Published in 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

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 77
Udgave nummer 5
Sider (fra-til) 684-689
ISSN 0003-4967
DOI
Status Udgivet - 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
Udgave nummer 1
Sider (fra-til) 52-57
Antal sider 6
ISSN 0022-202X
DOI
Status Udgivet - jan. 2018

Infographic. The Adductor Strengthening Programme prevents groin problems among male football players

Harøy, J., Pope, D., Clarsen, B., Wiger, E. G., Øyen, M. G., Serner, A., Thorborg, K., Hölmich, P., Andersen, T. E. & Bahr, R. 30 okt. 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 Udgivet - 30 okt. 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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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
Udgave nummer 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., nov. 2018, I : Clinical and Experimental Rheumatology.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 Udgivet - nov. 2018

Joining Parents' Bed at Night and Overweight among 2- to 6-Year-Old Children - Results from the 'Healthy Start' Randomized Intervention

Olsen, N. J., Rohde, J. F., Händel, M. N., Stougaard, M., Mortensen, E. L. & Heitmann, B. L., 2018, I : Obesity Facts. 11, 5, s. 372-380 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Parental and child co-sleeping has been suggested as a risk factor for short sleep duration and poor sleep quality that may lead to overweight. We examined if joining parent's bed during night was associated with child overweight.

METHODS: Cross-sectional data from the 'Healthy Start' study including 635 2- to 6-year-old Danish children, who were all considered obesity prone. Of these, 496 children had complete information on BMI and whether the child joined parents' bed during night and if so, how frequently. International cut-offs for overweight according to age and gender were applied, and logistic regression was used to estimate odds ratio (OR) and 95% Confidence Intervals (CI). Analyses were adjusted for the child's age and gender, overall family stress, parental educational level, and parental BMI.

RESULTS: Children who did not join their parent's bed were more likely to be overweight compared to children who did (OR 1.75 (95% CI 0.99-3.10)). Children who rarely joined their parents' bed had OR 2.74 of being overweight (95% CI 1.01-7.44) compared to children who joined every night.

CONCLUSION: Children who rarely joined parents' bed during night were almost three times more likely to be overweight than those who joined every night.

Originalsprog Engelsk
Tidsskrift Obesity Facts
Vol/bind 11
Udgave nummer 5
Sider (fra-til) 372-380
Antal sider 9
ISSN 1662-4025
DOI
Status Udgivet - 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
Udgave nummer 2
Sider (fra-til) 386-400
ISSN 1057-9249
DOI
Status Udgivet - 2018

Long-term exposure to road traffic noise and incidence of breast cancer: a cohort study

Andersen, Z. J., Jørgensen, J. T., Elsborg, L., Lophaven, S. N., Backalarz, C., Laursen, J. E., Pedersen, T. H., Simonsen, M. K., Bräuner, E. V. & Lynge, E., 5 okt. 2018, I : Breast Cancer Research. 20, 1, s. 119

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Exposure to road traffic noise was associated with increased risk of estrogen receptor (ER)-negative (ER-) breast cancer in a previous cohort study, but not with overall or ER-positive (ER+) breast cancer, or breast cancer prognosis. We examined the association between long-term exposure to road traffic noise and incidence of breast cancer, overall and by ER and progesterone receptor (PR) status.

METHODS: We used the data from a nationwide Danish Nurse Cohort on 22,466 female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported information on breast cancer risk factors. We obtained data on the incidence of breast cancer from the Danish Cancer Registry, and on breast cancer subtypes by ER and PR status from the Danish Breast Cancer Cooperative Group, up to 31 December 2012. Road traffic noise levels at the nurses' residences were estimated by the Nord2000 method between 1970 and 2013 as annual means of a weighted 24 h average (Lden) at the most exposed facade. We used time-varying Cox regression to analyze the associations between the 24-year, 10-year, and 1-year mean of Lden and breast cancer, separately for total breast cancer and by ER and PR status.

RESULTS: Of the 22,466 women, 1193 developed breast cancer in total during 353,775 person-years of follow up, of whom 611 had complete information on ER and PR status. For each 10 dB increase in 24-year mean noise levels at their residence, we found a statistically significant 10% (hazard ratio and 95% confidence interval 1.10; 1.00-1.20) increase in total breast cancer incidence and a 17% (1.17; 1.02-1.33) increase in analyses based on 611 breast cancer cases with complete ER and PR information. We found positive, statistically significant association between noise levels and ER+ (1.23; 1.06-1.43, N = 494) but not ER- (0.93; 0.70-1.25, N = 117) breast cancers, and a stronger association between noise levels and PR+ (1.21; 1.02-1.42, N = 393) than between noise levels and PR- (1.10; 0.89-1.37, N = 218) breast cancers. Association between noise and ER+ breast cancer was statistically significantly stronger in nurses working night shifts (3.36; 1.48-7.63) than in those not working at night (1.21; 1.02-1.43) (p value for interaction = 0.05).

CONCLUSION: Long-term exposure to road traffic noise may increase risk of ER+ breast cancer.

Originalsprog Engelsk
Tidsskrift Breast Cancer Research
Vol/bind 20
Udgave nummer 1
Sider (fra-til) 119
ISSN 1465-542X
DOI
Status Udgivet - 5 okt. 2018

Long-term wind turbine noise exposure and incidence of myocardial infarction in the Danish nurse cohort

Bräuner, E. V., Jørgensen, J. T., Duun-Henriksen, A. K., Backalarz, C., Laursen, J. E., Pedersen, T. H., Simonsen, M. K. & Andersen, Z. J., dec. 2018, I : Environment International. 121, Pt 1, s. 794-802 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Growing evidence supports the concept that traffic noise exposure leads to long-term health complications other than annoyance, including cardiovascular disease. Similar effects may be expected from wind turbine noise exposure, but evidence is sparse. Here, we examined the association between long-term exposure to wind turbine noise and incidence of myocardial infarction (MI).

METHODS: We used the Danish Nurse Cohort with 28,731 female nurses and obtained data on incidence of MI in the Danish National Patient and Causes of Death Registries until ultimo 2013. Wind turbine noise levels at residential addresses between 1982 and 2013 were estimated using the Nord2000 noise propagation model, as the annual means of a weighted 24-hour average (Lden) at the most exposed façade. Time-varying Cox proportional hazard regression was used to examine the association between the 11-, 5- and 1-year rolling means prior to MI diagnosis of wind turbine noise levels and MI incidence.

RESULTS: Of 23,994 nurses free of MI at cohort baseline, 686 developed MI by end of follow-up in 2013. At the cohort baseline (1993 or 1999), 10.4% nurses were exposed to wind turbine noise (≥1 turbine within a 6000-m radius of the residence) and 13.3% in 2013. Mean baseline residential noise levels among exposed nurses were 26.3 dB, higher in those who developed MI (26.6 dB) than among those who didn't develop MI (26.3 dB). We found no association between wind turbine noise and MI incidence: adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) comparing nurses with 11-years mean residential noise levels of <21.5 dB, 21.5-25.4 dB, 25.4-29.9 dB, and >29.9 dB, to non-exposed nurses were 0.89 (0.64-1.25), 1.20 (0.82-1.77), 1.38 (0.95-2.01), and 0.88 (0.53-1.28), respectively. Corresponding HR (95% CI) for the linear association between 11-year mean levels of wind turbine noise (per 10 dB increase) with MI incidence was 0.99 (0.77-1.28). Similar associations were observed when considering the 5- and 1-year running means, and with no evidence of dose-response.

CONCLUSIONS: The results of this comprehensive cohort study lend little support to a causal association between outdoor long-term wind-turbine noise exposure and MI. However, there were only few cases in the highest exposure groups and our findings need reproduction.

Originalsprog Engelsk
Tidsskrift Environment International
Vol/bind 121
Udgave nummer Pt 1
Sider (fra-til) 794-802
Antal sider 9
ISSN 0160-4120
DOI
Status Udgivet - dec. 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
Udgave nummer 4
Sider (fra-til) 927-935
Antal sider 9
ISSN 0937-941X
DOI
Status Udgivet - apr. 2018

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