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1.
  • Hanly, John G., et al. (författare)
  • A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach
  • 2016
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 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.
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2.
  • Hanly, John G., et al. (författare)
  • Cerebrovascular Events in Systemic Lupus Erythematosus : Results From an International Inception Cohort Study
  • 2018
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 70:10, s. 1478-1487
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE). Methods: A total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLE International Collaborating Clinics/American College of Rheumatology Damage Index), and Short Form 36 (SF-36) scores were collected. Time to event, linear and logistic regressions, and multistate models were used as appropriate. Results: CerVEs were the fourth most frequent NP event: 82 of 1,826 patients had 109 events; of these events, 103 were attributed to SLE, and 44 were identified at the time of enrollment. The predominant events were stroke (60 of 109 patients) and transient ischemia (28 of 109 patients). CerVEs were associated with other NP events attributed to SLE, non–SLE-attributed NP events, African ancestry (at US SLICC sites), and increased organ damage scores. Lupus anticoagulant increased the risk of first stroke and sinus thrombosis and transient ischemic attack. Physician assessment indicated resolution or improvement in the majority of patients, but patients reported sustained reduction in SF-36 summary and subscale scores following a CerVE. Conclusion: CerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician-reported outcomes, patients reported a sustained reduction in health-related quality of life following a CerVE.
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3.
  • Hanly, John G., et al. (författare)
  • Headache in Systemic Lupus Erythematosus Results From a Prospective, International Inception Cohort Study
  • 2013
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 65:11, s. 2887-2897
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo examine the frequency and characteristics of headaches and their association with global disease activity and health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE). MethodsA disease inception cohort was assessed annually for headache (5 types) and 18 other neuropsychiatric (NP) events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 (SF-36) mental and physical component summary scores were collected. Time to first headache and associations with SF-36 scores were analyzed using Cox proportional hazards and linear regression models with generalized estimating equations. ResultsAmong the 1,732 SLE patients enrolled, 89.3% were female and 48.3% were white. The mean SD age was 34.6 +/- 13.4 years, duration of disease was 5.6 +/- 5.2 months, and length of followup was 3.8 +/- 3.1 years. At enrollment, 17.8% of patients had headache (migraine [60.7%], tension [38.6%], intractable nonspecific [7.1%], cluster [2.6%], and intracranial hypertension [1.0%]). The prevalence of headache increased to 58% after 10 years. Only 1.5% of patients had lupus headache, as identified in the SLEDAI-2K. In addition, headache was associated with other NP events attributed to either SLE or non-SLE causes. There was no association of headache with SLEDAI-2K scores (without the lupus headache variable), SDI scores, use of corticosteroids, use of antimalarials, use of immunosuppressive medications, or specific autoantibodies. SF-36 mental component scores were lower in patients with headache compared with those without headache (mean +/- SD 42.5 +/- 12.2 versus 47.8 +/- 11.3; P < 0.001), and similar differences in physical component scores were seen (38.0 +/- 11.0 in those with headache versus 42.6 +/- 11.4 in those without headache; P < 0.001). In 56.1% of patients, the headaches resolved over followup. ConclusionHeadache is frequent in SLE, but overall, it is not associated with global disease activity or specific autoantibodies. Although headaches are associated with a lower HRQOL, the majority of headaches resolve over time, independent of lupus-specific therapies.
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4.
  • Hanly, John G., et al. (författare)
  • Mood Disorders in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study
  • 2015
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 67:7, s. 1837-1847
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo examine the frequency, characteristics, and outcome of mood disorders, as well as clinical and autoantibody associations, in a multiethnic/racial, prospective inception cohort of patients with systemic lupus erythematosus (SLE). MethodsPatients were assessed annually for mood disorders (4 types, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 18 other neuropsychiatric events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 subscales, mental and physical component summary scores were collected. Time to event, linear and ordinal regressions, and multi-state models were used as appropriate. ResultsAmong the 1,827 patients with SLE, 88.9% were female, and 48.9% were Caucasian. The mean SD age of the patients was 35.1 +/- 13.3 years, disease duration was 5.6 +/- 4.8 months, and the length of followup was 4.7 +/- 3.5 years. During the course of the study, 863 (47.2%) of the 1,827 patients had 1,627 neuropsychiatric events. Mood disorders occurred in 232 (12.7%) of 1,827 patients, and 98 (38.3%) of 256 mood disorder events were attributed to SLE. The estimated cumulative incidence of any mood disorder after 10 years was 17.7% (95% confidence interval 15.1, 20.2%). A greater risk of mood disorder was associated with concurrent neuropsychiatric events (P0.01), and a lower risk was associated with Asian race/ethnicity (P=0.01) and treatment with immunosuppressive drugs (P=0.003). Mood disorders were associated with lower mental health and mental component summary scores but not with the SLEDAI-2K, SDI, or lupus autoantibodies. Among the 232 patients with depression, 168 (72.4%) were treated with antidepressants. One hundred twenty-six (49.2%) of 256 mood disorders resolved in 117 (50.4%) of 232 patients. ConclusionMood disorders, the second most frequent neuropsychiatric event in patients with SLE, have a negative impact on health-related quality of life and improve over time. The lack of association with global SLE disease activity, cumulative organ damage, and lupus autoantibodies emphasizes the multifactorial etiology of mood disorders and a role for non-lupus-specific therapies.
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5.
  • Hanly, John G., et al. (författare)
  • Peripheral Nervous System Disease in Systemic Lupus Erythematosus : Results From an International Inception Cohort Study
  • 2020
  • Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 72:1, s. 67-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. Conclusion: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.
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6.
  • Hanly, John G., et al. (författare)
  • Psychosis in Systemic Lupus Erythematosus : Results From an International Inception Cohort Study
  • 2019
  • Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 71:2, s. 281-289
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To determine, in a large, multiethnic/multiracial, prospective inception cohort of patients with systemic lupus erythematosus (SLE), the frequency, attribution, clinical, and autoantibody associations with lupus psychosis and the short- and long-term outcomes as assessed by physicians and patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including psychosis. Scores on the Systemic Lupus Erythematosus Disease Activity Index 2000, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and the Short Form 36 (SF-36) were recorded. Time to event and linear regressions were used as appropriate. Results: Of 1,826 SLE patients, 88.8% were female and 48.8% were Caucasian. The mean ± SD age was 35.1 ± 13.3 years, the mean ± SD disease duration was 5.6 ± 4.2 months, and the mean ± SD follow-up period was 7.4 ± 4.5 years. There were 31 psychotic events in 28 of 1,826 patients (1.53%), and most patients had a single event (26 of 28 [93%]). In the majority of patients (20 of 25 [80%]) and events (28 of 31 [90%]), psychosis was attributed to SLE, usually either in the year prior to or within 3 years of SLE diagnosis. Positive associations (hazard ratios [HRs] and 95% confidence intervals [95% CIs]) with lupus psychosis were previous SLE NP events (HR 3.59 [95% CI 1.16–11.14]), male sex (HR 3.0 [95% CI 1.20–7.50]), younger age at SLE diagnosis (per 10 years) (HR 1.45 [95% CI 1.01–2.07]), and African ancestry (HR 4.59 [95% CI 1.79–11.76]). By physician assessment, most psychotic events resolved by the second annual visit following onset, in parallel with an improvement in patient-reported SF-36 summary and subscale scores. Conclusion: Psychosis is an infrequent manifestation of NPSLE. Generally, it occurs early after SLE onset and has a significant negative impact on health status. As determined by patient and physician report, the short- and long-term outlooks are good for most patients, although careful follow-up is required.
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7.
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8.
  • Legge, Alexandra, et al. (författare)
  • Construction of a frailty index as a novel health measure in systemic lupus erythematosus
  • 2020
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 47:1, s. 72-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods. The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values. Results. The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21. Conclusion. The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.
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9.
  • Legge, Alexandra, et al. (författare)
  • Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index
  • 2020
  • Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 72:4, s. 658-666
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. Methods: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. Results: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13–1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. Conclusion: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.
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10.
  • Little, Jayne, et al. (författare)
  • Glucocorticoid use and factors associated with variability in this use in the Systemic Lupus International Collaborating Clinics Inception Cohort
  • 2018
  • Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 57:4, s. 677-687
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. To describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use. Methods. Patients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were performed to explore factors associated with GC use at enrolment and over time. Results. We studied 1700 patients with a mean (S.D.) follow-up duration of 7.26 (3.82) years. Over the entire study period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received parenteral GCs at some point. GC use was strongly associated with treatment centre, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis. Conclusion. GCs remain a cornerstone in SLE management and there have been no significant changes in their use over the past 10-15 years. While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute. Evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SLE.
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