Published in 2020

The Relation between Red Meat and Whole-Grain Intake and the Colonic Mucosal Barrier: A Cross-Sectional Study

Jawhara, M., Sørensen, S. B., Heitmann, B. L., Halldórsson, Þ. I., Pedersen, A. K. & Andersen, V., 12 jun. 2020, I: Nutrients. 12, 6

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

The Colonic Mucosal Barrier (CMB) is the site of interaction between the human body and the colonic microbiota. The mucus is the outer part of the CMB and is considered as the front-line defense of the colon. It separates the host epithelial lining from the colonic content, and it has previously been linked to health and diseases. In this study, we assessed the relationship between red meat and whole-grain intake and (1) the thickness of the colonic mucus (2) the expression of the predominant mucin gene in the human colon (MUC2). Patients referred to colonoscopy at the University Hospital of Southern Denmark- Sonderjylland were enrolled between June 2017 and December 2018, and lifestyle data was collected in a cross-sectional study design. Colonic biopsies, blood, urine, and fecal samples were collected. The colonic mucus and bacteria were visualized by immunostaining and fluorescence in situ hybridization techniques. We found a thinner mucus was associated with high red meat intake. Similarly, the results suggested a thinner mucus was associated with high whole-grain intake, albeit to a lesser extent than red meat. This is the first study assessing the association between red meat and whole-grain intake and the colonic mucus in humans. This study is approved by the Danish Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). A study protocol was registered at clinical trials.gov under NCT04235348.

Originalsprog Engelsk
Tidsskrift Nutrients
Vol/bind 12
Udgave nummer 6
ISSN 2072-6643
DOI
Status Udgivet - 12 jun. 2020

The Role of Vitamin D in the Development of Diabetes Post Gestational Diabetes Mellitus: A Systematic Literature Review

Keller, A., Varela Vazquez, C., Dangol, R., Damm, P., Heitmann, B. L. & Händel, M. N., 1 jun. 2020, I: Nutrients. 12, 6, s. 1-17 17 s., 1733.

Publikation: Bidrag til tidsskriftReviewpeer review

Women diagnosed with gestational diabetes mellitus (GDM) are more likely to later develop diabetes. Evidence from some previous reviews suggests that low vitamin D status during pregnancy increases the risk of developing GDM, but whether vitamin D during pregnancy also influences the risk of diabetes post GDM is less well studied. Thus, the aim of this systematic literature review was to summarize the current available literature on that topic. This review considered observational studies and randomized controlled trials (RCTs). Five databases were searched. The risk of bias of the included studies was assessed. A total of six studies were included: three observational studies and three RCTs. Findings were inconsistent across the six included studies. However, when considering RCTs only, the findings more strongly suggested that vitamin D supplementation during and after pregnancy did not have an influence on markers of diabetes development or diabetes development post GDM. This systematic review highlights inconsistent findings on the associations between vitamin D supplementation or concentration during and after pregnancy and markers of diabetes development or diabetes development post GDM; and although results from randomized interventional studies more strongly suggested no associations, the conclusion holds a high degree of uncertainty.

Originalsprog Engelsk
Artikelnummer 1733
Tidsskrift Nutrients
Vol/bind 12
Udgave nummer 6
Sider (fra-til) 1-17
Antal sider 17
ISSN 2072-6643
DOI
Status Udgivet - 1 jun. 2020

Treatment effect sizes vary in randomized trials depending on the type of outcome measure

Berthelsen, D. B., Ginnerup-Nielsen, E., Juhl, C., Lund, H., Henriksen, M., Hróbjartsson, A., Nielsen, S. M., Voshaar, M. & Christensen, R., 23 mar. 2020, I : Journal of Clinical Epidemiology. 123, s. 27-38 12 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

OBJECTIVE: To compare estimated treatment effects of physical therapy (PT) between patient-reported outcome measures (PROMs) and outcomes measured in other ways.

STUDY DESIGN AND SETTING: We selected randomized trials of PT with both a PROM and a non-PROM included in Cochrane systematic reviews (CSRs). Two reviewers independently extracted data and risk-of-bias assessments. Our primary outcome was the ratio of odds ratios (RORs), used to quantify how effect varies between PROMs and non-PROMs; an ROR > 1 indicates larger effect when assessed by using PROMs. We used REML-methods to estimate associations of trial characteristics with effects and between-trial heterogeneity.

RESULTS: From 90 relevant CSRs, 205 PT trials were included. The summary ROR across all the comparisons was not statistically significant (ROR, 0.88 [95% CI: 0.70-1.12]; P = 0.30); however, the heterogeneity was substantial (I2 = 88.1%). When stratifying non-PROMs further into clearly objective non-PROMs (e.g., biomarkers) and other non-PROMs (e.g., aerobic capacity), the PROMs appeared more favorable than did clearly objective non-PROMs (ROR, 1.92 [95% CI: 0.99-3.72]; P = 0.05).

CONCLUSION: Estimated treatment effects based on PROMs are generally comparable with treatment effects measured in other ways. However, in our study, PROMs indicate a more favorable treatment effect compared with treatment effects based on clearly objective outcomes.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 123
Sider (fra-til) 27-38
Antal sider 12
ISSN 0895-4356
DOI
Status E-pub ahead of print - 23 mar. 2020

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

OBJECTIVES: To compare the efficacy, complications and re-operations after bottom-up tension-free vaginal tape (TVT) and inside-out tension-free vaginal tape - obturator (TVT-O) in the treatment of stress urinary incontinence (SUI) in adult women.

STUDY DESIGN: A systematic literature search and review was performed limited to randomized controlled trials. We searched Medline, Embase, Cochrane Library, Cinahl, Guideline International network (GIN), Trip Database and NICE (UK). The certainty in the estimates of the included outcomes was rated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method.

RESULTS AND CONCLUSIONS: We included 22 randomized controlled trials. The overall certainty in the evidence was moderate across all outcomes. TVT and TVT-O significantly improved the incontinence regarding number of incontinence episodes, subjective patient reported effect and incontinence related quality of life, and there was no difference between TVT and TVT-O. Leg or groin pain was significantly less common 6 months after TVT than TVT-O with RR 0.27 (CI 95 % 0.11 - 0.66), 9 studies, n = 1312. In absolute numbers 83 patients more developed chronic leg or groin pain per 1000 operations with TVT-O compared to TVT. We found no statistically significant differences between chronic pelvic or lower abdominal pain 6 months after TVT and TVT-O. Bladder perforations were significantly more common after TVT with RR 4.53 (CI 95 % 2.32-8.86), 21 studies, n = 3308. In absolute numbers this meant 5 more bladder perforations after TVT per 1000 operations. No statistically significant differences were noted in de novo urgency, re-operations, infection, hematoma, pain during sexual intercourse or sexual function. Bottom-up TVT and inside-out TVT-O showed equal efficacy, but leg and groin pain were much more common with TVT-O. The authors would recommend TVT instead of TVT-O as first line operation in patients who need surgery for SUI.

Originalsprog Engelsk
Tidsskrift European journal of obstetrics, gynecology, and reproductive biology
Vol/bind 258
Sider (fra-til) 146-151
Antal sider 6
ISSN 0028-2243
DOI
Status Udgivet - 13 dec. 2020

Bibliografisk note

Copyright © 2020 Elsevier B.V. All rights reserved.

Use and reporting of outcome measures in randomized trials for anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic literature review

Monti, S., Quinn, K. A., Christensen, R., Jayne, D., Langford, C., Lanier, G. E., Mahr, A., Pagnoux, C., Viðarsdóttir, M. B., Merkel, P. A. & Tomasson, G., dec. 2020, I: Seminars in Arthritis and Rheumatism. 50, 6, s. 1314-1325 12 s.

Publikation: Bidrag til tidsskriftReviewpeer review

BACKGROUND: A comprehensive review of outcome measures used in randomized controlled trials (RCTs) of ANCA-associated vasculitis (AAV) could advance trial conductance for this disease.

METHODS: A systematic literature review of outcome measures (as specified in methods section as primary and/or secondary outcomes) in RCTs of AAV was conducted. Medline, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception until April 30, 2019 for RCTs enrolling patients with granulomatosis with polyangiitis and/or microscopic polyangiitis. Outcome measures were organized according to domains (e.g. disease activity) and instruments [e.g. Birmingham Vasculitis Activity Score (BVAS)].

RESULTS: Out of 1101 identified records, 68 RCTs were eligible. Disease activity was an outcome domain collected in 67 (98%) of the RCTs. The BVAS was the most widely used instrument for disease assessment but definitions for remissions and relapse varied for the purpose of primary endpoint definitions. Damage, most often assessed by the Vasculitis Damage Index, was an outcome in 30 (44%) of the RCTs. Mortality was specified as an outcome in 26 (38%) studies. The following outcome domains were assessed: patient-reported outcomes (PROs) in 28 (41%), drug exposure/safety in 58 (85%), and biomarkers [acute phase reactants, ANCA levels] in 24 (35%). Timing for outcome assessment differed substantially, with 3, 6, or 12 months being the most frequent time points.

CONCLUSION: Outcome measures used in trials in AAV commonly included vasculitis-specific tools for disease assessment, but with heterogeneity in endpoint-definitions and timing of assessments. Other core outcomes in AAV, including PROs, and damage measures, are often omitted in AAV trials.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 50
Udgave nummer 6
Sider (fra-til) 1314-1325
Antal sider 12
ISSN 0049-0172
DOI
Status Udgivet - dec. 2020

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

Use of composite outcomes facilitate core outcome set uptake in rheumatoid arthritis trials

Kirkham, J., Christensen, R. & Boers, M., feb. 2020, I: Annals of the Rheumatic Diseases. 79, 2, s. 301-302 2 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Originalsprog Engelsk
Tidsskrift Annals of the Rheumatic Diseases
Vol/bind 79
Udgave nummer 2
Sider (fra-til) 301-302
Antal sider 2
ISSN 0003-4967
DOI
Status Udgivet - feb. 2020

Using betahistine in the treatment of patients with Menière's disease: a meta-analysis with the current randomized-controlled evidence

Devantier, L., Hougaard, D., Händel, M. N., Liviu-Adelin Guldfred, F., Schmidt, J. H., Djurhuus, B. & Callesen, H. E., okt. 2020, I: Acta Oto-Laryngologica. 140, 10, s. 845-853 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: Betahistine is used worldwide to treat patients with Menière's disease. However, despite it being used for decades, diverging opinions on the effect of betahistine on Menière's symptomatology still exist.Aims: The objective of this systematic review was to provide an overview and rate the certainty of the current evidence base regarding the use of betahistine to treat patients with Menière's disease.Materials and methods: A systematic literature search was conducted in October 2019. The search strategy was subdivided into searches for existing guidelines, systematic reviews and individual randomized controlled trials (RCT) investigating the usage of betahistine as compared to placebo, in patients with Ménière's disease. The primary outcome was the frequency of vertigo attack(s) and occurrence of serious adverse events.Results: We identified three relevant guidelines and three systematic reviews: however, neither included any relevant trials matching our inclusion criteria. An individual search for RCTs identified one trial. The results from this particular trial showed no difference in effects on symptoms following treatment with betahistine.Conclusions and Significance: There is a need for further well-conducted placebo RCTs. Currently, there is still a lack of substantial evidence supporting betahistine as a significant and adequate treatment for patients diagnosed with Menière's disease. Trial registration number: The protocol is registered in PROSPERO. Registration number: CRD42018110127 Accepted 11.10.2018.

Originalsprog Engelsk
Tidsskrift Acta Oto-Laryngologica
Vol/bind 140
Udgave nummer 10
Sider (fra-til) 845-853
Antal sider 9
ISSN 0001-6489
DOI
Status Udgivet - okt. 2020

Validation of the colostomy impact score in patients ostomized for a benign condition

Kristensen, H. Ø., Krogsgaard, M., Christensen, P. & Thomsen, T., 2 aug. 2020, (E-pub ahead of print) I: Colorectal Disease.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

AIM: The colostomy impact (CI) score is a patient-reported outcome measure assessing reduction in health-related quality of life (HRQL) due to a stoma. The score was originally developed and validated in a cohort of rectal cancer survivors with a permanent colostomy. For the CI score to be applied to patients with a colostomy after surgery for a benign condition it must be validated in this patient group. The aim of this study was to assess construct validity and known groups validity of the CI score in patients with a colostomy after surgery for a benign condition.

METHOD: In a cross-sectional survey among ostomates in the Capital Region of Denmark, patients completed the CI score and the SF-36 v2 questionnaires. Construct validity was assessed by Pearson's correlation coefficients and known groups validity was assessed by t-test when dividing patients into groups of minor or major CI.

RESULTS: The CI score showed a moderate negative correlation with the Physical Component Summary (PCS) of -0.41 and a weak negative correlation with the Mental Component Summary (MCS) of -0.39. The strength of the correlation depended on the underlying condition leading to stoma formation. Differences were significant between the minor and major CI groups in mean PSC and MCS with t-values of 5.32 and 3.86, respectively.

CONCLUSION: The CI score is a valid instrument for assessing stoma-related impact on HRQL regardless of the underlying condition leading to stoma formation, and the CI score discriminates meaningfully between groups with known differences in stoma-related reduced HRQL.

Originalsprog Engelsk
Tidsskrift Colorectal Disease
ISSN 1462-8910
DOI
Status E-pub ahead of print - 2 aug. 2020

Bibliografisk note

© 2020 The Association of Coloproctology of Great Britain and Ireland.

Vascular ultrasound for the diagnosis of giant cell arteritis: a reliability and agreement study based on a standardised training programme

Chrysidis, S., Terslev, L., Christensen, R., Fredberg, U., Larsen, K., Lorenzen, T., Døhn, U. M. & Diamantopoulos, A. P., 2020, I: RMD Open. 6, 3, s. e001337 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To evaluate the impact of a standardised training programme including equipment adjustment for experienced musculoskeletal ultrasonographers without previous experience in vascular ultrasound (US) on the reliability of US in the diagnosis of giant cell arteritis (GCA).

METHODS: In this prospective, non-interventional observational cohort study, patients suspected of GCA were evaluated by US by one of five rheumatologists with long-standing experience in musculoskeletal US (>8 years), trained using a standardised training programme including equipment adjustment. Images of cranial and large vessels were subsequently evaluated first by the performing ultrasonographer and thereafter by a blinded external expert (gold standard).

RESULTS: In three Danish centres, 112 patients suspected of GCA were included. According to the external expert, vasculitis changes were seen in 66 patients, in 45 of them with only cranial involvement, in 14 with both cranial and large vessel involvement, while in seven patients isolated large vessel vasculitis was found. The reliability was excellent between the local ultrasonographer and the US expert for the overall GCA diagnosis regarding the diagnosis of cranial and for large vessel GCA, with an interobserver agreement of 95-96%, mean kappa values of 0.88-0.92 (95% CI 0.78 to 0.99). Excellent reliability (mean kappa 0.86-1.00) was also found for the US examination of the individual arteries (temporal, facial, common carotid and axillary).

CONCLUSION: The US training programme resulted in excellent agreement between trainees and an expert in patients suspected of GCA and may thus be applicable for implementation of vascular US in clinical practice.

Originalsprog Engelsk
Tidsskrift RMD Open
Vol/bind 6
Udgave nummer 3
Sider (fra-til) e001337
Antal sider 7
ISSN 2056-5933
DOI
Status Udgivet - 2020

Bibliografisk note

COPECARE

Vitamin D and Calcium Milk Fortification in Pregnant Women with Periodontitis: A Feasibility Trial

Rodrigues Amorim Adegboye, A., Dias Santana, D., Cocate, P. G., Benaim, C., Teixeira Dos Santos, P. P., Heitmann, B. L., da Veiga Soares Carvalho, M. C., Schlüssel, M. M., Trindade de Castro, M. B. & Kac, G., 30 okt. 2020, I: International Journal of Environmental Research and Public Health. 17, 21

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

This study aims to assess the acceptability, adherence, and retention of a feasibility trial on milk fortification with calcium and vitamin D (Ca+VitD) and periodontal therapy (PT) among low income Brazilian pregnant women with periodontitis (IMPROVE trial). This 2 × 2 factorial feasibility trial used a mixed-methods evaluation. In total, 69 pregnant women were randomly allocated to four groups: 1. fortified sachet with Ca+VitD and milk plus early PT (throughout gestation); 2. placebo and milk plus early PT; 3. fortified sachet with Ca+VitD and milk plus late PT after childbirth; 4. placebo and milk plus late PT. Data were collected via questionnaires, field notes, participant flow logs, treatment diary, and focal group discussions. Quantitative and qualitative data were analysed using appropriate descriptive statistics and content analysis, respectively. Eligibility rate (12%) was below the target of 15%, but participation (76.1%) and recruitment rate (2 women/week) exceeded the targets. Retention rate (78.6%) was slightly below the target (80%). Adherence to the PT was significantly higher in the early treatment groups (98.8%) compared to the late treatment groups (29%). All women accepted the random allocation, and baseline groups were balanced. There was no report of adverse events. This multi-component intervention is acceptable, well-tolerated, and feasible among low-risk pregnant women in Brazil.

Originalsprog Engelsk
Tidsskrift International Journal of Environmental Research and Public Health
Vol/bind 17
Udgave nummer 21
ISSN 1661-7827
DOI
Status Udgivet - 30 okt. 2020

Weekly, seasonal and holiday body weight fluctuation patterns among individuals engaged in a European multi-centre behavioural weight loss maintenance intervention

Turicchi, J., O'Driscoll, R., Horgan, G., Duarte, C., Palmeira, A. L., Larsen, S. C., Heitmann, B. L. & Stubbs, J., 2020, I: PLoS One. 15, 4, s. e0232152

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Technological advances in remote monitoring offer new opportunities to quantify body weight patterns in free-living populations. This paper describes body weight fluctuation patterns in response to weekly, holiday (Christmas) and seasonal time periods in a large group of individuals engaged in a weight loss maintenance intervention.

METHODS: Data was collected as part The NoHoW Project which was a pan-European weight loss maintenance trial. Three eligible groups were defined for weekly, holiday and seasonal analyses, resulting in inclusion of 1,421, 1,062 and 1,242 participants, respectively. Relative weight patterns were modelled on a time series following removal of trends and grouped by gender, country, BMI and age.

RESULTS: Within-week fluctuations of 0.35% were observed, characterised by weekend weight gain and weekday reduction which differed between all groups. Over the Christmas period, weight increased by a mean 1.35% and was not fully compensated for in following months, with some differences between countries observed. Seasonal patterns were primarily characterised by the effect of Christmas weight gain and generally not different between groups.

CONCLUSIONS: This evidence may improve current understanding of regular body weight fluctuation patterns and help target future weight management interventions towards periods, and in groups, where weight gain is anticipated.

Originalsprog Engelsk
Tidsskrift PLoS One
Vol/bind 15
Udgave nummer 4
Sider (fra-til) e0232152
ISSN 1932-6203
DOI
Status Udgivet - 2020

What is spiritual care? Professional perspectives on the concept of spiritual care identified through group concept mapping

Hvidt, N. C., Nielsen, K. T., Kørup, A. K., Prinds, C., Hansen, D. G., Viftrup, D. T., Assing Hvidt, E., Hammer, E. R., Falkø, E., Locher, F., Boelsbjerg, H. B., Wallin, J. A., Thomsen, K. F., Schrøder, K., Moestrup, L., Nissen, R. D., Stewart-Ferrer, S., Stripp, T. K., Steenfeldt, V. Ø., Søndergaard, J. & Wæhrens, E. E., 28 dec. 2020, I: BMJ Open. 10, 12, s. e042142

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: The overall study aim was to synthesise understandings and experiences regarding the concept of spiritual care (SC). More specifically, to identify, organise and prioritise experiences with the way SC is conceived and practised by professionals in research and the clinic.

DESIGN: Group concept mapping (GCM).

SETTING: The study was conducted within a university setting in Denmark.

PARTICIPANTS: Researchers, students and clinicians working with SC on a daily basis in the clinic and/or through research participated in brainstorming (n=15), sorting (n=15), rating and validation (n=13).

RESULTS: Applying GCM, ideas were identified, organised and prioritised online. A total of 192 unique ideas of SC were identified and organised into six clusters. The results were discussed and interpreted at a validation meeting. Based on input from the validation meeting a conceptual model was developed. The model highlights three overall themes: (1) 'SC as an integral but overlooked aspect of healthcare' containing the two clusters SC as a part of healthcare and perceived significance; (2) 'delivering SC' containing the three clusters quality in attitude and action, relationship and help and support, and finally (3) 'the role of spirituality' containing a single cluster.

CONCLUSION: Because spirituality is predominantly seen as a fundamental aspect of each individual human being, particularly important during suffering, SC should be an integral aspect of healthcare, although it is challenging to handle. SC involves paying attention to patients' values and beliefs, requires adequate skills and is realised in a relationship between healthcare professional and patient founded on trust and confidence.

Originalsprog Engelsk
Tidsskrift BMJ Open
Vol/bind 10
Udgave nummer 12
Sider (fra-til) e042142
ISSN 2044-6055
DOI
Status Udgivet - 28 dec. 2020

Bibliografisk note

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Yngre patienter med hofteledssmerter

Dippmann, C., Albrecht-Olsen, P., Boesen, M., Chrintz, H., Hölmich, P., Jakobsen, S. S., Jørgensen, U., Konradsen, L., Kraemer, O., Lund, B., Maagaard, N., Mygind-Klavsen, B., Overgaard, S., Ovesen, O., Stürup, J., Søballe, K., Warming, T., Winther, N. & Krogsgaard, M., 6 jan. 2020, I: Ugeskrift for Laeger. 182, 2

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

This review summarises the present knowledge of diagnosing and treating hip joint pain. The results of joint preserving surgery are good in symptomatic patients with hip dysplasia, acetabular retroversion or impingement (cam or pincer) without signs of osteoarthritis. Confirmation of intraarticular pathology as the cause of symptoms is established clinically, and the pathology can in many cases be visualised by a standing, standardised radiograph of the pelvis, which is the basis for admission to the relevant orthopaedic department. We present an algorithm for this. Dysplasia and retroversion can be treated by periacetabular osteotomy and impingement by arthroscopic procedures.

Bidragets oversatte titel Younger patients with hip joint pain
Originalsprog Dansk
Tidsskrift Ugeskrift for Laeger
Vol/bind 182
Udgave nummer 2
ISSN 0041-5782
Status Udgivet - 6 jan. 2020

Published in 2019

A Phase II Trial of Lutikizumab, an Anti-Interleukin-1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis

Fleischmann, R. M., Bliddal, H., Blanco, F. J., Schnitzer, T. J., Peterfy, C., Chen, S., Wang, L., Feng, S., Conaghan, P. G., Berenbaum, F., Pelletier, J-P., Martel-Pelletier, J., Vaeterlein, O., Kaeley, G. S., Liu, W., Kosloski, M. P., Levy, G., Zhang, L., Medema, J. K. & Levesque, M. C., jul. 2019, I: Arthritis & rheumatology. 71, 7, s. 1056-1069 14 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To assess the efficacy and safety of the anti-interleukin-1α/β (anti-IL-1α/β) dual variable domain immunoglobulin lutikizumab (ABT-981) in patients with knee osteoarthritis (OA) and evidence of synovitis.

METHODS: Patients (n = 350; 347 analyzed) with Kellgren/Lawrence grade 2-3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or ultrasound) were randomized to receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at week 16 and change from baseline in MRI-assessed synovitis at week 26.

RESULTS: The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg (P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab-treated and placebo-treated patients. Changes from baseline in MRI-assessed synovitis at week 26 and other key symptom- and most structure-related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high-sensitivity C-reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations.

CONCLUSION: The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL-1 inhibitors, suggest that IL-1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis.

Originalsprog Engelsk
Tidsskrift Arthritis & rheumatology
Vol/bind 71
Udgave nummer 7
Sider (fra-til) 1056-1069
Antal sider 14
ISSN 2326-5191
DOI
Status Udgivet - jul. 2019

Bibliografisk note

© 2019, American College of Rheumatology.

A portfolio of biologic self-injection devices in rheumatology: how patient involvement in device design can improve treatment experience

van den Bemt, B. J. F., Gettings, L., Domańska, B., Bruggraber, R., Mountian, I. & Kristensen, L. E., dec. 2019, I: Drug Delivery . 26, 1, s. 384-392 9 s.

Publikation: Bidrag til tidsskriftReviewpeer review

Biologic drugs (e.g. anti-tumor necrosis factors) are effective treatments for multiple chronic inflammatory diseases including rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis. Administration of biologic drugs is usually via subcutaneous self-injection, which provides many patient benefits compared to infusions including increased flexibility, reduced costs, and reduced caregiver burden. However, it is also associated with challenges such as needle phobia, patient treatment misconceptions and incorrect drug administration, and can be impacted by dexterity problems. Evidence suggests these problems, along with other drug administration challenges (e.g. patient forgetfulness, busy lifestyles, and polypharmacy), can reduce patient adherence to treatment. To combat these challenges, patient feedback has been used to develop a range of self-injection devices, including pre-filled syringes, pre-filled pens, and electronic injection devices. Providing different devices for drug administration gives patients the opportunity to choose a device that addresses the challenges they face as an individual. Research suggests involving patients in medical device development, providing patients with a choice of devices and enrolling individuals in patient support programs can empower patients to take control of their treatment journey. By providing a portfolio of self-injection devices, designed based on patient needs, patient experience will improve, potentially improving adherence and hence, long-term treatment outcomes.

Originalsprog Engelsk
Tidsskrift Drug Delivery
Vol/bind 26
Udgave nummer 1
Sider (fra-til) 384-392
Antal sider 9
ISSN 1071-7544
DOI
Status Udgivet - dec. 2019

BACKGROUND: The fetal brain starts developing early and animal studies have suggested that iron plays several roles for the development, but results from epidemiological studies investigating associations between gestational iron and offspring neurodevelopment are inconsistent.

OBJECTIVE: To systematically examine results from observational studies and RCTs on gestational iron and offspring neurodevelopment, with focus on the importance of four domains: iron status indicators, exposure timing, neurodevelopmental outcomes, and offspring age.

METHODS: PRISMA guidelines were followed. Embase, PsychInfo, Scopus, and The Cochrane library were searched in September 2017 and February 2018. Overall, 3307 articles were identified and 108 retrieved for full-text assessment. Pre-specified eligibility criteria were used to select studies and 27 articles were included;19 observational and 8 RCTs.

RESULTS: Iron status in pregnancy was associated with offspring behavior, cognition, and academic achievement. The direction of associations with behavioral outcomes were unclear and the conclusions related to cognition and academic achievement were based on few studies, only. Little evidence was found for associations with motor development. Observed associations were shown to persist beyond infancy into adolescence, and results depended on iron status indicator type but not on the timing of exposure.

CONCLUSION: We conclude that there is some evidence that low pregnancy iron, possibly particularly in the 3rd trimester, may be associated with adverse offspring neurodevelopment. As most previous research used Hemoglobin, inferring results to iron deficiency should be done with caution. No conclusions could be reached regarding associations beyond early childhood, and supplementation with iron during pregnancy did not seem to influence offspring neurodevelopment.

Originalsprog Engelsk
Tidsskrift European Journal of Clinical Nutrition
Vol/bind 73
Udgave nummer 12
Sider (fra-til) 1561-1578
Antal sider 18
ISSN 0954-3007
DOI
Status Udgivet - dec. 2019

Adaptive Trial Designs in Rheumatology: Report from the OMERACT Special Interest Group

Pickles, T., Alten, R., Boers, M., Bykerk, V., Christensen, J., Christensen, R., van Hoogstraten, H., Simon, L. S., Tam, L-S. & Choy, E. H., okt. 2019, I: Journal of Rheumatology. 46, 10, s. 1406-1408 3 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Adaptive trial design was developed initially for oncology to improve trial efficiency. If optimized for rheumatology, it may improve trial efficiency by reducing sample size and time.

METHODS: A systematic review assessed design of phase II clinical trials in rheumatoid arthritis.

RESULTS: Fifty-six trials were reviewed. Most trials had 4 groups (1 control and 3 intervention), with an average group size of 34 patients. American College of Rheumatology 20 measured at 16 weeks was the most commonly used primary endpoint.

CONCLUSION: The next step is to undertake a systematic review of adaptive designs used in early-phase trials in nonrheumatic conditions.

Originalsprog Engelsk
Tidsskrift Journal of Rheumatology
Vol/bind 46
Udgave nummer 10
Sider (fra-til) 1406-1408
Antal sider 3
ISSN 0315-162X
DOI
Status Udgivet - okt. 2019

Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials

Tarp, S., Jørgensen, T. S., Furst, D. E., Dossing, A., Taylor, P. C., Choy, E. H., Suarez-Almazor, M. E., Lyddiatt, A., Kristensen, L. E., Bliddal, H. & Christensen, R., jun. 2019, I: Seminars in Arthritis and Rheumatism. 48, 6, s. 958-966 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA).

METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates.

RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence.

CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 48
Udgave nummer 6
Sider (fra-til) 958-966
Antal sider 9
ISSN 0049-0172
DOI
Status Udgivet - jun. 2019

Bibliografisk note

Copyright © 2018 Elsevier Inc. All rights reserved.

Adolescent wine consumption is inversely associated with long-term weight gain: results from follow-up of 20 or 22 years

Poudel, P., Ismailova, K., Andersen, L. B., Larsen, S. C. & Heitmann, B. L., 10 sep. 2019, I: Nutrition Journal. 18, 1, s. 56 56.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Several studies have suggested a link between the type of alcoholic beverage consumption and body weight. However, results from longitudinal studies have been inconsistent, and the association between adolescent alcohol consumption long-term weight gain has generally not been examined.

METHODS: The study was based on data from 720 Danish adolescents aged between 15 to 19 years at baseline from the Danish Youth and Sports Study (YSS). Self-reported alcohol use, height, weight, smoking, social economic status (SES) and physical activity levels were assessed in baseline surveys conducted in 1983 and 1985, and in the follow up survey which was conducted in 2005. Multiple linear regression analyses were used to examine the association between alcohol consumption in adolescence and subsequent weight gain later in midlife.

RESULTS: There was no significant association between total alcohol consumption during adolescence and change in BMI into midlife (P = 0.079) (β - 0.14; 95% CI -0.28, 0.005). Wine consumption was found to be inversely associated to subsequent BMI gain (P = 0.001) (β - 0.46; 95% CI -0.82, - 0.09) while the results were not significant for beer and spirit. The relationship did not differ by gender, but smoking status was found to modify the relationship, and the inverse association between alcohol and BMI gain was seen only among non-smokers (P = 0.01) (β - 0.24; 95% CI -0.41, - 0.06) while no association was found among smokers. Neither adolescent nor attained socioeconomic status in adulthood modified the relationship between alcohol intake and subsequent BMI gain.

CONCLUSION: Among non-smoking adolescents, consumption of alcohol, and in particular wine, seems to be associated with less weight gain until midlife.

TRIAL REGISTRATION: The YSS cohort was retrospectively registered on August 2017. (Study ID number: NCT03244150 ).

Originalsprog Engelsk
Artikelnummer 56
Tidsskrift Nutrition Journal
Vol/bind 18
Udgave nummer 1
Sider (fra-til) 56
ISSN 1475-2891
DOI
Status Udgivet - 10 sep. 2019
Originalsprog Engelsk
Artikelnummer P19
Tidsskrift Endocrine Abstracts
Vol/bind 58
Antal sider 1
ISSN 0804-4643
Status Udgivet - 2019

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