Published in 2018

Th17 Inhibitors in Active Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Naik, G. S., Ming, W. K., Magodoro, I. M., Akinwunmi, B., Dar, S., Poulsen, H. E., Kristensen, L. E. & Ellervik, C. feb. 2018 I : Dermatology (Basel, Switzerland). 233, 5, s. 366–377

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Several biologics targeting the Th17 pathway have been developed for the treatment of psoriatic arthritis (PsA), a disabling disease with moderate response and an increased incidence of serious infections to first-line biologics (TNF-α antagonists). Th17 inhibitors could replace TNF-α antagonists as first-line biologic agents. We determined the overall treatment effect of Th17 pathway inhibitors compared to placebo or active control on American College of Rheumatology (ACR) 20 response at week 12 (primary objective), risk of infections, discontinuation of treatment due to adverse events, and serious adverse events during the placebo-controlled period (12-24 weeks) in adults with active PsA in published randomized controlled trials.

METHODS: The SCOPUS database was searched. The Cochrane risk of bias tool was used for assessing quality. The pooled relative risk (RR) was derived from random effects models.

RESULTS: Seven randomized controlled trials were included which randomized 1,718 patients to Th17 inhibitors and 840 to placebo. Patients treated with Th17 inhibitors had an RR of 2.04 (95% CI: 1.79-2.33; p < 0.001) for achieving an ACR20 response at week 12 (I2 = 0%; p = 0.89) compared to placebo-treated patients. There was no evidence of publication bias. The result was consistent for study phase and outcome (ACR50/70), mechanism of action and TNF-α naivety. RR of infections was 1.06 (0.91-1.23), that of candida infections was 3.35 (0.75-14.95), that of serious adverse events was 0.82 (0.42-1.59) and that of discontinuation of treatment was 0.54 (0.31-0.93) among treated versus placebo subjects. No incident cases of tuberculosis were reported.

CONCLUSION: In patients with active PsA, biologics targeting the Th17 axis produce a clinically significant improvement in joint disease activity with acceptable safety and tolerability for short-term treatment compared to placebo.

Originalsprog Engelsk
Tidsskrift Dermatology (Basel, Switzerland)
Vol/bind 233
Tidsskriftsnummer 5
Sider (fra-til) 366–377
ISSN 1018-8665
DOI
Status Udgivet - feb. 2018

The complexity of self-regulating food intake in weight loss maintenance. A qualitative study among short- and long-term weight loss maintainers

Pedersen, S., Sniehotta, F. F., Sainsbury, K., Evans, E. H., Marques, M. M., Stubbs, R. J., Heitmann, B. L. & Lähteenmäki, L. jul. 2018 I : Social science & medicine (1982). 208, s. 18-24 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

RATIONALE: Whether self-regulation of food intake in weight loss maintenance (WLM) differs between being a short-term maintainer (having maintained without regaining less than 12 months) and a long-term maintainer (having maintained without regaining at least 12 months) is under-researched.

OBJECTIVE: The aim of this study was to explore the self-regulatory strategies and self-efficacy beliefs applied by short- and long-term maintainers to the complex set of behaviours comprising food intake in WLM, and to obtain a better understanding of their challenges in the various food-intake processes in WLM.

METHOD: Individual interviews (14 female/4 male) were conducted with nine Danish short- and nine long-term weight loss maintainers. The Health Action Process Approach (HAPA) was applied post-hoc to organise data and support analyses, since the approach focuses on both the cognitions (e.g., self-efficacy, the nature of which differs depending on the phase of behaviour change) and self-regulatory strategies (e.g., action planning and coping planning) involved in behaviour change.

RESULTS: Self-regulatory strategies and self-efficacy beliefs varied between the food-related behaviours and between short- and long-term maintainers. Consistent with the progression suggested by HAPA, with repeated use of action and coping planning, long-term maintainers had formed habitual routines, not only allowing them more flexibility, but also providing them stronger self-control in the behaviours related to WLM such as buying and storing food, and eating at social gatherings. The short-term maintainers often displayed a 'weight loss mind-set.' The short-term maintainers focused on the avoidance of certain behaviours, showed less self-regulatory flexibility, and exhibited more detailed action planning, but their interviews also inferred that they had ambitions to build strong WLM-habits, maintenance, and recovery self-efficacy.

CONCLUSION: The contribution of this study is a more comprehensive view on food intake as an outcome of a set of complex behaviours, revealing insights into the differences in cognitions and strategies applied to the task of WLM, between short- and long-term maintainers.

Originalsprog Engelsk
Tidsskrift Social science & medicine (1982)
Vol/bind 208
Sider (fra-til) 18-24
Antal sider 7
ISSN 0277-9536
DOI
Status Udgivet - jul. 2018

BACKGROUND: Evidence is emerging that pain in rheumatoid arthritis (RA) exists without underlying inflammation. Our objective was to evaluate the prognostic value of pain classification at treatment initiation using the painDETECT questionnaire (PDQ). Outcomes were change in DAS28-CRP and RAMRIS synovitis score.

METHODS: RA patients initiating a disease-modifying anti-rheumatic drug (DMARD) or initiating/ switching a biological agent were included. Follow-up time was 4 months. Clinical examination, imaging (MRI, dynamic contrast-enhanced MRI (DCE-MRI)), and patient-reported outcomes were undertaken. The PDQ was used to differentiate pain mechanisms. Mean change (95% CI) was calculated using ANCOVA. Multivariable regression models were used to determine a prognostic value.

RESULTS: A total of 102 patients were included; 75 were enrolled for MRI. Mean changes in baseline variables were greatest in the high PDQ classification group (> 18), while limited in the intermediate group (13-18). The 12 patients with high baseline PDQ score all changed pain classification group. No prognostic value of PDQ pain classification was found in relation to change of DAS28-CRP, RAMRIS score, or VAS pain. In the unadjusted model, RAMRIS score at baseline was associated with change in DAS28-CRP. The exploratory variables of DCE-MRI did not differ from other inflammatory variables.

CONCLUSIONS: In RA patients a high PDQ score (non-nociceptive pain) at baseline was not associated with worse outcomes, in fact these patients had numerically greater improvement in DAS28-CRP. However, pain classification by PDQ was not independently associated with change in DAS28-CRP, RAMRIS score, or VAS pain in the prognostic models. Furthermore, patients classified with a high baseline PDQ score changed pain classification group. Patients with unclear pain mechanism had reduced numerically treatment response.

TRIAL REGISTRATION: The study was approved by the Regional Ethics Committee of the Capital of Denmark April 18 2013; identification number H-3-2013-049 .

Originalsprog Engelsk
Tidsskrift Arthritis Research & Therapy
Vol/bind 20
Tidsskriftsnummer 1
Sider (fra-til) 105
ISSN 1478-6354
DOI
Status Udgivet - 30 maj 2018

The effectiveness and cost-effectiveness of screening for active tuberculosis among migrants in the EU/EEA: a systematic review

Greenaway, C., Pareek, M., Abou Chakra, C-N., Walji, M., Makarenko, I., Alabdulkarim, B., Hogan, C., McConnell, T., Scarfo, B., Christensen, R., Tran, A., Rowbotham, N., Noori, T., van der Werf, M. J., Pottie, K., Matteelli, A., Zenner, D. & Morton, R. L. apr. 2018 I : Eurosurveillance. 23, 14

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: The foreign-born population make up an increasing and large proportion of tuberculosis (TB) cases in European Union/European Economic Area (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods: We conducted a systematic review to determine effectiveness (yield and performance of chest radiography (CXR) to detect active TB, treatment outcomes and acceptance of screening) and a second systematic review on cost-effectiveness of screening for active TB among migrants living in the EU/EEA. Results: We identified six systematic reviews, one report and three individual studies that addressed our aims. CXR was highly sensitive (98%) but only moderately specific (75%). The yield of detecting active TB with CXR screening among migrants was 350 per 100,000 population overall but ranged widely by host country (110-2,340), migrant type (170-1,192), TB incidence in source country (19-336) and screening setting (220-1,720). The CXR yield was lower (19.6 vs 336/100,000) and the numbers needed to screen were higher (5,076 vs 298) among migrants from source countries with lower TB incidence (≤ 50 compared with ≥ 350/100,000). Cost-effectiveness was highest among migrants originating from high (> 120/100,000) TB incidence countries. The foreign-born had similar or better TB treatment outcomes than those born in the EU/EEA. Acceptance of CXR screening was high (85%) among migrants. Discussion: Screening programmes for active TB are most efficient when targeting migrants from higher TB incidence countries. The limited number of studies identified and the heterogeneous evidence highlight the need for further data to inform screening programmes for migrants in the EU/EEA.

Originalsprog Engelsk
Tidsskrift Eurosurveillance
Vol/bind 23
Tidsskriftsnummer 14
ISSN 1560-7917
DOI
Status Udgivet - apr. 2018

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review

Greenaway, C., Pareek, M., Abou Chakra, C-N., Walji, M., Makarenko, I., Alabdulkarim, B., Hogan, C., McConnell, T., Scarfo, B., Christensen, R., Tran, A., Rowbotham, N., van der Werf, M. J., Noori, T., Pottie, K., Matteelli, A., Zenner, D. & Morton, R. L. apr. 2018 I : Eurosurveillance. 23, 14

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit.

Originalsprog Engelsk
Tidsskrift Eurosurveillance
Vol/bind 23
Tidsskriftsnummer 14
ISSN 1560-7917
DOI
Status Udgivet - apr. 2018

The EULAR points to consider for health professionals undertaking musculoskeletal ultrasound for rheumatic and musculoskeletal diseases

Siddle, H. J., Mandl, P., Aletaha, D., Vliet Vlieland, T. P., Backhaus, M., Cornell, P., D'Agostino, M-A., Ellegaard, K., Iagnocco, A., Jakobsen, B., Jasinski, T., Kildal, N. H., Lehner, M., Möller, I., Supp, G. M., O'Connor, P., Redmond, A. C., Naredo, E. & Wakefield, R. J. feb. 2018 I : Annals of the Rheumatic Diseases. 77, 2, s. 311-313 3 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Tidsskriftsnummer 2
Sider (fra-til) 311-313
Antal sider 3
ISSN 0003-4967
DOI
Status Udgivet - feb. 2018

OBJECTIVE: The objective of this population-based cohort study was to investigate the impact of comorbidities on disease activity, treatment response and persistence with the first-tried tumor necrosis factor inhibitor (TNFi) in patients with psoriatic arthritis (PsA).

METHODS: Data on patient characteristics, disease activity and treatment response and persistence was obtained from the DANBIO registry. Information on comorbidities according to the Charlson Comorbidity Index (CCI) was obtained through linkage with the Danish National Patient Register. Kaplan-Meier plots and Cox proportional hazard regression analyses were performed. Percentages of patients achieving relevant clinical responses were calculated.

RESULTS: We identified 1750 patients eligible for analyses. Patients with higher CCI had higher disease activity measures at baseline and increased occurrence of depression and/or anxiety. Kaplan-Meier curves showed shorter persistence with treatment for patients with ≥ 2 CCI (log-rank: p < 0.001) and for patients with depression and/or anxiety (p = 0.027) compared to patients without comorbidities. In multivariate analysis a CCI score ≥ 2 was associated with reduced TNFi persistence compared with patients without comorbidities (hazard ratio 1.72, [1.26 to 2.37], p = 0.001). A smaller proportion of patients with a CCI score ≥ 2 achieved European League Against Rheumatism (EULAR) good response (p < 0.001) and EULAR good-or-moderate response (p < 0.001) at 6 months compared with patients without comorbidities.

CONCLUSION: Presence of comorbidities was associated with higher baseline disease activity, shorter TNFi persistence and reduced clinical response rates in a cohort of Danish patients with PsA. 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

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

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