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
Udgave nummer 1
Sider (fra-til) e0191288
ISSN 1932-6203
DOI
Status Udgivet - 25 jan. 2018

Female reproductive history and risk of type 2 diabetes: A prospective analysis of 126 721 women

Pandeya, N., Huxley, R. R., Chung, H-F., Dobson, A. J., Kuh, D., Hardy, R., Cade, J. E., Greenwood, D. C., Giles, G. G., Bruinsma, F., Demakakos, P., Simonsen, M. K., Adami, H-O., Weiderpass, E. & Mishra, G. D., sep. 2018, I : Diabetes, Obesity and Metabolism. 20, 9, s. 2103-2112 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

AIM: To examine the prospective associations between aspects of a woman's reproductive history and incident diabetes.

METHODS: We pooled individual data from 126 721 middle-aged women from eight cohort studies contributing to the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE). Associations between age at menarche, age at first birth, parity and menopausal status with incident diabetes were examined using generalized linear mixed models, with binomial distribution and robust variance. We stratified by body mass index (BMI) when there was evidence of a statistical interaction with BMI.

RESULTS: Over a median follow-up of 9 years, 4073 cases of diabetes were reported. Non-linear associations with diabetes were observed for age at menarche, parity and age at first birth. Compared with menarche at age 13 years, menarche at ≤10 years was associated with an 18% increased risk of diabetes (relative risk [RR] 1.18, 95% confidence interval [CI] 1.02-1.37) after adjusting for BMI. After stratifying by BMI, the increased risk was only observed in women with a BMI ≥25 kg/m2 . A U-shaped relationship was observed between parity and risk of diabetes. Compared with pre-/peri-menopausal women, women with a hysterectomy/oophorectomy had an increased risk of diabetes (RR 1.17, 95% CI 1.07-1.29).

CONCLUSIONS: Several markers of a woman's reproductive history appear to be modestly associated with future risk of diabetes. Maintaining a normal weight in adult life may ameliorate any increase in risk conferred by early onset of menarche.

Originalsprog Engelsk
Tidsskrift Diabetes, Obesity and Metabolism
Vol/bind 20
Udgave nummer 9
Sider (fra-til) 2103-2112
Antal sider 10
ISSN 1462-8902
DOI
Status Udgivet - sep. 2018

Gender differences in biologic treatment outcomes – A study of 1750 patients with psoriatic arthritis using Danish health care registers

Højgaard, P., Ballegaard, C., Cordtz, R. L., Zobbe, K., Clausen, M., Kristensen, L. E., Glintborg, B. & Dreyer, L., 2018, I : Annals of the Rheumatic Diseases. 77, Suppl. 2, s. 376 1 s., THU0316.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer THU0316
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Udgave nummer Suppl. 2
Sider (fra-til) 376
Antal sider 1
ISSN 0003-4967
Status Udgivet - 2018

Objective: We aimed to investigate gender differences in disease manifestations, patient-reported outcomes, comorbidities and treatment effectiveness among patients with PsA treated with their first TNFα inhibitor (TNFI).

Methods: In this observational cohort study, the DANBIO register provided prospectively collected data on PsA patients who initiated their first TNFI in 2000-15. Comorbidity information was achieved from the Danish Nationwide Patient Register. Response to treatment was assessed according to EULAR and ACR criteria at 3 and 6 months. Cox and logistic regression models analysed the impact of gender on TNFI persistence and response, respectively, while adjusting for a priori selected confounders including clinical-, laboratory- and patient-reported factors, comorbidities and lifestyle characteristics.

Results: A total of 1750 PsA patients (935 women) were included. At baseline, women were older (49 years/47 years), more often smokers (32%/26%), had worse patient-reported scores (e.g. global score 71 mm/65 mm) and higher frequencies of hospital-diagnosed anxiety or depression (7%/4%) and chronic pulmonary disease (7%/3%) than men (all P < 0.01). Median TNFI persistence was 3.8 years (95% CI: 3.0, 5.7) in men vs 1.4 (1.1, 1.8) in women (P < 0.001). Men had higher odds of achieving response after 3 and 6 months, for example, adjusted odds ratio = 3.2 (1.6, 6.1) for EULAR good/moderate response (vs women) at 6 months.

Conclusion: Male gender was strongly associated with greater TNFI treatment effectiveness. Adjustment for baseline risk factors including patient-reported outcomes, disease activity, comorbidities and lifestyle factors did not influence this relationship, which suggests a role of biological factors.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 57
Udgave nummer 9
Sider (fra-til) 1651-1660
Antal sider 10
ISSN 1462-0324
DOI
Status Udgivet - 1 sep. 2018

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

Sode, J., Bank, S., Vogel, U., Andersen, P. S., Sørensen, S. B., Bojesen, A. B., Andersen, M. R., Brandslund, I., Dessau, R. B., Hoffmann, H. J., Glintborg, B., Hetland, M. L., Locht, H., Heegaard, N. H. & Andersen, V. 12 sep. 2018 I : B M C Medical Genetics. 19, 1, s. 165

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Ankylosing spondylitis (AS) results from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the heritability of AS.

METHODS: Using a candidate gene approach in this case-control study, 51 mainly functional single nucleotide polymorphisms (SNPs) in genes regulating inflammation were assessed in 709 patients with AS and 795 controls. Data on the patients with AS were obtained from the DANBIO registry where patients from all of Denmark are monitored in routine care during treatment with conventional and biologic disease modifying anti-rheumatic drugs (bDMARDs). The results were analyzed using logistic regression (adjusted for age and sex).

RESULTS: Nine polymorphisms were associated with risk of AS (p < 0.05). The polymorphisms were in genes regulating a: the TNF-α pathway (TNF -308 G > A (rs1800629), and - 238 G > A (rs361525); TNFRSF1A -609 G > T (rs4149570), and PTPN22 1858 G > A (rs2476601)), b: the IL23/IL17 pathway (IL23R G > A (rs11209026), and IL18-137 G > C (rs187238)), or c: the NFkB pathway (TLR1 743 T > C (rs4833095), TLR4 T > C (rs1554973), and LY96-1625 C > G (rs11465996)). After Bonferroni correction the homozygous variant genotype of TLR1 743 T > C (rs4833095) (odds ratios (OR): 2.59, 95% confidence interval (CI): 1.48-4.51, p = 0.04), and TNFRSF1A -609 G > T (rs4149570) (OR: 1.79, 95% CI: 1.31-2.41, p = 0.01) were associated with increased risk of AS and the combined homozygous and heterozygous variant genotypes of TNF -308 G > A (rs1800629) (OR: 0.56, 95% CI: 0.44-0.72, p = 0.0002) were associated with reduced risk of AS.

CONCLUSION: We replicated associations between AS and the polymorphisms in TNF (rs1800629), TNFRSF1A (rs4149570), and IL23R (rs11209026). Furthermore, we identified novel risk loci in TNF (rs361525), IL18 (rs187238), TLR1 (rs4833095), TLR4 (rs1554973), and LY96 (rs11465996) that need validation in independent cohorts. The results suggest that genetically determined high activity of the TNF-α, IL23/IL17, and NFkB pathways increase risk of AS.

Originalsprog Engelsk
Tidsskrift B M C Medical Genetics
Vol/bind 19
Tidsskriftsnummer 1
Sider (fra-til) 165
ISSN 1471-2350
DOI
Status Udgivet - 12 sep. 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
Udgave nummer 1
Sider (fra-til) 87-97
ISSN 1470-269X
DOI
Status Udgivet - 2018

Good midterm results of hip arthroscopy for femoroacetabular impingement

Kaldau, N. C., Brorson, S., Hölmich, P. & Lund, B. jun. 2018 I : Danish Medical Journal. 65, 6

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: Short-term outcome after hip arthroscopy for femoroacetabular impingement (FAI) has been reported to improve hip function and decrease pain. Only few midterm and long-term studies have been published. The objective of this study was to report midterm results in a consecutive cohort and to study the relation between cartilage lesions and the conversion rate to total hip arthroplasty (THA).

METHODS: Eighty-four FAI patients were followed retrospectively for 6-8 years. The conversion rate to THA, the peri-operative findings and the patient-reported outcome measures were reported.

RESULTS: Fifteen of 84 (18%) patients were converted to THA. The five-year hip survival rate was 83.9% (confidence interval (CI): 75.1-91.5%). The THA group was significantly older, with a mean age of 46.9 years (CI: 42.8-50.8 years) compared with 39.0 years (CI: 36.6-41.6 years) in the non-THA group (p = 0.011). In the THA group, 13 of 15 patients were 40 years or older (p = 0.005). A high-grade acetabular or femoral cartilage lesion was associated with a higher risk of conversion to THA (p = 0.017 and p < 0.0001). Sixty-four of the 69 patients (93%) were willing to repeat their arthroscopy.

CONCLUSIONS: The midterm results for arthroscopic hip-preserving surgery show a high level of patient satisfaction and a good functional outcome. The conversion rate to THA was 18%. High-grade cartilage lesions and age of 40 years and older are risk factors for conversion to THA.

FUNDING: This work was supported by Aleris' Research Foundation, Box 47134, 100 74 Stockholm, Sweden. Registration number: 2014-24.

TRIAL REGISTRATION: not relevant. .

Originalsprog Engelsk
Tidsskrift Danish Medical Journal
Vol/bind 65
Tidsskriftsnummer 6
ISSN 1603-9629
Status Udgivet - jun. 2018

Gout is associated with an increased risk of cancer – A nationwide cohort study including over 70,000 gout patients

Zobbe, K., Prieto-Alhambra, D., Cordtz, R. L., Mellemkjær, L., Højgaard, P., Kristensen, L. E. & Dreyer, L., 2018, I : Annals of the Rheumatic Diseases. 77, Suppl. 2, s. 651-652 2 s., FRI0221.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer FRI0221
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Udgave nummer Suppl. 2
Sider (fra-til) 651-652
Antal sider 2
ISSN 0003-4967
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
Udgave nummer 3
Sider (fra-til) 345-355
Antal sider 11
ISSN 2326-5191
DOI
Status Udgivet - mar. 2018

Habitual coffee consumption and changes in measures of adiposity: a comprehensive study of longitudinal associations

Larsen, S. C., Mikkelsen, M-L., Frederiksen, P. & Heitmann, B. L., apr. 2018, I : International journal of obesity (2005). 42, 4, s. 880-886 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: A relationship between change in coffee consumption and reduced long-term weight gain has been suggested, but current evidence is inconsistent.

OBJECTIVE: To examine longitudinal associations between coffee consumption and changes in body mass index (BMI), fat mass index (FMI), fat-free mass index (FFMI), body fat percentage (BF %) and waist circumference (WC).

DESIGN: The study consisted of 2128 participants from the Danish part of the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) cohort with repeated information on coffee consumption, adiposity measures and covariates during an 11-year period. Linear regression analyses were conducted to assess the associations between baseline coffee consumption and subsequent change in adiposity measures. The same analyses were conducted analyzing associations between change in coffee consumption and concurrent as well as subsequent changes in adiposity measures.

RESULTS: We found no consistent evidence of associations between baseline coffee consumption and subsequent 6-year changes in adiposity measures. A statistically significant association between increased coffee consumption over a 6-year period and decreased concurrent gain in BMI, FMI, BF % and WC (-0.05 kg m-2 (95% confidence interval (CI): -0.07, -0.02), -0.04 kg m-2 (95% CI: -0.06, -0.02), -0.08% (95% CI: -0.13, -0.04) and -0.23 cm (95% CI: -0.34, -0.12), respectively, per 1 cup day-1 increase in coffee consumption) was found. No association was seen between change in coffee consumption and concurrent change in FFMI. Moreover, an initial change in coffee consumption during the first 5-year period was not associated with change in adiposity during the subsequent 6-year period.

CONCLUSIONS: Increased coffee consumption was associated with a decreased concurrent gain in body weight, fat mass and waist circumference, but the associations were weak. Moreover, a causal relationship could not be established, as we found no evidence of associations between an initial change in coffee consumption and subsequent change in adiposity.

Originalsprog Engelsk
Tidsskrift International journal of obesity (2005)
Vol/bind 42
Udgave nummer 4
Sider (fra-til) 880-886
Antal sider 7
ISSN 0307-0565
DOI
Status Udgivet - apr. 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
Udgave nummer 1
Sider (fra-til) 67
ISSN 1745-6215
DOI
Status Udgivet - 25 jan. 2018

INTRODUCTION: The introduction of biological disease-modifying antirheumatic drugs (bDMARDs) has improved the treatment of inflammatory rheumatic diseases dramatically. However, bDMARD treatment failure occurs in 30%-40% of patients due to lack of effect or adverse events, and the tools to predict treatment outcomes in individual patients are currently limited. The objective of the present study is to identify diagnostic, prognostic and predictive biomarkers, which can be used to (1) diagnose inflammatory rheumatic diseases early in the disease course with high sensitivity and specificity, (2) improve prognostication or (3) predict and monitor treatment effectiveness and tolerability for the individual patient.

METHODS AND ANALYSIS: The present study is an observational and translational open cohort study with prospective collection of clinical data and biological materials (primarily blood) in patients with inflammatory rheumatic diseases treated in routine care. Patients contribute with one cross-sectional blood sample and/or are enrolled for longitudinal follow-up on initiation of a new DMARD (blood sampling after 0, 3, 6, 12, 24, 36, 48, 60 months of treatment). Other biological materials will be collected when accessible and relevant. Demographics, disease characteristics, comorbidities and lifestyle factors are registered at inclusion; DMARD treatment and outcomes are collected repeatedly during follow-up. Currently (July 2017), >5000 samples from approximately 3000 patients have been collected. Data will be analysed using appropriate statistical analyses.

ETHICS AND DISSEMINATION: The protocol is approved by the Danish Ethics Committee and the Danish Data Protection Agency. Participants give written and oral informed consent. Biomarkers will be evaluated and published according to the Reporting Recommendations for Tumour Marker (REMARK) prognostic studies, Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines. Results will be published in peer-reviewed scientific journals and presented at international conferences.

TRIAL REGISTRATION NUMBER: NCT03214263.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 8
Udgave nummer 2
Sider (fra-til) e019325
ISSN 2044-6055
DOI
Status Udgivet - 1 feb. 2018

Identifying a Core Domain Set to Assess Psoriasis in Clinical Trials

Callis Duffin, K., Merola, J. F., Christensen, R., Latella, J., Garg, A., Gottlieb, A. B. & Armstrong, A. W., 1 okt. 2018, I : JAMA Dermatology. 154, 10, s. 1137-1144 8 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Importance: There is no consensus on which domains should be measured or which instruments should be used in clinical trials for psoriasis therapies.

Objective: To achieve international consensus among psoriasis stakeholders on a core set of domains that should be measured in all psoriasis clinical trials.

Design, Setting, and Participants: Literature review, pre-Delphi survey exercises, nominal group discussions, and audience voting at 4 stakeholder meetings were used to develop candidate domains for 2 rounds of a Delphi survey. Stakeholders were patients or advocates of patients with psoriasis and health care professionals (HCPs) with expertise in psoriasis, including physicians, scientists, advocacy organization representatives, and regulators. Delphi surveys were conducted electronically from October through December 2015 and between September and October 2016. Stakeholder discussions with audience response voting were conducted at live meetings in the United States, Canada, and Italy from January 2013 to December 2016 to refine and ratify the core set of domains.

Main Outcomes and Measures: Two rounds of an electronic Delphi survey were used to determine consensus. A domain was considered "core" (ie, should be measured in all trials) if a threshold consensus of at least 70% was met in both patient and HCP groups. Domains meeting consensus in only 1 group were considered to be important but were not required to be measured in all trials ("middle ring"). These domains were included for rerating in round 2. Domains that did not meet consensus in either of the groups ("outer ring") were considered to be of uncertain importance and were placed in the research agenda.

Results: In round 1 of the Delphi survey, 107 HCPs and 14 patients participated. Most HCPs (72 [67%]) were dermatologists between 46 and 64 years old (71 [66%]), white (78 [73%]), and male (75 [70%]) from North America (60 [57%]) and Europe (34 [32%]).There were 10 pharmaceutical industry clinical or health economic scientists, 3 advocacy organization representatives, 2 regulatory agency representatives, and 5 "other." In the second round, 77 HCPs and 15 patients participated. Of the 20 candidate domains, the following 6 met consensus as core domains: skin manifestations, psoriasis and psoriatic arthritis symptoms, health-related quality of life, investigator global assessment, patient global assessment, and treatment satisfaction. Secondary skin manifestations as well as nail, inverse, genital, and guttate psoriasis were classified as important but not mandatory. Psoriatic arthritis signs, work productivity or participation, economic impact (direct and indirect cost), and cardiovascular disease comprised the research agenda.

Conclusions and Relevance: This iterative Delphi process yielded international consensus among professional and patient stakeholders on 6 domains that should be measured in all clinical trials for psoriasis. Future International Dermatology Outcome Measures group efforts will focus on development of a core outcome measurement set for psoriasis trials.

Originalsprog Engelsk
Tidsskrift JAMA Dermatology
Vol/bind 154
Udgave nummer 10
Sider (fra-til) 1137-1144
Antal sider 8
ISSN 2168-6068
DOI
Status Udgivet - 1 okt. 2018

Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function: a Systematic Review of Human Evidence

Høyer, B. B., Lenters, V., Giwercman, A., Jönsson, B. A. G., Toft, G., Hougaard, K. S., Bonde, J. P. E. & Specht, I. O., mar. 2018, I : Current environmental health reports. 5, 1, s. 20-33 14 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

PURPOSE OF REVIEW: The purpose of this review is to systematically review the literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on reproductive health in adult males.

RECENT FINDINGS: Thirty-three papers were included of which 28 were cross-sectional. Twenty-one papers investigated semen samples, 18 investigated reproductive hormones, and three studies investigated time to pregnancy. Studies revealed some but inconsistent indications that higher urinary DEHP metabolite levels are associated with an increase in the proportion of spermatozoa with damaged DNA and to a decrease in sperm concentration and motility. A negative association between DEHP metabolites and testosterone levels was more consistent. DEHP metabolites do not seem to be associated with a delay in time to pregnancy, but data are sparse. The studies on DEHP exposure and reproductive biomarkers in men converge to support the hypothesis that DEHP exposure is related to impaired male reproductive function. Longitudinal studies are needed to establish if the observed associations are causal.

Originalsprog Engelsk
Tidsskrift Current environmental health reports
Vol/bind 5
Udgave nummer 1
Sider (fra-til) 20-33
Antal sider 14
ISSN 2196-5412
DOI
Status Udgivet - mar. 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
Udgave nummer 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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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
Udgave nummer 2
Sider (fra-til) e018166
ISSN 2044-6055
DOI
Status Udgivet - 8 feb. 2018

Impact of TNF inhibitors on need for joint replacement in patients with rheumatoid arthritis: A matched cohort analysis of UK biologics registry data

Hawley, S., Cordtz, R. L., Dreyer, L., Edwards, C. J., Arden, N. K., Cooper, C., Judge, A., Ali, S., Hyrich, K. & Prieto-Alhambra, D., 2018, I : Annals of the Rheumatic Diseases. 77, Suppl. 2, s. 108-109 2 s., OP0116.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer OP0116
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Udgave nummer Suppl. 2
Sider (fra-til) 108-109
Antal sider 2
ISSN 0003-4967
Status Udgivet - 2018
Originalsprog Engelsk
Artikelnummer 2503
Tidsskrift Arthritis & Rheumatology
Vol/bind 70
Udgave nummer S9
Antal sider 2
ISSN 1537-2960
Status Udgivet - 2018

In utero exposure to extra vitamin D from food fortification and the risk of subsequent development of gestational diabetes: the D-tect study

Keller, A., Stougård, M., Frederiksen, P., Thorsteinsdottir, F., Vaag, A., Damm, P., Jacobsen, R. & L Heitmann, B., 2 nov. 2018, I : Nutrition Journal. 17, 1, s. 100

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: The primary aim of this study was to assess whether exposure during fetal life to extra vitamin D from food fortification was associated with a reduction in the risk of subsequently developing gestational diabetes mellitus (GDM). Furthermore, we examined whether the effect of the vitamin D from fortification differed by women's season of birth.

METHODS: This semi-ecological study is based on the cancellation in 1985 of the mandatory policy to fortify margarine with vitamin D in Denmark, with inclusion of entire national adjacent birth cohorts either exposed or unexposed to extra vitamin D in utero. The identification of GDM cases later in life among both exposure groups was based on the Danish national health registers. Logistic regression analyses generating odds ratios (ORs) and 95% confidence intervals (95% CIs) were performed.

RESULTS: Women who were prenatally exposed to the extra vitamin D from fortification tended to have a lower risk of subsequently developing GDM than unexposed women (OR 0.87, 95%CI 0.74,1.02, P = 0.08). When analyses were stratified by women's season of birth, exposed women born in spring had a lower risk of developing GDM compared to unexposed subjects (OR 0.68, 95%CI 0.50,0.94, p = 0.02).

CONCLUSION: This study suggests that prenatal exposure to extra vitamin D from mandatory fortification may lower the risk of developing gestational diabetes among spring-born women.

TRIAL REGISTRATION: This study is part of the D-tect project, which is registered on clinicaltrials.gov: NCT03330301 .

Originalsprog Engelsk
Tidsskrift Nutrition Journal
Vol/bind 17
Udgave nummer 1
Sider (fra-til) 100
ISSN 1475-2891
DOI
Status Udgivet - 2 nov. 2018

In vivo differentiation of common basal cell carcinoma subtypes by microvascular and structural imaging using dynamic optical coherence tomography

Themstrup, L., De Carvalho, N., Nielsen, S. M., Olsen, J., Ciardo, S., Schuh, S., Nørnberg, B. M-H., Welzel, J., Ulrich, M., Pellacani, G. & Jemec, G. B. E., feb. 2018, I : Experimental Dermatology. 27, 2, s. 156-165 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

The subtype of basal cell carcinoma (BCC) influences the choice of treatment. Optical coherence tomography (OCT) is a non-invasive imaging tool, and a recent development of an angiographic version of OCT has extended the application of OCT to image the cutaneous microvasculature (so-called dynamic OCT, D-OCT). This study explores D-OCT's ability to differentiate the common BCC subtypes by microvascular and structural imaging. Eighty-one patients with 98 BCC lesions, consisting of three subtypes: 27 superficial BCC (sBCC), 55 nodular BCC (nBCC) and 16 infiltrative BCC (iBCC) were D-OCT scanned at three European dermatology centres. Blinded evaluations of microvascular and structural features were performed, followed by extensive statistical analysis of risk ratio (RR) and multiple correspondence analysis. nBCC lesions displayed most characteristic structural and vascular features. Serpiginous vessels, branching vessels, vessels creating a circumscribed figure and sharply demarcated hyporeflective ovoid structures in the dermis were all associated with a higher risk of the subtype being nBCC. The presence of highly present lines and dark peripheral borders at the margin of ovoid structures was negatively associated with iBCC. Lastly, the finding of hyporeflective ovoid structures protruding from epidermis correlated with sBCC. We identified various microvascular and structural D-OCT features that may aid non-invasive identification of BCC subtypes. This would allow clinicians to individualize and optimize BCC treatment as well as aid follow-up of non-surgical treatment.

Originalsprog Engelsk
Tidsskrift Experimental Dermatology
Vol/bind 27
Udgave nummer 2
Sider (fra-til) 156-165
Antal sider 10
ISSN 0906-6705
DOI
Status Udgivet - feb. 2018

Pages