Published in 2018

Extra vitamin D from fortification and the risk of preeclampsia: The D-tect Study

Stougaard, M., Damm, P., Frederiksen, P., Jacobsen, R. & Heitmann, B. L. 25 jan. 2018 I : P L o S One. 13, 1, s. e0191288

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

The objective of the study was to examine if exposure to extra vitamin D from food fortification was associated with a decrease in the risk of preeclampsia. The study was based on a natural experiment exploring the effect of the abolition of the Danish mandatory vitamin D fortification of margarine in 1985. The effect of the extra vitamin D (1.25μg vitamin D/100 g margarine) was examined by comparing preeclampsia risk in women who have been exposed or unexposed to extra vitamin D from the fortified margarine during pregnancy, and who gave birth in the period from June 1983 to August 1988. The Danish National Patient Registry allowed the identification of pregnancies complicated by preeclampsia. The study included 73,237 women who gave birth during 1983-1988. We found no association between exposure to vitamin D fortification during pregnancy and the risk of any of the pregnancy related hypertensive disorders, including preeclampsia: Odds ratios (OR, 95%) for all hypertensive pregnancy related disorders among exposed vs. unexposed women was (OR 1.04, 95%CI: 0.98,1.10). In conclusion, the extra vitamin D from the mandatory vitamin D fortification did not influence the risk of preeclampsia.

Originalsprog Engelsk
Tidsskrift P L o S One
Vol/bind 13
Tidsskriftsnummer 1
Sider (fra-til) e0191288
ISSN 1932-6203
DOI
Status Udgivet - 25 jan. 2018

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy

Bank, S., Andersen, P. S., Burisch, J., Pedersen, N., Roug, S., Galsgaard, J., Turino, S. Y., Brodersen, J. B., Rashid, S., Rasmussen, B. K., Avlund, S., Olesen, T. B., Hoffmann, H. J., Nexø, B. A., Sode, J., Vogel, U. & Andersen, V. 2018 I : The pharmacogenomics journal. 18, 1, s. 87-97

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.The Pharmacogenomics Journal advance online publication, 31 January 2017; doi:10.1038/tpj.2016.84.

Originalsprog Engelsk
Tidsskrift The pharmacogenomics journal
Vol/bind 18
Tidsskriftsnummer 1
Sider (fra-til) 87-97
ISSN 1470-269X
DOI
Status Udgivet - 2018

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome Measures in Rheumatology Consensus-Based Recommendations and Research Agenda for Use of Composite Measures and Treatment Targets in Psoriatic Arthritis

Coates, L. C., FitzGerald, O., Merola, J. F., Smolen, J., van Mens, L. J. J., Bertheussen, H., Boehncke, W-H., Callis Duffin, K., Campbell, W., de Wit, M., Gladman, D., Gottlieb, A., James, J., Kavanaugh, A., Kristensen, L. E., Kvien, T. K., Luger, T., McHugh, N., Mease, P., Nash, P., Ogdie, A., Rosen, C. F., Strand, V., Tillett, W., Veale, D. J. & Helliwell, P. S. mar. 2018 I : Arthritis & rheumatology (Hoboken, N.J.). 70, 3, s. 345-355 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: A meeting was convened by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) to further the development of consensus among physicians and patients regarding composite disease activity measures and targets in psoriatic arthritis (PsA).

METHODS: Prior to the meeting, physicians and patients completed surveys on outcome measures. A consensus meeting of 26 rheumatologists, dermatologists, and patient research partners reviewed evidence on composite measures and potential treatment targets plus results of the surveys. The meeting consisted of plenary presentations, breakout sessions, and group discussions. International experts including members of GRAPPA and OMERACT were invited to the meeting, including the developers of all of the measures discussed. After discussions, participants voted on proposals for use, and consensus was established in a second survey.

RESULTS: Survey results from 128 health care professionals and 139 patients were analyzed alongside a systematic literature review summarizing evidence. A weighted vote was cast for composite measures. For randomized controlled trials, the most popular measures were the PsA disease activity score (40 votes) and the GRAPPA composite index (28 votes). For clinical practice, the most popular measures were an average of scores on 3 visual analog scales (45 votes) and the disease activity in PsA score (26 votes). After discussion, there was no consensus on a composite measure. The group agreed that several composite measures could be used and that future studies should allow further validation and comparison. The group unanimously agreed that remission should be the ideal target, with minimal disease activity (MDA)/low disease activity as a feasible alternative. The target should include assessment of musculoskeletal disease, skin disease, and health-related quality of life. The group recommended a treatment target of very low disease activity (VLDA) or MDA.

CONCLUSION: Consensus was not reached on a continuous measure of disease activity. In the interim, the group recommended several composites. Consensus was reached on a treatment target of VLDA/MDA. An extensive research agenda was composed and recommends that data on all PsA clinical domains be collected in ongoing studies.

Originalsprog Engelsk
Tidsskrift Arthritis & rheumatology (Hoboken, N.J.)
Vol/bind 70
Tidsskriftsnummer 3
Sider (fra-til) 345-355
Antal sider 11
ISSN 2326-5191
DOI
Status Udgivet - mar. 2018

Harm, benefit and costs associated with low-dose glucocorticoids added to the treatment strategies for rheumatoid arthritis in elderly patients (GLORIA trial): study protocol for a randomised controlled trial

Hartman, L., Rasch, L. A., Klausch, T., Bijlsma, H. W. J., Christensen, R., Smulders, Y. M., Ralston, S. H., Buttgereit, F., Cutolo, M., Da Silva, J. A. P., Opris, D., Rovenský, J., Szamosi, S., Middelink, L. M., Lems, W. F. & Boers, M. 25 jan. 2018 I : Trials. 19, 1, s. 67

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints affecting 1% of the world population. It has major impact on patients through disability and associated comorbidities. Current treatment strategies have considerably improved the prognosis, but recent innovations (especially biologic drugs and the new class of so-called "JAK/STAT inhibitors") have important safety issues and are very costly. Glucocorticoids (GCs) are highly effective in RA, and could reduce the need for expensive treatment with biologic agents. However, despite more than 65 years of clinical experience, there is a lack of studies large enough to adequately document the benefit/harm balance. The result is inappropriate treatment strategies, i.e. both under-use and over-use of GCs, and consequently suboptimal treatment of RA.

METHODS: The GLORIA study is a pragmatic multicentre, 2-year, randomised, double-blind, clinical trial to assess the safety and effectiveness of a daily dose of 5 mg prednisolone or matching placebo added to standard of care in elderly patients with RA. Eligible participants are diagnosed with RA, have inadequate disease control (disease activity score, DAS28 ≥ 2.6), and are ≥ 65 years. The primary outcome measures are the time-averaged mean value of the DAS28 and the occurrence of serious adverse events or adverse events of special interest. During the trial, change in antirheumatic therapy is permitted as clinically indicated, except for GCs. Cost-effectiveness and cost-utility are secondary outcomes. The main challenge is the interpretation of the trial result with two primary endpoints and the pragmatic trial design that allows co-interventions. Another challenge is the definition of safety and the relative lack of power to detect differences between treatment groups. We have chosen to define safety as the number of patients experiencing at least one serious adverse event. We also specify a decision tree to guide our conclusion on the balance of benefit and harm, and our methodology to combat potential confounding caused by co-interventions.

DISCUSSION: Pragmatic trials minimise impact on daily practice and maximise clinical relevance of the results, but analysis and interpretation of the results is challenging. We expect that the results of this trial are of importance for all rheumatologists who treat elderly patients with RA.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02585258 . Registered on 20 October 2015.

Originalsprog Engelsk
Tidsskrift Trials
Vol/bind 19
Tidsskriftsnummer 1
Sider (fra-til) 67
ISSN 1745-6215
DOI
Status Udgivet - 25 jan. 2018

Impact of patient-reported flares on radiographic progression and functional impairment in patients with rheumatoid arthritis: a cohort study based on the AMBRA trial

Kuettel, D., Primdahl, J., Christensen, R., Ørnbjerg, L. M. & Hørslev-Petersen, K. mar. 2018 I : Scandinavian Journal of Rheumatology. 47, 2, s. 87-94 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To investigate the impact of patient-reported flares on radiographic damage and disability in rheumatoid arthritis (RA).

METHOD: Patients with low-active (Disease Activity Score based on 28-joint count with C-reactive protein < 3.2) RA were followed for 2 years. Based on annual questionnaires about incidence of flares, three 'flare phenotypes' were distinguished: no flares (NF), transient flares (TF), and a mixed category reporting persistent joint complaints (PJC) in at least one year. Baseline and 2 year radiographs of hands and feet were evaluated according to the Sharp/van der Heijde method. Major outcomes were change from baseline in Total Sharp Score (ΔTSS) and functional impairment, expressed by the Health Assessment Questionnaire (ΔHAQ). Their association with flare phenotype was analysed by logistic regression.

RESULTS: The study included 268 RA patients (70% female; 73% immunoglobulin M rheumatoid factor positive), with a median age (interquartile range) of 63 (55-70) years, and 7 (4-13) years' disease duration. Flares were recalled as NF (n = 77), TF (n = 141), and PJC (n = 50). ΔTSS > 0 was observed in 35%, 37%, and 46%, respectively (p = 0.42), but statistically significantly (p = 0.01) more patients progressed in the TF (10%) and PJC (14%) compared to NF (0%), based on the smallest detectable change (> 4.4 ΔTSS unit). ΔHAQ above the minimal clinically important difference (> 0.22) was seen in 13% (NF), 21% (TF), and 40% (PJC) (p = 0.0015), with PJC being associated with statistically significant impairment in function (odds ratio 4.47, 95% confidence interval 1.87-10.69) compared to NF.

CONCLUSION: In RA patients with low disease activity, the incidence of radiographic progression and functional impairment was higher in patients with flares and persistent complaints, compared to those without flares.

Originalsprog Engelsk
Tidsskrift Scandinavian Journal of Rheumatology
Vol/bind 47
Tidsskriftsnummer 2
Sider (fra-til) 87-94
Antal sider 8
ISSN 0300-9742
DOI
Status Udgivet - mar. 2018

Impact of red and processed meat and fibre intake on treatment outcomes among patients with chronic inflammatory diseases: protocol for a prospective cohort study of prognostic factors and personalised medicine

Christensen, R., Heitmann, B. L., Andersen, K. W., Nielsen, O. H., Sørensen, S. B., Jawhara, M., 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., Frøjk, J., Dahlerup, J. F., Bojesen, A. B., Sorensen, G. L., Thiel, S., Færgeman, N. J., Brandslund, I., Bennike, T. B., Stensballe, A., Schmidt, E. B., Franke, A., Ellinghaus, D., Rosenstiel, P., Raes, J., Boye, M., Werner, L., Nielsen, C. L., Munk, H. L., Nexøe, A. B., Ellingsen, T., Holmskov, U., Kjeldsen, J. & Andersen, V. 8 feb. 2018 I : BMJ Paediatrics Open . 8, 2, s. e018166

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INTRODUCTION: Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes.

METHODS AND ANALYSIS: This prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14-16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics.

ETHICS AND DISSEMINATION: The principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.

TRIAL REGISTRATION NUMBER: NCT03173144; Pre-results.

Originalsprog Engelsk
Tidsskrift BMJ Paediatrics Open
Vol/bind 8
Tidsskriftsnummer 2
Sider (fra-til) e018166
ISSN 2044-6055
DOI
Status Udgivet - 8 feb. 2018

OBJECTIVES: To study the impact of the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and associated rheumatoid arthritis (RA) management guidelines on the incidence of total hip (THR) and knee replacements (TKR) in Denmark.

METHODS: Nationwide register-based cohort and interrupted time-series analysis. Patients with incident RA between 1996 and 2011 were identified in the Danish National Patient Register. Patients with RA were matched on age, sex and municipality with up to 10 general population comparators (GPCs). Standardised 5-year incidence rates of THR and TKR per 1000 person-years were calculated for patients with RA and GPCs in 6-month periods. Levels and trends in the pre-bDMARD (1996-2001) were compared with the bDMARD era (2003-2016) using segmented linear regression interrupted by a 1-year lag period (2002).

RESULTS: We identified 30 404 patients with incident RA and 297 916 GPCs. In 1996, the incidence rate of THR and TKR was 8.72 and 5.87, respectively, among patients with RA, and 2.89 and 0.42 in GPCs. From 1996 to 2016, the incidence rate of THR decreased among patients with RA, but increased among GPCs. Among patients with RA, the incidence rate of TKR increased from 1996 to 2001, but started to decrease from 2003 and throughout the bDMARD era. The incidence of TKR increased among GPCs from 1996 to 2016.

CONCLUSION: We report that the incidence rate of THR and TKR was 3-fold and 14-fold higher, respectively among patients with RA compared with GPCs in 1996. In patients with RA, introduction of bDMARDs was associated with a decreasing incidence rate of TKR, whereas the incidence of THR had started to decrease before bDMARD introduction.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
ISSN 0003-4967
DOI
Status E-pub ahead of print - 2018

Increased Suicide Risk in Patients with Hidradenitis Suppurativa

Thorlacius, L., Cohen, A. D., Gislason, G. H., Jemec, G. B. E. & Egeberg, A. jan. 2018 I : The Journal of investigative dermatology. 138, 1, s. 52-57 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Patients with skin disorders are considered at a higher risk of depression and anxiety than the background population. Patients with hidradenitis suppurativa (HS) may be particularly affected. We explored the association between HS and depression, anxiety, and completed suicides in the Danish national registries, expanding to include data on suicidal behavior, using both a cross-sectional and a cohort study design. Both designs included 7,732 patients with HS and a background population of 4,354,137. The cohort study revealed that HS patients had an increased risk of completed suicide after adjustment for confounding factors (11 per 7,732 vs. 2,904 per 4,354,137) (hazard ratio [95% confidence interval] = 2.42 [1.07-5.45]; P = 0.0334) and an increased risk of antidepressant drug use (1.30 [1.17-1.45]; P < 0.0001). In contrast to previous studies, the cross-sectional baseline data revealed nonsignificant association with depression (odds ratio [95% confidence interval] = 1.13; 0.87-1.47]; P = 0.36 and hospitalization due to depression (1.32 [0.94-1.85]; P = 0.1083). To the best of our knowledge, no previous studies have reported on the increased risk of completed suicide among HS patients. The increased risk of completed suicide is not solely explained by lifestyle and demographic differences and the results highlight the profound impact HS has on the lives of patients with this often devastating disease.

Originalsprog Engelsk
Tidsskrift The Journal of investigative dermatology
Vol/bind 138
Tidsskriftsnummer 1
Sider (fra-til) 52-57
Antal sider 6
ISSN 0022-202X
DOI
Status Udgivet - jan. 2018

Interventions to Improve Vaccination Uptake and Cost Effectiveness of Vaccination Strategies in Newly Arrived Migrants in the EU/EEA: A Systematic Review

Hui, C., Dunn, J., Morton, R., Staub, L. P., Tran, A., Hargreaves, S., Greenaway, C., Biggs, B. A., Christensen, R. & Pottie, K. 20 sep. 2018 I : International Journal of Environmental Research and Public Health. 15, 10

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Newly arrived migrants to the EU/EEA (arrival within the past five years), as well as other migrant groups in the region, might be under-immunised and lack documentation of previous vaccinations, putting them at increased risk of vaccine-preventable diseases circulating in Europe. We therefore performed a systematic review conforming to PRISMA guidelines (PROSPERO CRD42016045798) to explore: (i) interventions that improve vaccine uptake among migrants; and (ii) cost-effectiveness of vaccination strategies among this population. We searched MEDLINE, Embase, CINAHL, and Cochrane Database of Systematic Reviews (CDSR) between 1 January 2006 to 18 June 2018. We included three primary intervention studies performed in the EU/EEA or high-income countries and one cost effectiveness study relevant to vaccinations in migrants. Intervention studies showed small but promising impact only on vaccine uptake with social mobilization/community outreach, planned vaccination programs and education campaigns. Targeting migrants for catch-up vaccination is cost effective for presumptive vaccination for diphtheria, tetanus, and polio, and there was no evidence of benefit of carrying out pre-vaccination serological testing. The cost-effectiveness is sensitive to the seroprevalence and adherence to vaccinations of the migrant. We conclude that scarce but direct EU/EEA data suggest social mobilization, vaccine programs, and education campaigns are promising strategies for migrants, but more research is needed. Research should also study cost effectiveness of strategies. Vaccination of migrants should continue to be a public heath priority in EU/EEA.

Originalsprog Engelsk
Tidsskrift International Journal of Environmental Research and Public Health
Vol/bind 15
Tidsskriftsnummer 10
ISSN 1661-7827
DOI
Status Udgivet - 20 sep. 2018

Intra-articular 2.5% polyacrylamide hydrogel for the treatment of knee osteoarthritis: an observational proof-of-concept cohort study

Henriksen, M., Overgaard, A. F., Hartkopp, A. & Bliddal, H. 18 jul. 2018 I : Clinical and Experimental Rheumatology.

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OBJECTIVES: There is a drought of effective treatments of knee osteoarthritis (OA) and new therapies are needed. The present study has been conducted to establish an initial estimate of effectiveness of intra-articular (IA) injection of a proprietary 2.5% cross-linked polyacrylamide hydrogel (PAAG) for the treatment of knee OA symptoms and signs.

METHODS: Patients with knee OA were invited into a prospective open-label cohort study. The patients received up to two IA injections of 3 ml of PAAG 1 month apart. The WOMAC questionnaire was used to estimate effectiveness, and was collected at baseline and after 4, 7 and 13 months. Primary outcome was change from baseline for the WOMAC pain subscale after 4 months (Normalised to 0-100 points; 100 worst). Data was analysed using a mixed-effect model without imputation of missing data.

RESULTS: 84 patients (48 females) received IA PAAG. Of these WOMAC data were available from 62 after 4 months, 59 after 7 months, and 56 after 13 months. There were statistically and clinically significant reductions in WOMAC pain after 4 months (mean change -14.6 points [95% CI: -18.9 to -10.2]; p<.0001). Similar results were found in WOMAC stiffness, physical function, and WOMAC total. The improvement was sustained throughout the observation period.

CONCLUSIONS: These results suggest beneficial effects of IA injection of PAAG on knee OA symptoms, even in the long term (1 year). This initial estimation of effectiveness is promising but needs to be confirmed in a randomised study with adequate measures taken to reduce risk of bias.

Originalsprog Engelsk
Tidsskrift Clinical and Experimental Rheumatology
ISSN 0392-856X
Status E-pub ahead of print - 18 jul. 2018

Kind of blue: A systematic review and meta-analysis of music interventions in cancer treatment

Bro, M. L., Jespersen, K. V., Hansen, J. B., Vuust, P., Abildgaard, N., Gram, J. & Johansen, C. 2018 I : Psycho-Oncology. 27, 2, s. 386-400

Publikation: Bidrag til tidsskriftReviewForskningpeer review

OBJECTIVES: Music may be a valuable and low-cost coping strategy for cancer patients. We conducted a systematic review and meta-analysis to identify the psychological and physical effects of music interventions in cancer treatment.

METHODS: We included randomized, controlled trials with adult patients in active cancer treatment exposed to different music interventions versus control conditions. Qualitative studies and systematic reviews were excluded. We identified a total of 2624 records through 2 systematic searches (June 2015 and September 2016) in PubMed, Scopus, EMBASE, Cinahl, Web of Science, Cochrane, and PsycINFO and used Risk of Bias Assessment, GRADE and Checklist for Reporting Music-Based Interventions to evaluate the music applied and quality of the studies. We conducted meta-analyses using Review Manager (version 5.3). PROSPERO reg. no. CRD42015026024.

RESULTS: We included 25 RCT's (N = 1784) of which 20 were eligible for the meta-analysis (N = 1565). Music reduced anxiety (SMD -0·80 [95% CI, -1.35 to -0.25]), pain (SMD -0.88 [95% CI -1.45 to -0.32]), and improved mood (SMD -0.55 [95% CI, -0.98 to -0.13]). However, studies were hampered by heterogeneity with I2 varying between 54% and 96%. Quality of the studies ranged from very low to low. The most effective mode of music intervention appeared to be passive listening to self-selected, recorded music in a single session design.

CONCLUSIONS: Music may be a tool in reducing anxiety, pain, and improving mood among patients with cancer in active treatment. However, methodological limitations in the studies conducted so far prevent firm conclusions.

Originalsprog Engelsk
Tidsskrift Psycho-Oncology
Vol/bind 27
Tidsskriftsnummer 2
Sider (fra-til) 386-400
ISSN 1057-9249
DOI
Status Udgivet - 2018

Lower risk of hip fractures among Swedish women with large hips?

Klingberg, S., Mehlig, K., Sundh, V., Heitmann, B. L. & Lissner, L. apr. 2018 I : Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 29, 4, s. 927-935 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

In women, a large hip circumference (HC) related to lower hip fracture risk, independent of age and regardless if HC was measured long before or closer to the fracture. In older women, body mass index (BMI) explained the protection.

INTRODUCTION: In postmenopausal women, HC has been suggested to inversely associate with hip fracture while this has not been investigated in middle-aged women. We examined the association between HC, measured at two different time points, and hip fracture in a Swedish female population-based sample monitored for incident hip fractures over many years.

METHODS: Baseline HC, measured in 1968 or 1974 (n = 1451, mean age 47.6 years), or the HC measures that were the most proximal before event or censoring (n = 1325, mean age 71.7 years), were used to assess the effects of HC on hip fracture risk in women participating in the Prospective Population Study of Women in Gothenburg. HC was parameterized as quintiles with the lowest quintile (Q1) as reference. Incident hip fractures over 45 years of follow-up (n = 257) were identified through hospital registers.

RESULTS: Higher quintiles of HC at both baseline and proximal to event were inversely associated with hip fracture risk in age-adjusted models, but only baseline HC predicted hip fractures independently of BMI and other covariates (HR (95% CI) Q2, 0.85 (0.56-1.27); Q3, 0.59 (0.36-0.96); Q4, 0.57 (0.34-0.96); Q5, 0.58 (0.31-1.10)).

CONCLUSIONS: A large HC is protective against hip fracture in midlife and in advanced age, but the association between proximal HC and hip fracture was explained by concurrent BMI suggesting that padding was not the main mechanism for the association. The independent protection seen in middle-aged women points to other mechanisms influencing bone strength.

Originalsprog Engelsk
Tidsskrift Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
Vol/bind 29
Tidsskriftsnummer 4
Sider (fra-til) 927-935
Antal sider 9
ISSN 0937-941X
DOI
Status Udgivet - apr. 2018

Make it REAL: four simple points to increase clinical relevance in sport and exercise medicine research

Bandholm, T., Henriksen, M., Treweek, S. & Thorborg, K. 7 sep. 2018 I : British Journal of Sports Medicine.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Tidsskrift British Journal of Sports Medicine
ISSN 0306-3674
DOI
Status E-pub ahead of print - 7 sep. 2018

Multicentric reticulohistiocytosis is a rare form of paraneoplasia

Anderson, A. M., Todberg, T., Kofoed, K., Iversen, T. Z., Andersen, M., Hjorth, S. V. & Fassi, D. E. 1 jan. 2018 I : Ugeskrift for laeger. 180, 1

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

A 59-year-old woman developed a rash and severe arthralgia, which primarily affected her fingers. She displayed digital arthritis and nodules on the hands, chest, face, and oral cavity. Blood samples were normal. Skin biopsies revealed histiocytic proliferation. The surface marker profile and clinical findings were consistent with multicentric reticulohistiocytosis, which may occur as a paraneoplastic phenomenon. On workup, she was diagnosed with an otherwise asymptomatic stage IVC fallopian tube cancer. She experienced little effect of prednisolone, but her condition improved on antineoplastic treatment.

Originalsprog Dansk
Tidsskrift Ugeskrift for laeger
Vol/bind 180
Tidsskriftsnummer 1
ISSN 0041-5782
Status Udgivet - 1 jan. 2018

National Clinical Guidelines for non-surgical treatment of patients with recent onset low back pain or lumbar radiculopathy

Stochkendahl, M. J., Kjaer, P., Hartvigsen, J., Kongsted, A., Aaboe, J., Andersen, B. M., Andersen, M. Ø., Fournier, G., Højgaard, B., Jensen, M. B., Jensen, L. D., Karbo, T., Kirkeskov, L., Melbye, M., Morsel-Carlsen, L., Nordsteen, J., Palsson, T. S., Rasti, Z., Silbye, P. F., Steiness, M. Z., Tarp, S. & Vaagholt, M. 2018 I : European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 27, 1, s. 60-75

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: To summarise recommendations about 20 non-surgical interventions for recent onset (<12 weeks) non-specific low back pain (LBP) and lumbar radiculopathy (LR) based on two guidelines from the Danish Health Authority.

METHODS: Two multidisciplinary working groups formulated recommendations based on the GRADE approach.

RESULTS: Sixteen recommendations were based on evidence, and four on consensus. Management of LBP and LR should include information about prognosis, warning signs, and advise to remain active. If treatment is needed, the guidelines suggest using patient education, different types of supervised exercise, and manual therapy. The guidelines recommend against acupuncture, routine use of imaging, targeted treatment, extraforaminal glucocorticoid injection, paracetamol, NSAIDs, and opioids.

CONCLUSION: Recommendations are based on low to moderate quality evidence or on consensus, but are well aligned with recommendations from international guidelines. The guideline working groups recommend that research efforts in relation to all aspects of management of LBP and LR be intensified.

Originalsprog Engelsk
Tidsskrift European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
Vol/bind 27
Tidsskriftsnummer 1
Sider (fra-til) 60-75
ISSN 0940-6719
DOI
Status Udgivet - 2018

One year effectiveness of neuromuscular exercise compared with instruction in analgesic use on knee function in patients with early knee osteoarthritis: the EXERPHARMA randomized trial

Holsgaard-Larsen, A., Christensen, R., Clausen, B., Søndergaard, J., Andriacchi, T. P. & Roos, E. M. jan. 2018 I : Osteoarthritis and Cartilage. 26, 1, s. 28-33 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To test long-term effectiveness of neuromuscular exercise (NEMEX) with instructions in optimized pharmacological treatment (PHARMA) on activities of daily living (ADL) in patients with early knee osteoarthritis.

DESIGN: 12-months follow-up from a randomized controlled trial. Participants with mild-to-moderate medial tibiofemoral knee osteoarthritis were randomly allocated to 8 weeks NEMEX or PHARMA. The primary outcome measure was the ADL-subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcome measures included the other four KOOS-subscales, the University of California Activity Score (UCLA) and the European Quality of Life-5 Dimensions.

RESULTS: Ninety-three patients (57% women, 58 ± 8 years, body mass index 27 ± 4 kg/m2) were randomized to NEMEX (n = 47) or PHARMA group (n = 46) with data from 85% being available at 12-months follow-up. Good compliance was achieved for 49% of the participants in NEMEX (≥12 sessions) and 7% in PHARMA (half the daily dose of acetaminophen/NSAIDs ≥ 28 days). Within-group improvements in NEMEX were considered to be clinically relevant (≥10 points) for all KOOS-subscales, except Sport/Rec whereas, no between-groups difference in the primary outcome KOOS ADL (3.6 [-2.1 to 9.2]; P = 0.216) was observed. For KOOS Symptoms, a statistically significant difference of 7.6 points (2.6-12.7; P = 0.004) was observed in favor of NEMEX with 47% improving ≥10 points.

CONCLUSIONS: No difference in improvement in difficulty with ADL was observed. NEMEX improved knee symptoms to a greater extent with half of patients reporting clinically relevant improvements. CLINICALTRIALS.

GOV IDENTIFIER: NCT01638962 (July 3, 2012).

ETHICAL COMMITTEE: S-20110153.

Originalsprog Engelsk
Tidsskrift Osteoarthritis and Cartilage
Vol/bind 26
Tidsskriftsnummer 1
Sider (fra-til) 28-33
Antal sider 6
ISSN 1063-4584
DOI
Status Udgivet - jan. 2018

Opportunities and challenges for real-world studies on chronic inflammatory joint diseases through data enrichment and collaboration between national registers: the Nordic example

Chatzidionysiou, K., Hetland, M. L., Frisell, T., Di Giuseppe, D., Hellgren, K., Glintborg, B., Nordström, D., Aaltonen, K., Törmänen, M. R., Klami Kristianslund, E., Kvien, T. K., Provan, S. A., Björn Guðbjörnsson, B., Dreyer, L., Kristensen, L. E., Jørgensen, T. S., Jacobsson, L. & Askling, J. 2018 I : RMD Open. 4, 1, s. e000655

Publikation: Bidrag til tidsskriftReviewForskningpeer review

There are increasing needs for detailed real-world data on rheumatic diseases and their treatments. Clinical register data are essential sources of information that can be enriched through linkage to additional data sources such as national health data registers. Detailed analyses call for international collaborative observational research to increase the number of patients and the statistical power. Such linkages and collaborations come with legal, logistic and methodological challenges. In collaboration between registers of inflammatory arthritides in Sweden, Denmark, Norway, Finland and Iceland, we plan to enrich, harmonise and standardise individual data repositories to investigate analytical approaches to multisource data, to assess the viability of different logistical approaches to data protection and sharing and to perform collaborative studies on treatment effectiveness, safety and health-economic outcomes. This narrative review summarises the needs and potentials and the challenges that remain to be overcome in order to enable large-scale international collaborative research based on clinical and other types of data.

Originalsprog Engelsk
Tidsskrift RMD Open
Vol/bind 4
Tidsskriftsnummer 1
Sider (fra-til) e000655
ISSN 2056-5933
DOI
Status Udgivet - 2018

Outcome Measures in Rheumatology - Interventions for medication Adherence (OMERACT-Adherence) Core Domain Set for Trials of Interventions for Medication Adherence in Rheumatology: 5 Phase Study Protocol

OMERACT-Adherence Group 27 mar. 2018 I : Trials. 19, 1, s. 204

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Over the last 20 years, there have been marked improvements in the availability of effective medications for rheumatic conditions such as gout, osteoporosis and rheumatoid arthritis (RA), which have led to a reduction in disease flares and the risk of re-fracture in osteoporosis, and the slowing of disease progression in RA. However, medication adherence remains suboptimal, as treatment regimens can be complex and difficult to continue long term. Many trials have been conducted to improve adherence to medication. Core domains, which are the outcomes of most relevance to patients and clinicians, are a pivotal component of any trial. These core domains should be measured consistently, so that all relevant trials can be combined in systematic reviews and meta-analyses to reach conclusions that are more valid. Failure to do this severely limits the potential for trial-based evidence to inform decisions on how to support medication adherence. The Outcome Measures in Rheumatology (OMERACT) - Interventions for Medication Adherence study by the OMERACT-Adherence Group aims to develop a core domain set for interventions that aim to support medication adherence in rheumatology.

METHODS/DESIGN: This OMERACT-Adherence study has five phases: (1) a systematic review to identify outcome domains that have been reported in interventions focused on supporting medication adherence in rheumatology; (2) semi-structured stakeholder interviews with patients and caregivers to determine their views on the core domains; (3) focus groups using the nominal group technique with patients and caregivers to identify and rank domains that are relevant to them, including the reasons for their choices; (4) an international three-round modified Delphi survey involving patients with diverse rheumatic conditions, caregivers, health professionals, researchers and other stakeholders to develop a preliminary core domain set; and (5) a stakeholder workshop with OMERACT members to review, vote on and reach a consensus on the core domain set for interventions to support medication adherence in rheumatology.

DISCUSSION: Establishing a core domain set to be reported in all intervention studies undertaken to support patients with medication adherence will enhance the relevance and the impact of these results and improve the lives of people with rheumatic conditions.

Originalsprog Engelsk
Tidsskrift Trials
Vol/bind 19
Tidsskriftsnummer 1
Sider (fra-til) 204
ISSN 1745-6215
DOI
Status Udgivet - 27 mar. 2018

Background: Biomechanical studies show varying results regarding the elongation of adjustable fixation devices. This has led to growing concern over the stability of the ToggleLoc with ZipLoop used in anterior cruciate ligament (ACL) reconstruction (ACLR) in vivo.

Purpose/Hypothesis: The purpose of this study was to compare passive knee stability 1 year after ACLR in patients in whom the Endobutton or ToggleLoc with ZipLoop was used for femoral graft fixation. The hypothesis was that the ToggleLoc with ZipLoop would be inferior in knee stability to the Endobutton 1 year after primary ACLR.

Study Design: Cohort study; Level of evidence, 2.

Methods: Data from 3175 patients (Endobutton: n = 2807; ToggleLoc with ZipLoop: n = 368) were included from the Danish Knee Ligament Reconstruction Registry (DKRR) between June 2010 and September 2013. Data were retrieved from standardized ACL forms filled out by the operating surgeon preoperatively, during surgery, and at a clinical examination 1 year after surgery. Passive knee stability was evaluated using 1 of 2 arthrometers (Rolimeter or KT-1000 arthrometer) and the pivot-shift test. Using the same database, the number of reoperations performed up to 4 years after primary surgery was examined.

Results: Full data were available for 1654 patients (Endobutton: n = 1538; ToggleLoc with ZipLoop: n = 116). ACLR with both devices resulted in increased passive knee stability (P < .001). Patients who received the ToggleLoc with ZipLoop were found to have a better preoperative (P = .005 ) and postoperative (P < .001) pivot-shift test result. No statistically significant difference regarding the number of reoperations (P = .086) or the time to reoperation (P = .295) was found.

Conclusion: Patients who underwent fixation with the ToggleLoc with ZipLoop had improved passive knee stability 1 year after surgery, measured by anterior tibial translation and pivot-shift test results, similar to patients who underwent fixation with the Endobutton. No difference was seen in knee stability or reoperation rates between the 2 devices.

Originalsprog Engelsk
Tidsskrift Orthopaedic Journal of Sports Medicine
Vol/bind 6
Tidsskriftsnummer 6
ISSN 2325-9671
DOI
Status Udgivet - 1 aug. 2018

Background It has been demonstrated that weight loss improves symptoms in obese subjects with knee osteoarthritis (KOA). A parallel change in cartilage morphology remains to be demonstrated. Purpose To demonstrate a parallel change in cartilage morphology. Material and Methods Obese patients with KOA were examined before and after weight loss over 16 weeks. Target knee joints were radiographically assessed by the Kellgren/Lawrence grading (KLG) system. Patients with KLG-1 and 2 changes in the lateral compartment were included. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was performed using intra-articular contrast. Results Nine patients with lateral KLG-1 and ten patients with lateral KLG-2 were studied. There were no group differences regarding the lateral compartment baseline dGEMRIC T1 values: median = 497 ms (KLG-1) and 533 ms (KLG-2) ( P = 0.12), or regarding reduction in body mass index (BMI) after 16 weeks: 12.8% versus 11.4% ( P = 0.74). In the KLG-1 group, several cases of increased dGEMRIC T1 values were seen and median value decreased significantly less than in KLG-2 group (15 ms versus 41 ms, P = 0.03) after weight loss. Conclusion Improvement of cartilage quality, assessed with dGEMRIC, after weight loss might be possible in early stage KOA (KLG-1), but not in later stage KOA (KLG-2). The results may suggest a point of no return for improvement of cartilage quality that should be tested in larger trials.

Originalsprog Engelsk
Tidsskrift Acta Radiologica
Vol/bind 59
Tidsskriftsnummer 3
Sider (fra-til) 336-340
Antal sider 5
ISSN 0284-1851
DOI
Status Udgivet - mar. 2018

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