Publications by authors named "Joe Sexton"

22 Publications

  • Page 1 of 1

Two-year reduction of dual-energy CT urate depositions during a treat-to-target strategy in gout in the NOR-Gout longitudinal study.

Rheumatology (Oxford) 2021 Jul 10. Epub 2021 Jul 10.

Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: There is a lack of large longitudinal studies of urate deposition measured by dual-energy computed tomography (DECT) during urate lowering therapy (ULT) in people with gout. We explored longitudinal changes in DECT urate depositions during a treat-to-target strategy with ULT in gout.

Methods: Patients with a recent gout flare and serum-urate (sUA) >360 µmol/l attended tight-control visits during escalating ULT. The treatment target was sUA <360 µmol/l, and <300 µmol/l if presence of tophi.A DECT scanner (General Electric Discovery CT750 HD) acquired data from bilateral forefeet and ankles at baseline and after one and two years. Images were scored in known order, using the semi-quantitative Bayat method, by one experienced radiologist who was blinded to serum urate and clinical data. Four regions were scored: the first metatarsophalangeal (MTP1) joint, the other joints of the toes, the ankles and midfeet, and all tendons in the feet and ankles.

Results: DECT was measured at baseline in 187 of 211 patients. The mean (S.D.) serum urate level (μmol/l) decreased from 501 (80) at baseline to 311 (48) at 12 months, and 322 (67) at 24 months.DECT scores at all locations decreased during both the first and the second year (p< 0.001 for all comparisons vs baseline), both for patients achieving and not achieving the sUA treatment target.

Conclusions: In patients with gout, urate depositions in ankles and feet as measured by DECT decreased both in the first and the second year, when patients were treated using a treat-to-target ULT strategy.
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http://dx.doi.org/10.1093/rheumatology/keab533DOI Listing
July 2021

An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis-results from 19 countries.

Eur Heart J Cardiovasc Pharmacother 2021 Jul 7. Epub 2021 Jul 7.

Center of Cardiology of Russian Ministry of Healthcare, Moscow, Russia.

Aims: To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions. Further to evaluate the management and goal attainment of lipids and blood pressure (BP).

Methods And Results: The SUrvey of CVD Risk Factors in patients with RA was conducted in 14503 patients from 19 countries during 2014-2019. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high-risk group, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two % had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three drug combination.

Conclusion: We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.
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http://dx.doi.org/10.1093/ehjcvp/pvab052DOI Listing
July 2021

Viral respiratory infections in patients treated with hydroxychloroquine.

Clin Exp Rheumatol 2021 Sep-Oct;39(5):1146. Epub 2021 Apr 7.

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

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April 2021

Risk of solid cancers overall and by subtypes in patients with psoriatic arthritis treated with TNF inhibitors - a Nordic cohort study.

Rheumatology (Oxford) 2021 08;60(8):3656-3668

Bispebjerg and Frederiksberg, The Parker Institute, Copenhagen University Hospital, Hellerup, Denmark.

Objectives: To investigate whether TNF inhibitors (TNFi) are associated with increased risk of solid cancer in patients with psoriatic arthritis (PsA).

Methods: From the Nordic clinical rheumatology registers (CRR) here: SRQ/ARTIS (Sweden), DANBIO (Denmark), NOR-DMARD (Norway), ROB-FIN (Finland) and ICEBIO (Iceland) we identified PsA patients who started a first TNFi 2001-2017 (n = 9655). We identified patients with PsA not treated with biologics from (i) the CRR (n = 14 809) and (ii) the national patient registers (PR, n = 31 350). By linkage to the national cancer registers, we collected information on incident solid cancer overall and for eight cancer types. We used Cox regression to estimate hazard ratio (HR) with 95% CI of cancer (per country and pooled) in TNFi-exposed vs biologics-naïve, adjusting for age, sex, calendar period, comorbidities and disease activity. We also assessed standardized incidence ratios (SIR) in TNFi-exposed PsA vs the general population (GP).

Results: We identified 296 solid cancers among the TNFi-exposed PsA patients (55 850 person-years); the pooled adjusted HR for solid cancer overall was 1.0 (0.9-1.2) for TNFi-exposed vs biologics-naïve PsA from the CRR, and 0.8 (0.7-1.0) vs biologics-naïve PsA from the PRs. There were no significantly increased risks for any of the cancer types under study. The pooled SIR of solid cancer overall in TNFi treated PsA vs GP was 1.0 (0.9-1.1).

Conclusion: In this large cohort study from five Nordic countries, we found no increased risk of solid cancer in TNFi-treated PsA patients, neither for solid cancer overall nor for eight common cancer types.
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http://dx.doi.org/10.1093/rheumatology/keaa828DOI Listing
August 2021

Fatigue is cross-sectionally not associated with objective assessments of inflammation, but changes in fatigue are associated with changes of disease activity assessments during biologic treatment of patients with established rheumatoid arthritis.

Clin Rheumatol 2021 May 11;40(5):1739-1749. Epub 2020 Oct 11.

Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, N-0319, Oslo, Norway.

Objective: The associations between fatigue and disease activity in patients with rheumatoid arthritis (RA) have not been defined. The present objectives were to explore in RA patients the cross-sectional and longitudinal relation of fatigue with subjective as well as objective assessments of disease activity.

Methods: RA patients were consecutively included when initiating biologic disease-modifying anti-rheumatic drugs (DMARDs) and assessed at baseline, 1, 2, 3, 6, and 12 months with investigation of fatigue, patient-reported outcome measures (PROMs; joint pain and patient's global disease activity, MHAQ, pain catastrophizing, Mental Health score), clinical examinations (examiner's global disease activity, 28 tender and swollen joint counts), and laboratory variables (ESR, CRP, calprotectin). Ultrasound examinations (semi-quantitative scoring (0-3)) with grey scale and power Doppler were performed of 36 joints and 4 tendons. Statistics included one-way analysis of variance, Pearson's correlations, and multiple linear and logistic regression analysis.

Results: A total of 208 RA patients (mean (SD) age 53.2 (13.2) years, disease duration 9.8 (8.5) years) were included. Fatigue levels diminished during follow-up (mean (SD) baseline/12 months; 4.8 (2.8)/3.0 (2.5) (p < 0.001)). Substantial correlations were cross-sectionally found between fatigue and PROMs (median (IQR) r=0.61 (0.52-0.71)) but not with the objective inflammatory assessments. During follow-up, baseline fatigue was associated with PROMs (p < 0.001) but not with objective inflammatory assessments. However, change of fatigue was associated with change in all variables. Higher baseline fatigue levels were associated with lower clinical composite score remission rates.

Conclusion: Fatigue was cross-sectionally associated to subjective but not to objective disease assessments. However, change of fatigue during treatment was associated to all assessments of disease activity.

Trial Registration Number: Anzctr.org.au identifier ACTRN12610000284066, Norwegian Regional Committee for Medical and Health Research Ethics South East reference number 2009/1254 Key Points • In this longitudinal study of patients with established RA, fatigue was associated with patient reported outcome measures at each visit, but not with objective assessments of inflammation including calprotectin and comprehensive ultrasound examinations. • Changes in fatigue during biological treatment were associated with changes in patient reported outcome measures, clinical, laboratory and ultrasound assessments. • Baseline fatigue was associated with all patient reported outcome measures, but not objective assessments of inflammation at all the prospective visits. • Higher baseline fatigue levels were associated with lower remission rates as assessed by clinical composite scores.
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http://dx.doi.org/10.1007/s10067-020-05402-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102439PMC
May 2021

Efficacy and Safety of CT-P13 in Inflammatory Bowel Disease after Switching from Originator Infliximab: Exploratory Analyses from the NOR-SWITCH Main and Extension Trials.

BioDrugs 2020 Oct;34(5):681-694

Department of Gastroenterology, Akershus University Hospital, Sykehusveien 75, 1478, Lørenskog, Norway.

Background: The NOR-SWITCH main and extension trials demonstrated that switching from originator to biosimilar infliximab (CT-P13) is efficacious and safe across six diseases. However, a subgroup analysis of Crohn's disease (CD) in the main trial displayed a close to significant difference favouring originator infliximab, and more scientific data have therefore been requested.

Objective: The aim was to assess treatment efficacy, safety, and immunogenicity in an explorative subgroup analysis in CD and ulcerative colitis (UC) in the NOR-SWITCH trials.

Patients And Methods: The 52-week, randomised, non-inferiority, double-blind, multicentre, phase 4 NOR-SWITCH study was followed by a 26-week open extension trial where all patients received treatment with CT-P13. Treatment efficacy, safety, and immunogenicity in CD and UC were assessed throughout the 78-week study period.

Results: The main and extension trials included 155 and 93 patients with CD and 93 and 80 patients with UC, respectively. Demographic and baseline characteristics were comparable in both treatment arms within patient groups. There were no differences in the main and extension trials regarding changes in activity indices, C-reactive protein, faecal calprotectin, patient's and physician's global assessment of disease activity and patient-reported outcome measures in CD and UC. Moreover, comparable results were also demonstrated for trough serum levels, presence of anti-drug antibodies, and reported adverse events.

Conclusion: Efficacy, safety, and immunogenicity of both the originator and biosimilar infliximab were comparable in CD and UC in the NOR-SWITCH main and extension trials. These explorative subgroup analyses confirm that there are no significant concerns related to switching from originator infliximab to CT-P13 in CD and UC.

Trial Registration: ClinicalTrials.gov, number NCT02148640.
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http://dx.doi.org/10.1007/s40259-020-00438-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519917PMC
October 2020

Trends in all-cause and cardiovascular mortality in patients with incident rheumatoid arthritis: a 20-year follow-up matched case-cohort study.

Rheumatology (Oxford) 2020 03;59(3):505-512

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objectives: To examine all-cause and cardiovascular disease (CVD) mortality in consecutive cohorts of patients with incident RA, compared with population comparators.

Methods: The Oslo RA register inclusion criteria were diagnosis of RA (1987 ACR criteria) and residency in Oslo. Patients with disease onset 1994-2008 and 10 matched comparators for each case were linked to the Norwegian Cause of Death Registry. Hazard ratios for all-cause and CVD mortality were calculated for 5, 10, 15 and 20 years of observation using stratified cox-regression models. Mortality trends were estimated by multivariate cox-regression.

Results: 443, 479 and 469 cases with disease incidence in the periods 94-98, 99-03 and 04-08 were matched to 4430, 4790 and 4690 comparators, respectively. For cases diagnosed between 1994 and 2003, the all-cause mortality of cases diverged significantly from comparators after 10 years of disease duration [hazard ratio (95% CI) 94-98 cohort 1.42 (1.15-1.75): 99-03 cohort 1.37 (1.08-1.73)]. CVD related mortality was significantly increased after 5 years for the 94-98 cohort [hazard ratio (95% CI) 1.86 (1.16-2.98) and after 10 years for the 99-03 cohort 1.80 (1.20-2.70)]. Increased mortality was not observed in the 04-08 cohort where cases had significantly lower 10-year all-cause and CVD mortality compared with earlier cohorts.

Conclusion: All-cause and CVD mortality were significantly increased in RA patients diagnosed from 1994 to 2003, compared with matched comparators, but not in patients diagnosed after 2004. This may indicate that modern treatment strategies have a positive impact on mortality in patients with RA.
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http://dx.doi.org/10.1093/rheumatology/kez371DOI Listing
March 2020

Assessing synovitis in the hands in patients with rheumatoid arthritis by ultrasound: an agreement study exploring the most inflammatory active side from two Norwegian trials.

Arthritis Res Ther 2019 07 5;21(1):166. Epub 2019 Jul 5.

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Objective: To assess if the right hand, the dominant hand, or the hand with more clinically swollen joints (SwJ) is per se the most inflamed and exhibits the greatest change during treatment and hence preferred for unilateral scoring of synovitis by ultrasound in rheumatoid arthritis (RA) patients.

Methods: Using data from two previously published Norwegian RA patient cohorts initiating treatment, bilateral metacarpophalangeal joint 1-5, proximal phalangeal joint 2+3, and wrists were evaluated by ultrasound. Using a 0-3 scoring system a grey-scale (GS), power Doppler (PD) and global synovitis score (GLOESS) was calculated for each hand (0-30). For precision, a difference of < ± 3 in sum score was pre-specified as indicating clinically insignificant difference in inflammatory activity for all three scores.

Results: Four hundred thirty-seven RA patients were included. Baseline ultrasound inflammation was statistically significantly higher in hands with more vs fewer SwJ ([mean difference, 95%CI] GS sum score 2.21[1.30 to 3.12], PD sum score 1.70 [0.94 to 2.47] and GLOESS 2.31[1.36 to 3.26]) and also exhibited significantly more change for all sum scores at 3 months follow-up (GS sum score 1.34 [0.60 to 2.08], PD sum score 1.17 [0.44 to 1.91], and GLOESS 1.43 [0.63 to 2.22]). No such differences were found between the dominant and the non-dominant or the right and the left hands at any time points.

Conclusion: The hand with clinically more SwJ is statistically more inflammatory active according to GS, Doppler, and GLOESS sum scores, exhibits a change during treatment, and is potentially the best choice for unilateral scoring systems.
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http://dx.doi.org/10.1186/s13075-019-1930-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612125PMC
July 2019

Tender Joint Count and Inflammatory Activity in Patients With Established Rheumatoid Arthritis: Results From a Longitudinal Study.

Arthritis Care Res (Hoboken) 2020 01;72(1):27-35

Diakonhjemmet Hospital, Oslo, Norway.

Objective: The tender joint count (TJC) is included in composite disease activity scores (CDAS) (the Disease Activity Score in 28 joints, the Clinical Disease Activity Index, and the Simplified Disease Activity Index). The impact of having predominantly tender joints was explored by use of the Tender-Swollen Joint Count Difference (TSJD), and ultrasound (US) provided a measure of joint inflammation. The current study aimed to explore the cross-sectional and longitudinal associations between the TSJD and a spectrum of outcome measures, including US scores in patients with established rheumatoid arthritis (RA) during follow-up and while receiving treatment with biologic disease-modifying antirheumatic drugs (bDMARDs).

Methods: This was an observational study of 209 patients with established RA consecutively included upon initiation of bDMARD treatment and followed-up with clinical, laboratory, and comprehensive US examinations at 0, 1, 2, 3, 6, and 12 months. Patients were categorized into 2 groups: those with predominantly tender joints (TSJD >0) and those with predominantly swollen joints (TSJD ≤0). Statistical analyses included Pearson's correlation coefficient, an independent samples t-test, and regression analyses.

Results: The TJC had high correlations only with patient-reported outcomes (PROMs) (P < 0.001). Levels from CDAS and PROMs were significantly higher (P < 0.001) at all visits in patients with TSJD >0 compared to those with TSJD <0. Laboratory markers and assessor's global visual analog scale scores were similar, and US sum scores were significantly lower (P < 0.001-0.03). The baseline TSJD positively predicted levels of all CDAS at 6 months (P < 0.001-0.019) but was a negative predictor of US sum scores (gray-scale and power Doppler) at 6 and 12 months (P < 0.001).

Conclusion: Patients with predominantly tender joints had higher CDAS but lower levels of inflammation as defined by US. These findings indicate that inclusion of the TJC in the CDAS may contribute to misleading information about inflammatory activity.
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http://dx.doi.org/10.1002/acr.23815DOI Listing
January 2020

Is synovial hypertrophy without Doppler activity sensitive to change? Post-hoc analysis from a rheumatoid arthritis ultrasound study.

Arthritis Res Ther 2018 10 3;20(1):224. Epub 2018 Oct 3.

Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.

Background: To explore to what extent synovial hypertrophy in joints without Doppler activity is a sign of active disease, we investigated the sensitivity to change of synovial hypertrophy without Doppler activity during biological disease-modifying antirheumatic drug (bDMARD) treatment in rheumatoid arthritis (RA) patients.

Method: RA patients initiating or switching bDMARD treatment had ultrasound (US) performed on 36 joints at baseline, and at 3 and 6 months. Synovial hypertrophy by grayscale US and Doppler activity were graded separately from 0 to 3 at the joint level for all time points. Changes in synovial hypertrophy in joints without Doppler activity during treatment were assessed and compared with changes in synovial hypertrophy in joints with Doppler activity.

Results: We included 151 patients (82.8% women, 80.1% seropositive for anticyclic citrullinated peptide) with a mean ± standard deviation age of 51.4 ± 13.2 years, a disease duration of 9.9 ± 7.9 years, and baseline Disease Activity Score 28-joint count C-reactive peptide (DAS28-CRP) of 4.14 ± 1.32. At baseline, 44.8% of all joints examined (n = 5225) had synovial hypertrophy ≥ 1 and 50.7% of these had synovial hypertrophy without Doppler activity. The improvement in synovial hypertrophy was similar in joints with and without Doppler activity but, when adjusting for the baseline score of synovial hypertrophy, joints with synovial hypertrophy without Doppler had a higher tendency towards a decrease than joints with synovial hypertrophy with Doppler activity independent of grade (3 months: p < 0.0001; 6 months: p = 0.0003).

Conclusion: Joints with synovial hypertrophy without Doppler activity improve during treatment, independent of the grade. Thus, SH without Doppler activity is not a sign of inactive disease. These findings indicate that joints with synovial hypertrophy without Doppler activity should also be taken in to account when assessing disease activity by US.
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http://dx.doi.org/10.1186/s13075-018-1709-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235232PMC
October 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 Rheumatol 2018 08 29;70(8):1192-1199. Epub 2018 Jun 29.

University of Oslo and Diakonhjemmet Hospital, Oslo, Norway.

Objective: Intraarticular glucocorticoid injections are common in rheumatoid arthritis (RA) treatment. This study was undertaken to investigate whether ultrasound in combination with clinical examination is better than clinical examination alone at identifying joints that will benefit from intraarticular injections, and to compare the efficacy of ultrasound-guided versus palpation-guided procedures.

Methods: In the treat-to-target Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasonography in a Clinical Tight Control Regimen (ARCTIC), patients with early RA were randomized 1:1 to follow-up with or without ultrasound. In addition to disease-modifying antirheumatic drugs, intraarticular glucocorticoids were used to treat inflamed joints. The distribution of injections was assessed in both study groups. The relationship of clinical and ultrasound findings at the time of injection with treatment efficacy was examined, with non-swollen joint at the next visit as the outcome measure. Treatment success was compared across study groups to evaluate ultrasound-guided versus palpation-guided procedures.

Results: More injections were administered in the ultrasound group than in the conventional strategy group (n = 770 versus 548), especially in intercarpal joints (n = 58 versus 5) and metatarsophalangeal joints (n = 200 versus 104). Injecting clinically swollen joints without power Doppler (PD) activity on ultrasound was not efficacious compared to not injecting (odds ratio [OR] 1.3; P = 0.59). Efficacy was best in swollen joints (OR 9.0; P = 0.001) and non-swollen joints (OR 8.4; P = 0.016) with moderate PD activity. Treatment success was similar for the ultrasound-guided and palpation-guided procedures.

Conclusion: Our findings indicate that the efficacy of intraarticular glucocorticoid injections varies according to ultrasound findings at the time of injection, supporting the use of ultrasound as a tool to select joints that will benefit from intraarticular injections. However, ultrasound needle guidance was not superior to palpation guidance.
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http://dx.doi.org/10.1002/art.40494DOI Listing
August 2018

Improved neurocognitive functions correlate with reduced inflammatory burden in atrial fibrillation patients treated with intensive cholesterol lowering therapy.

J Neuroinflammation 2013 Jun 28;10:78. Epub 2013 Jun 28.

Divison of Internal Medicine, Nordland Hospital, Norway and University of Tromsø, Bodø, Norway.

Background: Atrial fibrillation (AF) is associated with increased mortality and morbidity, including risk for cerebral macro- and microinfarctions and cognitive decline, even in the presence of adequate oral anticoagulation. AF is strongly related to increased inflammatory activity whereby anti-inflammatory agents can reduce the risk of new or recurrent AF. However, it is not known whether anti-inflammatory therapy can also modify the deterioration of neurocognitive function in older patients with AF. In the present study, older patients with AF were treated with intensive lipid-lowering therapy with atorvastatin 40 mg and ezetimibe 10 mg, or placebo. We examined the relationship between neurocognitive functions and inflammatory burden.

Findings: Analysis of inflammatory markers revealed significant reductions in high sensitivity C-reactive protein (hs-CRP), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 receptor antagonist (IL-1RA), interleukin (IL)-9, IL-13 and IL-17, and interferon-γ (IFNγ) in the treatment group compared to placebo. Reduction in plasma concentration of IL-1RA, IL-2, IL-9 and IL-12, and macrophage inflammatory protein-1β (MIP-1β) correlated significantly with improvement in the neurocognitive functions memory and speed. Loss of volume in amygdala and hippocampus, as determined by magnetic resonance imaging (MRI), was reduced in the treatment arm, statistically significant for left amygdala.

Conclusions: Anti-inflammatory therapy through intensive lipid-lowering treatment with atorvastatin 40 mg and ezetimibe 10 mg can modify the deterioration of neurocognitive function, and the loss of volume in certain cerebral areas in older patients with AF. TRIAL REGISTRATION ClinicalTrials.gov: NCT00449410.
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http://dx.doi.org/10.1186/1742-2094-10-78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699385PMC
June 2013

Persisting thrombin activity in elderly patients with atrial fibrillation on oral anticoagulation is decreased by anti-inflammatory therapy with intensive cholesterol-lowering treatment.

J Clin Lipidol 2011 Jul-Aug;5(4):273-80. Epub 2011 May 20.

Department of Cardiology, Radboud University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

Background: It has been demonstrated that the occurrence of ischemic stroke is more prevalent in AF patients, when increased levels of inflammatory markers are present.

Objective: The aim of this study was to evaluate the effect of intensive cholesterol lowering therapy on inflammatory markers and evidence of thrombotic in elderly AF patients treated with OAC.

Methods: 34 elderly patients (69-85 yrs) were randomized to double blind treatment with atorvastatin 40 mg plus ezetimibe 10 mg (n = 17) or double placebo (n = 17) for one year. All were anticoagulated with warfarin (target INR 2.5-3.5). Every 3 months inflammatory markers and parameters for evaluation of haemostatic and fibrinolytic activity were measured.

Results: Anti-inflammatory effects in the treatment arm were reflected by a significant decrease from baseline in hs-CRP, FGF, G-CSF, GM-CSF, IL-1ra, IL-9, IL-13, IL-17 and interferon-γ (P < .05). There was no significant decrease in the control group. Endogenous thrombin potential was still present and active but decreased during treatment (P = .0005) compared to the placebo group. After 12 months treatment, a significant correlation was found between changes in endogenous thrombin potential and hs-CRP, interferon-γ and G-CSF, respectively. No hemorrhagic complications occurred.

Conclusion: Intensive cholesterol lowering significantly reduced inflammation and was accompanied by reduced thrombin generation. Larger clinical studies should determine which inflammatory markers are most specific and sensitive for estimating the inflammatory burden in these patients and at which corresponding thrombin activity level it is beneficial and safe to add intensive cholesterol lowering therapy even if normal cholesterol levels are present.
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http://dx.doi.org/10.1016/j.jacl.2011.05.003DOI Listing
November 2011

Gated SPECT offers improved interobserver agreement compared with echocardiography.

Clin Nucl Med 2010 Dec;35(12):927-30

Coronary Care Unit, Department of Internal Medicine, Nordland Hospital, Bodø, Norway.

Purpose: Left ventricular ejection fraction (EF) is a powerful predictor of prognosis in coronary artery disease. The purpose of the present study was to measure interobserver differences for gated SPECT (GSPECT) software and echocardiography, and to compare these modalities regarding left ventricular volumes and EF.

Materials And Methods: Eighty-four patients scheduled for nuclear imaging underwent a 1-day GSPECT with Tc-99m-tetrofosmin. Images were processed by 2 raters who calculated volumes and EF using Cedar-Sinai quantitative gated-SPECT (QGS), Emory Cardiac Toolbox (ECT), and 4D-MSPECT of the University of Michigan. Echocardiographic volumes were measured by 2 raters. Interobserver reliability was assessed by intraclass correlation coefficient (ICC). Differences in volumes and EF between echocardiography and GSPECT were compared with t-tests.

Results: ICC was 0.61 for echocardiography, 0.94 for QGS, 0.88 for ECT, and 0.91 for 4D-MSPECT (P < 0.0001 compared with echocardiography). For small ventricles (ESV ≤30 mL), ICC was 0.58 for echocardiography and 0.90 for QGS (P = 0.008 compared with echocardiography); 0.77 and 0.73 for ECT and 4D-MSPECT, respectively (P = ns). End-diastolic and end-systolic volumes were significantly larger with GSPECT than with echocardiography, also echocardiographic ejection fraction was significantly different from GSPECT.

Conclusions: There is better interobserver reliability in GSPECT as compared with echocardiography, and QGS seems more robust in this study especially when it comes to small ventricles.
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http://dx.doi.org/10.1097/RLU.0b013e3181f9ddfbDOI Listing
December 2010

Concurrent validity of the Health of the Nation Outcome Scales compared with a patient-derived measure, the Symptom Checklist-90-Revised in out-patient clinics.

Psychiatry Res 2011 May 20;187(1-2):297-300. Epub 2010 Nov 20.

University of Tromsø, Institute of Clinical Medicine, Tromsø, Norway.

The psychometric properties of the Health of the Nation Outcome Scales (HoNOS) have been questioned. The present study examined the concurrent validity of the HoNOS against a patient-derived measure (the Symptom Checklist-90-R (SCL-90-R)) in out-patients. This relationship has previously only been investigated in in-patients. The study considered newly admitted patients, and only those with a complete data set were analyzed (N=118). Internal consistency (Cronbach's alpha) and effect sizes were calculated on pre- and post-treatment data. Concurrent validity was assessed using correlation (Spearman's rho) as well as agreement (kappa) on reliable and clinically significant change (RCSC). The internal consistencies associated with the SCL-90-R were satisfactory, a property shared only by the HoNOS sum score. The pre- to post-treatment changes in both instruments corresponded to medium to large effect sizes and were comparable in size. However, the correlations between the two were low, as was their agreement. This suggests that the HoNOS and the SCL-90-R measure somewhat different phenomena. The findings shed doubt on whether the patient-derived measures should be regarded as the "gold standard". The instruments seem to complement each other.
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http://dx.doi.org/10.1016/j.psychres.2010.10.023DOI Listing
May 2011

Different inflammatory responses induced by three LDL-lowering apheresis columns.

J Clin Apher 2009 ;24(6):247-53

Coronary Care Unit, Department of Internal Medicine, Nordland Hospital, Bodø, Norway.

Low-density lipoprotein (LDL) apheresis is well-established in selected patients with uncontrolled LDL levels. As such treatment affects biomarkers important in atherosclerosis and acute coronary syndromes, we systematically compared the inflammatory response induced by three LDL apheresis columns. Three patients with heterozygous familial hypercholesterolemia participated in a cross-over study with six consecutive treatments with three different LDL apheresis columns: DL-75 (whole blood adsorption), LA-15 (plasma adsorption), and EC-50W (plasma filtration). Biochemical parameters and inflammatory biomarkers, including complement activation products and 27 cytokines, chemokines, and growth factors were measured before and after treatment. Complement was activated through the alternative pathway. The final end product sC5b-9 increased significantly (P < 0.01) and equally with all devices, whereas the anaphylatoxins C3a and C5a were lower by use of the adsorption columns. Hs-CRP was reduced by 77% (DL-75), 72% (LA-15), and 43% (EC-50W). The cytokines were consistently either increased (IL-1ra, IP-10, MCP-1), decreased (IFN-gamma, TNF-alpha, RANTES, PDGF, VEGF), or hardly changed (including IL-6, IL8, MIP-1alphabeta) during treatment. The changes were in general less pronounced with the adsorption columns. All columns reduced LDL significantly and to the same extent. In conclusion, three LDL-apheresis devices with equal cholesterol-lowering effect differed significantly with respect to the inflammatory response.
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http://dx.doi.org/10.1002/jca.20223DOI Listing
February 2010

Sensitivity analysis for unmeasured confounding in a marginal structural Cox proportional hazards model.

Lifetime Data Anal 2009 Jun 25;15(2):278-94. Epub 2008 Dec 25.

Akershus University Hospital, Helse Øst Health Services Research Centre, Nordbyhagen, Norway.

Sensitivity analysis for unmeasured confounding should be reported more often, especially in observational studies. In the standard Cox proportional hazards model, this requires substantial assumptions and can be computationally difficult. The marginal structural Cox proportional hazards model (Cox proportional hazards MSM) with inverse probability weighting has several advantages compared to the standard Cox model, including situations with only one assessment of exposure (point exposure) and time-independent confounders. We describe how simple computations provide sensitivity for unmeasured confounding in a Cox proportional hazards MSM with point exposure. This is achieved by translating the general framework for sensitivity analysis for MSMs by Robins and colleagues to survival time data. Instead of bias-corrected observations, we correct the hazard rate to adjust for a specified amount of unmeasured confounding. As an additional bonus, the Cox proportional hazards MSM is robust against bias from differential loss to follow-up. As an illustration, the Cox proportional hazards MSM was applied in a reanalysis of the association between smoking and depression in a population-based cohort of Norwegian adults. The association was moderately sensitive for unmeasured confounding.
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http://dx.doi.org/10.1007/s10985-008-9109-xDOI Listing
June 2009

[Acute myocardial infarction in Bodø over a period of 15 years].

Tidsskr Nor Laegeforen 2007 Jun;127(12):1631-3

Kardiologisk seksjon, Medisinsk avdeling, Nordlandssykehuset, 8092 Bodø.

Background: Studies show that both incidence and mortality in acute myocardial infarction are declining. It was expected that introduction of the troponin biomarkers in 2000 would lead to an increase in the number of diagnosed myocardial infarctions. We aimed at establishing how introduction of troponin and the fact that elderly comprise an increasing part of the population with an inherent increased risk for myocardial infarction, affected myocardial infarctions in our region with respect to incidence, age distribution and mortality.

Material And Methods: All patients admitted to our hospital with a diagnosis of acute myocardial infarction (ICD 9 and 10) from 1990 to 2005 were included in the study. Data were imported from our electronic journal system with a database tool (Qlikview). Information about the incidence of myocardial infarction in all of Norway was taken from The Norwegian Inpatient Registry and population data were taken from Statistics Norway. Data were transferred from Qlikview to Excel and SPSS for statistical analysis.

Results: The incidence of myocardial infarction varied from year to year in our hospital area; it increased from 2000, but then decreased during the last two years. The proportion of patients aged 80 and older increased from 13 to 36% (p < 0.0001) in our hospital during the 15 years. One-year mortality declined for the following age groups from 1990 to 2004; 0-59 years (p = 0.0005), 60-69 years (p = 0.009) and 70-79 years (p = 0.003). This decline was not seen in the age group of 80 years and older (p = 0.66). In 2003, one-year mortality in these four age groups was 3, 15, 23 and 45% respectively.

Interpretation: The incidence of myocardial infarction increased in our hospital after the introduction of troponin in 2000; but decreased the last two years of the study in our area, but not in Norway in general. The proportion of patients from 80 years and older increased more than what the general increase in the population would warrant. Mortality decreased in all age groups over the 15-year period, except for those aged 80 years and older.
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June 2007

Video information combined with individualized information sessions: Effects upon emotional well-being following coronary artery bypass surgery--A randomized trial.

Patient Educ Couns 2007 Feb 7;65(2):180-8. Epub 2006 Sep 7.

Department of Clinical Psychiatry, University of Tromsø, N-9291 Tromsø, Norway.

Objective: To test the efficacy of an information intervention upon emotional recovery following coronary artery bypass surgery.

Methods: Randomized trial. Video information was combined with individualized information sessions carried out by nurses at admission and at discharge from the hospital. The video was shown pre-operatively and again during the session at admission. Patients were helped to express their questions and worries and congruent information and support was provided. Control group patients received standardized information and no video. Recordings were made at baseline, discharge from hospital and during a 2 years follow-up period.

Results: One hundred and nine patients were randomized to the intervention or the control groups. A MANOVA was used to test of the variance of the outcome variables at each time point. At discharge intervention patients reported less anxiety (p = 0.046) and better subjective health (p = 0.005). They reported better subjective health during the whole follow-up period (0.040 > or = p > or = 0.000), less anxiety up to 1 year (0.042 > or = p > or = 0.004), and less depression from 6 months to 2 years following discharge (0.023 > or = p > or = 0.004).

Conclusion: The effects of the intervention probably relate to the combined use of the video and patient centered information sessions.

Practice Implications: The intervention can easily be implemented in clinical practice and nurses strongly identified with its principles.
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http://dx.doi.org/10.1016/j.pec.2006.07.006DOI Listing
February 2007

Role of granulocytes and monocytes in the polyvinyl chloride-induced synthesis of interleukin 8, monocyte chemoattractant protein 1, and leukotriene B4.

J Biomed Mater Res A 2005 Aug;74(2):230-6

Department of Medicine, Nordland Hospital, Bodø, and University of Tromsø, Norway.

In an in vitro whole blood model of artificial surface-induced inflammation, we have studied the contribution of leukocyte populations in the synthesis of inflammatory mediators. This was done by depleting the blood of specific cell types using magnetic beads coated with monoclonal antibodies against leukocyte surface antigens. Synthesis of interleukin 8 (IL-8) was highly dependent on CD15+ cells and was reduced by 80% when these cells were removed from the blood. Correspondingly, IL-8 production showed a high correlation with the concentration of granulocytes (r = 0.77, p < 0.0001). Synthesis of monocyte chemoattractant protein 1 (MCP-1) was dependent on CD14+ cells and was reduced by 35% when these cells were removed from the blood. Correspondingly, MCP-1 production correlated with the concentration of monocytes (r = 0.39, p < 0.0001). Synthesis of leukotriene B4 (LTB4) was highly dependent on CD15+ cells and was reduced by 75% when these cells were removed from the blood. Correspondingly, LTB4 production correlated strongly with the granulocyte concentration (r = 0.54, p < 0.0001). As expected, complement activation was not affected by cell depletion and did not correlate with the concentration of any of the cell types. Thus, artificial surface-induced IL-8 and LTB4 synthesis was almost exclusively granulocyte dependent. However, MCP-1 synthesis was mainly a product of monocytes, although granulocytes and other subpopulations may partly contribute. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005.
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http://dx.doi.org/10.1002/jbm.a.30372DOI Listing
August 2005
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