Published in 2021

Evidence-Based Research Series-Paper 3: Using an Evidence-Based Research approach to place your results into context after the study is performed to ensure usefulness of the conclusion

Lund, H., Juhl, C. B., Nørgaard, B., Draborg, E., Henriksen, M., Andreasen, J., Christensen, R., Nasser, M., Ciliska, D., Tugwell, P., Clarke, M., Blaine, C., Martin, J., Ban, J-W., Brunnhuber, K., Robinson, K. A. & Evidence-Based Research Network, jan. 2021, I: Journal of Clinical Epidemiology. 129, s. 167-171 5 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background and Objective: There is considerable actual and potential waste in research. Using evidence-based research (EBR) can ensure the value of a new study. The aim of this article, the third in a series, is to describe an EBR approach to putting research results into context. Study Design and Setting: EBR is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner. In this third and final article of a series, we describe how to use the context of existing evidence to reach and present a trustworthy and useful conclusion when reporting results from a new clinical study. Results: We describe a method, the EBR approach, that by using a systematic and transparent consideration of earlier similar studies when interpreting and presenting results from a new original study will ensure usefulness of the conclusion. Conclusion: Using an EBR approach will improve the usefulness of a clinical study by providing the context to draw more valid conclusions and explicit information about new research needs.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 129
Sider (fra-til) 167-171
Antal sider 5
ISSN 0895-4356
DOI
Status Udgivet - jan. 2021

Bibliografisk note

Funding Information:
This work has been prepared as part of the Evidence-Based Research Network (ebrnetwork.org). The EBRNetwork is an international network that promotes the use of systematic reviews when prioritizing, designing, and interpreting research. Evidence-based research is the use of prior research in a systematic and transparent way to inform the new study so that it is answering questions that matter in a valid, efficient, and accessible manner. The authors thank the Centre for Evidence-Based Practice, Western Norway University of Applied Sciences for their very generous support of the EBRNetwork. The Parker Institute, Bispebjerg and Frederiksberg Hospital (Professor Christensen and Professor Henriksen) are supported by a core grant from the Oak Foundation USA (OCAY-18-774-OFIL). Financial support, This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Funding Information:
The Parker Institute, Bispebjerg and Frederiksberg Hospital (Professor Christensen and Professor Henriksen) are supported by a core grant from the Oak Foundation USA ( OCAY-18-774-OFIL ).

BACKGROUND: Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the 'active' ingredients are unknown. Designing and executing an adequate and 'blindable placebo' version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used 'state-of-art' exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA.

METHODS: In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients' global assessment of disease impact, physical performance tests, and presence of knee joint swelling.

DISCUSSION: This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA.

TRIAL REGISTRATION: www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019.

Originalsprog Engelsk
Artikelnummer 18
Tidsskrift Trials
Vol/bind 22
Udgave nummer 1
Sider (fra-til) 18
ISSN 1745-6215
DOI
Status Udgivet - 6 jan. 2021

Experience and impact of crystal pyrophosphate deposition (CPPD) from a patient and caregiver perspective: A qualitative exploration from the OMERACT CPPD working group

Fuller, A., Cai, K., Filippou, G., Pascart, T., Diaz-Torne, C., Hensey, O., Grossberg, D., Christensen, R., Shea, B., Singh, J. A., Tedeschi, S. K., Dalbeth, N. & Abhishek, A., jun. 2021, I: Seminars in Arthritis and Rheumatism. 51, 3, s. 655-660 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To explore the lived experience of people with calcium pyrophosphate deposition (CPPD) disease and the impact of this condition on their daily lives.

METHODS: Patients with CPPD and their caregivers were invited to take part in a one-to-one (patient only) or paired (patient and caregiver) semi-structured interview. Interviews covered patients' diagnosis and treatment experiences, and the impact of CPPD on their daily lives. Transcribed interviews were analysed using inductive thematic analysis.

RESULTS: 28 patient interviews, six of which included a caregiver, were conducted across five countries. Acute CPP crystal arthritis flares resulted in temporary but profound disability for most patients, disrupting their ability to go about day-to-day activities, and they sought immediate medical attention. CPPD+OA and chronic CPP crystal inflammatory arthritis presented patients with longer term limitations in daily lives. Patients and their caregivers described these disruptions and limitations, which included a reduced ability or inability to complete household and self-care tasks, exercise, socialise, work and drive. They also described how arthritis pain and resulting limitations adversely impacted upon patients' psychological wellbeing. Delays in referral to specialists and diagnostic uncertainty were described by many. Lack of appropriate treatment or access to treatments only upon worsening of symptoms impacted upon the length of time some patients spent in pain and with functional limitations.

CONCLUSION: This study is the first to demonstrate the wide-ranging impact of CPPD, and highlights the need for improved diagnosis, physician training, as well as greater emphasis upon finding targeted therapies to specifically treat CPPD.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 51
Udgave nummer 3
Sider (fra-til) 655-660
Antal sider 6
ISSN 0049-0172
DOI
Status Udgivet - jun. 2021

Exploratory Efficacy of Calcium-Vitamin D Milk Fortification and Periodontal Therapy on Maternal Oral Health and Metabolic and Inflammatory Profile

Rodrigues Amorim Adegboye, A., Dias Santana, D., Teixeira Dos Santos, P. P., Guedes Cocate, P., Benaim, C., Trindade de Castro, M. B., Maia Schlüssel, M., Kac, G. & Lilienthal Heitmann, B., 27 feb. 2021, I: Nutrients. 13, 3

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

In this 2 × 2 factorial, outcome-assessor blinded, feasibility randomised trial we explored the effect of a non-pharmaceutical multi-component intervention on periodontal health and metabolic and inflammatory profiles among pregnant women with periodontitis receiving prenatal care in a Brazilian public health centre. 69 pregnant women (gestational age ≤20 weeks, T0) were randomly allocated into four groups: (1) fortified sachet (vitamin D and calcium) and powdered milk plus periodontal therapy during pregnancy (early PT) (n = 17); (2) placebo sachet and powdered milk plus early PT (n = 15); (3) fortified sachet and powdered milk plus late PT (after delivery) (n = 19); (4) placebo sachet and powdered milk plus late PT (n = 18). Third trimester (T1) and 6-8 weeks postpartum (T2) exploratory outcomes included periodontal health (% sites with bleeding on probing (BOP)), glucose, insulin, C-Reactive Protein, serum calcium and vitamin D. The mean BOP was significantly reduced in the early PT groups, while BOP worsened in the late PT groups. No significant effect of fortification on BOP was observed. Changes in glucose levels and variation on birthweight did not differ among groups This feasibility trial provides preliminary evidence for estimating the minimum clinically important differences for selected maternal outcomes. A large-scale trial to evaluate the interventions' clinical benefits and cost-effectiveness is warranted.

Originalsprog Engelsk
Tidsskrift Nutrients
Vol/bind 13
Udgave nummer 3
ISSN 2072-6643
DOI
Status Udgivet - 27 feb. 2021

Facilitators and Barriers for Young Medical Doctors Writing Their First Manuscript for Publication

Raffing, R., Jensen, T. B., Larsen, S., Konge, L., Møller, C. & Tønnesen, H., 13 aug. 2021, I: International Journal of Environmental Research and Public Health. 18, 16, 8571.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Although scientific publication is often mandatory in medical professions, writing the first research article for publication is challenging, especially as medical curricula have only a minor focus on scientific writing. The aim was therefore to identify facilitators and barriers experienced by medical doctors writing their first scientific article for publication. An explorative inductive approach made use of semi-structured interviews for collecting data until saturation. Data were analyzed with systematic text condensation. Several barriers were identified: (a) writing in general; (b) writing in English; (c) dealing with content, structure, and presentation; and (d) navigating in the author group. Good supervision in the initial writing phase was a facilitating factor. Medical doctors requested a course in which they could work on their own articles and give feedback to fellow students. They valued skilled lecturers and individual supervision, and they wanted to learn about author instructions, how to present text correctly, and how to sell their core message. Their goal was to create a useful end product and to obtain European Credit Transfer System (ECTS) points. The facilitators and barriers that medical doctors experience when writing their first scientific article for publication and their course requests should be reflected in the learning objectives and content of future courses.

Originalsprog Engelsk
Artikelnummer 8571
Tidsskrift International Journal of Environmental Research and Public Health
Vol/bind 18
Udgave nummer 16
ISSN 1661-7827
DOI
Status Udgivet - 13 aug. 2021

Feasibility of ABLE 1.0-a program aiming at enhancing the ability to perform activities of daily living in persons with chronic conditions

Nielsen, K. T., Guidetti, S., von Bülow, C., Klokker, L. & Wæhrens, E. E., 18 feb. 2021, I: Pilot and Feasibility Studies. 7, 1, s. 52 52.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: The "A Better everyday LifE" (ABLE) intervention was developed to accommodate the need of a program addressing ability to perform activities of daily living (ADL) in persons with chronic conditions living at home. During intervention development, it is necessary to evaluate relevant aspects of the feasibility of a program. Thus, the aim was to evaluate the feasibility of content and delivery of ABLE version 1.0.

METHODS: A one group pre- and post-test design was applied. Thirty persons with chronic conditions, two occupational therapists (OTs), and five occupational therapy students (OTSs) participated. ABLE 1.0 is an 8-week program consisting of ADL evaluation (session 1); goal setting and reasons for ADL problems (session 2); intervention (sessions 3-7); and re-evaluation (final session), conducted in the clients' home-setting and local area. Sessions 1-4 and the final session was mandatory. To evaluate the feasibility of content and delivery, the OTs, after each session, reported on applied intervention component(s), time-use, needed equipment, adjustments, meaningfulness, confidence, progress toward goal attainment, and side effects using registration forms. The clients reported on progress toward goal attainment, meaningfulness, and satisfaction. Clinically relevant improvements in ADL ability were identified using the ADL-Interview (ADL-I) and the Assessment of Motor and Process Skills (AMPS). Goal attainment was evaluated using the Goal Attainment Scaling (GAS).

RESULTS: Twenty clients (67%) completed ABLE 1.0 and received four sessions (median = 4, range 4-7) each lasting between 30 and 94 min. Most frequently applied component was "Changing habits related to task performance". Generally, OTs reported having the needed equipment. Deviations from the manual were made by omission of GAS and AMPS and less than mandatory number of sessions per client. The OTs reported confidence in delivering the program and the clients perceived the program as meaningful and satisfying, and experienced progress toward goal attainment. Goal attainment was found in 52% of the goals. Sixteen (80%) clients obtained clinically relevant improvements in self-reported or observed ADL ability.

CONCLUSIONS: The content and delivery of ABLE 1.0 was feasible. However, the study revealed a need to adjust the recruitment procedure and make minor changes in the intervention manual. A pilot randomized controlled trial (RCT) study is recommended.

TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with registration no. NCT03335709 on November 8, 2017.

Originalsprog Engelsk
Artikelnummer 52
Tidsskrift Pilot and Feasibility Studies
Vol/bind 7
Udgave nummer 1
Sider (fra-til) 52
ISSN 2055-5784
DOI
Status Udgivet - 18 feb. 2021

Forebyggelse af overvægt blandt børn og unge København

Bruun, J. M., Bjerregaard, L. G., Due, P., Heitmann, B. L., Høy, T. V., Kierkegaard, L., Michaelsen, KF., Morgen, C. S., Olsen, N. J., Sørensen, T. I. A., Toft, U. N. & Østergaard, J. N., 2021, Vidensråd for Forebyggelse.

Publikation: Bog/antologi/afhandling/rapportRapportForskning

Originalsprog Dansk
Forlag Vidensråd for Forebyggelse
Status Udgivet - 2021

Gaps in Alcohol Screening and Intervention Practices in Surgical Healthcare: A Qualitative Study

Fernandez, A. C., Guetterman, T. C., Borsari, B., Mello, M. J., Mellinger, J., Tonnesen, H., Hosanagar, A., Morris, A. M. & Blow, F. C., 1 apr. 2021, I: Journal of addiction medicine. 15, 2, s. 113-119 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: Risky alcohol use before surgery is associated with an increased risk of postoperative complications and longer hospital stays. Preoperative alcohol interventions can improve surgical outcomes but are not commonly integrated into routine care. This study sought to better understand patient's and provider's perceptions of alcohol-related surgical health and healthcare practices and illuminate gaps in care and how they could be improved. METHODS: This study used a descriptive qualitative research design. Data were collected between July 2017 and March 2018. One-on-one interviews assessed domains related to knowledge, gaps in alcohol-related screening and intervention, and interest in enhancing alcohol-related care. Key themes emerged from a process of iterative coding and thematic analysis. RESULTS: Participants included elective surgical patients who met alcohol screening criteria (n = 20) and surgical healthcare providers (n = 9). Participants had modest or low awareness of alcohol-related surgical health risks. Basic alcohol screening was a routine part of care, but results were often discounted or overlooked. Providers did not routinely initiate preoperative alcohol education or intervention. Providers viewed improving alcohol-related clinical practices as a low priority. Patients were interested in receiving alcohol interventions before surgery if they were delivered in a nonjudgement style and focused on surgical health optimization. CONCLUSIONS: This study highlights potential gaps in alcohol-related knowledge and care, and found providers place a low priority on alcohol interventions in the perioperative context. Given the high complication rate associated with preoperative alcohol use, these topics are worthy of future research. To be successful strategies to overcome specific barriers to alcohol screening and intervention must address the needs of patients and providers.

Originalsprog Engelsk
Tidsskrift Journal of addiction medicine
Vol/bind 15
Udgave nummer 2
Sider (fra-til) 113-119
Antal sider 7
DOI
Status Udgivet - 1 apr. 2021

Bibliografisk note

Publisher Copyright:
Copyright © 2020 American Society of Addiction Medicine.

GRADE guidelines 32: GRADE offers guidance on choosing targets of GRADE certainty of evidence ratings

Zeng, L., Brignardello-Petersen, R., Hultcrantz, M., Siemieniuk, R. A. C., Santesso, N., Traversy, G., Izcovich, A., Sadeghirad, B., Alexander, P. E., Devji, T., Rochwerg, B., Murad, M. H., Morgan, R., Christensen, R., Schünemann, H. J. & Guyatt, G. H., sep. 2021, I: Journal of Clinical Epidemiology. 137, s. 163-175 13 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: To provide practical principles and examples to help GRADE users make optimal choices regarding their ratings of certainty of evidence using a minimally or partially contextualized approach.

STUDY DESIGN AND SETTING: Based on the GRADE clarification of certainty of evidence in 2017, a project group within the GRADE Working Group conducted iterative discussions and presentations at GRADE Working Group meetings to refine this construct and produce practical guidance.

RESULTS: Systematic review and health technology assessment authors need to clarify what it is in which they are rating their certainty of evidence (i.e., the target of their certainty rating). The decision depends on the degree of contextualization (partially or minimally contextualized), thresholds (null, small, moderate or large effect threshold), and where the point estimate lies in relation to the chosen threshold(s). When the 95% confidence interval crosses multiple possible thresholds (i.e., including both large benefit and large harm), it is not worthwhile for authors to determine the target of certainty rating.

CONCLUSION: GRADE provides practical principles to help systematic review and health technology assessment authors specify the target of their certainty of evidence rating.

Originalsprog Engelsk
Tidsskrift Journal of Clinical Epidemiology
Vol/bind 137
Sider (fra-til) 163-175
Antal sider 13
ISSN 0895-4356
DOI
Status Udgivet - sep. 2021

Hair cortisol concentration, weight loss maintenance and body weight variability: a prospective study based on data from the European NoHoW Trial

Larsen, S. C., Turicchi, J., Christensen, G. L., Larsen, C. S., Jørgensen, N. R., Mikkelsen, M-L. K., Horgan, G., O'Driscoll, R., Michalowska, J., Duarte, C., Scott, S. E., Santos, I., Encantado, J., Palmeira, A. L., Stubbs, R. J. & Heitmann, B. L., 2021, I: Frontiers in Endocrinology. 12, 655197.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Several cross-sectional studies have shown hair cortisol concentration to be associated with adiposity, but the relationship between hair cortisol concentration and longitudinal changes in measures of adiposity are largely unknown. We included 786 adults from the NoHoW trial, who had achieved a successful weight loss of ≥5% and had a body mass index of ≥25 kg/m2 prior to losing weight. Hair cortisol concentration (pg/mg hair) was measured at baseline and after 12 months. Body weight and body fat percentage were measured at baseline, 6-month, 12-month and 18-month visits. Participants weighed themselves at home ≥2 weekly using a Wi-Fi scale for the 18-month study duration, from which body weight variability was estimated using linear and non-linear approaches. Regression models were conducted to examine log hair cortisol concentration and change in log hair cortisol concentration as predictors of changes in body weight, change in body fat percentage and body weight variability. After adjustment for lifestyle and demographic factors, no associations between baseline log hair cortisol concentration and outcome measures were observed. Similar results were seen when analysing the association between 12-month concurrent development in log hair cortisol concentration and outcomes. However, an initial 12-month increase in log hair cortisol concentration was associated with a higher subsequent body weight variability between month 12 and 18, based on deviations from a nonlinear trend (β: 0.02% per unit increase in log hair cortisol concentration [95% CI: 0.00, 0.04]; P=0.016). Our data suggest that an association between hair cortisol concentration and subsequent change in body weight or body fat percentage is absent or marginal, but that an increase in hair cortisol concentration during a 12-month weight loss maintenance effort may predict a slightly higher subsequent 6-months body weight variability.

Clinical Trial Registration: ISRCTN registry, identifier ISRCTN88405328.

Originalsprog Engelsk
Artikelnummer 655197
Tidsskrift Frontiers in Endocrinology
Vol/bind 12
ISSN 1664-2392
DOI
Status Udgivet - 2021

Bibliografisk note

Copyright © 2021 Larsen, Turicchi, Christensen, Larsen, Jørgensen, Mikkelsen, Horgan, O’Driscoll, Michalowska, Duarte, Scott, Santos, Encantado, Palmeira, Stubbs and Heitmann.

Harms reported by patients in rheumatology drug trials: a systematic review of randomized trials in the cochrane library from an OMERACT working group

OMERACT Safety Working Group, jun. 2021, I: Seminars in Arthritis and Rheumatism. 51, 3, s. 607-617 11 s.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

BACKGROUND: Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms.

METHODS: We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting.

RESULTS: The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review.

CONCLUSIONS: Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives.

REGISTRATION: PROSPERO: CRD42018108393.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 51
Udgave nummer 3
Sider (fra-til) 607-617
Antal sider 11
ISSN 0049-0172
DOI
Status Udgivet - jun. 2021

Impact of intensive lifestyle intervention on gut microbiota composition in type 2 diabetes: a post-hoc analysis of a randomized clinical trial

Wei, S., Brejnrod, A. D., Trivedi, U., Mortensen, M. S., Johansen, M. Y., Karstoft, K., Vaag, A. A., Ried-Larsen, M. & Sørensen, S. J., 30 dec. 2021, (E-pub ahead of print) I: Gut Microbes. 14, 1, s. 2005407 2005407.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Type 2 diabetes (T2D) management is based on combined pharmacological and lifestyle intervention approaches. While their clinical benefits are well studied, less is known about their effects on the gut microbiota. We aimed to investigate if an intensive lifestyle intervention combined with conventional standard care leads to a different gut microbiota composition compared to standard care alone treatment in individuals with T2D, and if gut microbiota is associated with the clinical benefits of the treatments. Ninety-eight individuals with T2D were randomized to either an intensive lifestyle intervention combined with standard care group (N = 64), or standard care alone group (N = 34) for 12 months. All individuals received standardized, blinded, target-driven medical therapy, and individual counseling. The lifestyle intervention group moreover received intensified physical training and dietary plans. Clinical characteristics and fecal samples were collected at baseline, 3-, 6-, 9-, and 12-month follow-up. The gut microbiota was profiled with 16S rRNA gene amplicon sequencing. There were no statistical differences in the change of gut microbiota composition between treatments after 12 months, except minor and transient differences at month 3. The shift in gut microbiota alpha diversity at all time windows did not correlate with the change in clinical characteristics, and the gut microbiota did not mediate the treatment effect on clinical characteristics. The clinical benefits of intensive lifestyle and/or pharmacological interventions in T2D are unlikely to be explained by, or causally related to, changes in the gut microbiota composition.

Originalsprog Engelsk
Artikelnummer 2005407
Tidsskrift Gut Microbes
Vol/bind 14
Udgave nummer 1
Sider (fra-til) 2005407
ISSN 1949-0976
DOI
Status E-pub ahead of print - 30 dec. 2021

Impact of MRI on decision-making in ICU patients with disorders of consciousness

Albrechtsen, S. S., Riis, R. G. C., Amiri, M., Tanum, G., Bergdal, O., Blaabjerg, M., Simonsen, C. Z. & Kondziella, D., 31 dec. 2021, (E-pub ahead of print) I: Behavioural Brain Research. 421, s. 113729 113729.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Recovery of consciousness is the most important survival factor in patients with acute brain injury and disorders of consciousness (DoC). Since most deaths in the intensive care unit (ICU) occur after withdrawal of life-support, medical decision-making is crucial for acute DoC patients. Neuroimaging informs decision-making, yet the precise effects of MRI on decision-making in the ICU are poorly understood. We investigated the impact of brain MRI on prognostication, therapeutic decisions and physician confidence in ICU patients with DoC.

METHODS: In this simulated decision-making study utilizing a prospective ICU cohort, a panel of neurocritical experts first reviewed clinical information (without MRI) from 75 acute DoC patients and made decisions about diagnosis, prognosis and treatment. Following review of the MRI, the panel then decided if the initial decisions needed revision. In parallel, a blinded neuroradiologist reassessed all neuroimaging.

RESULTS: MRI led to changes in clinical management of 57 (76%) of patients (Number-Needed-to-Test for any change: 1.32), including revised diagnoses (20%), levels of care (21%), diagnostic confidence (43%) and prognostications (33%). Decisions were revised more often with stroke than with other brain injuries (p = 0.02). However, although MRI revealed additional pathology in 81%, this did not predict revised clinical decision-making (p-values ≥0.08).

CONCLUSION: MRI results changed decision-making in 3 of 4 ICU patients, but radiological findings were not predictive of clinical decision-making. This highlights the need to better understand the effects of neuroimaging on management decisions. How MRI influences decision-making in the ICU is an important avenue for research to improve acute DoC management.

Originalsprog Engelsk
Artikelnummer 113729
Tidsskrift Behavioural Brain Research
Vol/bind 421
Sider (fra-til) 113729
ISSN 0166-4328
DOI
Status E-pub ahead of print - 31 dec. 2021

Bibliografisk note

Copyright © 2022. Published by Elsevier B.V.

Improving benefit-harm assessment of glucocorticoid therapy incorporating the patient perspective: The OMERACT glucocorticoid core domain set

Tieu, J., Cheah, J. T., Black, R. J., Christensen, R., Ghosh, N., Richards, P., Robson, J., Shea, B., Simon, L. S., Singhi, J. A., Tugwell, P., Boers, M., Garibay, M. A. A., Campochiaro, C., Decary, S., de Witt, M., Fernandez, A. P., Keen, H. I., King, L., Hinojosa-Azaola, A., Hofstetter, C., Gaydukova, I., George, M. D., Gupta, L., Lyne, S., Makol, A., Mukhtyar, C., Oo, W. M., Petri, M., Pisaniello, H. L., Sattui, S. E., Russell, O., Teixeira, V., Toupin-April, K., Uhunmwangho, C., Whitstock, M., Yip, K., Mackie, S. L., Goodman, S. M. & Hill, C. L., okt. 2021, I: Seminars in Arthritis and Rheumatism. 51, 5, s. 1139-1145 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVE: Our primary objective was to develop an Outcome Measures in Rheumatology (OMERACT) core domain set to capture the impact of glucocorticoids (GC), both positive and negative, on patients with Rheumatic conditions.

METHODS: The OMERACT Filter 2.1 was used to guide core domain selection. Systematic literature reviews, qualitative studies and quantitative surveys were conducted by the OMERACT GC Impact working group to identify candidate domains for a core domain set. A summary of prior work and Delphi exercise were presented at the OMERACT 2020 virtual GC workshop. A proposed GC Impact core domain set derived from this work was presented for discussion in facilitated breakout groups. Participants voted on the proposed GC Impact core domain set.

RESULTS: 113 people, including 23 patient research partners, participated in two virtual workshops conducted at different times on the same day. The proposed mandatory domains to be evaluated in clinical trials involving GCs were: infection, bone fragility, hypertension, diabetes, weight, fatigue, mood disturbance and death. In addition, collection of disease specific outcomes was included in the core domain set as "mandatory in specific circumstances". The proposed core domain set was endorsed by 100% (23/23) of the patient research partners and 92% (83/90) of the remaining participants, including clinicians, researchers and industry stakeholders.

CONCLUSION: A GC Impact core domain set was endorsed at the OMERACT 2020 virtual workshop. The OMERACT GC Impact working group will now progress to identify, develop and validate measurement tools to best address these domains in clinical trials.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 51
Udgave nummer 5
Sider (fra-til) 1139-1145
Antal sider 7
ISSN 0049-0172
DOI
Status Udgivet - okt. 2021

Bibliografisk note

Copyright © 2021. Published by Elsevier Inc.

Improving domain definition and outcome instrument selection: Lessons learned for OMERACT from imaging

D'Agostino, M. A., Beaton, D. E., Maxwell, L. J., Cembalo, S. M., Hoens, A. M., Hofstetter, C., Zabalan, C., Bird, P., Christensen, R., de Wit, M., Doria, A. S., Maksymowych, W. P., Oo, W. M., Østergaard, M., Serban, T., Sloan, V. S., Terslev, L., van Rossum, M. A., Conaghan, P. G. & Boers, M., okt. 2021, I: Seminars in Arthritis and Rheumatism. 51, 5, s. 1125-1133 9 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: Imaging is one of the most rapidly evolving fields in medicine. Unfortunately, many imaging technologies have been applied as measurement instruments without rigorous evaluation of the evidence supporting their truth, discriminatory capability and feasibility for that context of use. The Outcome Measures in Rheumatology (OMERACT) Filter 2.1 Instrument Selection Algorithm (OFISA) is used to evaluate such evidence for use of an instrument in a research setting. The objectives of this work are to: [1] define and describe the key conceptual aspects that are essential for the evaluation of imaging as an outcome measurement instrument and [2] describe how these aspects can be assessed through OFISA.

METHODS: Experts in imaging and/or methodology met to formalize concepts and define key steps. These concepts were discussed with a team of patient research partners with interest in imaging to refine technical and methodological aspects into comprehensible information. A workshop was held at OMERACT2020 and feedback was incorporated into existing OMERACT process for domain and instrument selection.

RESULTS: Three key lessons were identified: (1) a clear definition of the domain we want to measure is a necessary prerequisite to the selection of a good instrument, (2) the sources of variability that can directly influence the instrument should be clearly identified, (3) incorporating these first two lessons into OFISA improves the quality of every instrument selection process.

CONCLUSIONS: The incorporation of these lessons in the updated OMERACT Filter (now 2.2) will improve the quality of the selection process for all types of outcome measurement instruments.

Originalsprog Engelsk
Tidsskrift Seminars in Arthritis and Rheumatism
Vol/bind 51
Udgave nummer 5
Sider (fra-til) 1125-1133
Antal sider 9
ISSN 0049-0172
DOI
Status Udgivet - okt. 2021

Bibliografisk note

Copyright © 2021. Published by Elsevier Inc.

Increased cancer risk in patients with cutaneous lupus erythematosus and systemic lupus erythematosus compared with the general population: A Danish nationwide cohort study

Westermann, R., Zobbe, K., Cordtz, R., Haugaard, J. H. & Dreyer, L., apr. 2021, I: Lupus. 30, 5, s. 752-761 10 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To investigate if patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) have an increased risk of cancer compared with the general population, and furthermore to identify specific cancer types associated with increased risk.

METHODS: This is an observational cohort study of 5310 patients with CLE or SLE identified in the Danish National Patient Register from 1 January 1995 to 31 December 2014. The cohort was followed up for cancer by linkage to the Danish Cancer Registry. Based on the age, sex, and calendar specific cancer rates of the general population of Denmark, standardised incidence ratios (SIRs) were calculated.

RESULTS: The patients with CLE or SLE were followed for 40.724 person-years, each group's average duration of follow-up being 6.9 and 8.1 years. The SIR for overall cancer (except non-melanoma skin cancer (NMSC)) was increased in patients with CLE 1.35 (95%CI 1.15 to 1.58) and patients with SLE 1.45 (95%CI 1.30 to 1.62). Both groups had high risks of hematological - including a 3-4-fold increased risk of non-Hodgkin lymphoma -, pancreatic, and lung cancers. Several cancers associated with oncogenic viruses as liver and tongue/mouth/pharynx were increased in the SLE group, while the risk of ovarian cancer was increased 2-4-fold only in the CLE group.

CONCLUSION: The overall risk of cancer was significantly increased in both patients with CLE and SLE. SIRs for hematological, pancreatic and lung cancers were elevated in both groups. Extra awareness of cancer in patients with SLE and patients with CLE should be considered.

Originalsprog Engelsk
Tidsskrift Lupus
Vol/bind 30
Udgave nummer 5
Sider (fra-til) 752-761
Antal sider 10
ISSN 0961-2033
DOI
Status Udgivet - apr. 2021

BACKGROUND AND PURPOSE: Mortality following infections in dementia has not yet been comprehensively explored. The aim of this cohort study was to investigate the short- and long-term mortality following infections in dementia.

METHODS: Follow-up was from 1 January 2000 or the 65-year birthday until death, immigration, or 31 December 2015. Exposure was incident dementia and a first infection. The outcome was all-cause mortality. Mortality rate ratios (MRRs) were calculated using Poisson regression in 4 exposure groups (dementia yes/no, infection yes/no) by sex, infection site, and time since infection.

RESULTS: 1,496,436 people were followed with 12,739,135 person-years. MRR in dementia/infection was 6.52 (95% confidence interval: 6.43-6.60) and was increased for infections of all sites. Increased mortality was short term (30 days) and long term (10 years).

CONCLUSIONS: Increased mortality in people with dementia identifies them as a particularly vulnerable group that needs clinical attention.

Originalsprog Engelsk
Artikelnummer 2
Tidsskrift European Journal of Neurology
Vol/bind 28
Sider (fra-til) 411-420
ISSN 1351-5101
DOI
Status Udgivet - feb. 2021

Bibliografisk note

© 2020 European Academy of Neurology.

Inflammatory hallmarks of lesser prominence in psoriatic arthritis patients starting biologics: a Nordic population-based cohort study

Lund Hansen, R., Schoedt Jørgensen, T., Dreyer, L., Hetland, M. L., Glintborg, B., Askling, J., Di Giuseppe, D., Jacobsson, L. T. H., Wallman, J. K., Nordstrom, D., Aaltonen, K., Kristianslund, E. K., Kvien, T. K., Provan, S. A., Gudbjornsson, B., Love, T. J. & Kristensen, L. E., 1 jan. 2021, I: Rheumatology (Oxford, England). 60, 1, s. 140-146 7 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

OBJECTIVES: To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries.

METHODS: PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment.

RESULTS: A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association.

CONCLUSION: Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.

Originalsprog Engelsk
Tidsskrift Rheumatology (Oxford, England)
Vol/bind 60
Udgave nummer 1
Sider (fra-til) 140-146
Antal sider 7
ISSN 1462-0324
DOI
Status Udgivet - 1 jan. 2021

Bibliografisk note

COPECARE

OBJECTIVE: The aim of this study is to investigate the influence of local anesthetic (LA), operator experience level and needle type on patient procedural pain in relation to diagnostic lumbar puncture (LP).

METHODS: LP was performed with either a 22 gauge traumatic needle (22 TN) or a 22 gauge atraumatic needle (22 ATN). Immediately after LP patients documented a procedural pain score (PPS) on a 10-point Likert scale. Use of LA, needle type, anesthetic time interval (ATI), number of needle insertions and the LP operator experience level were registered. ATI was defined as the time from administration of LA to first needle insertion.

RESULTS: 104 patients had the LP procedure performed by 66 physicians (40 novices and 26 experienced physicians). Patients having the procedure performed by novices had a lower PPS of 2.56 if LA was administered compared to a higher PPS of 5.80 if LA was not administered (P = .046). Among experienced physicians there was no difference in PPS regardless of administration of LA. If novices administered LA, patient PPS was equal to patients having the procedure performed by an experienced operator. If novices performed the procedure with a 22 TN PPS decreased with increasing ATI (P = .01). No similar correlation was identified with the 22 ATN.

CONCLUSION: Our study suggests that LP operator experience level, the needle type used and ATI may influence patient PPS. Further studies are necessary for final conclusions. These studies must consider these factors to avoid fault conclusions.

Originalsprog Engelsk
Tidsskrift International Journal of Emergency Medicine
ISSN 0735-6757
DOI
Status E-pub ahead of print - 2021

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

Influence of Wearing Ballistic Vests on Physical Performance of Danish Police Officers: A Cross-Over Study

Koblauch, H., Zebis, M. K., Jacobsen, M. H., Haraldsson, B. T., Klinge, K. P., Alkjær, T., Bencke, J. & Andersen, L. L., 5 mar. 2021, I: Sensors. 21, 5, s. 1-12 12 s., 1795.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

PURPOSE: We aimed to investigate the influence of wearing a ballistic vest on physical performance in police officers.

METHODS: We performed a cross-over study to investigate the influence of wearing a ballistic vest on reaction and response time, lumbar muscle endurance and police vehicle entry and exit times. Reaction and response time was based on a perturbation setup where the officers' pelvises were fixed and EMG of lumbar and abdominal muscles was recorded. We used a modified Biering-Sørensen test to assess the lumbar muscle endurance and measured duration of entry and exit maneuvers in a variety of standard-issue police cars.

RESULTS: There was a significant difference of 24% in the lumbar muscle endurance test (no vest: 151 s vs. vest: 117 s), and the police officers experienced higher physical fatigue after the test when wearing a vest. Furthermore, officers took longer to both enter and exit police cars when wearing a vest (range: 0.24-0.56 s) depending on the model of the vehicle. There were no significant differences in reaction and response times between the test conditions (with/without vest).

DISCUSSION AND CONCLUSION: Wearing of a ballistic vest significantly influenced the speed of movement in entry and exit of police cars and lumbar muscle endurance, although it does not seem to affect reaction or response times. The ballistic vest seems to impair performance of tasks that require maximal effort, which calls for better designs of such vests.

Originalsprog Engelsk
Artikelnummer 1795
Tidsskrift Sensors
Vol/bind 21
Udgave nummer 5
Sider (fra-til) 1-12
Antal sider 12
ISSN 1424-3210
DOI
Status Udgivet - 5 mar. 2021

Bibliografisk note

Funding Information:
Funding: This study was partly funded by The Danish National Police.

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