgivet - 1 maj 2017

Ankylosing Spondylitis versus Nonradiographic Axial Spondyloarthritis: Comparison of Tumor Necrosis Factor Inhibitor Effectiveness and Effect of HLA-B27 Status. An Observational Cohort Study from the Nationwide DANBIO Registry

Glintborg, B., Sørensen, I. J., Østergaard, M., Dreyer, L., Mohamoud, A. A., Krogh, N. S., Hendricks, O., Andersen, L. S., Raun, J. L., Kowalski, M. R., Danielsen, L., Pelck, R., Nordin, H., Pedersen, J. K., Kraus, D. G., Christensen, S. R., Hansen, I. M., Esbesen, J., Schlemmer, A., Loft, A. G., Al Chaer, N., Salomonsen, L. & Hetland, M. L. jan. 2017 I : Journal of Rheumatology. 44, 1, s. 59-69 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status).

METHODS: Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e.g., Bath Ankylosing Spondylitis Activity Index (BASDAI) 50%/20 mm].

RESULTS: The study included 1250 TNFi-naive patients with axSpA (29% nr-axSpA, 50% AS, 21% lacked radiographs of sacroiliac joints). Patients with nr-axSpA were more frequently women (50%/27%) and HLA-B27-negative (85/338 = 25%), compared to AS (81/476 = 17%; p < 0.01). At TNFi start patients with nr-axSpA had higher visual analog scale scores [median (quartiles)] for pain: 72 mm (55-84)/65 mm (48-77); global: 76 mm (62-88)/68 mm (50-80); fatigue: 74 mm (55-85)/67 mm (50-80); and BASDAI: 64 (54-77)/59 (46-71); all p < 0.01. However, patients with nr-axSpA had lower C-reactive protein: 7 mg/l (3-17)/11 mg/l (5-22); and BAS Metrology Index: 20 (10-40)/40 (20-50); all p < 0.01. Median (95% CI) treatment adherence was poorer in nr-axSpA than in AS: 1.59 years (1.15-2.02) versus 3.67 years (2.86-4.49), p < 0.0001; but only in univariate and not confounder-adjusted analyses (p > 0.05). Response rates were similar in AS and nr-axSpA (p > 0.05). HLA-B27 negativity was associated with poorer treatment adherence [HLA-B27 negative/positive, nr-axSpA: HR 1.74 (1.29-2.36), AS: HR 2.04 (1.53-2.71), both p < 0.0001]; and lower response rates (nr-axSpA: 18/61 = 30% vs 93/168 = 55%; AS: 17/59 = 29% vs 157/291 = 54%, both p < 0.05).

CONCLUSION: In this nationwide cohort, patients with nr-axSpA had higher subjective disease activity at start of first TNFi treatment, but similar outcomes to patients with AS after confounder adjustment. HLA-B27 positivity was associated with better outcomes irrespective of axSpA subdiagnosis.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 44
Tidsskriftsnummer 1
Sider (fra-til) 59-69
Antal sider 11
ISSN 0315-162X
DOI
Status Udgivet - jan. 2017

OBJECTIVE: To examine the hypothesis that change in pain self-efficacy is associated with observed and self-reported activity, pain intensity, catastrophizing, and quality of life after multi-disciplinary rehabilitation of fibromyalgia patients.

DESIGN: In-depth analyses of secondary outcomes of a randomized-controlled trial.

SUBJECTS: Women (N = 187) with fibromyalgia.

METHODS: Outcomes were Pain Self-Efficacy, Assessment of Motor and Process Skills (AMPS), SF-36 Physical Function (SF-36-PF), pain intensity, and SF-36 Mental Composite Score (SF-36-MCS) to assess quality of life and pain catastrophizing. Individual and group associations between outcomes were examined.

RESULTS: Individual changes in pain self-efficacy were not associated with changes in observed activity: AMPS motor (rs = 0.08, p = 0.27) and process (rs = 0.12, p = 0.11), not even in those patients with a clinically relevant improvement in observed functioning (38.5%), and only weakly or moderatly with changes in SF-36-PF; (rs = 0.31, p < 0.0001), SF-36-MSC; (rs = 0.41, p < 0.0001), and pain catastrophizing (rs = -0.31, p < 0.0001). No differences in pain self-efficacy were observed between the rehabilitated group and controls (difference: 1.61; 95% CI: -0.84 to 4.06; p = 0.24). However, a subgroup (34%) had a clinically relevant improvement in pain self-efficacy. This group was younger (mean age 41.4 vs. 45.8, p = 0.01), more recently diagnosed (1.8 vs. 2.8 years, p = 0.003), but had an unresolved welfare situation (59% vs. 40%, p = 0.02).

CONCLUSION: The main hypothesis was falsified, as there was no association between pain self-efficacy and actual performance of activity. The relation to functioning may be limited to perceived, cognitive-emotional aspects, as indicated by the weak to moderate correlations to the self-reported measures. Implications for Rehabilitation Improvement in observed activity post multi-disciplinary rehabilitation was not associated with change in pain self-efficacy. Patients performed better after rehabilitation, but did not perceive to have improved their capacity. The relationship between pain self-efficacy and functioning may be limited to cognitive-emotional aspects rather than actual activity. Both observational and self-reported measures should be included in evaluating outcomes of rehabilitation for patients with fibromyalgia.

Originalsprog Engelsk
Tidsskrift Disability and rehabilitation
Vol/bind 39
Tidsskriftsnummer 17
Sider (fra-til) 1744-1752
Antal sider 9
ISSN 1464-5165
DOI
Status Udgivet - aug. 2017

BACKGROUND AND PURPOSE: Older adults acutely hospitalized for medical illness typically have comorbidity and disability, and inhospital physical inactivity greatly increases the likelihood of developing new disability. Thus, assessment of the patients' mobility status is crucial for planning and carrying out targeted interventions that ensure mobilization during hospital admission. The aim of this study was to determine convergent validity, known group validity, floor and ceiling effects, and anchor-based minimal clinically important difference (MCID) of the more time-consuming de Morton Mobility Index (DEMMI) and the less time-consuming Cumulated Ambulation Score (CAS) in older adults acutely hospitalized for medical illness.

METHODS: In this multicenter cohort study, 235 older hospitalized adults, with a mean (standard deviation) age of 84.8 (7.1) years, were consecutively included. Assessments of mobility using the DEMMI (score range 0-100), the CAS (score range 0-6), and the Barthel Index (BI, score range 0-100) were performed by physical or occupational therapists at hospital admission and discharge. In addition, at discharge patients and therapists were independently asked to assess the patients' current mobility status compared with their mobility status at hospital admission using the Global Rating of Change scale.

RESULTS AND DISCUSSION: Complete data sets were obtained for 155 patients. Baseline characteristics of those with complete data sets did not differ from those with incomplete data sets, except for the number of secondary diagnoses, which was lower in the latter. Significant and moderate relationships existed both at admission and at discharge between scores in the DEMMI and the BI (rs = 0.68, P < .0001, and rs = 0.71, P < .0001), and between scores in the CAS and the BI (rs = 0.60, P < .0001, and rs = 0.57, P < .0001). Use of a gait aid and discharge to inpatient rehabilitation or nursing home were associated with significantly lower DEMMI and CAS scores. No floor or ceiling effects were present in the DEMMI, while a ceiling effect was present in the CAS. The MCID scores based on patients' assessments were 10.7 points for the DEMMI and 0.67 for the CAS.

CONCLUSIONS: These data show that the DEMMI is valid and responsive to changes in mobility and can be considered to have the required properties for measuring mobility in older adults who are hospitalized in medical and geriatric wards. In contrast, the CAS appears to be appropriate to identify whether a patient is independently mobile or needs assistance, while the measure is less suitable for measuring improvements in mobility.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Originalsprog Engelsk
Tidsskrift Journal of geriatric physical therapy (2001)
ISSN 1539-8412
DOI
Status E-pub ahead of print - 15 dec. 2017

Association between baseline vitamin D metabolite levels and long-term cardiovascular events in patients with rheumatoid arthritis from the CIMESTRA trial: protocol for a cohort study with patient-record evaluated outcomes

Herly, M., Stengaard-Pedersen, K., Hørslev-Petersen, K., Hetland, M. L., Østergaard, M., Christensen, R., Løgstrup, B. B., Vestergaard, P., Pødenphant, J., Junker, P. & Ellingsen, T. 8 apr. 2017 I : B M J Open. 7, 4, s. e014816

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Cardiovascular morbidity and mortality is increased in patients with rheumatoid arthritis (RA), and among these patients, the prevalence of hypovitaminosis D is high. Moreover, low vitamin D levels have been associated with increased cardiovascular risk in healthy subjects.

OBJECTIVE: To evaluate the long-term risk of cardiovascular events in patients having low total 25-hydroxyvitamin D levels at baseline compared with patients with normal levels, in an efficiently treated, closed cohort of patients with an early diagnosis of RA.

METHODS AND ANALYSIS: This study is a prospective, closed, blinded endpoint cohort study, based on secondary analyses from a previous randomised trial (CIMESTRA study; NCT00209859, approved September 1999) including 160 patients with an early diagnosis of RA from Danish University clinics. Primary outcome will be the proportion of patients with any cardiovascular event in the follow-up period, evaluated using systematic journal audits. Logistic regression models will test the hypothesis that there are more cardiovascular events in enrolled patients with a low level of vitamin D (< 50 nmol/L). Secondarily, Cox regression models, based on survival analysis, will determine the extent to which independent variables (including different levels of vitamin D at baseline) predict whether a cardiovascular event will occur, and also when this will be.

ETHICS AND DISSEMINATION: All patients have received verbal and written information before enrolment, and have given written consent at baseline. To disseminate comprehension of factors of prognostic importance to cardiovascular outcome in RA, we will attempt to have a first draft ready no later than 1 year after the adjudication process has finished. If low vitamin D levels can predict cardiovascular events in RA, it is relevant to take into account in a prediction model, to be considered by patients, physicians and other decision-makers.

TRIAL REGISTRATION NUMBER: The parental controlled trial is registered as NCT00209859.

Originalsprog Engelsk
Tidsskrift B M J Open
Vol/bind 7
Tidsskriftsnummer 4
Sider (fra-til) e014816
ISSN 2044-6055
DOI
Status Udgivet - 8 apr. 2017

Association Between Use of Cannabis in Adolescence and Weight Change into Midlife

Jin, L. Z., Rangan, A., Mehlsen, J., Andersen, L. B., Larsen, S. C. & Heitmann, B. L. 2017 I : P L o S One. 12, 1, s. e0168897

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Cannabis use has been found to stimulate appetite and potentially promote weight gain via activation of the endocannabinoid system. Despite the fact that the onset of cannabis use is typically during adolescence, the association between adolescence cannabis use and long-term change in body weight is generally unknown. This study aims to examine the association between adolescence cannabis use and weight change to midlife, while accounting for the use of other substances. The study applied 20 to 22 years of follow-up data on 712 Danish adolescents aged between 15 and 19 years at baseline. Self-reported height and weight, cannabis, cigarette and alcohol use, socioeconomic status (SES) and physical activity levels were assessed in baseline surveys conducted in 1983 and 1985. The follow-up survey was conducted in 2005. In total 19.1% (n = 136) of adolescents reported having used/using cannabis. Weight gain between adolescence and midlife was not related to cannabis exposure during adolescence in either crude or adjusted models, and associations were not modified by baseline alcohol intake or smoking. However, cannabis use was significantly associated with cigarette smoking (p<0.001) and alcohol intake (p<0.001) and inversely associated with physical activity levels (p = 0.04). In conclusion, this study does not provide evidence of an association between adolescence cannabis use and weight change from adolescence to midlife.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 12
Tidsskriftsnummer 1
Sider (fra-til) e0168897
ISSN 1932-6203
DOI
Status Udgivet - 2017

Authors' reply: Refers to: Prognostic factors associated with mortality in patients with septic arthritis: a descriptive cohort study

Andreasen, R. A., Andersen, N. S., Just, S. A., Christensen, R. & Hansen, I. M. J. 31 maj 2017 I : Scandinavian Journal of Rheumatology. 46, 4, s. 332-333 2 s.

Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Rheumatology
Vol/bind 46
Tidsskriftsnummer 4
Sider (fra-til) 332-333
Antal sider 2
ISSN 0300-9742
DOI
Status Udgivet - 31 maj 2017

Bandager til Knælidelser

Henriksen, M. & Skou, S. T. 18 sep. 2017 I : Ugeskrift for laeger. 179, 38

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

The use of knee braces is common, and there is an abundance of different brace types available both "over the counter" and as "prescription devices". The braces are used for a range of knee problems ranging from minor knee discomfort to post-surgical rehabilitation. The available evidence is generally in favour of brace applications although the amount and quality of evidence is moderate to low with a positive benefit-harm balance. However, braces should generally not be used as a stand-alone or primary treatment strategy, but can be used as a potentially beneficial supplement to patients with knee disorders if needed.

Originalsprog Dansk
Tidsskrift Ugeskrift for laeger
Vol/bind 179
Tidsskriftsnummer 38
ISSN 0041-5782
Status Udgivet - 18 sep. 2017

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