Photo: Nicolas Tourrenc, Diakonhjemmet sykehus.
Publications
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Viermyr, Hans-Kittil; Halvorsen, Bente; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Barratt-Due, Andreas & Kåsine, Trine
[Show all 73 contributors for this article]
(2024).
High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial.
Journal of Internal Medicine.
ISSN 0954-6820.
296(3),
p. 249–259.
doi:
10.1111/joim.13820.
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Objectives To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline. Conclusions An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.
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Holten, Karen; Sundlisæter, Nina Paulshus; Sexton, Joseph; Kjørholt, Kaja Eriksrud; Nordberg, Lena Bugge & Uhlig, Tillmann
[Show all 11 contributors for this article]
(2024).
Agreement between patient-reported flares and clinically significant flare status in patients with rheumatoid arthritis in sustained remission: data from the ARCTIC REWIND trials.
RMD Open.
10(3).
doi:
10.1136/rmdopen-2024-004444.
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Objectives To explore the agreement between patient-reported flare status and clinically significant flare status in patients with rheumatoid arthritis (RA) in sustained remission. Method Patients with RA in remission for ≥12 months on stable treatment were included in the ARCTIC REWIND tapering trials and pooled 12-month data used in current analyses. Patient-reported flare status was assessed according to the Outcome Measures in Rheumatology flare questionnaire; ‘Are you having a flare of your RA at this time?’ (yes/no). A clinically significant flare was defined as a combination of Disease Activity Score (DAS) >1.6, increase in DAS of ≥0.6 and 2 swollen joints, or the rheumatologist and patient agreed that a clinically significant flare had occurred. Agreement coefficient, sensitivity, specificity and predictive values of patient-reported flare status with regard to clinically significant flare status were determined. Results Of 248 patients, 64% were women, age 56.1 (11.8) years, disease duration 4.1 (2.8–7.4) years, DAS 0.8 (0.3). 35% of patients reported a flare at least once, clinically significant flares were recorded in 21%. 48/53 clinically significant flares (91%) led to an intensification of disease-modifying antirheumatic drugss. In 621/682 (91%) visits, patient-reported and clinically significant flare status were in agreement, agreement coefficient 0.89. Sensitivity and specificity were both 91%, positive predictive value of patient-reported flare status 46% and negative predictive value 99%. Conclusion Among patients in sustained remission, patient-reported flare status was accurate in ruling out a clinically significant flare. About half of the patient-reported flares were assessed to be clinically significant. These findings support a potential for using patient-reported flare status in remote monitoring of patients with RA in sustained remission.
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Holten, Karen; Sundlisæter, Nina Paulshus; Sexton, Joseph; Nordberg, Lena Bugge; Uhlig, Till & Kvien, Tore Kristian Aaserud
[Show all 10 contributors for this article]
(2024).
Performance of the Rheumatoid Arthritis Impact of Disease (RAID) score in relation to flares in disease activity.
RMD Open.
10(1).
doi:
10.1136/rmdopen-2023-003486.
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Objectives To explore the performance of the EULAR-initiated patient-reported Rheumatoid Arthritis Impact of Disease (RAID) questionnaire in relation to flares in disease activity, including comparison with other disease activity outcomes. Methods Patients with rheumatoid arthritis in sustained remission were randomised to continued stable treatment or tapering in the ARCTIC REWIND project. In patients with flares within 12 months, we compared RAID (total score and components) at the flare visit with the visit prior to and the visit following flare, using Wilcoxon signed-rank test. Similar analyses were performed for patient global assessment, Disease Activity Score (DAS) and C reactive protein (CRP). The discriminative accuracies of RAID, patient global assessment, DAS and CRP with respect to disease activity flares were assessed by receiver operating characteristic (ROC) analyses based on logistic regression models. Flare was defined as a combination of DAS >1.6, a DAS increase ≥0.6 and ≥two swollen joints (of 44 examined) or could be recorded if patient and rheumatologist agreed that a clinically significant flare had occurred. Results In total, 248 patients were included in the analyses, with 56 flares. RAID, patient global assessment, DAS and CRP all changed significantly at the visits related to flare (p<0.001). Area under the curve (95% CI) values indicated that RAID (0.88 (0.83 to 0.93)) was significantly more accurate than CRP (0.76 (0.69 to 0.84)) in discriminating flare, and less accurate than patient global assessment (0.92 (0.87 to 0.97)) and DAS (0.94 (0.90 to 0.98)). The RAID components with highest and lowest discriminative accuracies were pain (0.91 (0.86 to 0.95)) and sleep (0.69 (0.59 to 0.79)). Conclusion Disease activity flares were associated with a significant increase in median RAID, supporting its ability to respond to flare.
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Sundin, Ulf Gunnar; Sundlisæter, Nina Beate Paulshus; Aga, Anna-Birgitte; Sexton, Joseph; Nordberg, Lena Kristine Bugge & Hammer, Hilde Berner
[Show all 10 contributors for this article]
(2021).
Value of MRI and ultrasound for prediction of therapeutic response and erosive progression in patients with early rheumatoid arthritis managed by an aggressive treat-To-Target strategy.
RMD Open.
7:e001525(1),
p. 1–11.
doi:
10.1136/rmdopen-2020-001525.
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Objectives To investigate if inflammation detected by MRI or ultrasound at rheumatoid arthritis (RA) onset is predictive of erosive progression or poor response to methotrexate monotherapy, and to investigate if subclinical inflammation in remission is predictive of future treatment escalation or erosive progression. Methods In a 2-year study, 218 patients with disease-modifying antirheumatic drug-naïve early RA were treated by a tight-control treat-to-target strategy corresponding to current recommendations. MRI and ultrasound were performed at regular intervals. Baseline imaging-based inflammation measures were analysed as predictors for early methotrexate failure and erosive progression using univariate and multivariate regression adjusted for clinical, laboratory and radiographic measures. In patients in remission after 1 year, imaging measures were analysed as predictors of treatment escalation and erosive progression during the second year. The added value of imaging in prediction models was assessed using receiver operating characteristic analyses. Results Baseline MRI inflammation was associated with MRI erosive progression and ultrasound with radiographic erosive progression. No imaging inflammation measure was associated with early methotrexate failure. Imaging inflammation was present in a majority of patients in clinical remission. Tenosynovitis was associated with treatment escalation, and synovitis and tenosynovitis with MRI/radiographic erosive progression during the second year. Imaging information did not improve prediction models for any of the outcomes. Conclusions Imaging-detected inflammation, both at diagnosis and in remission, is associated with elements of future disease development. However, the lack of a significant effect on prediction models indicates limited value of systematic MRI and ultrasound in management of early RA.
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Holten, Karen; Sundlisæter, Nina Beate Paulshus; Lillegraven, Siri; Sexton, Joseph; Nordberg, Lena Kristine Bugge & Moholt, Ellen
[Show all 11 contributors for this article]
(2021).
Fatigue in patients with early rheumatoid arthritis undergoing treat-to-target therapy: predictors and response to treatment.
Annals of the Rheumatic Diseases.
ISSN 0003-4967.
doi:
10.1136/annrheumdis-2021-220750.
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Objectives: Fatigue is a frequent symptom in rheumatoid arthritis (RA) and has high impact on quality of life. We explored associations between disease activity and fatigue in patients with early RA during the initial 24 months of modern treat-to-target therapy and predictors of fatigue after 24 months of follow-up.
Methods: Data were obtained from the treat-to-target, tight control Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regime (ARCTIC) trial. Fatigue was measured on a visual analogue scale (VAS) from 0 to 100 mm and defined as clinically relevant if VAS was ≥20 mm. Baseline predictors of fatigue at 24 months were analysed by multivariable logistic regression.
Results: 205 patients with fatigue data at baseline and 24 months were included. Median (25th, 75th percentiles) symptom duration was 5.4 months (2.8, 10.4), fatigue VAS 37.0 mm (13.0, 62.0) and mean Disease Activity Score (DAS) 3.4 (SD 1.1) at baseline. Prevalence of fatigue declined from 69% at baseline to 38% at 24 months. Fewer swollen joints (OR 0.92, 95% CI 0.87 to 0.98, p=0.006), lower power Doppler ultrasound score (OR 0.95, 95% CI 0.90 to 0.99, p=0.027) and higher patient global assessment (PGA) (OR 1.03, 95% CI 1.01 to 1.04, p<0.001) increased the risk of clinically relevant fatigue at 24 months. Not achieving remission at 6 months was associated with a higher risk of reporting fatigue at 24 months.
Conclusions: Fatigue in patients with early RA was prevalent at disease onset, with a rapid and sustained reduction during treatment. Low objective disease activity and high PGA at baseline were predictors of clinically relevant fatigue at 24 months.
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Sundin, Ulf Gunnar; Aga, Anna-Birgitte; Skare, Øivind; Nordberg, Lena Kristine Bugge; Uhlig, Till & Hammer, Hilde Berner
[Show all 10 contributors for this article]
(2020).
Conventional versus ultrasound treat to target: No difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis.
Rheumatology.
ISSN 1462-0324.
59(9),
p. 2550–2555.
doi:
10.1093/rheumatology/kez674.
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Abstract Objective To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy. Methods A total of 230 DMARD-naïve early RA patients were randomized to an ultrasound tight control strategy targeting DAS &lt;1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS &lt;1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms. Results MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P = 0.40]. Conclusion Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA. Trial registration number Clinicaltrials.gov, http://clinicaltrials.gov, NCT01205854.
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Nordberg, Lena Kristine Bugge; Lillegraven, Siri; Aga, Anna-Birgitte; Sexton, Joseph; Olsen, Inge Christoffer & Lie, Elisabeth
[Show all 11 contributors for this article]
(2018).
Comparing the disease course of patients with seronegative and seropositive rheumatoid arthritis fulfilling the 2010 ACR/EULAR classification criteria in a treat-to-target setting: 2-year data from the ARCTIC trial.
RMD Open.
4(2),
p. 11–17.
doi:
10.1136/rmdopen-2018-000752.
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Objectives Recent studies suggest that implementation of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) leads to higher inflammatory activity in seronegative compared with seropositive patients at time of diagnosis. Our aim was to compare the disease course in seronegative and seropositive patients classified according to the 2010 criteria. Methods DMARD-naïve patients with RA fulfilling the 2010 criteria were included in the treat-to-target ARCTIC trial and followed for 24 months. We stratified patients as seropositive (rheumatoid factor (RF)+, anticitrullinated protein antibodies (ACPA)+ or both) or seronegative (RF– and ACPA–) and compared disease activity, radiographic progression, treatment response and remission rates across groups. Results 230 patients were included with mean (SD) age 51.4 (13.7) years, and 61% were female. 34 patients (15%) were seronegative. At 24 months, disease activity measures, radiographic progression and remission rates were similar between groups, despite more inflammatory activity in seronegative patients at baseline. Treatment response was slower in seronegative compared with seropositive patients. The groups received similar treatment. Conclusion Our findings suggest that among patients with RA classified according to the 2010 ACR/EULAR criteria, seronegative patients respond well to modern treatment strategies. However, treatment response was somewhat slower in seronegative patients and radiographic progression was similar in seronegative and seropositive patients. Our results indicate that seronegative RA is not a mild form of the disease and requires intensive treat-to-target therapy similar to treatment of seropositive RA.
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Nordberg, Lena Kristine Bugge; Lillegraven, Siri; Aga, Anna-Birgitte; Sexton, Joseph; Lie, Elisabeth & Hammer, Hilde Berner
[Show all 11 contributors for this article]
(2018).
The impact of ultrasound on the use and efficacy of intraarticular glucocorticoid injections in early rheumatoid arthritis: Secondary analyses from a randomized trial examining the benefit of ultrasound in a clinical tight control regimen.
Arthritis & Rheumatology.
ISSN 2326-5191.
70(8),
p. 1192–1199.
doi:
10.1002/art.40494.
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Nordberg, Lena Kristine Bugge; Lillegraven, Siri; Lie, Elisabeth; Aga, Anna-Birgitte; Olsen, Inge Christoffer & Hammer, Hilde Berner
[Show all 11 contributors for this article]
(2017).
Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naïve patients classified according to the 2010 ACR/EULAR criteria.
Annals of the Rheumatic Diseases.
ISSN 0003-4967.
76(2),
p. 341–345.
doi:
10.1136/annrheumdis-2015-208873.
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Haavardsholm, Espen A.; Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde Berner & Uhlig, Till
[Show all 19 contributors for this article]
(2016).
Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial.
The BMJ.
354.
doi:
10.1136/bmj.i4205.
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Objective: To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. <p>Design: Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. <p>Setting: Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. <p>Participants: 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. <p>Interventions: 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. <p>Main outcome measures: The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and nonprogression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. <p>Results: 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. <p>Conclusions: The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology.
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Nordberg, Lena Bugge
(2024).
Ber forskere og industri beregne klimaavtrykk i kliniske studier.
[Journal].
Health Talk.
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Nordberg, Lena Bugge
(2024).
Norske forskere med internasjonalt initiativ for å beregne klimaavtrykk før medisinske behandlinger.
[Journal].
Dagens Medisin.
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Nordberg, Lena Bugge; Pohl, Heiko; Haavardsholm, Espen A.; Lillegraven, Siri & Bretthauer, Michael
(2024).
Carbon-Footprint Analyses in RCTs — Toward Sustainable Clinical Practice.
390(24),
p. 2234–2236.
doi:
10.1056/NEJMp2402018.
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Nordberg, Lena Bugge
(2024).
Lege og forsker Lena Bugge Nordberg om klimagassutslipp i helsesektoren.
[Radio].
Nyhetsmorgen.
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Santervas, Leonor Roa; Wyller, Torgeir Bruun; Skovlund, Eva; Jensen, Janicke Liaaen; Fjeld, Katrine Gahre & Hove, Lene Hystad
[Show all 11 contributors for this article]
(2024).
Cooperation across healthcare service levels for medication reviews in older people with polypharmacy admitted to a municipal in-patient acute care unit (The COOP II Study): study protocol for a randomized controlled trial.
Trials.
25(1).
doi:
10.1186/s13063-024-08442-w.
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Background: Polypharmacy and inappropriate drug use are associated with adverse health outcomes in older people. Collaborative interventions between geriatricians and general practitioners have demonstrated effectiveness in improving clinical outcomes for complex medication regimens in home-dwelling patients. Since 2012, Norwegian municipalities have established municipal in-patient acute care (MipAC) units, designed to contribute towards reducing the number of hospital admissions. These units predominantly serve older people who typically benefit from multidisciplinary approaches. The primary objective of this study is to evaluate the effect of cooperative medication reviews conducted by MipAC physicians, supervised by geriatricians, and in collaboration with general practitioners, on health-related quality of life and clinical outcomes in MipAC patients ≥ 70 years with polypharmacy. Additionally, the study aims to assess the carbon footprint of the intervention. Methods: This is a randomized, single-blind, controlled superiority trial with 16 weeks follow-up. Participants will be randomly assigned to either the control group, receiving usual care at the MipAC unit, or to the intervention group which in addition receive clinical medication reviews that go beyond what is considered usual care. The medication reviews will evaluate medication appropriateness using a structured but individualized framework, and the physicians will receive supervision from geriatricians. Following the clinical medication reviews, the MipAC physicians will arrange telephone meetings with the participants’ general practitioners to combine their assessments in a joint medication review. The primary outcome is health-related quality of life as measured by the 15D instrument. Secondary outcomes include physical and cognitive functioning, oral health, falls, admissions to healthcare facilities, and mortality. Discussion: This study aims to identify potential clinical benefits of collaborative, clinical medication reviews within community-level MipAC units for older patients with polypharmacy. The results may offer valuable insights into optimizing patient care in comparable municipal healthcare settings. Trial registration: The study was registered prospectively on ClinicalTrials.gov 30.08.2023 with identifier NCT06020391.
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Published
Mar. 21, 2025 3:16 PM
- Last modified
Apr. 29, 2025 11:50 AM
