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1.
Semin Arthritis Rheum ; 68: 152520, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39106780

RESUMO

BACKGROUND: Since the development of the OMERACT Systemic Lupus Erythematosus (SLE) Core Outcome Set (COS) in 1998, many new SLE domains have been identified and measures developed, creating a need to update the SLE COS. To revisit the 1998 SLE COS and research agenda domains, and generate new candidate domains, we conducted this study of patients with SLE and collaborators. OBJECTIVE: (1) To evaluate existing candidate SLE domains for inclusion in the SLE COS. (2) To generate additional candidate SLE domains for COS consideration. (3) To engage SLE collaborators, including patients, in developing the updated SLE COS. METHODS: The OMERACT SLE Working Group's steering committee developed a survey to assess the importance of candidate SLE domains and generate additional domains for consideration towards the SLE COS. Patients with SLE followed at the University of Toronto Lupus Clinic (patient group) and members of the OMERACT SLE Working Group (collaborator group) were invited to complete the survey between August 2022 and February 2023. RESULTS: A total of 175 patients were invited and 100 completed the survey. Of 178 collaborators invited, 145 completed the survey. Patients tended to prioritize life-impact domains while collaborators prioritized clinical domains. Both patients and collaborators recommended additional domains to those included in the 1998 SLE COS and research agenda. CONCLUSION: The domain inclusion and importance results demonstrate that patients and collaborators prioritize different domains, so capturing the perspectives of both groups is essential to ensure a holistic assessment of SLE. The results of the study identify domains that already have a high level of agreement for potential inclusion in the SLE COS, domains that require further explanation, and novel domains that warrant consideration.

2.
Lupus Sci Med ; 10(2)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37429671

RESUMO

OBJECTIVE: Cognitive dysfunction (CD) is detectable in approximately 40% of patients with SLE. Despite this high prevalence, there are no approved pharmacological treatment options for this detrimental condition. Preliminary murine studies show potential for targeting microglial activation as a treatment of SLE-CD, which may be ameliorated with centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use. The aim of this study is to determine if there is an association of cACEi/cARB use with cognitive function in a human SLE cohort. METHODS: The American College of Rheumatology neuropsychological battery was administered to patients with consecutive SLE at a single academic health centre at baseline, 6 and 12 months. Scores were compared with sex-matched and age-matched control subjects. Clinical and demographic data were gathered at each visit. The primary outcome was CD defined as dysfunction in two or more cognitive domains. The primary predictor was a total cumulative dose of cACEi/cARB in milligrams per kilogram, recorded as an equivalent ramipril dose. Odds of CD with respect to cACEi/cARB use were determined through generalised linear mixed modelling. RESULTS: A total of 300 patients, representing 676 visits, completed this study. One hundred sixteen (39%) met the criteria for CD. Fifty-three participants (18%) were treated with a cACEi or cARB. Mean cumulative dose was 236 mg/kg (calculated as equivalent ramipril dose). Cumulative cACEi/cARB dose was not protective against SLE-CD. Caucasian ethnicity, current employment status and azathioprine cumulative dose were each associated with reduced odds of SLE-CD. Increasing Fatigue Severity Scale score was associated with increased odds of CD. CONCLUSIONS: In a single-centre SLE cohort, cACEi/cARB use was not associated with absence of CD. Many important confounders may have influenced the results of this retrospective study. A randomised trial is required to accurately determine if cACEi/cARB is a potential treatment for SLE-CD.


Assuntos
Disfunção Cognitiva , Lúpus Eritematoso Sistêmico , Humanos , Animais , Camundongos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Ramipril , Antagonistas de Receptores de Angiotensina/efeitos adversos , Estudos Retrospectivos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia
4.
Rheumatology (Oxford) ; 62(5): 1860-1869, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36135792

RESUMO

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.


Assuntos
Azatioprina , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Azatioprina/uso terapêutico , Ácido Micofenólico/uso terapêutico , Imunossupressores/uso terapêutico , Inibidores Enzimáticos , Cognição , Lúpus Eritematoso Sistêmico/tratamento farmacológico
5.
BMC Nephrol ; 21(1): 450, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115441

RESUMO

BACKGROUND: SLE manifestations after ESRD may be underdiagnosed and undertreated, contributing to increased morbidity and mortality. Whether specific symptoms persist after ESRD or a shift towards new manifestations occurs has not been extensively studied, especially in the non-Caucasian patients in the United States. In addition, hydroxychloroquine (HCQ) prescribing patterns post-ESRD have not been described. The objective of this study was to assess lupus activity and HCQ prescribing before and after ESRD development. Knowledge gained from this study may aid in the identification of SLE manifestations and improve medication management post-ESRD. METHODS: We performed a retrospective cohort study of SLE patients with incident ESRD between 2010 and 2017. SLE-related symptoms, serologic markers of disease activity, and medication use were collected from medical records before and after ESRD development. RESULTS: Fifty-nine patients were included in the study. Twenty-five (43%) patients had at least one clinical (non-renal) SLE manifestation documented within 12 months before ESRD. Of them, 11/25 (44%) continued to experience lupus symptoms post-ESRD; 9 patients without clinical or serological activity pre-ESRD developed new symptoms of active SLE. At the last documented visit post-ESRD, 42/59 (71%) patients had one or more clinical or serological markers of lupus activity; only 17/59 (29%) patients achieved clinical and serological remission. Thirty-three of 59 (56%) patients had an active HCQ prescription at the time of ESRD. Twenty-six of the 42 (62%) patients with active SLE manifestations post-ESRD were on HCQ. Patients who continued HCQ post-ESRD were more likely to be followed by a rheumatologist (26 [87%] vs 17 [61%], p = 0.024), had a higher frequency of documented arthritis (10 [32%] vs 1 [4%], p = 0.005), CNS manifestations (6 [20%] vs 1 [4%], p = 0.055), and concurrent immunosuppressive medication use (22 [71%] vs 12 [43%], p = 0.029). CONCLUSIONS: Lupus activity may persist after the development of ESRD. New onset arthritis, lupus-related rash, CNS manifestations, low complement and elevated anti-dsDNA may develop. HCQ may be underutilized in patients with evidence of active disease pre- and post ESRD. Careful clinical and serological monitoring for signs of active disease and frequent rheumatology follow up is advised in SLE patients both, pre and post-ESRD.


Assuntos
Inibidores Enzimáticos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Falência Renal Crônica/etiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/complicações , Adulto , Autoanticorpos/sangue , Biomarcadores/sangue , Proteínas do Sistema Complemento/metabolismo , DNA/imunologia , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Clin Immunol ; 206: 53-62, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-29510235

RESUMO

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder marked by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). At the present time, treatment is primarily focused on anticoagulation. However, there is increasing awareness of the mechanisms involved in APS pathogenesis, which has led to the trial of novel therapies targeting those mechanisms. Following a brief review of the etiopathogenesis of and current management strategies in APS, this paper focuses on the evidence for these potential, targeted APS treatments, e.g., hydroxychloroquine, statins, rituximab, belimumab, eculizumab, defibrotide, sirolimus, and peptide therapy.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Imunossupressores/uso terapêutico , Anticorpos Antifosfolipídeos/imunologia , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/imunologia , Humanos
7.
J Thromb Thrombolysis ; 43(2): 241-247, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27738784

RESUMO

The worldwide prevalence of chronic kidney disease is 10-15 % of the adult population, is rising and increases susceptibility to venous thromboembolism (VTE). In this narrative review we discuss the underlying evidence behind the association of VTE/CKD and examine the role of worsening CKD stage, proteinuria, and the risk of recurrent VTE. As CKD may alter therapeutic options we discuss the role of emerging therapies, the non-vitamin K oral anticoagulants (NOAC), in the treatment of VTE.


Assuntos
Insuficiência Renal Crônica/epidemiologia , Tromboembolia Venosa/epidemiologia , Anticoagulantes/uso terapêutico , Humanos , Proteinúria/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Índice de Gravidade de Doença , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia
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