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The transcription factor AhR modulates immunity at multiple levels. Here we report that phagocytes exposed to apoptotic cells exhibited rapid activation of AhR, which drove production of the cytokine IL-10. Activation of AhR was dependent on interactions between apoptotic-cell DNA and the pattern-recognition receptor TLR9 that was required for the prevention of immune responses to DNA and histones in vivo. Moreover, disease progression in mouse systemic lupus erythematosus (SLE) correlated with strength of the AhR signal, and the disease course could be altered by modulation of AhR activity. Deletion of AhR in the myeloid lineage caused systemic autoimmunity in mice, and an enhanced AhR transcriptional signature correlated with disease in patients with SLE. Thus, AhR activity induced by apoptotic cell phagocytes maintains peripheral tolerance.
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Apoptose/imunologia , Tolerância Imunológica/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Macrófagos/imunologia , Receptores de Hidrocarboneto Arílico/imunologia , Animais , Humanos , Camundongos , Transdução de Sinais/imunologia , Receptor Toll-Like 9/imunologiaRESUMO
OBJECTIVES: Membranous lupus nephritis (MLN) is thought to have a more benign course than proliferative lupus nephritis (PLN). We aimed to determine the differences in short and long-term outcomes between patients with MLN and PLN. METHODS: We included patients with first biopsy-proven MLN and PLN. Short-term outcomes included complete proteinuria recovery (CPR), complete renal response (CRR), and primary efficacy renal response (PERR). Long-term outcomes included a sustained ≥40% reduction in baseline estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), cardiovascular (CV) events, ≥2 increase in SDI, and death. Univariable and multivariable Cox proportional hazard models were used to examine the effect of baseline characteristics on long-term outcomes. RESULTS: Of 215 patients, 51 had pure MLN, and 164 had PLN. We found no significant differences between the two groups in achieving CPR, CRR, and PERR at 1 and 2 years. Median time to outcomes was slightly, but insignificantly, longer in the MLN group.For long-term outcomes, PLN was associated with worse renal and non-renal outcomes, but this was not statistically significant.In the multivariable Cox proportional hazard models, ESKD was associated with the following baseline variables: younger age (HR 0.92, 95% CI 0.87-0.97), higher creatinine (HR 1.01, 95% CI 1.01-1.02), low complement (HR 4.0, 95% CI 1.04-11.10), and higher chronicity index (HR 1.28, 95% CI 1.08-1.51). CONCLUSION: The resolution of proteinuria in LN is slow. MLN is not a benign disease and may be associated with deterioration of renal function, ESKD, damage, CV events, and death.
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PURPOSE: Although comprehensive and widespread guidelines on how to conduct systematic reviews of outcome measurement instruments (OMIs) exist, for example from the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) initiative, key information is often missing in published reports. This article describes the development of an extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline: PRISMA-COSMIN for OMIs 2024. METHODS: The development process followed the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines and included a literature search, expert consultations, a Delphi study, a hybrid workgroup meeting, pilot testing, and an end-of-project meeting, with integrated patient/public involvement. RESULTS: From the literature and expert consultation, 49 potentially relevant reporting items were identified. Round 1 of the Delphi study was completed by 103 panelists, whereas round 2 and 3 were completed by 78 panelists. After 3 rounds, agreement (≥ 67%) on inclusion and wording was reached for 44 items. Eleven items without consensus for inclusion and/or wording were discussed at a workgroup meeting attended by 24 participants. Agreement was reached for the inclusion and wording of 10 items, and the deletion of 1 item. Pilot testing with 65 authors of OMI systematic reviews further improved the guideline through minor changes in wording and structure, finalized during the end-of-project meeting. The final checklist to facilitate the reporting of full systematic review reports contains 54 (sub)items addressing the review's title, abstract, plain language summary, open science, introduction, methods, results, and discussion. Thirteen items pertaining to the title and abstract are also included in a separate abstract checklist, guiding authors in reporting for example conference abstracts. CONCLUSION: PRISMA-COSMIN for OMIs 2024 consists of two checklists (full reports; abstracts), their corresponding explanation and elaboration documents detailing the rationale and examples for each item, and a data flow diagram. PRISMA-COSMIN for OMIs 2024 can improve the reporting of systematic reviews of OMIs, fostering their reproducibility and allowing end-users to appraise the quality of OMIs and select the most appropriate OMI for a specific application. NOTE: In order to encourage its wide dissemination this article is freely accessible on the web sites of the journals: Health and Quality of Life Outcomes; Journal of Clinical Epidemiology; Journal of Patient-Reported Outcomes; Quality of Life Research.
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Técnica Delphi , Avaliação de Resultados em Cuidados de Saúde , Revisões Sistemáticas como Assunto , Humanos , Guias como Assunto , Lista de Checagem , Projetos de Pesquisa/normas , ConsensoRESUMO
PURPOSE: Although comprehensive and widespread guidelines on how to conduct systematic reviews of outcome measurement instruments (OMIs) exist, for example from the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) initiative, key information is often missing in published reports. This article describes the development of an extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline: PRISMA-COSMIN for OMIs 2024. METHODS: The development process followed the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines and included a literature search, expert consultations, a Delphi study, a hybrid workgroup meeting, pilot testing, and an end-of-project meeting, with integrated patient/public involvement. RESULTS: From the literature and expert consultation, 49 potentially relevant reporting items were identified. Round 1 of the Delphi study was completed by 103 panelists, whereas round 2 and 3 were completed by 78 panelists. After 3 rounds, agreement (≥ 67%) on inclusion and wording was reached for 44 items. Eleven items without consensus for inclusion and/or wording were discussed at a workgroup meeting attended by 24 participants. Agreement was reached for the inclusion and wording of 10 items, and the deletion of 1 item. Pilot testing with 65 authors of OMI systematic reviews further improved the guideline through minor changes in wording and structure, finalized during the end-of-project meeting. The final checklist to facilitate the reporting of full systematic review reports contains 54 (sub)items addressing the review's title, abstract, plain language summary, open science, introduction, methods, results, and discussion. Thirteen items pertaining to the title and abstract are also included in a separate abstract checklist, guiding authors in reporting for example conference abstracts. CONCLUSION: PRISMA-COSMIN for OMIs 2024 consists of two checklists (full reports; abstracts), their corresponding explanation and elaboration documents detailing the rationale and examples for each item, and a data flow diagram. PRISMA-COSMIN for OMIs 2024 can improve the reporting of systematic reviews of OMIs, fostering their reproducibility and allowing end-users to appraise the quality of OMIs and select the most appropriate OMI for a specific application. NOTE: In order to encourage its wide dissemination this article is freely accessible on the web sites of the journals: Health and Quality of Life Outcomes; Journal of Clinical Epidemiology; Journal of Patient-Reported Outcomes; Quality of Life Research.
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Técnica Delphi , Avaliação de Resultados em Cuidados de Saúde , Revisões Sistemáticas como Assunto , Humanos , Guias como Assunto , Projetos de Pesquisa/normas , Lista de ChecagemRESUMO
Glucocorticoids (GCs) are the gold standard for treatment of giant cell arteritis (GCA); however, there is a need for studies on GC-sparing agents, given that up to 85% of patients receiving GC only develop adverse events. Previous randomised controlled trials (RCTs) have applied different primary endpoints, limiting the comparison of treatment effects in meta-analyses and creating an undesired heterogeneity of outcomes. The harmonisation of response assessment is therefore an important unmet need in GCA research. In this viewpoint article, we discuss the challenges and opportunities with the development of new, internationally accepted response criteria. A change of disease activity is a fundamental component of response; however, it is debatable whether the ability to taper GC and/or the maintenance of a disease state for a specific time period, as applied in recent RCTs, should be part of response assessment. The role of imaging and novel laboratory biomarkers as possible objective markers of disease activity needs further investigation but might be a possibility when drugs directly or indirectly influence the levels of traditional acute-phase reactants such as erythrocyte sedimentation rate and C reactive protein. Futures response criteria might be constructed as a multidomain set, but the questions about which domains will be included and what their relative weights will be still need to be answered.
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Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/tratamento farmacológico , Resultado do Tratamento , Glucocorticoides/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: The objectives of this study were to determine the trajectories of depressive symptoms in patients with SLE and to identify baseline characteristics that are associated with a patient's trajectory of depression. METHODS: Data from the Lupus Outcomes Study at the University of California, San Francisco were analysed. Depressive symptomatology was assessed in years two through seven using the Center for Epidemiologic Studies Depression Scale (CES-D), with higher scores representing more severe depressive symptoms. Group-based trajectory modelling was used to determine latent classes of CES-D scores over time. Ordinal logistic regression analyses were performed to identify baseline characteristics associated with worse classes of depressive symptoms. RESULTS: CES-D scores for 763 individuals with SLE over 6 years were mapped into four distinct classes. Class 1 (36%) and class 2 (32%) comprised the largest proportion of the cohort and were defined by the lowest and low CES-D scores (no depression), respectively. Class 3 (22%) and class 4 (10%) had high and the highest scores (depression), respectively. Greater age [odds ratio (OR): 0.97, 95% CI: 0.96, 0.99] and higher education level (OR: 0.79, 95% CI: 0.70, 0.89) at baseline were associated with lower odds of membership in worse classes of depressive symptoms. Conversely, lower income (OR: 1.73, 95% CI: 1.03, 2.92), worse SF-36 physical functioning scores (OR: 1.12, 95% CI: 1.12, 1.13) and worse SF-36 bodily pain scores (OR: 1.58, 95% CI: 1.55, 1.61) were positively associated with membership in worse classes of depressive symptoms. CONCLUSION: Four classes of depressive symptoms were identified in patients with SLE. Understanding the trajectories of depressive symptoms and the associated risk factors can aid in the management of these symptoms in individuals living with SLE.
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Depressão , Lúpus Eritematoso Sistêmico , Humanos , Depressão/epidemiologia , Depressão/etiologia , Fatores de Risco , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
OBJECTIVES: Genetics plays an important role in SLE risk, as well as osteonecrosis (ON), a significant and often debilitating complication of SLE. We aimed to identify genetic risk loci for ON in people with childhood-onset (cSLE) and adult-onset (aSLE) SLE. METHODS: We enrolled participants from two tertiary care centres who met classification criteria for SLE. Participants had prospectively collected clinical data and were genotyped on a multiethnic array. Un-genotyped single nucleotide polymorphisms (SNPs) were imputed, and ancestry was inferred using principal components (PCs). Our outcome was symptomatic ON confirmed by imaging. We completed time-to-ON and logistic regression of ON genome-wide association studies (GWASs) with covariates for sex, age of SLE diagnosis, five PCs for ancestry, corticosteroid use and selected SLE manifestations. We conducted separate analyses for cSLE and aSLE and meta-analysed results using inverse-variance weighting. Genome-wide significance was P < 5 × 10-8. RESULTS: The study included 940 participants with SLE, 87% female and 56% with cSLE. ON was present in 7.6% (n = 71). Median age of SLE diagnosis was 16.9 years (interquartile range [IQR]: 13.5, 29.3), with median follow-up of 8.0 years (IQR: 4.2, 15.7). Meta-GWAS of cSLE and aSLE time-to-ON of 4 431 911 SNPs identified a significant Chr.2 SNP, rs34118383 (minor allele frequency = 0.18), intronic to WIPF1 (hazard ratio = 3.2 [95% CI: 2.2, 4.8]; P = 1.0 × 10-8). CONCLUSION: We identified an intronic WIPF1 variant associated with a 3.2 times increased hazard for ON (95% CI: 2.2, 4.8; P = 1.0 × 10-8) during SLE follow-up, independent of corticosteroid exposure. The effect of the SNP on time-to-ON was similar in cSLE and aSLE. This novel discovery represents a potential ON risk locus. Our results warrant replication.
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Estudo de Associação Genômica Ampla , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Criança , Feminino , Adolescente , Masculino , Idade de Início , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/diagnóstico , Genótipo , Índice de Gravidade de Doença , Proteínas do Citoesqueleto/genética , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
OBJECTIVES: Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. METHODS: Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤-1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. RESULTS: A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. CONCLUSION: AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.
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Azatioprina , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Azatioprina/uso terapêutico , Ácido Micofenólico/uso terapêutico , Imunossupressores/uso terapêutico , Inibidores Enzimáticos , Cognição , Lúpus Eritematoso Sistêmico/tratamento farmacológicoRESUMO
OBJECTIVES: Genome-wide association studies (GWAS) have identified loci associated with estimated glomerular filtration rate (eGFR). Few LN risk loci have been identified to date. We tested the association of SLE and eGFR polygenic risk scores (PRS) with repeated eGFR measures from children and adults with SLE. METHODS: Patients from two tertiary care lupus clinics that met ≥4 ACR and/or SLICC criteria for SLE were genotyped on the Illumina MEGA or Omni1-Quad arrays. PRSs were calculated for SLE and eGFR, using published weighted GWA-significant alleles. eGFR was calculated using the CKD-EPI and Schwartz equations. We tested the effect of eGFR- and SLE-PRSs on eGFR mean and variance, adjusting for age at diagnosis, sex, ancestry, follow-up time, and clinical event flags. RESULTS: We included 1158 SLE patients (37% biopsy-confirmed LN) with 36 733 eGFR measures over a median of 7.6 years (IQR: 3.9-15.3). LN was associated with lower within-person mean eGFR [LN: 93.8 (s.d. 26.4) vs non-LN: 101.6 (s.d. 17.7) mL/min per 1.73 m2; P < 0.0001] and higher variance [LN median: 157.0 (IQR: 89.5, 268.9) vs non-LN median: 84.9 (IQR: 46.9, 138.2) (mL/min per 1.73 m2)2; P < 0.0001]. Increasing SLE-PRSs were associated with lower mean eGFR and greater variance, while increasing eGFR-PRS was associated with increased eGFR mean and variance. CONCLUSION: We observed significant associations between SLE and eGFR PRSs and repeated eGFR measurements, in a large cohort of children and adults with SLE. Longitudinal eGFR may serve as a powerful alternative outcome to LN categories for discovery of LN risk loci.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Adulto , Criança , Estudo de Associação Genômica Ampla , Lúpus Eritematoso Sistêmico/complicações , Taxa de Filtração Glomerular , Genótipo , Rim , Nefrite Lúpica/genética , Nefrite Lúpica/complicaçõesRESUMO
OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function. METHODS: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests. RESULTS: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B. CONCLUSION: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments.
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Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto , Masculino , Qualidade de Vida/psicologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Ansiedade , Aprendizado de MáquinaRESUMO
OBJECTIVES: To explore the safety and efficacy of filgotinib (FIL), a Janus kinase 1 inhibitor, and lanraplenib (LANRA), a spleen kinase inhibitor, in cutaneous lupus erythematosus (CLE). METHODS: This was a phase 2, randomized, double-blind, placebo-controlled, exploratory, proof-of-concept study of LANRA (30 mg), FIL (200 mg) or placebo (PBO) once daily for 12 weeks in patients with active CLE. At week 12, PBO patients were rerandomized 1:1 to receive LANRA or FIL for up to 36 additional weeks. RESULTS: Of 47 randomized patients, 45 were treated (PBO, n = 9; LANRA, n = 19; FIL, n = 17). The primary endpoint [change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at week 12] was not met. The least squares mean CLASI-A score change from baseline was -5.5 (s.e. 2.56) with PBO, -4.5 (1.91) with LANRA and -8.7 (1.85) with FIL. Numerical differences between FIL and PBO were greater in select subgroups. A ≥5-point improvement in the CLASI-A score at week 12 was achieved by 50.0%, 56.3% and 68.8% in the PBO, LANRA and FIL arms, respectively. A numerically greater proportion of patients in the FIL arm (50%) also achieved ≥50% improvement in the CLASI-A score at week 12 (37.5% PBO, 31.3% LANRA). Most adverse events (AEs) were mild or moderate in severity. Two serious AEs were reported with LANRA and one with FIL. CONCLUSION: The primary endpoint was not met. Select subgroups displayed a numerically greater treatment response to FIL relative to PBO. LANRA and FIL were generally well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03134222.
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Inibidores de Janus Quinases , Lúpus Eritematoso Cutâneo , Método Duplo-Cego , Humanos , Inibidores de Janus Quinases/efeitos adversos , Lúpus Eritematoso Cutâneo/induzido quimicamente , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento , Triazóis/uso terapêuticoRESUMO
OBJECTIVE: We investigated the autoantibody (autoAb) profiles in ANA+ individuals lacking systemic autoimmune rheumatic disease (SARD) and early SARD patients to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next 2 years in ANA+ individuals. METHODS: Using custom antigen (Ag) microarrays, 144 IgM and IgG autoAbs were surveyed in 84 asymptomatic and 123 symptomatic (48 UCTD and 75 SARD patients) ANA+ individuals. AutoAbs were compared in ANA+ individuals lacking a SARD diagnosis with ≥2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset. RESULTS: We show that ANA+ individuals have autoAb to many self-Ags that are not being captured by current screening techniques and very high levels of these autoAbs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more autoAgs than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of autoAbs. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years of follow-up the levels of autoAbs remained remarkably stable regardless of whether individuals progressed or not. CONCLUSION: Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing.
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Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Doenças Reumáticas/sangue , Doenças Reumáticas/imunologia , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Adulto JovemRESUMO
OBJECTIVE: We previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM's concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis. METHODS: 300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM's criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs. RESULTS: Two models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results. CONCLUSION: We provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.
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Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Reumatologia , Adulto , Benchmarking , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Testes NeuropsicológicosRESUMO
OBJECTIVES: We investigated the association of SLE flares with patient-reported outcomes (PRO) and healthcare resource utilisation (HCRU) using real-world data. METHODS: Rheumatologists from the USA, France, Germany, Spain, Italy provided demographic, clinical, and HCRU data for patients with SLE, who provided PRO data. "Flaring" was defined as ≥1 rheumatologist-reported flare in the past 12 months. Demographic/clinical data were analysed descriptively, and findings compared statistically by flaring status. Logistic regression estimated a propensity score for flaring based on ethnicity, disease duration, and severity at diagnosis. Propensity score-matched flaring and non-flaring patients were compared for their HCRU, PROs, income loss and treatment satisfaction. RESULTS: Physicians (n=263) provided data for 1,278 patients (408 flaring/870 non-flaring); 729 patients (241 flaring/488 non-flaring) provided matched patient data. Patients had a mean 2.1 flares in the previous 12 months. Propensity score matched analyses indicated worse outcomes and greater HCRU in the past 12 months in flaring than non-flaring patients: EuroQoL 5D-3L Utility Index: 0.72 vs. 0.83; Functional Assessment of Chronic Illness Therapy-Fatigue scale: 30.06 vs. 36.48; Work Productivity and Activity Impairment Index: absenteeism 5.87% vs. 2.53% / presenteeism 33.44% vs. 19.16% / overall work impairment 35.98% vs. 20.66% / total activity impairment 42.47% vs. 30.23%; healthcare consultations (8.10 vs. 6.41), hospitalisations (24.26 vs. 7.63), emergency department visits (20.83 vs. 4.19), tests (46.59 vs. 38.90); current medications (2.76 vs. 2.19) (all p<0.001 except absenteeism, p=0.004). CONCLUSIONS: Similar flaring SLE patients had worse PROs and higher HCRU than non-flaring patients, underscoring the need for more effective strategies and treatments to alleviate or prevent flaring.
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Lúpus Eritematoso Sistêmico , Medidas de Resultados Relatados pelo Paciente , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Absenteísmo , Aceitação pelo Paciente de Cuidados de Saúde , AlemanhaRESUMO
OBJECTIVE: To determine the ominosity of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Systemic Lupus Erythematosus Classification Criteria by determining its predictive role for disease severity in the first 5 years following diagnosis. METHODS: 867 patients with systemic lupus erythematosus (SLE) from the Toronto Lupus Clinic were included (all first 12 months after SLE diagnosis). The EULAR/ACR criteria score was calculated based on baseline information. To determine disease severity in the first 5 years after diagnosis, adjusted mean SLE Disease Activity Index 2000 (AMS), flares, remission and immunosuppressive treatment were used as outcomes. The Systemic Lupus International Collaborating Clinics (SLICC) registry comprised the validation cohort. RESULTS: Based on receiver operating characteristic analysis, a EULAR/ACR score of 20 was used as a threshold to compare outcomes between groups. In the first 5 years of disease course, patients with a score of ≥20 had higher AMS scores (p<0.001) and were more likely to ever experience a flare (p<0.001). These patients had lower probabilities of achieving remission and higher requirements for immunosuppressives. Results were confirmed in the SLICC validation cohort. Patients with a score of ≥20 had higher AMS during the first 5 years of disease (5.4 vs 3.1% and ≥20 vs <20 respectively, p≤0.001). The score correlated with AMS (r=0.43, p≤0.001) in the same time frame. CONCLUSION: A EULAR/ACR score of ≥20 is an indicator of ominosity in SLE. Patients with a score of ≥20 were characterised by a more active disease course throughout the first 5 years. These criteria provide prognostic information regarding disease severity in the first 5 years following diagnosis.
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Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Reumatologia , Estudos de Coortes , Progressão da Doença , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Reumatologia/métodos , Índice de Gravidade de DoençaRESUMO
BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.
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Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Reumatologia , Anticorpos Antinucleares , Estudos de Coortes , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Doenças Reumáticas/diagnóstico , Reumatologia/métodos , Sensibilidade e Especificidade , Estados UnidosRESUMO
OBJECTIVES: Fatigue is one of the most common symptoms reported in patients living with SLE. We aim to: 1) determine if different trajectories of fatigue associate with specific latent classes of disease activity and 2) define the patient characteristics and associated factors in different latent classes. METHODS: Data from an inception cohort of adult patients from the Toronto Lupus Clinic from 1997-2018 were analyzed. Fatigue levels were measured using Fatigue Severity Scale (FSS) and disease activity by the Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AMS). Dual latent class trajectory analysis, for fatigue and AMS, was performed. Univariable and multivariable logistic regression analyses assessed the association of baseline variables with class membership. RESULTS: Among 280 patients, 4 dual classes (C) of fatigue and disease activity were identified: C1- lowest disease activity and second highest fatigue trajectory (27%); C2- second highest disease activity and highest fatigue trajectory (30%); C3-moderate disease activity and lowest fatigue trajectory (33%); and C4- highest disease activity and moderate fatigue trajectory (10%). CONCLUSION: 4 distinct latent classes of dual fatigue and disease activity trajectories were identified. Fatigue and disease activity follow distinct trajectories and disease activity alone cannot fully explain fatigue trajectories. Trajectories with higher FSS scores were associated with more fibromyalgia and trajectories with higher disease activity were associated with higher cumulative glucocorticoid use. Higher baseline glucocorticoid use was more likely associated with more fatigue while older age at SLE diagnosis was associated with less fatigue.
Assuntos
Fadiga/etiologia , Fibromialgia/complicações , Glucocorticoides/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Adulto , Fatores Etários , Canadá/epidemiologia , Estudos de Coortes , Fadiga/diagnóstico , Feminino , Fibromialgia/diagnóstico , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de TempoRESUMO
INTRODUCTION: At least 38% of patients with Systemic Lupus Erythematosus (SLE) experience cognitive impairment (CI). Patients report CI impacts their health-related quality of life (HRQoL) and social role participation. OBJECTIVES: To synthesize and critically appraise the quantitative literature on the relationship of CI to HRQoL and social role participation in individuals with SLE. METHODS: Six electronic databases were searched in December 2018 and June 2020 by an information specialist. Two reviewers independently completed all screening phases and data extraction; a third reviewer resolved disagreements. The Mixed Methods Appraisal Tool was used to critically appraise the quality of included studies. Data has been synthesized and analyzed descriptively to present evidence on the relationship of CI to HRQoL and social role participation. RESULTS: A total of 7182 references were identified and screened, with 14 articles included. Four of the included articles investigated the relationship between CI and HRQoL and all identified a negative relationship. Ten of the 14 studies investigated CI and social role participation, eight identified a negative relationship. There was heterogeneity of measures used between studies to examine CI, HRQoL, and social role participation. As such, results were interpreted descriptively and could not be pooled for meta-analysis. CONCLUSION: The presence of CI is negatively related to HRQoL and social role participation in patients with SLE. Healthcare professionals should be aware of this relationship so that it can be addressed in clinical practice. Further research, using consistent methods of quantifying CI, HRQoL and social role participation, is needed to enable data pooling.
Assuntos
Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Disfunção Cognitiva/etiologia , Humanos , Qualidade de VidaRESUMO
BACKGROUND: The evaluation of Patient Reported Outcomes Measurement Information System (PROMIS) computerized adaptive test (CAT) in adults with systemic lupus erythematous (SLE) is an emerging field of research. We aimed to examine the test-retest reliability and construct validity of the PROMIS CAT in a Canadian cohort of patients with SLE. METHODS: Two hundred twenty-seven patients completed 14 domains of PROMIS CAT and seven legacy instruments during their clinical visits. Test-retest reliability of PROMIS was evaluated 7-10 days from baseline using intraclass correlation coefficient (ICC (2; 1)). The construct validity of the PROMIS CAT domains was evaluated against the commonly used legacy instruments, and also in comparison to disease activity and disease damage using Spearman correlations. A multitrait-multimethod matrix (MMM) approach was used to further assess construct validity comparing selected 10 domains of PROMIS and SF-36 domains. RESULTS: Moderate to excellent reliability was found for all domains (ICC [2;1] ranging from lowest, 0.66 for Sleep Disturbance and highest, 0.93 for the Mobility domain). Comparing seven legacy instruments with 14 domains of PROMIS CAT, moderate to strong correlations (0.51-0.91) were identified. The average time to complete all PROMIS CAT domains was 11.7 min. The MMM further established construct validity by showing moderate to strong correlations (0.55-0.87) between select PROMIS and SF-36 domains; the average correlations from similar traits (convergent validity) were significantly greater than the average correlations from different traits. CONCLUSIONS: These results provide evidence on the reliability and validity of PROMIS CAT in SLE in a Canadian cohort.
Assuntos
Lúpus Eritematoso Discoide , Lúpus Eritematoso Sistêmico , Canadá , Eritema , Humanos , Sistemas de Informação , Lúpus Eritematoso Sistêmico/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.