Published in 2018

Diverse hepatic microbial DNA fingerprints in healthy lean and obese steatotic humans

Bagger, J. I., Suppli, M. P., Nielsen, T., Lelouvier, B., Broha, A., Demant, M. G., Kønig, M. J., Strandberg, C., Lund, A., Vilsbøll, T. & Knop, F. K. 2 okt. 2018 (Accepteret/In press)

Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

Originalsprog Engelsk
Publikationsdato 2 okt. 2018
Status Accepteret/In press - 2 okt. 2018
Begivenhed 54th EASD Annual Meeting: EASD 2018 - Berlin, Tyskland
Varighed: 1 okt. 20185 okt. 2018
https://www.easd.org/programme-2018.html

Konference

Konference 54th EASD Annual Meeting
Land Tyskland
By Berlin
Periode 01/10/201805/10/2018
Internetadresse

Dose tapering and discontinuation of biological therapy in rheumatoid arthritis patients in remission in routine care – 2-year outcomes and identification of predictors

Brahe, C. C. H., Krabbe, S., Østergaard, M., Ørnbjerg, L. M., Glinatsi, D. E., Røgind, H., Jensen, H. S., Hansen, A., Nørregaard, J., Jacobsen, S., Terslev, L., Huynh, T. K., Jensen, D. V., Manilo, N., Asmussen, K., Frandsen, P. B., Boesen, M., Rastiemadabadi, Z., Morsel-Carlsen, L., Møller, J. M., Krogh, N. S. & Hetland, M. L., 2018, I : Annals of the Rheumatic Diseases. 77, Suppl. 2, s. 70-1 2 s., OP0038.

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

Originalsprog Engelsk
Artikelnummer OP0038
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Tidsskriftsnummer Suppl. 2
Sider (fra-til) 70-1
Antal sider 2
ISSN 0003-4967
Status Udgivet - 2018

Infants who are breastfed are introduced to a variety of flavours from the maternal milk, and thus the transition from maternal milk to complementary foods may be easier for these children. The aim of this study was to investigate if duration of exclusive breastfeeding was associated with pickiness or dietary intake of vegetables, fruit, starchy foods or sugar sweetened beverages among obesity prone normal weight children aged 2-6 years. This cohort study was based on data from the Healthy Start primary intervention study, the Danish Medical Birth registry and the Danish Health Visitor's Child Health Database. Infant feeding was registered by health nurses while home-visiting the mother and child up to four times within the first year. Information on eating behaviour and diet intake at age 2-6 years was obtained by parents. Crude and adjusted logistic and general linear regression models were used to investigate associations. A total of 236 children had complete information on all variables. Data showed lower odds of picky eating behaviour when exclusively breastfed until age 4-5 months compared to exclusively breastfed for 0-1 months (OR = 0.35, 95CI = 0.16;0.76, p = 0.008). In the crude analysis only, exclusively breastfed until age 6-10 months was associated with a higher daily intake of vegetables (p = 0.04). This study suggests that exclusive breastfeeding duration seems to influence pickiness and may contribute to facilitate the consumption of more vegetables in later childhood in obesity prone normal weight children.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 13
Tidsskriftsnummer 7
Sider (fra-til) e0200388
ISSN 1932-6203
DOI
Status Udgivet - 2018

Effects of Lifestyle on Muscle Strength in a Healthy Danish Population

Bartels, E. M., Robertson, S., Danneskiold-Samsøe, B., Appleyard, M. & Stockmarr, A., jan. 2018, I : Journal of lifestyle medicine. 8, 1, s. 16-22 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: Lifestyle is expected to influence muscle strength. This study aimed at assessing a possible relationship between smoking, alcohol intake and physical activity, and muscle strength in a healthy Danish population aged 20-79 years. Population study based on data collected from The Copenhagen City Heart Study (CCHS) and measurements of Isokinetic muscle strength from a sub-study of randomly selected healthy participants from CCHS.

Methods: 126 women and 63 men were studied. All participants completed a questionnaire regarding their lifestyle, including physical activity, alcohol intake and smoking habits. Isokinetic muscle strength was measured over the upper extremities (UE), trunk, and lower extremities (LE). Multivariate analyses including all of the variables were carried out.

Results: The level of daily physical activity during leisure was positively correlated to muscle strength in the lower extremities (p = 0.03) for women, and lower extremities (p = 0.03) and trunk (p = 0.007) for men. Alcohol Intake was in general not correlated to muscle strength. No clear effect of smoking was seen on muscle strength.

Conclusion: Our results show that physical activity during leisure is associated with a positive effect on muscle strength in both sexes. When keeping alcohol intake within the recommended limits, alcohol does not seem to affect muscle strength negatively. No effect of smoking on muscle strength was found in our group of healthy subjects. The findings are of importance when considering recommendation on life style when wishing to keeping fit with age to be able to carry out daily activities.

Originalsprog Engelsk
Tidsskrift Journal of lifestyle medicine
Vol/bind 8
Tidsskriftsnummer 1
Sider (fra-til) 16-22
Antal sider 7
ISSN 2234-8549
DOI
Status Udgivet - jan. 2018

Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial

Kragsnaes, M. S., Kjeldsen, J., Horn, H. C., Munk, H. L., Pedersen, F. M., Holt, H. M., Pedersen, J. K., Holm, D. K., Glerup, H., Andersen, V., Fredberg, U., Kristiansen, K., Christensen, R. & Ellingsen, T., 27 apr. 2018, I : BMJ Open. 8, 4, s. e019231

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA.

METHODS AND ANALYSIS: This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study.

ETHICS AND DISSEMINATION: This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s).

TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 8
Tidsskriftsnummer 4
Sider (fra-til) e019231
ISSN 2044-6055
DOI
Status Udgivet - 27 apr. 2018

Epidemiology of time loss groin injuries in a men's professional football league: a 2-year prospective study of 17 clubs and 606 players.

Mosler, A. B., Weir, A., Eirale, C., Farooq, A., Thorborg, K., Whiteley, R. J., Hølmich, P. & Crossley, K. M. 2018 I : British Journal of Sports Medicine. 52, 5, s. 292-297 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND/AIM: Groin injury epidemiology has not previously been examined in an entire professional football league. We recorded and characterised time loss groin injuries sustained in the Qatar Stars League. METHODS: Male players were observed prospectively from July 2013 to June 2015. Time loss injuries, individual training and match play exposure were recorded by club doctors using standardised surveillance methods. Groin injury incidence per 1000 playing hours was calculated, and descriptive statistics used to determine the prevalence and characteristics of groin injuries. The Doha agreement classification system was used to categorise all groin injuries. RESULTS: 606 footballers from 17 clubs were included, with 206/1145 (18%) time loss groin injuries sustained by 150 players, at an incidence of 1.0/1000 hours (95% CI 0.9 to 1.1). At a club level, 21% (IQR 10%-28%) of players experienced groin injuries each season and 6.6 (IQR 2.9-9.1) injuries were sustained per club per season. Of the 206 injuries, 16% were minimal (1-3 days), 25% mild (4-7 days), 41% moderate (8-28 days) and 18% severe (>28 days), with a median absence of 10 days/injury (IQR 5-22 days). The median days lost due to groin injury per club was 85 days per season (IQR 35-215 days). Adductor-related groin pain was the most common entity (68%) followed by iliopsoas (12%) and pubic-related (9%) groin pain. CONCLUSION: Groin pain caused time loss for one in five players each season. Adductor-related groin pain comprised 2/3 of all groin injuries. Improving treatment outcomes and preventing adductor-related groin pain has the potential to improve player availability in professional football.
Originalsprog Engelsk
Tidsskrift British Journal of Sports Medicine
Vol/bind 52
Tidsskriftsnummer 5
Sider (fra-til) 292-297
Antal sider 6
ISSN 1473-0480
DOI
Status Udgivet - 2018

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization

Skaaby, T., Taylor, A. E., Thuesen, B. H., Jacobsen, R. K., Friedrich, N., Møllehave, L. T., Hansen, S., Larsen, S. C., Völker, U., Nauck, M., Völzke, H., Hansen, T., Pedersen, O., Jørgensen, T., Paternoster, L., Munafò, M., Grarup, N. & Linneberg, A., 2018, I : Allergy. 73, 1, s. 153-64

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC).

METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI).

RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m(2) higher BMI.

CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Originalsprog Engelsk
Tidsskrift Allergy
Vol/bind 73
Tidsskriftsnummer 1
Sider (fra-til) 153-64
ISSN 0105-4538
DOI
Status Udgivet - 2018

EULAR recommendations for the health professional's approach to pain management in inflammatory arthritis and osteoarthritis

Geenen, R., Overman, C. L., Christensen, R., Åsenlöf, P., Capela, S., Huisinga, K. L., Husebø, M. E. P., Köke, A. J. A., Paskins, Z., Pitsillidou, I. A., Savel, C., Austin, J., Hassett, A. L., Severijns, G., Stoffer-Marx, M., Vlaeyen, J. W. S., Fernández-de-Las-Peñas, C., Ryan, S. J. & Bergman, S., jun. 2018, I : Annals of the Rheumatic Diseases. 77, 6, s. 797-807 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional's approach to pain management. A multidisciplinary task force including professionals and patient representatives conducted a systematic literature review of systematic reviews to evaluate evidence regarding effects on pain of multiple treatment modalities. Overarching principles and recommendations regarding assessment and pain treatment were specified on the basis of reviewed evidence and expert opinion. From 2914 review studies initially identified, 186 met inclusion criteria. The task force emphasised the importance for the health professional to adopt a patient-centred framework within a biopsychosocial perspective, to have sufficient knowledge of IA and OA pathogenesis, and to be able to differentiate localised and generalised pain. Treatment is guided by scientific evidence and the assessment of patient needs, preferences and priorities; pain characteristics; previous and ongoing pain treatments; inflammation and joint damage; and psychological and other pain-related factors. Pain treatment options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta-analyses, these recommendations enable health professionals to provide knowledgeable pain-management support for people with IA and OA.

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Tidsskriftsnummer 6
Sider (fra-til) 797-807
Antal sider 11
ISSN 0003-4967
DOI
Status Udgivet - jun. 2018

Evaluation of an intervention programme addressing ability to perform activities of daily living among persons with chronic conditions: study protocol for a feasibility trial (ABLE)

Guidetti, S., Nielsen, K. T., von Bülow, C., Pilegaard, M. S., Klokker, L. & Wæhrens, E. E., 20 maj 2018, I : BMJ Open. 8, 5, s. e020812

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

INTRODUCTION: The number of persons living with a chronic condition is increasing worldwide. Conditions are considered chronic when lasting 1 year or more and requiring ongoing medical attention and/or limiting activities of daily living (ADL). Besides medical treatment, physical exercise to improve body functions is recommended and prescribed. However, improvements in body functions do not necessarily improve ability to perform ADL. Thus, it is necessary to develop interventions aiming directly at enhancing ADL ability. As a part of the research programme 'A Better Everyday Life', the first version of the ABLE intervention programme was developed.

METHODS AND ANALYSIS: This feasibility study examine the perceived value and acceptability of the ABLE programme by evaluating the fidelity, reach, dose and potential outcomes using a pretest and post-test design involving 30 persons living with chronic conditions. Qualitative interviews among occupational therapists delivering and participants receiving the ABLE programme will be conducted to explore aspects affecting the intervention.

ETHICS AND DISSEMINATION: The results will form the base for refinement of the ABLE programme and planning of a large-scale randomised controlled trial investigating the effect of the programme on self-reported and observed ADL ability. Dissemination will include peer-reviewed publications and presentations at national and international conferences.

PROTOCOL VERSION: 7 November 2017: v ersion 1.0. 19 February 2018: v ersion 2.0.

TRIAL REGISTRATION NUMBER: NCT03335709; Pre-results.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 8
Tidsskriftsnummer 5
Sider (fra-til) e020812
ISSN 2044-6055
DOI
Status Udgivet - 20 maj 2018

Exposure to vitamin D from fortified margarine during fetal life and later risk of pre-eclampsia: the D-tect Study

Stougaard, M., Damm, P., Frederiksen, P., Jacobsen, R. & Heitmann, B. L., 24 mar. 2018, I : Public Health Nutrition. 21, 4, s. 721-731 11 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To examine if fetal exposure to a small dosage of extra vitamin D from food fortification was associated with a decrease in the risk of pre-eclampsia later in life.

DESIGN: Cancellation of the mandatory vitamin D fortification of margarine in 1985 created a societal experiment, with entire adjacent birth cohorts exposed or unexposed to extra vitamin D during fetal development. The Danish national medical health registries allowed the identification of pre-eclampsia cases later in life among all exposed and unexposed female individuals.

SETTING: Denmark.

SUBJECTS: Women born between June 1983 and August 1988, who gave birth to their first child at age 14·5-27·5 years (n 32 621).

RESULTS: OR (95 % CI) for pre-eclampsia among women exposed v. unexposed to extra vitamin D from fortification during fetal development was 0·86 (0·76, 0·97). Exposure to extra vitamin D was associated with further reduced odds of pre-eclampsia (0·49 (0·34, 0·72)) among current smokers, but not among former smokers and non-smokers.

CONCLUSIONS: Additional vitamin D in fetal life from food fortification seems to reduce the risk of pre-eclampsia later in life. The risk reduction may be particularly strong among women who smoke during pregnancy.

Originalsprog Engelsk
Tidsskrift Public Health Nutrition
Vol/bind 21
Tidsskriftsnummer 4
Sider (fra-til) 721-731
Antal sider 11
ISSN 1368-9800
DOI
Status Udgivet - 24 mar. 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

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
Tidsskriftsnummer 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
Tidsskriftsnummer 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
Tidsskriftsnummer 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
Tidsskriftsnummer 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
Tidsskriftsnummer 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
Tidsskriftsnummer 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
Tidsskriftsnummer 4
Sider (fra-til) 880-886
Antal sider 7
ISSN 0307-0565
DOI
Status Udgivet - apr. 2018

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