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  • Barber, Megan R.W., et al. (författare)
  • Economic Evaluation of Damage Accrual in an International Systemic Lupus Erythematosus Inception Cohort Using a Multistate Model Approach
  • 2020
  • Ingår i: Arthritis Care and Research. - : John Wiley and Sons. - 2151-464X .- 2151-4658. ; 72:12, s. 1800-1808
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling. Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model. Results: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6–18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0. Conclusion: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies.
  • Bengtsson, Christine, et al. (författare)
  • Cardiovascular event in systemic lupus erythematosus in northern Sweden: Incidence and predictors in a 7-year follow-up study
  • 2012
  • Ingår i: Lupus. - London : SAGE Publications. - 0961-2033 .- 1477-0962. ; 21:4, s. 452-459
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. An increased rate of cardiovascular disease (CVD) has been suggested in patients with systemic lupus erythematosus (SLE). The risk for myocardial infarction (MI), coronary artery disease and stroke has been reported as particularly prevalent in younger females compared with the reference population. This study was performed to analyse the standard incidence ratio (SIR) of and predictors for cardiovascular events (CVEs) in patients with SLE from northern Sweden, with a fairly homogenous population. Methods. In 2000 all prevalent patients with SLE (>= 4 American College of Rheumatology [ACR] criteria; n=277) from the four northern-most counties of Sweden were assessed with clinical and laboratory analyses. Seven years follow-up data concerning MI and stroke were extracted from the national registers of hospitalization and death in Sweden. The incidence ratio among the patients was compared with that for the general population from the same catchment area using data from the same register and Statistics Sweden. To identify time to event and CVE predictors, two matched controls for each patient were used and disease related variables as CVD predictors. Results. The SIR for a CVE was 1.27 (95% CI 0.82-1.87) and for females separately aged 40-49 years was 8.00 (95% CI 1.65-23.38). The overall SIR for MI was 2.31 (95% CI 1.34-3.7), for females overall was 1.75 (95% CI 0.84-3.22) and for females aged between 40 and 49 years was 8.7 (95% CI 1.1-31.4). The time to an event was significantly shorter among SLE patients (p<0.001) and was predicted by hypertension adjusted for smoking and disease. High SLEDAI and anti-cardiolipin IgG antibodies predicted an event in Cox proportional hazards regression models adjusted for age and previous MI. Diabetes, smoking ever and sex did not affect the prediction models. Conclusion. The risk of a CVE, or MI, was eight-or nine-fold greater among middle-aged female SLE patients. Time to event was significantly shorter and CVE was associated with SLE-related factors including hypertension and age. Lupus (2012) 21, 452-459.
  • Bengtsson, Christine, et al. (författare)
  • Systemic lupus erythematosus and cardiac risk factors: medical record documentation and patient adherence
  • 2011
  • Ingår i: Lupus. - Houndmills, Basingstoke, Hampshire : SAGE Publications. - 0961-2033 .- 1477-0962. ; 20:10, s. 1057-1062
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores patients' knowledge of cardiac risk factors (CRFs), analyses how information and advice about CRFs are documented in clinical practice, and assesses patient adherence to received instructions to decrease CRFs. Systemic lupus erythematosus (SLE) patients with >= 4 ACR criteria participated through completing a validated cardiovascular health questionnaire (CHQ). Kappa statistics were used to compare medical records with the self-reported CHQ (agreement) and to evaluate adherence. Two hundred and eleven (72%) of the known patients with SLE participated. The mean age of the patients was 55 years. More than 70% of the SLE patients considered hypertension, obesity, smoking and hypercholesterolaemia to be very important CRFs. The agreement between medical record documentation and patients' reports was moderate for hypertension, overweight and hypercholesterolaemia (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). Patients' self-reported adherence to advice they had received regarding medication was substantial to perfect (kappa 0.65-1.0). For lifestyle changes in patients with hypertension and overweight, adherence was only fair to moderate (kappa 0.13-0.47). Swedish SLE patients' awareness of traditional CRFs was good in this study. However, the agreement between patients' self-reports and medical record documentation of CRF profiles, and patients' adherence to medical advice to CRF profiles, could be improved. Lupus (2011) 20, 1057-1062.
  • Bjarnegard, N, et al. (författare)
  • Increased aortic pulse wave velocity in middle aged women with systemic lupus erythematosus
  • 2006
  • Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 15:10, s. 644-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is a connective tissue disease where inflammatory activity affects several organ systems. An increased risk of cardiovascular disease has been identified in these patients, even after correction for traditional risk factors. The aim of the present study was to evaluate arterial stiffness and central hemodynamics in women with SLE in comparison to controls. Arterial tonometry was used to measure aortic (carotid-femoral) and arm (carotid-radial) pulse wave velocity (PWV), reflected pressure waves, and aortic augmentation index (AIx) in 27 women with SLE (52 to 68 years) and 27 controls. Aortic PWV was higher in women with SLE than controls, 9.8 m/s versus 8.2 m/s (P < 0.01), after correction for mean arterial pressure and body mass index, 9.5 m/s versus 8.5 m/s (P < 0.05). Other parameters were similar, arm PWV, 8.4 versus 8.5 m/s, AIx 34 versus 33% and calculated central aortic pulse pressure 48 versus 43 mmHg, in SLE and controls, respectively (NS). Aortic PWV was positively associated to C-reactive protein (CRP) and complement factor 3 (C3). Women with SLE have increased stiffness of their elastic central arteries. This may be one factor contributing to the increased cardiovascular risk seen in this cohort.
  • Brodszki, J, et al. (författare)
  • Abnormal mechanical properties of larger arteries in postmenopausal women with systemic lupus erythematosus
  • 2004
  • Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 13:12, s. 917-923
  • Tidskriftsartikel (refereegranskat)abstract
    • There is limited knowledge of potential defects in arterial wall properties in female systemic lupus erythematosus (SLE) patients without manifest cardiovascular disease (CVD) and significant atherosclerotic lesions. The aim of the present study was to investigate the mechanical properties of larger vessels in these patients and to compare them with healthy controls. B-mode ultrasound was used to assess vessel wall structure and to exclude presence of plaque. The ankle/brachial pressure index was measured to exclude occlusive arterial disease. An ultrasound echo-tracking system was used to determine stiffness of the abdominal aorta, common carotid artery (CCA) and popliteal artery (PA) in 39 female patients with SLE and 55 female, healthy controls. SLE had an independent effect on stiffening of the CCA (P = 0.01) and PA (P = 0.005). In addition, larger vessel diameters were observed in the CCA (P = 0.002) after adjustments for the effects of mean arterial pressure and age. Thus, this investigation demonstrated an increased arterial stiffness and signs of premature vascular ageing in the SLE patients without manifest cardiovascular disease and without significant atherosclerotic lesions. The results of this study indicate that other mechanisms besides atherosclerosis might be involved in the pathogenesis of arterial stiffening in SLE patients.
  • Enocsson, Helena, et al. (författare)
  • Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus
  • 2020
  • Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 106
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. Methods: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). Results: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03–1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). Conclusion: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.
  • Ferreira, Isabel, et al. (författare)
  • Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study
  • 2017
  • Ingår i: Arthritis Research and Therapy. - : BioMed Central (BMC). - 1478-6354 .- 1478-6362. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. Methods: We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event. Results: Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P = 0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety. Conclusions: Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.
  • Hanly, John G., et al. (författare)
  • A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach
  • Ingår i: Arthritis & Rheumatology. - : John Wiley and Sons. - 2326-5191. ; 68:8, s. 1932-1944
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach. Methods: Patients in the Systemic Lupus International Collaborating Clinics inception cohort were classified annually into estimated GFR state 1 (>60 ml/minute), state 2 (30–60 ml/minute), or state 3 (3.0 gm/day), or end-stage renal disease (ESRD) or death. Using multistate modeling, relative transition rates between states indicated improvement and deterioration. Results: Of 1,826 lupus patients, 700 (38.3%) developed LN. During a mean ± SD follow-up of 5.2 ± 3.5 years, the likelihood of improvement in estimated GFR and estimated proteinuria was greater than the likelihood of deterioration. After 5 years, 62% of patients initially in estimated GFR state 3 and 11% of patients initially in estimated proteinuria state 3 transitioned to ESRD. The probability of remaining in the initial states 1, 2, and 3 was 85%, 11%, and 3%, respectively, for estimated GFR and 62%, 29%, and 4%, respectively, for estimated proteinuria. Male sex predicted improvement in estimated GFR states; older age, race/ethnicity, higher estimated proteinuria state, and higher renal biopsy chronicity scores predicted deterioration. For estimated proteinuria, race/ethnicity, earlier calendar years, damage scores without renal variables, and higher renal biopsy chronicity scores predicted deterioration; male sex, presence of lupus anticoagulant, class V nephritis, and mycophenolic acid use predicted less improvement. Conclusion: In LN, the expected improvement or deterioration in renal outcomes can be estimated by multistate modeling and is preceded by identifiable risk factors. New therapeutic interventions for LN should meet or exceed these expectations.
  • Hanly, J G, et al. (författare)
  • Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis
  • 2008
  • Ingår i: Arthritis and Rheumatism. - : John Wiley and Sons. - 1529-0131 .- 0004-3591. ; 58:3, s. 843-853
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To examine, in an inception cohort of systemic lupus erythematosus (SLE) patients, the association between neuropsychiatric (NP) events and anti-ribosomal P (anti-P), antiphospholipid (lupus anticoagulant [LAC], anticardiolipin), anti-beta 2-glycoprotein I, and anti-NR2 glutamate receptor antibodies. Methods. NP events were identified using the American College of Rheumatology case definitions and clustered into central/peripheral and diffuse/focal events. Attribution of NP events to SLE was determined using decision rules of differing stringency. Autoantibodies were measured without knowledge of NP events or their attribution. Results. Four hundred twelve patients were studied (87.4% female; mean +/- SD age 34.9 +/- 13.5 years, mean +/- SD disease duration 5.0 +/- 4.2 months). There were 214 NP events in 133 patients (32.3%). The proportion of NP events attributed to SLE varied from 15% to 36%. There was no association between autoantibodies and NP events overall. However, the frequency of anti-P antibodies in patients with central NP events attributed to SLE was 4 of 20 (20%), versus 3 of 107 (2.8%) in patients with other NP events and 24 of 279 (8.6%) in those with no NP events (P = 0.04). Among patients with diffuse NP events, 3 of 11 had anti-P antibodies (27%), compared with 4 of 111 patients with other NP events (3.6%) and 24 of 279 of those with no NP events (8.6%) (P 0.02). Specific clinical-serologic associations were found between anti-P and psychosis attributed to SLE (P = 0.02) and between LAC and cerebrovascular disease attributed to SLE (P = 0.038). There was no significant association between other autoantibodies and NP events. Conclusion. Clinically distinct NP events attributed to SLE and occurring around the time of diagnosis were found to be associated with anti-P antibodies and LAC. This Suggests that there are different autoimmune pathogenetic mechanisms, although low sensitivity limits the clinical application of testing for these antibodies.
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